Unnamed: 0 int64 0 2.34M | titles stringlengths 5 21.5M | abst stringlengths 1 21.5M |
|---|---|---|
2,332,300 | Propofol effective concentration 50 and its relationship to bispectral index. | Sixty unpremedicated healthy adult patients were studied during induction of anaesthesia with intravenous propofol delivered by a 'Diprifusor' target-controlled infusion. Bispectral index (BIS) and spectral edge frequency (SEF95) were measured concurrently with the predicted blood and effect site propofol concentrations. Logistic regression was used to calculate the predicted propofol blood and effect site concentrations required to produce unconsciousness and no response to a noxious stimulus in 50% and 95% of patients and to correlate BIS with these end-points. The Diprifusor TCI software produces anaesthesia at consistent target concentrations. Bispectral index correlates well with clinical end-points and may be useful during propofol anaesthesia. |
2,332,301 | Spinal anaesthesia with 0.5% hyperbaric bupivacaine in elderly patients: effects of duration spent in the sitting position. | Sixty patients, aged 65-84 yr, undergoing minor urological surgery under spinal anaesthesia remained sitting for 2 (group 1, n = 15), 5 (group 2, n = 15), 10 (group 3, n = 15), or 20 (group 4, n = 15) min after completion of the subarachnoid administration of 3 ml of a 0.5% hyperbaric bupivacaine solution. They were then placed in the supine position. Analgesia levels were assessed bilaterally using pinprick. Motor block was scored using a 12-point scale. Systolic and diastolic arterial pressures and heart rate were also recorded. Twenty minutes after the injection the upper analgesia levels were lower (P<0.05) in group 4 (median T9.0) than in the groups 1-3 (medians T6.6-T8.5). The highest obtained levels (medians T5.7-T8.0) did not differ between the groups, but occurred later (P<0.05) in group 4 (median 35 min) than in groups 1-3 (medians 19-24 min). There were no significant differences in the maximum degree of motor block or haemodynamic changes between the four study groups. |
2,332,302 | The effect of 10 degrees head-up tilt in the right lateral position on the systemic blood pressure after subarachnoid block for Caesarean section. | Forty women presenting for elective Caesarean section under spinal anaesthesia were randomly assigned to have anaesthesia induced in the right lateral position either in the horizontal position or with 10 degrees head-up tilt. Hyperbaric bupivacaine 2 ml 0.5% with 0.1 mg of morphine was injected intrathecally before the parturients were placed in the supine position with 15 degrees left lateral tilt. Blood pressure and heart rate were monitored every minute and the sensory level (loss of sharp sensation to pinprick) was monitored every 3 min until clamping of the umbilical cord. Ephedrine 6 mg was given every minute that the systolic blood pressure decreased below 90 mmHg. The mean systolic blood pressure during the first 5 min after induction of spinal anaesthesia was lower in the control group compared to the tilted group (99 mmHg vs. 109 mmHg; p = 0.043). The upper limit of block was higher in the control group compared to the tilted group (p = 0.002). The use of 10 degrees head-up tilt resulted in a reduced incidence of hypotension initially and less extensive sensory block. |
2,332,303 | [Tolerance to cardiotoxic effect of strophanthane K in experimental total heart block and electrocardiostimulation].<Pagination><StartPage>34</StartPage><EndPage>36</EndPage><MedlinePgn>34-6</MedlinePgn></Pagination><Abstract><AbstractText>Tolerance to the cardiotoxic effect of strophanthin K was studied in narcotized dogs with experimental complete heart block (CHB) and ventricular electrostimulation. A threshold to the toxic arrhythmogenic effect of strophanthin K was significantly reduced as compared to that in the control group. As the electrocardiostimulation (ECS) frequency increased, the minimum arrhythmogenic dose of strophanthin K showed a growth, while not reaching a level for the sinus rhythm. It is concluded that the basic mechanisms of the arrhythmogenic effect of strophanthin K under the conditions studied are the trigger activity in dogs with ECS and the increased peacemaker's activity in dogs with CHB.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Iskenderov</LastName><ForeName>B G</ForeName><Initials>BG</Initials><AffiliationInfo><Affiliation>Department of Therapy, Penza State Institute of Postgraduate Medical Training, ul. Stasova 8, Penza, 440060 Russia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Izuchenie tolerantnosti k kardiotoksicheskomu deĭstviiu strofantina K pri éksperimental'noĭ polnoĭ poperechnoĭ blokade serdtsa i élektrokardiostimuliatsii.</VernacularTitle></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Eksp Klin Farmakol</MedlineTA><NlmUniqueID>9215981</NlmUniqueID><ISSNLinking>0869-2092</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013328">Strophanthins</NameOfSubstance></Chemical><Chemical><RegistryNumber>O6I3I9267L</RegistryNumber><NameOfSubstance UI="C029082">strophanthin K</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001145" MajorTopicYN="N">Arrhythmias, Cardiac</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001161" MajorTopicYN="N">Arteriosclerosis</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004558" MajorTopicYN="N">Electric Stimulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="Y">Heart Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013328" MajorTopicYN="N">Strophanthins</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2002</Year><Month>3</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2002</Year><Month>4</Month><Day>16</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2002</Year><Month>3</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11871235</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11869646</PMID><DateCompleted><Year>2002</Year><Month>05</Month><Day>28</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>11</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>1</Issue><PubDate><Year>2002</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal>Cardioselective beta-blockers for reversible airway disease. | Tolerance to the cardiotoxic effect of strophanthin K was studied in narcotized dogs with experimental complete heart block (CHB) and ventricular electrostimulation. A threshold to the toxic arrhythmogenic effect of strophanthin K was significantly reduced as compared to that in the control group. As the electrocardiostimulation (ECS) frequency increased, the minimum arrhythmogenic dose of strophanthin K showed a growth, while not reaching a level for the sinus rhythm. It is concluded that the basic mechanisms of the arrhythmogenic effect of strophanthin K under the conditions studied are the trigger activity in dogs with ECS and the increased peacemaker's activity in dogs with CHB.</Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Iskenderov</LastName><ForeName>B G</ForeName><Initials>BG</Initials><AffiliationInfo><Affiliation>Department of Therapy, Penza State Institute of Postgraduate Medical Training, ul. Stasova 8, Penza, 440060 Russia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>rus</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Izuchenie tolerantnosti k kardiotoksicheskomu deĭstviiu strofantina K pri éksperimental'noĭ polnoĭ poperechnoĭ blokade serdtsa i élektrokardiostimuliatsii.</VernacularTitle></Article><MedlineJournalInfo><Country>Russia (Federation)</Country><MedlineTA>Eksp Klin Farmakol</MedlineTA><NlmUniqueID>9215981</NlmUniqueID><ISSNLinking>0869-2092</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D013328">Strophanthins</NameOfSubstance></Chemical><Chemical><RegistryNumber>O6I3I9267L</RegistryNumber><NameOfSubstance UI="C029082">strophanthin K</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001145" MajorTopicYN="N">Arrhythmias, Cardiac</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001161" MajorTopicYN="N">Arteriosclerosis</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004558" MajorTopicYN="N">Electric Stimulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006321" MajorTopicYN="N">Heart</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="Y">Heart Block</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013328" MajorTopicYN="N">Strophanthins</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2002</Year><Month>3</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2002</Year><Month>4</Month><Day>16</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2002</Year><Month>3</Month><Day>2</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11871235</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11869646</PMID><DateCompleted><Year>2002</Year><Month>05</Month><Day>28</Day></DateCompleted><DateRevised><Year>2020</Year><Month>05</Month><Day>11</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1469-493X</ISSN><JournalIssue CitedMedium="Internet"><Issue>1</Issue><PubDate><Year>2002</Year></PubDate></JournalIssue><Title>The Cochrane database of systematic reviews</Title><ISOAbbreviation>Cochrane Database Syst Rev</ISOAbbreviation></Journal><ArticleTitle>Cardioselective beta-blockers for reversible airway disease.</ArticleTitle><Pagination><StartPage>CD002992</StartPage><MedlinePgn>CD002992</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Beta-blocker therapy has mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with reversible airway disease.<AbstractText Label="OBJECTIVES" NlmCategory="OBJECTIVE">To assess the effect of cardioselective beta1-blockers on respiratory function of patients with reversible airway disease. Reversible airway disease was defined as asthma or chronic obstructive pulmonary disease with a reversible obstructive component.<AbstractText Label="SEARCH STRATEGY" NlmCategory="METHODS">A comprehensive search of EMBASE, MEDLINE and CINAHL was performed using the Cochrane Airways Group registry to identify randomized blinded placebo-controlled trials from 1966 to May 2001. The search was completed using the terms: asthma*, bronchial hyperreactivity*, respiratory sounds*, wheez*, obstructive lung disease* or obstructive airway disease*, and adrenergic antagonist*, sympatholytic* or adrenergic receptor block*. We did not exclude trials on the basis of language.<AbstractText Label="SELECTION CRITERIA" NlmCategory="METHODS">Randomized, blinded, placebo-controlled trials of single dose or longer duration that studied the effects of cardioselective beta1-blockers on the forced expiratory volume in 1 second (FEV1), symptoms and use of short-acting inhaled beta2-agonists, in patients with reversible airway disease. Reversible airway disease was documented by response to methacholine challenge, by an increase in FEV1 of at least 15% to beta2-agonist administration, or the presence of asthma as defined by the American Thoracic Society.<AbstractText Label="DATA COLLECTION AND ANALYSIS" NlmCategory="METHODS">Two independent reviewers extracted data from the selected articles, reconciling differences by consensus. Cardioselective beta1-blockers were divided into 2 groups, those with or without intrinsic sympathomimetic activity (ISA). Two interventions studied were the administration of beta1-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug.<AbstractText Label="MAIN RESULTS" NlmCategory="RESULTS">Nineteen studies for single-dose treatment and 10 for treatment of longer duration met selection criteria. The patients had mild-moderate airways obstruction. For cardioselective beta1-blockers taken as a group, administration of a single dose was associated with a 7.98% (CI, 6.19 to 9.77%) reduction in FEV1, but with a 13.16% (CI, 10.76 to 15.56%) increase in beta2-agonist response, as compared to placebo. There was no increase in symptoms. After treatment lasting a few days to a few weeks, there was no decrement in FEV1 compared to placebo and no increase in symptoms or inhaler use. Regular use of cardioselective beta1-blockers without ISA produced a 13.13% (CI, 5.97 to 20.30) increase in beta2-agonist response compared to placebo, a response not seen with beta1-blockers containing ISA (-0.60% [CI, -11.7 to +10.5%]).<AbstractText Label="REVIEWER'S CONCLUSIONS" NlmCategory="CONCLUSIONS">Cardioselective beta1-blockers, given to patients with mild-moderate reversible airway disease, do not produce clinically significant adverse respiratory effects in the short term. It is not possible to comment on their effects in patient with more severe or less reversible disease, or on their effect on the frequency or severity of acute exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta1-blockers should not be withheld from patients with mild-moderate reversible airway disease. |
2,332,304 | Amphiphilic block copolymers as bile acid sorbents: 2. Polystyrene-b-poly(N,N,N-trimethylammoniumethylene acrylamide chloride): self-assembly and application to serum cholesterol reduction. | This paper presents morphological studies and preliminary bile salt binding properties of the new amphiphilic diblock copolymer polystyrene-b-poly(N,N,N-trimethylammoniumethylene acrylamide chloride) (PS-b-PTMEACl)(1) (see Figure 1), a derivative of PS-b-poly(tert-butylacrylate) (PS-b-PtBuA). In an aqueous environment, PS-b-PTMEACl forms simple spheres (approximately 20 nm diameter), large compound micelles (>100 nm diameter), and larger, more complex architectures as presented and discussed below. The colloidal stability with respect to sodium chloride and as a function of particle concentration is also considered. Finally, PS-b-PTMEACl aggregates were prepared and tested as an alternative to the commercially available bile salt sequestrant resins that target coronary heart disease due to elevated cholesterol levels. Electron micrographs were employed to visualize the colloid-based polyelectrolyteminus signbiosurfactant interaction and chromatographic separation analytical methods were used to quantify the sequestration. The results indicate that although at this preliminary stage they require laborious preparation, self-assembled aggregates may present an interesting alternative to the clinically used bile salt sequestrants. |
2,332,305 | Lateralisation of projections from the rostral ventrolateral medulla to sympathetic preganglionic neurons in the rat. | Spinally projecting sympathoexcitatory neurons in the rostral ventrolateral medulla (RVLM), synapse with sympathetic preganglionic neurons (SPN) and regulate the activity of sympathetic nerves that control the heart, blood pressure and the adrenal medulla (AM). However, the degree of lateralization of the bulbospinal projections to SPN innervating specific targets is poorly understood. Three approaches were used in this study. Anterograde tracer was iontophoresed into a pressor site in the RVLM (left or right) and retrograde tracer injected into the superior cervical ganglion (SCG, right) and the AM (left). Close appositions between anterogradely labelled axons and retrogradely labelled SCG- or AM-SPN were counted. Projections to the SCG were bilateral. Projections to the AM were markedly ipsilateral. In the second part, retrograde tracers were injected unilaterally into the region of the intermediolateral cell column at spinal segment T2 or T8 on one side and the number of labelled neurons in the RVLM counted. The results from each level of injection were similar showing that approximately 63-64% of the neurons were ipsilateral. Responses to glutamate microinjection into the RVLM on adrenal nerve (left) and superior cervical nerve (left) activity were measured. The ratio of the nerve responses was the same even when different sides of the RVLM were injected. The anterograde data strongly suggest that the RVLM projections to AM-SPN are predominantly ipsilateral. Although other experimental approaches also attempted to investigate lateralization, the retrograde data target different and functionally heterogeneous pools of SPN that may mask the ipsilateral projection to the AM. Similarly, chemical stimulation of the RVLM will excite not only monosynaptic projections but also polysynaptic projections that may also mask the predominant ipsilateral monosynaptic projection to AM. |
2,332,306 | Spiral wave generation in heterogeneous excitable media. | As the coupling in a heterogeneous excitable medium is reduced, three different types of behavior are encountered: plane waves propagate without breaking up, plane waves break up into spiral waves, and plane waves block. We illustrate these phenomena in monolayers of chick embryonic heart cells using calcium sensitive fluorescent dyes. Following the addition of heptanol, an agent that reduces the electrical coupling between cells, we observe breakup of spiral waves. These results are modeled in a heterogeneous cellular automaton model in which the neighborhood of interaction is modified. |
2,332,307 | Inhibition of cardiac potassium currents by pentobarbital. | The inhibitory effects of the anesthetic barbiturate pentobarbital on the slow ( I(Ks)) and fast component ( I(Kr)) of cardiac delayed rectifier potassium currents ( I(K)) and on the inward rectifier potassium currents ( I(K1)) were examined in Xenopus oocytes expressing the human minK, human ether-á-go-go related gene (HERG) and guinea pig Kir2.2, respectively. Block of native I(K) ( I(Ks) and I(Kr)) and inward rectifier potassium current ( I(K1)) by pentobarbital was examined in guinea pig ventricular myocytes. In oocytes using the two electrode voltage clamp technique potassium currents of hminK-, HERG- and Kir2.2-expressing oocytes were inhibited by pentobarbital with IC50 values of 0.20, 1.58 and 0.54 mM, respectively. I(Ks) block was time- and voltage-independent and had no influence on activation at positive voltages although it shifted voltage-dependent activation to more positive voltages. Pentobarbital-induced HERG inhibition was not dependent on voltage but influenced the deactivation kinetics and shifted half-maximal activation to more negative voltages. In guinea pig cardiomyocytes, using the patch clamp technique, I(Ks) and I(Kr) were inhibited by pentobarbital with IC50 values of 0.18 mM and 2.75 mM, respectively. I(Kr) deactivation and I(Ks) activation kinetics were only slightly influenced by pentobarbital, if at all. Block of I(K1) was weakly voltage-dependent with IC(50) values of 0.26 mM (-40 mV) and 0.91 mM (-120 mV). The data show that pentobarbital suppresses both cloned ( I(K), I(Kir2.2)) and native ( I(K), I(K1)) cardiac potassium currents with the highest affinity for I(Ks). |
2,332,308 | [A case of renal cell carcinoma complicated with interstitial pneumonitis, complete A-V block and pleural effusion during interferon-alpha therapy]. | A 76-year-old man with postoperative renal cell carcinoma accompanied by multiple lung metastasis was being treated with recombinant interferon-alpha. After administration of 3 MU/day on 3 days/week for 1 month, he complained of headache and tinnitus. During continuous treatment for 3 months, he complained of appetite loss, low-grade fever and dyspnea. He was then referred to our Department of Internal Medicine. Electrocardiography indicated a complete A-V block, and chest radiography (CXR) showed a reticular shadow in both lower lung fields and bilateral pleural effusion. Chest computed tomography (CT) indicated subpleural emphysematous changes, multiple nodules, consolidation shadow with ground glass opacity in both lower lobes, and bilateral pleural effusion. The findings in the bronchoalveolar lavage (BAL) fluid included increases in the numbers of lymphocytes and eosinophils. We reached a diagnosis of interferon-alpha-induced pneumonitis on the basis of the patient's clinical course, and the CXR, chest CT and BAL fluid findings. Treatment with methylprednisolone pulse therapy for 3 days and then administration of prednisolone for 1 month resulted in marked improvement in the complete A-V block and interstitial pneumonitis. At day 7 after discontinuation of prednisolone, the serum level of C-reactive protein increased, and CXR showed bilateral pleural effusion. We therefore believe that the pleural effusion was probably also induced by interferon-alpha. Interferon is an effective drug for chronic hepatitis C and malignant diseases. Many complications have been reported during interferon therapy. However, although these complications, such as interstitial pneumonitis, complete A-V block and pleural effusion, have rarely been reported, careful attention is required during interferon therapy in case any appear. |
2,332,309 | Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents. | Using whole-cell patch clamp recording of heterologous HERG-mediated currents in transfected mammalian cells, we observed that the selective serotonin re-uptake inhibitor citalopram blocks HERG with an IC(50) of 3.97 microM. This is slightly less potent than fluoxetine in our system (IC(50) of 1.50 microM). In isolated guinea pig ventricular cardiomyocytes citalopram inhibited L-type calcium current (I(Ca,L)). The voltage dependence of I(Ca,L) inactivation in the presence of 100 microM citalopram was shifted significantly leftward. As a result, the I(Ca,L) 'window' in citalopram was found to be (a) smaller and (b) leftward-shifted compared to control. The effects of citalopram on both calcium current amplitude and the I(Ca,L) 'window' may help to explain citalopram's good cardiac safety profile, given its propensity to block HERG at excessive dosages. |
2,332,310 | Alpha-adrenergic receptor stimulation produces late preconditioning through inducible nitric oxide synthase in mouse heart. | Inducible nitric oxide synthase (iNOS) mediates late preconditioning (PC) induced by ischemia and pharmacological agents. Since alpha -adrenoceptor (alpha -AR) stimulation is one of the key triggers of PC, we hypothesized that activation of this receptor may induce delayed cardioprotective effect via iNOS-sensitive mechanisms. Adult male ICR mice were treated i.p. with either vehicle/inhibitors or phenylephrine (10 mg/kg) and subjected to 30 min of global ischemia and 30 min reperfusion in Langendorff mode 24 h later. 5-Methyl-urapidil (3 mg/kg) and chloroethylclonidine (3 mg/kg) were injected 15 min prior to phenylephrine to block alpha -AR(1A) and alpha -AR(1B) receptors respectively. S-Methylisothiourea (3 mg/kg), an iNOS inhibitor, was given 60 min prior to ischemia in phenylephrine-pretreated mice. Preischemic NO(x) was measured using a chemoluminescence reaction. Phenylephrine treatment reduced infarct size from 31.10 +/- 0.79% (vehicle) to 14.24 +/- 0.84% (P<0.001). Chloroethylclonidine blocked the effect of phenylephrine (infarct size 31.31 +/- 1.69%) but 5-methyl-urapidil (17.72 +/- 1.25%) did not. Phenylephrine-induced delayed cardioprotection was abolished by S-methylisothiourea and absent in iNOS knockout mice. Baseline NO(x) content was significantly increased in phenylephrine and 5-methyl-urapidil+phenylephrine treated hearts, but remained at baseline levels in hearts treated with chloroethylclonidine, 5-methyl-urapidil or S-methylisothiourea. Western blot analysis revealed a 1.8-fold increase in iNOS with phenylephrine, which was inhibited by chloroethylclonidine but not by 5-methyl-urapidil. We conclude that phenylephrine-induced delayed PC is mediated by selective activation of alpha-AR(1B). Enhanced iNOS expression concomitant with increased NO synthesis, as well as pharmacological blockade and absence of cardioprotection in iNOS knockout mice suggests an essential role of NO in phenylephrine triggered late PC. |
2,332,311 | Intracellular [Na+] and Na+ pump rate in rat and rabbit ventricular myocytes. | Intracellular [Na+] ([Na+]i) is centrally involved in regulation of cardiac Ca2+ and contractility via Na+-Ca2+ exchange (NCX) and Na+-H+ exchange (NHX). Previous work has indicated that [Na+]i is higher in rat than rabbit ventricular myocytes. This has major functional consequences, but the reason for the higher [Na+]i in rat is unknown. Here, resting [Na+]i was measured using the fluorescent indicator SBFI, with both traditional calibration and a novel null-point method (which circumvents many limitations of prior methods). In rabbit, resting [Na+]i was 4.5 +/- 0.4 mM (traditional calibration) and 4.4 mM (null-point). Resting [Na+]i in rat was significantly higher using both the traditional calibration (11.1 +/- 0.7 mM) and the null-point approach (11.2 mM). The rate of Na+ transport by the Na+ pump was measured as a function of [Na+]i in intact cells. Rat cells exhibited a higher V(max) than rabbit (7.7 +/- 1.1 vs. 4.0 +/- 0.5 mM x min(-1)) and a higher K(m) (10.2 +/- 1.2 vs. 7.5 +/- 1.1 mM). This results in little difference in pump activity for a given [Na+]i below 10 mM, but at measured resting [Na+]i levels the pump-mediated Na+ efflux is much higher in rat. Thus, Na+ pump rate cannot explain the higher [Na+]i in rat. Resting Na+ influx rate was two to four times higher in rat, and this accounts for the higher resting [Na+]i. Using tetrodotoxin, HOE-642 and Ni2+ to block Na+ channels, NHX and NCX, respectively, we found that all three pathways may contribute to the higher resting Na+ influx in rat (albeit differentially). We conclude that resting [Na+]i is higher in rat than in rabbit, that this is caused by higher resting Na+ influx in rat and that a higher Na+,K+-ATPase pumping rate in rat is a consequence of the higher [Na+]i. |
2,332,312 | Imipramine, mianserine and maprotiline block delayed rectifier potassium current in ventricular myocytes. | Imipramine, mianserine and maprotiline are three widely used antidepressant drugs with different chemical structure. In the present work we have studied the effects of these drugs on the delayed rectifier potassium current (I(K)) in myocytes isolated from rat ventricle. The delayed rectifier potassium current, responsible for action potential termination, is blocked by all of the three drugs I(K)studied in a state-independent manner. Imipramine and mianserine block I(K)in a 1 : 1 drug-receptor interaction, whereas maprotiline shows a negative cooperativity in the interaction between the channel complex and drug molecules. |
2,332,313 | Glycopyrronium and hypotension following combined spinal-epidural anaesthesia for elective Caesarean section in women with relative bradycardia. | The ability of glycopyrronium to reduce the severity of hypotension following subarachnoid block in parturients with a relative bradycardia was evaluated in a double-blind randomised controlled study. Women with a resting heart rate of < or = 80 beat x min(-1) presenting for elective Caesarean section were randomly allocated to receive either glycopyrronium 2 microg x kg(-1) or normal saline intravenously once positioned for combined spinal-epidural anaesthesia. Following spinal injection of 2.6 ml hyperbaric bupivacaine 0.5% and fentanyl 15 microg, women randomly allocated to the saline group were given 6 mg ephedrine so that all parturients received some prophylaxis against hypotension other than the fluid preload. Further ephedrine and fluid boluses were administered if mean arterial pressure fell 20% or more from resting values. Using a sequential analysis technique, analysis after the first 20 subjects indicated the study should be stopped, with no difference in ephedrine requirements or hypotension between the groups. We conclude that pretreatment with glycopyrronium 2 microg x kg(-1) is no more effective than 6 mg ephedrine in preventing hypotension following subarachnoid block in parturients with relatively low resting heart rates. |
2,332,314 | [The use of RNAi as a technique to study the functions of heart-related genes in Drosophila]. | RNAi is a recently developed method to block the activity of cellular genes by artificially providing sense and anti-sense RNA corresponding to a target gene. By inducing rapid degradation of the corresponding endogenous mRNA and blocking new mRNA synthesis, RNAi leads to post-transcriptional gene silencing. Now this phenomenon has been claimed to exist in C. elegans, Drosophila, buds, fungi and plants and is being used to study the functions of some special genes or the known genes at specific time point. It is extremely useful for those genes or organisms that their mutants are not easily obtained. The Drosophila heart related genes, tinman and wingless, have been shown to play an important role in coordinating the early formation of heart progenitor cells and precursors, yet the late function is still unexplored. In this experiment, we took the advantage of RNAi technique, microinjected tinman and wingless dsRNA into the early embryos in Drosophila respectively and got these two genes' RNAi phenotypes, which were very similar to that of their mutant, showing heart tube defects or no heart precursors formation. tinman dsRNA even caused visceral mesoderm defects and the somatic muscles disruption, yet wingless dsRNA only affected heart precursors and had no effect on visceral mesoderm and somatic muscles, indication that the heart-related genes dsRNA interference worked effectively and exclusively in Drosophila. |
2,332,315 | Inhibition of cardiac Na+ current by primaquine. | The electrophysiological effects of the anti-malarial drug primaquine on cardiac Na(+) channels were examined in isolated rat ventricular muscle and myocytes. In isolated ventricular muscle, primaquine produced a dose-dependent and reversible depression of dV/dt during the upstroke of the action potential. In ventricular myocytes, primaquine blocked I(Na)(+) in a dose-dependent manner, with a K(d) of 8.2 microM. Primaquine (i) increased the time to peak current, (ii) depressed the slow time constant of I(Na)(+) inactivation, and (iii) slowed the fast component for recovery of I(Na)(+) from inactivation. Primaquine had no effect on: (i) the shape of the I - V curve, (ii) the reversal potential for Na(+), (iii) the steady-state inactivation and g(Na)(+) curves, (iv) the fast time constant of inactivation of I(Na)(+), and (v) the slow component of recovery from inactivation. Block of I(Na)(+) by primaquine was use-dependent. Data obtained using a post-rest stimulation protocol suggested that there was no closed channel block of Na(+) channels by primaquine. These results suggest that primaquine blocks cardiac Na(+) channels by binding to open channels and unbinding either when channels move between inactivated states or from an inactivated state to a closed state. Cardiotoxicity observed in patients undergoing malaria therapy with aminoquinolines may therefore be due to block of Na(+) channels, with subsequent disturbances of impulse conductance and contractility. |
2,332,316 | Temperature-sensitive intracellular Mg2+ block of L-type Ca2+ channels in cardiac myocytes. | We examined the concentration-dependent blocking effects of intracellular Mg2+ on L-type Ca2+ channels in cardiac myocytes using the whole cell patch-clamp technique. The increase of L-type Ca2+ channel current (I(Ca)) (due to relief of Mg2+ block) occurred in two temporal phases. The rapid phase (runup) transiently appeared early (<5 min) in dialysis of the low-Mg2+ solution; the slow phase began later in dialysis (>10 min). Runup was not blocked by intracellular GTP (GTP(i)). The late phase of the I(Ca) increase (late I(Ca)) was suppressed by GTP(i) (0.4 mM) and was observed in myocytes of the guinea pig or frog at higher (32 or 24 degrees C, respectively) rather than lower temperatures (24 or 17.5 degrees C, respectively). At pMg = 6.0, raising the temperature from 24 to 32 degrees C evoked late I(Ca) with a Q10 of 14.5. Restoring the temperature to 24 degrees C decreased I(Ca) with a Q10 of only 2.4. The marked difference in the Q10 values indicated that late I(Ca) (pMg = 5-6) is an irreversible phenomenon. Phosphorylation suppressed the intracellular [Mg2+] dependency of late I(Ca). This effect of phosphorylation together with the inhibitory action of GTP(i) on Mg2+-dependent blocking of I(Ca) are common properties of mammalian and amphibian cardiomyocytes. |
2,332,317 | Endotoxin stress-response in cardiomyocytes: NF-kappaB activation and tumor necrosis factor-alpha expression. | Although tumor necrosis factor (TNF)-alpha is implicated in numerous cardiac pathologies, the intracellular events leading to its production by heart cells are largely unknown. The goal of the present study was to identify the role of the transcription factor nuclear factor (NF)-kappaB in this process. Among the many inducers of TNF-alpha expression in myeloid cells, only lipopolysaccharide (LPS) led to its induction in cultured neonatal myocytes. LPS also activated the NF-kappaB pathway, as evidenced by the degradation of the inhibitory protein IkappaB and the appearance of NF-kappaB-binding complexes in nuclear extracts. Furthermore, inhibitors of NF-kappaB activation, such as lactacystin, MG132, and pyrrolidine dithiocarbamate, were found to completely block the production of TNF-alpha in response to LPS stimulation, indicating a requirement of NF-kappaB for TNF-alpha expression. However, interleukin-1beta and phorbol 12-myristate 13-acetate also activated NF-kappaB but did not evoke TNF-alpha expression, revealing that this factor is not sufficient for cytokine production. Detailed examination of the NF-kappaB cascade revealed that cardiac cells displayed a unique pattern of IkappaB degradation in response to LPS, with IkappaBbeta but not IkappaBalpha being degraded upon stimulation. Additionally, two specific p65-containing DNA-binding complexes were observed in the nuclear extracts of neonatal cardiomyocytes: an inducible complex that is necessary for TNF-alpha expression and a constitutive species. Taken together, these results reveal that NF-kappaB is not only involved in cytokine production but also may be linked to other pathways that subserve a constitutive, protective mechanism for the heart cell. |
2,332,318 | Hemodynamic effects of agmatine in Dahl salt-sensitive hypertensive and Dahl salt-resistant rats. | The hemodynamic effects of agmatine were investigated in anaesthetized Dahl salt-sensitive (DS) hypertensive and Dahl salt-resistant (DR) rats. The results are as follows. (1) Agmatine (1, 10, 20 mg/kg i.v.) decreased heart rate (HR), mean arterial pressure (MAP), left ventricular blood pressure (LVP), the first derivative of LVP (LV dp/dt), cardiac index (CI) and total peripheral resistance index (TPRI) in a dose-dependent manner in both DS and DR rats, and the decreases in MAP, LVP, +/- LV dp/dtmax and TPRI at the same dose of agmatine in DR rats were less than those in DS hypertensive rats. Specifically, agmatine at high dose (20 mg/kg) induced a delayed increment of hemodynamic parameters in DS hypertensive rats, but not in DR rats. (2) Idazoxan (2.5 mg/kg), an antagonist for I2 over I1-imidazoline receptors and alpha 2-adrenoceptor receptors (alpha 2-AR), only partially blocked the effects of agmatine (10 mg/kg). (3) Yohimbine (4 mg/kg), a selective alpha 2-AR antagonist, also partially attenuated the effects of agmatine. (4) Efaroxan (2.5 mg/kg), a selective antagonist for I1 over I2-imidazoline receptors and alpha 2-AR, could completely block the effects of agmatine. Taken together, the results indicate that agmatine can dose-dependently decrease HR, MAP, LVP, +/- LV dp/dtmax, CI and TPRI in DS hypertensive and DR normotensive rats. The hemodynamic effects of agmatine are mediated mainly by I1-IR with the participation of I2-IR and alpha 2-AR. |
2,332,319 | A review of HNS-32: a novel azulene-1-carboxamidine derivative with multiple cardiovascular protective actions. | HNS-32 [N(1),N(1)-dimethyl-N(2)-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1- carboxamidine] (CAS Registry Number: 186086-10-2) is a newly synthesized azulene derivative. Computer simulation showed that its three dimensional structure is similar to that of the class Ib antiarrhythmic drugs, e.g., lidocaine or mexiletine. HNS-32 potently suppressed ventricular arrhythmias induced by ischemia due to coronary ligation and/or ischemia-reperfusion in dogs and rats. In the isolated dog and guinea pig cardiac tissues, HNS-32 had negative inotropic and chronotropic actions, prolonged atrial-His and His-ventricular conduction time and increased coronary blood flow. In the isolated guinea pig ventricular papillary muscle, HNS-32 decreased maximal rate of action potential upstroke (Vmax) and shortened action potential duration (APD). These findings suggest that HNS-32 inhibits inward Na+ and Ca2+ channel currents. In the isolated pig coronary and rabbit conduit arteries, HNS-32 inhibited both Ca2+ channel-dependent and -independent contractions induced by a wide variety of chemical stimuli. HNS-32 is a potent inhibitor of protein kinase C (PKC)-mediated constriction of cerebral arteries. It is likely to block both, Na+ and Ca2+ channels expressed in cardiac and vascular smooth muscles. These multiple ion channel blocking effects are largely responsible for the antiarrhythmic and vasorelaxant actions of HNS-32. This drug may represent a novel approach to the treatment of arrhythmias. |
2,332,320 | Tedisamil blocks BK-type Ca(2+)-dependent K(+) channels and modulates action potentials in rat hippocampal neurons. | Tedisamil, a bradycardic compound in heart, also acts on K(+) channels in neurons. We determined the actions of tedisamil on action potentials in CA1 pyramidal neurons in hippocampal slices and on BK-type Ca(2+)-activated K(+) channel activity in inside-out patches excised from hippocampal neurons. In slices, tedisamil (5 microM) attenuated the fast afterhyperpolarization (AHP) and prolonged the repolarization phase of the action potential. Additionally, the compound induced burst-firing activity and enhanced the slow AHP that follows a train of action potentials. The single channel data showed tedisamil actions to be consistent with open channel blockade of the BK-type of K(+) channel. Together, the results are consistent with the possibility that prolongation of the action potential by tedisamil is mediated by a tetraethylammonium-like effect of the agent to block BK-type Ca(2+)-activated K(+) channels. The study also points to a number of effects that may contribute to the known nervous system toxicity induced by tedisamil. |
2,332,321 | Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions. | Neonatal lupus is characterized by typical clinical features and the presence of maternal autoantibodies. Mothers can have systemic lupus erythematosus (SLE) or Sjögren's syndrome, but are commonly not affected with any clinical disease. The major clinical manifestations in the infants are cardiac, dermatological and hepatic with rare instances of hemolytic anemia, thrombocytopenia or neutropenia. We describe an infant born to a mother with anti-Ro and anti-La, who had neutropenia and mildly abnormal liver functions without other major clinical features of neonatal lupus such as cardiac or dermatological manifestations. Neutropenia improved as maternal antibody was metabolized. Antibodies from both the infant and mother bound intact neutrophils, and this binding was inhibited by 60 kDa Ro. These data imply neutropenia may be an isolated manifestation of neonatal lupus. We studied the anti-Ro antibodies of 2 other mothers who gave birth to infants with complete congenital heart block and neutropenia. Their sera also bound neutrophils. Because healthy infants do not commonly undergo complete blood counts, the incidence of neutropenia among infants of anti-Ro-positive mothers may be much higher than previously recognized. Furthermore, although other factors may contribute, these data suggest that anti-60 kDa Ro is directly involved in the pathogenesis of neutropenia. |
2,332,322 | Reduction mammaplasty with the "owl" incision and no undermining. | Reduction mammaplasty has traditionally been done using the Wise pattern of incision. Because of the box-like effect in breast shape, the lack of projection, and the long scars associated with the inverted T incision, two techniques have emerged as alternatives: the vertical reduction of Lassus/Lejour and the "round block" periareolar technique popularized by Benelli. Each of these techniques has its pros and cons. The "owl" incision combines the features of the large periareolar reduction (Benelli's) and the vertical reduction (Lassus/Lejour); the horizontal inframammary scar is either made very short or completely eliminated. Volume reduction is done through a heart-shaped parenchymal resection, leaving the nipple-areolar complex over a supero-central pedicle. Maintenance of the central parenchyma behind the nipple-areolar complex and mobilization of the vertical pillars toward the center of the breast give excellent projection and diminish the lateral fullness. Enlargement of the periareolar skin resection diminishes the length and pleating of the vertical scar; conversely, inclusion of the vertical component to the periareolar technique eliminates the pleating effect of the periareolar incision. The short horizontal excision eliminates any resultant "dog ears" in the new inframammary fold. Thus, the discrepancy in the length of scars is better distributed. There is no skin or parenchymal undermining, so drains are not needed. Excellent results are obtained immediately on the operating table, and large volumes of glandular resection and correction of severe ptosis can be accomplished without compromising vascularity of either the nipple-areolar complex or the skin flaps.Ninety-four patients in a 7-year period were operated upon using this technique. Seventy-two had bilateral reductions up to 1900 gm per breast, 12 had unilateral reduction for symmetry following breast reconstruction, and 10 were patients with severe ptosis. Complications were rare and of a minor nature. No conversion to free grafts was done, even in the larger resections. One case required minor revision under local anesthesia, one case required bilateral re-reduction, and another case required unilateral re-reduction for continued growth of breast tissue. Almost 90 percent of the patients underwent procedures as outpatients. The owl-type incision and the supero-central pedicle flap are elements of a reduction mammaplasty technique that provides excellent projection and shape with minimal visible scars. It takes advantage of the positive features of the periareolar and vertical reduction techniques and minimizes their negative features. The new design of parenchymal resection improves the vascularity of the residual flaps. Additionally, it may better preserve the sensation to the nipple-areolar complex and lactation is not compromised. |
2,332,323 | Antioxidant supplementation decreases lipid peroxidation biomarker F(2)-isoprostanes in plasma of smokers. | Free radicals in cigarette smoke (CS) cause oxidative damage to proteins, DNA, and lipids, contributing to the pathobiology of atherosclerosis, heart disease, and cancer. In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS. It is hypothesized that a combination of antioxidants is more effective than a single antioxidant, due to their interactions. To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination, we conducted an intervention study in smokers. In a randomized double-blind placebo-controlled trial, we investigated whether vitamin C or an antioxidant mixture containing vitamin C, alpha-lipoic acid, and vitamin E decreases plasma F(2)-isoprostane levels, an index of oxidant stress, in smokers. Plasma of 126 smokers (mean age, 46 years; age range, 20-78 years) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo. In smokers with a body mass index (BMI) above the median, 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group (P = 0.001); levels in the mixture group were 7.45 pmol/liter lower after treatment, but this difference was not statistically significant (P = 0.14). There was no treatment effect in smokers with a low BMI. BMI was significantly positively associated with plasma F(2)-isoprostane levels (trend P = 0.001). Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI. Our results do not indicate that an antioxidant combination is more effective than vitamin C alone. The intake of antioxidants may help prevent smoking-related diseases. Smoking cessation should still be considered the most effective way to prevent smoking-related diseases. |
2,332,324 | Apoptosis in young rats with adriamycin-induced cardiomyopathy--comparison with pirarubicin, a new anthracycline derivative. | In a previous study, we demonstrated that apoptosis in rats with adriamycin (ADR)-induced cardiomyopathy occurred through a Fas-dependent pathway. Pirarubicin, a new anthracycline derivative, seems to have a lower cardiotoxicity than ADR. To investigate whether pirarubicin has a lower chronic cardiotoxicity compared with ADR, ADR or pirarubicin were injected weekly for 8 wk into young Wister rats via the tail vein. To block the Fas-Fas ligand interaction, an anti-Fas ligand antibody (FasL) was injected with ADR 7, 8, and 9 wk after first administration of ADR. In the control group, saline was injected instead of ADR. ADR significantly induced apoptosis and left ventricular dysfunction 10 wk after the first administration of ADR. Pirarubicin also induced apoptosis, however, its apoptosis was significantly (p = 0.0069) less than that induced by ADR. Fas antigen was overexpressed in the hearts of ADR and ADR+FasL groups, however, an expression of Fas antigen in the pirarubicin group was similar to the expression of Fas antigen in the control group. Thus, pirarubicin has a significantly lower chronic cardiotoxicity compared with ADR. |
2,332,325 | Cytosolic malate dehydrogenase confers selectivity of the nucleic acid-conducting channel. | We have described previously a cell surface channel that is highly selective for nucleic acids. Nucleic acid conductance is 10 pS and the channel is at least 10,000-fold more selective for oligodeoxynucleotides than any anion tested (1). Herein we provide evidence that the nucleic acid-conducting channel (NACh) is a heteromultimeric complex of at least two proteins; a 45-kDa pore-forming subunit (p45) and a 36-kDa regulatory subunit (p36). Reconstitution of p45 in planar lipid bilayers resulted in formation of a channel which gated in the absence of nucleic acid and which was more selective for anions (including oligonucleotide) than cations. This channel exhibited transitions from one level of current to another (or to the closed state); however the incidence of transitions was rare. Channel activity was not observed when p36 was reconstituted alone. Reconstitution of p36 with p45 restored nucleic acid dependence and selectivity to the channel. Protein sequence analysis identified p36 as cytosolic malate dehydrogenase (cMDH). Experiments were performed to prove that cMDH is a regulatory subunit of NACh. Selective activity was observed when p45 was reconstituted with pig heart cMDH but not with mitochondrial MDH. Both the enzyme substrate l-malate and antiserum raised against cMDH block NACh activity. These data demonstrate that a nucleic acid conducting channel is a complex of at least two proteins, p45 and cMDH. Furthermore, these data establish that cMDH confers nucleic acid selectivity of the channel. |
2,332,326 | Sick sinus syndrome in a bull terrier. | The occurrence of ideopathic sick sinus syndrome in a previously unrecognized breed is described. An initially asymptomatic bull terrier was diagnosed with sick sinus syndrome without significant detectable underlying cardiac disease. |
2,332,327 | A comparison of actual registered costs and costs derived from diagnosis-related groups (DRGs) for patients undergoing heart transplantation, lung transplantation, and thoracotomy for other lung diseases. | The Norwegian health care system, like other health care systems in the world, is in the midst of a changing financial environment for hospital reimbursement for patient care. Since 1997 the Norwegian government has introduced a new financing model of block grant and activity-based financing. In this model, diagnosis-related groups (DRGs) play an important role in hospital financing. The initial motive for developing the DRGs was to improve hospital productivity and efficiency and to develop a tool to control increasing hospital costs better. We raised the question as to whether the DRG system in fact covers actual costs in patient groups undergoing heart transplantation (n = 12), lung transplantation (n = 4), and thoracotomy for other diseases (n = 10). A new prospective cost model was developed to measure actual costs related to individual patients. The patients were closely observed and the related data collected during the hospital stay. Each patient's hospital stay was divided into four different categories of resource requirements, defined as heavy intensive care, light intensive care, intermediate care, and ordinary care. In addition, the number of staff involved and the duration of surgery and procedures were recorded, as were medicine costs and material costs. Based on these data, the actual costs for each patient were calculated. These were then compared with the respective DRG reimbursement (100 % coverage) for the corresponding group. We found that the median cost for heart transplantation was US$ 50,590 (1 US$ = 7.5 NOK based on the exchange rate at the time of the study), while the respective DRG reimbursement was US$ 65,662. For lung transplantation, the respective figures were US$ 46,668 vs US$ 65,662, and for thoracotomy, US$ 24,307 vs. US$ 11,004. We found that our method was applicable to a hospital setting. DRG coverage for heart and lung transplantation seems to overestimate the actual costs. For the thoracotomy procedure, the DRG coverage did not cover the actual costs. |
2,332,328 | Experience modifies olfactory acuity: acetylcholine-dependent learning decreases behavioral generalization between similar odorants. | Perceptual learning has been demonstrated in several thalamocortical sensory systems wherein experience enhances sensory acuity for trained stimuli. This perceptual learning is believed to be dependent on changes in sensory cortical receptive fields. Sensory experience and learning also modifies receptive fields and neural response patterns in the mammalian olfactory system; however, to date there has been little reported evidence of learned changes in behavioral olfactory acuity. The present report used a bradycardial orienting response and cross-habituation paradigm that allowed assessment of behavioral discrimination of nearly novel odorants, and then used the same paradigm to examine odorant discrimination after associative olfactory conditioning with similar or dissimilar odorants. The results demonstrate that associative conditioning can enhance olfactory acuity for odors that are the same as or similar to the learned odorant, but not for odors dissimilar to the learned odorant. Furthermore, scopolamine injected before associative conditioning can block the acquisition of this learned enhancement in olfactory acuity. These results could have important implications for mechanisms of olfactory perception and memory, as well as for correlating behavioral olfactory acuity with observed spatial representations of odorant features in the olfactory system. |
2,332,329 | Inhibitor of beta-hydroxy-beta-methylglutaryl coenzyme A reductase decreases energy supply to the myocardium in rats. | Hypocholesterolemic preparations, inhibitors of the key enzyme of cholesterol biosynthesis beta-hydroxy-beta-methylglutaryl coenzyme A reductase (statins), block the synthesis of ubiquinone Q10, intermediate electron carrier in the mitochondrial respiratory chain. This should decrease energy supply to tissues. Daily peroral administration of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor simvastatin (24 mg/kg perorally) for 30 days had no effect on the contents of macroergic phosphates (ATP and creatine phosphate) in the liver, but decreased these parameters in the myocardium. |
2,332,330 | Selective inhibitor of Janus tyrosine kinase 3, PNU156804, prolongs allograft survival and acts synergistically with cyclosporine but additively with rapamycin. | Janus kinase 3 (Jak3) is a cytoplasmic tyrosine (Tyr) kinase associated with the interleukin-2 (IL-2) receptor common gamma chain (gamma(c)) that is activated by multiple T-cell growth factors (TCGFs) such as IL-2, -4, and -7. Using human T cells, it was found that a recently discovered variant of the undecylprodigiosin family of antibiotics, PNU156804, previously shown to inhibit IL-2-induced cell proliferation, also blocks IL-2-mediated Jak3 auto-tyrosine phosphorylation, activation of Jak3 substrates signal transducers and activators of transcription (Stat) 5a and Stat5b, and extracellular regulated kinase 1 (Erk1) and Erk2 (p44/p42). Although PNU156804 displayed similar efficacy in blocking Jak3-dependent T-cell proliferation by IL-2, -4, -7, or -15, it was more than 2-fold less effective in blocking Jak2-mediated cell growth, its most homologous Jak family member. A 14-day alternate-day oral gavage with 40 to 120 mg/kg PNU156804 extended the survival of heart allografts in a dose-dependent fashion. In vivo, PNU156804 acted synergistically with the signal 1 inhibitor cyclosporine A (CsA) and additively with the signal 3 inhibitor rapamycin to block allograft rejection. It is concluded that inhibition of signal 3 alone by targeting Jak3 in combination with a signal 1 inhibitor provides a unique strategy to achieve potent immunosuppression. |
2,332,331 | Technical factors associated with radiation pneumonitis after local +/- regional radiation therapy for breast cancer. | To assess the incidence of, and clinical factors associated with, symptomatic radiation pneumonitis (RP) after tangential breast/chest wall irradiation with or without regional lymph node treatment.</AbstractText>The records of 613 patients irradiated with tangential photon fields for breast cancer with >6 months follow-up were reviewed. Clinically significant RP was defined as the presence of new pulmonary symptoms requiring steroids. Data on clinical factors previously reported to be associated with RP were collected, e.g., tamoxifen or chemotherapy exposure and age. The central lung distance (CLD) and the average of the superior and inferior mid lung distance (ALD) in the lateral tangential field were measured on simulator films as a surrogate for irradiated lung volume. Many patients were treated with partly wide tangential fields that included a heart block shielding a part of the lower lung.</AbstractText>RP developed in 15/613 (2.4%) patients. In the univariate analysis, there was an increased incidence of RP among patients treated with local-regional radiotherapy (RT) (4.1%) vs. those receiving local RT only (0.9%) (p = 0.02), and among patients receiving chemotherapy (3.9%) vs. those not treated with chemotherapy (1.4%) (p = 0.06). According to multivariate analysis, only the use of nodal RT remained independently associated with RP (p = 0.03). There was no statistically significant association between ranked CLD or ALD measurements and RP among patients treated with nodal irradiation with tangential beams. However, there was a statistically nonsignificant trend for increasing rates of RP with grouped ALD values: below 2 cm (4% RP rate), between 2 and 3 cm (6%), and above 3 cm (14%).</AbstractText>RP was an uncommon complication, both with local and local-regional RT. The addition of regional lymph node irradiation slightly increased the incidence of RP among patients treated with the partly wide tangential field technique. Concern for RP should, however, not deter patients with node-positive breast cancer from receiving local-regional RT.</AbstractText> |
2,332,332 | Effects of phytoestrogens on DNA synthesis and creatine kinase activity in vascular cells. | The aim of this study was to assess the effect of phytoestrogens on the human vascular wall in vitro.</AbstractText>We compared the effects of E2 to those of genistein (G), daidzein (D), biochanin A (BA), equol (EQ), and quecertin (Qu) on 3[H] thymidine incorporation and creatine phosphokinase (CK) activity in human vascular smooth muscle cells (VSMC) and in a human endothelial cell line (E304).</AbstractText>In VSMC, E2, the estrogen antagonist raloxifene (RAL), G, and D stimulated DNA synthesis at low concentrations and suppressed 3[H] thymidine incorporation at higher concentrations. In contrast, BA and EQ had a monophasic stimulatory effect on 3[H] thymidine incorporation (87% +/- 9% and 54% +/- 17%, respectively) whereas Qu had only an inhibitory effect (-36 +/- 16% at 30 nmol/L). In E304 cells, all phytoestrogens stimulated DNA synthesis in a dose-related manner. In both cell types E2, RAL as well as all phytoestrogens increased CK-specific activity. The administration of phytoestrogens to immature female rats resulted in increased CK in the aorta (Ao) (60% to 220%) and in the left ventricle of the heart (Lv) (45% to 160%). Similar increases in Ao and Lv CK were also induced by E2 and all five phytoestrogens in ovariectomized (OVX) female rats. RAL antagonized phytoestrogen-induced CK activity in human vascular cells and in the rat Ao and Lv tissue but did not block phytoestrogen effects on DNA synthesis in human VSMC.</AbstractText>Although phytoestrogens have estrogen-mimetic effects on cell growth and CK in cultured human vascular cells and on CK in rat vascular tissues in vivo, the effects on human VSMC replication are highly dependent on the concentration and the particular phytoestrogen under investigation.</AbstractText> |
2,332,333 | Comparison of analgesic techniques for antler removal in wapiti. | The purpose of this research was to compare the effectiveness of ring block anesthesia (LA) and electroanesthesia (A) for antler removal in elk given a long-acting tranquilizer to remove stress from restraint. Thirty-two male wapiti were given 1 mg/kg body weight of zuclopenthixol acetate; the next day, they were restrained in a hydraulic chute, provided with electroanesthesia or a lidocaine ring block, and had their antlers removed. Behavioral response to antler removal was scored. Significantly more (P = 0.032) animals responded to antler removal in the EA group. Heart rates and arterial pressures were measured by a catheter connected to a physiological monitor. Heart rate increased significantly over time with EA, but not with LA. Heart rate increased from baseline significantly more in the EA group immediately prior to antler removal (P = 0.017), immediately post antler removal (P = 0.001), and at 1 min post antler removal (P = 0.037). It was concluded that EA is not as effective a method of anesthesia as is LA for antler removal. |
2,332,334 | Transport of Ca2+ from sarcoplasmic reticulum to mitochondria in rat ventricular myocytes. | Studies with electron microscopy have shown that sarcoplasmic reticulum (SR) and mitochondria locate close to each other in cardiac muscle cells. We investigated the hypothesis that this proximity results in a transient exposure of mitochondrial Ca2+ uniporter (CaUP) to high concentrations of Ca2+ following Ca2+ release from the SR and thus an influx of Ca2+ into mitochondria. Single ventricular myocytes of rat were skinned by exposing them to a physiological solution containing saponin (0.2 mg/ml). Cytosolic Ca2+ concentration ([Ca2+]c) and mitochondrial Ca2+ concentration ([Ca2+]m) were measured with fura-2 and rhod2, respectively. Application of caffeine (10 mM) induced a concomitant increase in [Ca2+]c and [Ca2+]m. Ruthenium red, at concentrations that block CaUP but not SR release, diminished the caffeine-induced increase in [Ca2+]m but not [Ca2+]c. In the presence of 1 mM BAPTA, a Ca2+ chelator, the caffeine-induced increase in [Ca2+]m was reduced substantially less than [Ca2+]c. Moreover, inhibition of SR Ca2+ pump with two different concentrations of thapsigargin caused an increase in [Ca2+]m, which was related to the rate of [Ca2+]c increase. Finally, electron microscopy showed that sites of junctions between SR and T tubules from which Ca2+ is released, or Ca2+ release units, CRUs, are preferentially located in close proximity to mitochondria. The distance between individual SR Ca2+ release channels (feet or ryanodine receptors) is very short, ranging between approximately 37 and 270 nm. These results are consistent with the idea that there is a preferential coupling of Ca2+ transport from SR to mitochondria in cardiac muscle cells, because of their structural proximity. |
2,332,335 | Effect of an acute oral ibuprofen intake on urinary aquaporin-2 excretion in healthy humans. | Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase and thereby block the prostaglandin (PG) synthesis in the kidneys. In animals, PG interferes with the formation of aquaporin 2 in the distal renal tubules. The purpose was to measure the effect of ibuprofen on urinary excretion of aquaporin-2 (u-AQP2), urinary output, urinary osmolality (u-osm) and plasma concentration of vasopressin (AVP) in a dose-response study using placebo and ibuprofen 600mg and 1200mg. In 12 healthy subjects, urine was collected in 6 periods between 07.00 h and 13.00 h, and blood samples were drawn at 60-min intervals. The study medication was given 10 h and 1 h before the study. U-AQP2 and AVP were determined by radioimmunoassays. U-AQP2 decreased 33% in the placebo group and increased 47% in the ibuprofen groups. There was a highly significant difference between the placebo group, on the one hand, and the ibuprofen groups, on the other. There was a small but significant increase in AVP in the placebo group and the 600 mg ibuprofen group, but not in the 1200 mg ibuprofen group. Urinary output was at maximum after 2 h, with a 394%, 1020% and 714% increase for placebo, 600 mg ibuprofen and 1200 mg ibuprofen, respectively. U-osm decreased during the experiment in all three groups. Inhibition of renal prostaglandin synthesis by ibuprofen affects the distal part of the nephron by increasing u-AQP2. This increase was not related to changes in AVP, urinary output or urinary osmolality. We suggest that the increased excretion of AQP2 can be explained by an increase in the ratio of AQP2 that is shed into the urine because the endocytic retrieval of AQP2 from the apical membrane is impaired. This could not be revealed by changes in the osmoregulatory system by the low doses of ibuprofen used in the present study. |
2,332,336 | An approach to dissecting the congenitally malformed heart in the forensic autopsy: the value of sequential segmental analysis. | The demonstration of congenital heart disease at autopsy necessitates the careful preservation and examination of the heart, the vessels, and their connections. Techniques preserving these connections and using a reproducible and systematic approach are preferred. The Rokitansky method of organ block dissection, in combination with a system of heart examination termed sequential segmental analysis, provides such an approach. This study is based on the examination of heart specimens accessioned into the Frank E. Sherman, M.D., and Cora C. Lenox, M.D., Heart Museum (containing approximately 2400 specimens) of the Pathology Department, Children's Hospital of Pittsburgh. Specimens received in consultation during a 25-year period from hospitals and coroners'/medical examiners' offices were examined, and the corresponding reports were reviewed. Of 46 total heart specimens examined (1975-1999), 29 (63%) were dissected properly or left intact for dissection at Children's Hospital of Pittsburgh, and 17 (37%) were incorrectly dissected for the demonstration of congenital heart disease. Of these 17 cases, 11 (24%) displayed dissection errors, which did not hinder a complete diagnosis, 3 cases (6.5%) had errors that enabled only an incomplete diagnosis, and in 3 cases (6.5%), no diagnosis of congenital heart disease could be made. Dissection mistakes and means of avoiding them are discussed. Review of medical and family history, external and internal examination, and a reproducible and sequential method of examining the heart and its connections enables documentation of even the most complex cardiovascular anomalies. |
2,332,337 | Structural basis of differences in isoform-specific gating and lidocaine block between cardiac and skeletal muscle sodium channels. | Voltage-gated Na(+) channels underlie rapid conduction in heart and skeletal muscle. Cardiac sodium channels open and close over more negative potentials than do skeletal muscle sodium channels; heart channels are also more sensitive to lidocaine block. The structural basis of these differences is poorly understood. We mutated nine isoform-specific micro1 (rat skeletal muscle) channel residues in domain IV to those at equivalent locations in hH1 (human cardiac) channels. Channel constructs were expressed in tsA-201 cells and screened for changes in gating and lidocaine sensitivity. Only L1373E, located in the linker between the S1 and S2 transmembrane segments, shifted activation gating and use-dependent block by lidocaine toward that seen in hH1. The converse mutation, hH1-E1555L, shifted the phenotype of hH1 to resemble that of micro1. Therefore, we identified a previously unsuspected glutamate-to-leucine isoform-specific variant site (i.e., 1555 in hH1 and 1373 in micro1) that significantly influences gating and drug block in sodium channels. The identification of the residue at this position plays a major role in shaping the responses of sodium channels to voltage and to lidocaine, helping to rationalize the distinctive behavior of cardiac sodium channels. |
2,332,338 | Association of multiple developmental defects and embryonic lethality with loss of microsomal NADPH-cytochrome P450 oxidoreductase. | The microsomal flavoprotein NADPH-cytochrome P450 oxidoreductase (CYPOR) is believed to function as the primary, if not sole, electron donor for the microsomal cytochrome P450 mixed-function oxidase system. Development of the mammalian embryo is dependent upon temporally and spatially regulated expression of signaling factors, many of which are synthesized and/or degraded via the cytochromes P450 and other pathways involving NADPH-cytochrome P450 oxidoreductase as the electron donor. Expression of CYPOR as early as the two-cell stage of embryonic development (The Institute for Genomic Research Mouse Gene Index, version 5.0, www.tigr.org/tdb/mgi) suggests that CYPOR is essential for normal cellular functions and/or early embryogenesis. Targeted deletion of the translation start site and membrane-binding domain of CYPOR abolished microsomal CYPOR expression and led to production of a truncated, 66-kDa protein localized to the cytoplasm. Although early embryogenesis was not affected, a variety of embryonic defects was observable by day 10.5 of gestation, leading to lethality by day 13.5. Furthermore, a deficiency of heterozygotes was observed in 2-week-old mice as well as late gestational age embryos, suggesting that loss of one CYPOR allele produced some embryonic lethality. CYPOR -/- embryos displayed a marked friability, consistent with defects in cell adhesion. Ninety percent of CYPOR -/- embryos isolated at days 10.5 or 11.5 of gestation could be classified as either Type I, characterized by grossly normal somite formation but having neural tube, cardiac, eye, and limb abnormalities, or Type II, characterized by a generalized retardation of development after approximately day 8.5 of gestation. No CYPOR -/- embryos were observed after day 13.5 of gestation. These studies demonstrate that loss of microsomal CYPOR does not block early embryonic development but is essential for progression past mid-gestation. |
2,332,339 | Pacemaker channels produce an instantaneous current. | Spontaneous rhythmic activity in mammalian heart and brain depends on pacemaker currents (I(h)), which are produced by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here, we report that the mouse HCN2 pacemaker channel isoform also produced a large instantaneous current (I(inst(HCN2))) in addition to the well characterized, slowly activating I(h). I(inst(HCN2)) was specific to expression of HCN2 on the plasma membrane and its amplitude was correlated with that of I(h). The two currents had similar reversal potentials, and both were modulated by changes in intracellular Cl(-) and cAMP. A mutation in the S4 domain of HCN2 (S306Q) decreased I(h) but did not alter I(inst(HCN2)), and instantaneous currents in cells expressing either wild type HCN2 or mutant S306Q channels were insensitive to block by Cs(+). Co-expression of HCN2 with the accessory subunit, MiRP1, decreased I(h) and increased I(inst(HCN2)), suggesting a mechanism for modulation of both currents in vivo. These data suggest that expression of HCN channels may be accompanied by a background conductance in native tissues and are consistent with at least two open states of HCN channels: I(inst(HCN2)) is produced by a Cs(+)-open state; hyperpolarization produces an additional Cs(+)-sensitive open state, which results in I(h). |
2,332,340 | Hamster cardiac xenografts are protected against antibody mediated damage, early after transplantation to Lewis rats. | Antibodies play a crucial role in the rejection of xenografts. We tested the hypothesis that xenografts are protected against antibody-mediated attack early after transplantation in a concordant model. We investigated the role of xenoreactive antibodies as a stimulus for protection and the effects of a total blockade of the antibody response by the leflunomide analog malononitrilamide 279. Hamster cardiac xenografts were transplanted to Lewis rat recipients. Second transplants and retransplants of xenografts were performed to untreated rats that had a xenograft in place for 3 d. Untreated rats rejected hamster cardiac xenografts after 4.0 +/- 0.0 d. Significant levels of anti-donor IgM, as measured by flowcytometry, were present on day 3 after transplantation (11.2% +/- 2.8 vs. 1.2% +/- 0.0 on day 0, P < 0.001). 'Fresh' second xenografts transplanted to rats that had a first xenograft in place for 3 d and had anti-hamster antibodies, underwent hyperacute rejection. The first xenografts remained functioning. Xenografts that were removed on day 3 from untreated rats and then retransplanted remained functioning. Xenografts that were removed on d 3 from rats that had been treated with malononitrilamide 279, 15 mg/kg/d and were retransplanted underwent hyperacute rejection. IgM levels at the time of removal were 1.1% +/- 0.5 in these rats and not different from baseline (P = 0.96). We conclude that xenografts are protected against antibody-mediated damage early after transplantation. The presence of anti-donor antibodies might be an essential stimulus for the induction of protection. There seems to be a delicate balance between the injurious and protective effects of antibodies. Treatment strategies that are designed to block antibody formation completely might prevent the induction of protection. |
2,332,341 | Activation of connexin-43 hemichannels can elevate [Ca(2+)]i and [Na(+)]i in rabbit ventricular myocytes during metabolic inhibition. | ATP depletion due to ischemia or metabolic inhibition (MI) causes Na(+) and Ca(2+) accumulation in myocytes, which may be in part due to opening of connexin-43 hemichannels. Halothane (H) has been shown to reduce conductance of connexin-43 hemichannels and to protect the heart against ischemic injury. We therefore investigated the effect of halothane on [Ca(2+)]i and [Na(+)]i in myocytes during MI. Isolated rabbit left ventricular myocytes were loaded with 4 microM fluo-3 AM for 30 min, or with 5 microM sodium green AM for 60 min at 37 degrees C. After washing, the myocytes were exposed to: (1) Normal HEPES solution; (2) MI solution (2 mM NaCN, 20 mM 2-deoxy-D-glucose and 0-glucose); or (3) MI+H (0.95 mM, 4.7 mM) for 60 min. Propidium iodide (PI, 25 microM) was added to all samples before data acquisition. The fluorescence intensity was measured by flow cytometry with 488 nm excitation and 530 nm emission for fluo-3 or sodium green, and 670 nm for PI. The [Ca(2+)]i and [Na(+)]i were then calculated by calibration. In some experiments, the effect of 10 microM tetrodotoxin (TTX) and 20 microM nifedipine (NIF) were studied. Metabolic inhibition for 60 min caused a significant increase in [Ca(2+)]i and [Na(+)]i in myocytes when compared to controls, which was significantly reduced by halothane in a dose-dependent fashion. In the presence of TTX and NIF, halothane also significantly reduced the rise in the [Ca(2+)]i and [Na(+)]i in myocytes subjected to MI. 1-heptanol, another gap junction blocker, had similar effects. Thus, halothane reduced [Ca(2+)]i and [Na(+)]i overload produced by MI in myocytes. This effect is not solely due to block of voltage-gated Na(+) and Ca(2+) channels, and is likely mediated by inhibiting the opening of connexin-43 hemichannels. |
2,332,342 | Neonatal lupus erythematosus in association with anti-RNP antibody: a case report. | Neonatal lupus erythematosus (NLE) is a syndrome with the manifestation of dermatological, cardiac, hepatic, or hematological abnormalities. Thrombocytopenia has been documented infrequently in association with congenital heart block or lupus dermatitis in NLE. However, isolated neonatal thrombocytopenia may be the only manifestation of NLE. The strong association with maternal anti-SSA/Ro antibodies suggests a role for these antibodies in the pathogenesis of NLE. There are some data to suggest that anti-SSB/La and, rarely, anti-RNP antibodies play an important pathological role in some cases of NLE. The manifestation of anti-RNP-positive NLE was somewhat atypical. We report a case of anti-RNP-positive NLE with the manifestation of thrombocytopenia. Anti-SSA/Ro antibodies, which were negative based on the use of immunodiffusion, did exhibit low titer when later tested by enzyme-linked immunoadsorbent assay (ELISA). |
2,332,343 | Interactive effects of dietary sodium and chloride on the incidence of spontaneous cardiomyopathy (round heart) in turkeys. | Two pen trials were conducted in Utah, altitude 1,630 m, with Large White female turkey poults to evaluate effects of dietary Na and chloride (Cl) concentrations on live performance and deaths caused by spontaneous cardiomyopathy (STC, "round heart") from 0 to 35 d of age. A randomized block 2 x 2 factorial arrangement with four replicate pens per treatment was used. Pen size was 3.8 x 5.6 m. In each trial, four starter diets were formulated from a common basal diet (corn-soy-meat) to obtain the following sodium and chloride concentrations: High Na (0.24%):High Cl (0.40%); High Na (0.24%):Low Cl (0.16%); Low Na (0.14%):High Cl (0.40%); and Low Na (0.14%):Low Cl (0.16%). Supplements were NaCl, NaHCO3, NH4Cl, or combinations. After laboratory analysis, true values of Na were slightly lower than expected, Cl was near expected values to slightly low, and K was 1.145%. Body weight and feed conversion ratio at 35 d of age were unaffected in both trials. In both experiments, STC mortality was significantly reduced by the Low Na:High Cl treatment compared to the other treatments. In conclusion, a diet containing 0.10 to 0.12% Na and 0.38 to 0.40% Cl, significantly improved poult livability by reducing STC mortality without adverse effects on poult weight or feed conversion ratio. |
2,332,344 | Survivors of childhood cancers: implications for obstetric anaesthesia. | Treatment of many childhood malignancies involves surgery, radiotherapy and chemotherapy. If the child survives, normal physical development can be impaired and abnormalities with anaesthetic implications may be present. We discuss two women with a range of problems who presented for obstetric anaesthesia, having survived childhood malignancies. Common features included anthracycline cardiotoxicity and short stature. Both patients received incremental spinal anaesthesia in order to titrate the dose of local anaesthetic required to produce an adequate block height and to minimize cardiovascular instability. |
2,332,345 | The six hyaluronidase-like genes in the human and mouse genomes. | The human genome contains six hyaluronidase-like genes. Three genes (HYAL1, HYAL2 and HYAL3) are clustered on chromosome 3p21.3, and another two genes (HYAL4 and PH-20/SPAM1) and one expressed pseudogene (HYALP1) are similarly clustered on chromosome 7q31.3. The extensive homology between the different hyaluronidase genes suggests ancient gene duplication, followed by en masse block duplication, events that occurred before the emergence of modern mammals. Very recently we have found that the mouse genome also has six hyaluronidase-like genes that are also grouped into two clusters of three, in regions syntenic with the human genome. Surprisingly, the mouse ortholog of HYALP1 does not contain any mutations, and unlike its human counterpart may actually encode an active enzyme. Hyal-1 is the only hyaluronidase in mammalian plasma and urine, and is also found at high levels in major organs such as liver, kidney, spleen, and heart. A model is proposed suggesting that Hyal-2 and Hyal-1 are the major mammalian hyaluronidases in somatic tissues, and that they act in concert to degrade high molecular weight hyaluronan to the tetrasaccharide. Twenty-kDa hyaluronan fragments are generated at the cell surface in unique endocytic vesicles resulting from digestion by the glycosylphosphatidyl-inositol-anchored Hyal-2, transported intracellularly by an unknown process, and then further digested by Hyal-1. The two beta-exoglycosidases, beta-glucuronidase and beta-N-acetyl glucosaminidase, remove sugars from reducing termini of hyaluronan oligomers, and supplement the hyaluronidases in the catabolism of hyaluronan. |
2,332,346 | In situ measurement of nitric oxide production in cardiac isografts and rejecting allografts by an electrochemical method. | A number of previous studies have indirectly (electron paramagnetic resonance, nitrite/nitrate, ribonuclease protection assay for inducible nitric oxide synthase (iNOS) mRNA, l-citrulline assay) demonstrated the production of nitrogen monoxide (NO) during early cardiac allograft rejection. This study reports the first direct, quantitative measurement using an electrochemical method of NO produced from rejecting allograft tissue studied in vitro. A rat heterotopic abdominal transplant preparation was utilized. Day 7 isograft (ACI to ACI) or allograft (Lewis to ACI) transplanted hearts were atraumatically harvested and suspended at 4 degrees C in Ringers-Hepes solution. An electrochemical system highly sensitive and specific for NO consisting of a Nafion-coated platinum disk electrode (lower limit, 50 nM NO) coupled to an analysis system measured ongoing oxidation of NO. Measurements were carried out after inserting the electrode in the tissue block and warming the block to 25 degrees C. Additional measurements were also made after incubation of tissue with aminoguanidine (AG), a relatively selective iNOS inhibitor. Direct measurements (mean +/- SEM) from allograft tissue indicated a fourfold increase in NO as compared with isografts (13.41 +/- 4.40 microM NO vs. 3.43 +/- 2.04 microM NO). Incubation of allograft tissue with AG reduced NO levels to isograft levels (13.41 +/- 4.40 microM NO vs. 5.94 +/- 3.14 microM NO); AG had no effect on measured isograft NO levels. Direct, quantitative measurement of NO from tissue is feasible and reproducible, and discrimination between different levels of NO production can be made. These results confirm the imputed results from the previous studies using this experimental model. This technology promises to be a valuable tool for evaluating specific modulators of NO production studied under a variety of physiologic and pathophysiologic conditions. |
2,332,347 | [An approach for comparative quantification of myocardial blood flow (O-15-H2O-PET), perfusion (Tc-99m-tetrofosmin-SPECT) and metabolism (F-18-FDG-PET)]. | In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices.</AbstractText>42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin SPECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All data sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, midventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (> 70% TT-SPECT) were used for comparative quantification.</AbstractText>First and second mean global MBF values were 0.85 ml x min-1 x g-1 and 0.84 ml x min-1 x g-1, respectively, with a repeatability coefficient of 0.30 ml x min-1 x g-1. After sectorization mean MBF_micr was between 0.58 ml x min-1 x ml-1 and 0.68 ml x min-1 x ml-1 in well perfused areas. Corresponding TT-SPECT values ranged from 83% to 91%, and FDG-PET values from 91% to 103%. All procedures yielded higher values for the lateral than the septal regions.</AbstractText>Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.</AbstractText> |
2,332,348 | Neostigmine combined with bupivacaine, clonidine, and sufentanil for spinal labor analgesia. | We previously found that spinal clonidine prolongs labor analgesia when combined with spinal bupivacaine and sufentanil. We sought to determine whether the addition of spinal neostigmine to these drugs would further enhance labor analgesia. By use of a combined spinal/epidural technique, 36 patients were randomized to receive a hyperbaric spinal injection of bupivacaine 2.5 mg plus clonidine 50 microg and sufentanil 10 microg with or without neostigmine 10 microg. Pain, maternal hemodynamics, fetal heart rate, nausea, pruritus, sedation, motor block, sensory levels to pinprick, and maternal oxygen saturation were assessed at regularly specified intervals after spinal injection until additional analgesia was requested. The duration of spinal analgesia was similar between groups (215 +/- 60 min in the Control group versus 205 +/- 62 min in the Neostigmine group). Likewise, pain scores, the duration of labor, Apgar scores, and side effects were similar between groups except that patients administered neostigmine experienced significantly more nausea and vomiting (53% vs 7%, P = 0.01). We conclude that spinal neostigmine 10 microg produces severe nausea and does not potentiate the duration of spinal analgesia in laboring women from spinal bupivacaine, clonidine, and sufentanil.</AbstractText>Spinal neostigmine 10 microg as an adjunct to spinal bupivacaine, clonidine, and sufentanil produces severe nausea and fails to potentiate analgesia in laboring women.</AbstractText> |
2,332,349 | Effect of mivacurium 200 and 250 &mgr;g/kg in infants during isoflurane anesthesia: a randomized controlled trial [ISRCTN07742712]. | BACKGROUND: Infants usually respond differently to a neuromuscular relaxant compared to children or adults. Isoflurane is commonly used as an anesthetic gas in infants. In an RCT design, we investigated whether a dose of mivacurium 250 &mgr;g/kg results in faster onset of action than 200 &mgr;g/kg in infants under isoflurane anesthesia. Spontaneous recovery times and cardiovascular response were also evaluated. METHODS: Twenty-four low surgical risk children, aged 6-24 months, undergoing an elective surgery and requiring tracheal intubation were selected. After anesthetic induction, patients randomly received an iv bolus dose of mivacurium 200 or 250 &mgr;g/kg. After maximal relaxation, the patient was intubated. Isoflurane was administered to maintain anesthetic level during the surgical procedure. Neuromuscular function was monitored by accelerometry (TOF-Guard) at the adductor pollicies. The first twitch (T) of the TOF and the T4/T1 were measured. The time-course of heart rate and systolic and diastolic blood pressure were analysed by transforming them into their respective areas under the curve. RESULTS: Mivacurium 250 &mgr;g/kg produced a maximal T block faster than 200 &mgr;g/kg, i.e. 2.4 +/- 1.1 vs. 3.5 +/- 1.4 min (p < 0.05). Spontaneous recovery times were similar in both groups. Heart rate was similar between doses while systolic and diastolic blood pressures were lower with the higher dose (p < 0.05). Flushing was observed in two cases, one in each group. CONCLUSIONS: The maximal effect of mivacurium 250 &mgr;g/kg, in infants under isoflurane anesthesia, was present one minute faster than 200 &mgr;g/kg. However, it produced a significant cardiovascular response. |
2,332,350 | Cardiac-specific external paths for lidocaine, defined by isoform-specific residues, accelerate recovery from use-dependent block. | Local anesthetic antiarrhythmic drugs block voltage-gated Na(+) channels from the cytoplasmic side. In addition, cardiac Na(+) channels can be also blocked by the membrane-impermeant local anesthetic QX via external paths not present in skeletal muscle or brain channels. Introduction of cardiac isoform-specific residues into wild-type skeletal muscle or brain channels creates access paths for external QX block. These paths should affect the characteristics of use-dependent block by influencing drug on- and off-rates. We investigated the effects of these external paths on drug kinetics of lidocaine, a lipophilic drug of clinical relevance, by studying use-dependent block using a two-electrode voltage clamp in Xenopus oocytes. Recovery from use-dependent block was slowed when cardiac isoform-specific residues important for external QX access were mutated to skeletal muscle or brain isoform-specific residues. As the fraction of charged lidocaine was decreased by raising external pH, differences in recovery kinetics diminished, indicating that these mutations mostly influenced block by charged lidocaine molecules. Data were fit into a model in which bound drug distributes into charged and neutral forms based on its pK(a) and external pH with separate dissociation paths and recovery-time constants. These isoform-specific mutations altered the recovery-time constants for the charged molecules with smaller effects on those for the neutral molecules. We conclude that the external egress paths created by isoform-specific residues influence the drug kinetics of lidocaine, and these residues define cardiac-specific external paths for local anesthetic drugs. |
2,332,351 | [Cardiac conduction abnormalities after neoadjuvant chemotherapy with doxorubicin and docetaxel for primary breast carcinoma: a case report]. | A 65-year-old woman with primary breast carcinoma (T 3 N 0 M 0) received neoadjuvant chemotherapy consisting of 4 cycles of 50 mg.m-2 doxorubicin (ADM) and 60 mg.m-2 docetaxel (TXT). The patient received 50 mg.m-2 ADM and 60 mg.m-2 TXT intravenously on day 1 of each cycle every three weeks. The patient underwent transthoracic echocardiography and electrocardiography (ECG) before surgery and these results were normal. ECG showed bigeminy, trigeminy after intubation and incomplete AV block (Mobitz type II) during and after surgery. The patient recovered from these arrhythmias on the first postoperative day. Our data indicate one possibility that the management of anesthetic condition might easily induce the cardiac conduction abnormalities of this patient using ADM as neoadjuvant chemotherapy. |
2,332,352 | Effects of antisense oligodeoxynucleotide targeting of the alpha(2B)-adrenergic receptor messenger RNA in the central nervous system. | The results of previous studies with genetically engineered mice have suggested that an intact central alpha(2B)-adrenergic receptor (alpha(2B)-AR) subtype mediates the development and maintenance of salt-induced hypertension. In the present study, we sought to further define the role of this receptor by injecting antisense oligodeoxynucleotides (AS-ODNs), targeting a selected sequence of the alpha(2B)-AR mRNA, into the lateral cerebral ventricle of rats that had undergone prior subtotal nephrectomy and dietary salt loading. Cell culture studies showed that these AS-ODNs could block alpha(2B)-AR protein generation. Before AS-ODN injection, blood pressure (BP) averaged 133+/-5 mm Hg during the daytime and rose to 165+/-4 mm Hg during the nighttime activity hours (P<0.001 versus baseline average of 120+/-2 mm Hg). The injection of AS-ODNs during the early afternoon prevented the BP rise and was associated with a significant fall in heart rate (from 385+/-12 to 306+/-15 bpm, P<0.05) and symptoms of sedation that lasted for several hours, with a peak at 3 to 6 hours and full recovery by 24 hours. At that time, a second injection produced identical effects in all rats (n=9). Control rats (n=10) that received scrambled ODN injections had no changes in BP or heart rate patterns, and neither group had evidence of neurotoxicity, indicating that these effects are specifically due to translational inhibition of central alpha(2B)-AR. We conclude that a fully functional central alpha(2B)-AR is necessary for the induction of salt-dependent hypertension. |
2,332,353 | Simulation and prediction of functional block in the presence of structural and ionic heterogeneity. | Inhomogeneities in myocardial structure and action potential duration (APD) lead to dispersion of APD throughout the heart. APD gradients in the range of 20-125 ms/cm have been reported to produce functional block. In this study, a multicellular fiber model was used to examine the effect of structural and ionic inhomogeneities on the likelihood of premature stimuli to produce functional block. With the use of both the Fenton-Karma and Luo-Rudy phase II membrane models, functional block is found to occur in tissue with a maximum gradient <45 ms/cm and depends on the spatial extent. In general, the narrower the extent the larger the magnitude needed for block. A simple relationship for predicting block is presented that only requires information about the conduction velocity (CV) restitution properties of the tissue and the APD gradients. Analysis reveals that the effects of a steep CV restitution slope may be beneficial in overcoming intrinsic cellular heterogeneity for a single premature beat. |
2,332,354 | Assessment of QT interval and QT dispersion following stellate ganglion block using computerized measurements. | Prolongation of QT interval and QT dispersion (QTD) may be associated with an increased risk of arrhythmias. This study was designed to investigate the effects of right or left stellate ganglion block (SGB) on RR interval, QT interval, the rate-corrected QT (QTc) interval, QTD and the rate-corrected QTD (QTcD) using computerized measurements.</AbstractText>Ten healthy volunteers underwent both right and left SGBs using 7 mL 1% mepivacaine with a 7-day interval between the 2 blocks. The measurement from the 12-lead electrocardiogram was performed for 60 minutes after SGB.</AbstractText>Right SGB induced a significant decrease of RR interval immediately after the block, and significant increases of QT interval, QTc interval, QTD, and QTcD from immediately through 50 minutes after the block (P <.01). Left SGB induced a significant decrease of RR interval, and significant increases of QTc interval and QTD immediately after the block (P <.01). Left SGB also produced a significant decrease of QT interval from 20 through 50 minutes after the block, and a significant decrease of QTc interval from 30 through 50 minutes after the block (P <.05).</AbstractText>Right SGB induces increases of the QT interval, QTc interval, QTD, and QTcD, and left SGB induces decreases of the QT interval and QTc interval.</AbstractText> |
2,332,355 | Epidural fentanyl speeds the onset of sensory block during epidural lidocaine anesthesia. | Shortening the onset time of sensory block is a practical goal to improve the quality of epidural anesthesia. The addition of fentanyl to a local anesthetic solution is widely used during epidural anesthesia. This randomized double-blind study examined the onset time of sensory block during epidural lidocaine anesthesia with and without added fentanyl to the epidural solution.</AbstractText>Thirty-six young male patients undergoing knee arthroscopy were randomly allocated into 3 groups of 12 patients each: epidural fentanyl (EF, epidural administration of 17 mL of 2% lidocaine plus 100 microg fentanyl and followed by intravenous (IV) injection of 2 mL of normal saline); IV fentanyl (IF, epidural administration of 17 mL of 2% lidocaine plus 2 mL of normal saline and followed by IV injection of 100 microg of fentanyl); and control (C, epidural administration of 17 mL of 2% lidocaine plus 2 mL of normal saline and followed by IV injection of 2 mL of normal saline). The sensory block was assessed by pinprick method. The hemodynamic changes, postepidural shivering, and side effects of epidural fentanyl were also recorded.</AbstractText>There was no difference in the distribution of age, weight, and height among the 3 groups. The onset time of sensory block up to T(10) dermatome was significantly more rapid in the EF group (8.3 +/- 3.7 minutes) than that of the IF group (13.1 +/- 4.2 minutes, P <.05) or C group (14.2 +/- 5.4 minutes, P <.05). The upper level of sensory block was also significantly higher in the EF group. Although the incidence of shivering was lower in the EF group, this did not reach statistical significance. Postepidural arterial blood pressures and heart rates were no different among the 3 groups. No nausea, vomiting, pruritus, respiratory depression, urinary retention, or hypotension were observed in any patients.</AbstractText>Epidural injection of the mixture of 100 microg fentanyl and 2% lidocaine solution accelerated the onset of sensory block during epidural lidocaine anesthesia without increased side effects.</AbstractText> |
2,332,356 | Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. | 3-[[4-(2-Methoxyphenyl)piperazin-1-yl]methyl]-5-(methylthio)-2,3-dihydroimidazo[1,2-c]quinazoline (DL-017), a quinazoline derivative, exhibits alpha 1 -adrenoceptor antagonistic and type I antiarrhythmic effects on mammalian cardiac tissues. In the current study, the effects of DL-017 on the hemodynamic profile in anesthetized, spontaneously hypertensive rats were evaluated. Intravenous administration of DL-017 induced dose-dependent reductions of heart rate and blood pressure, which persisted over 2 h. DL-017 exerted a maximal antihypertensive effect at 0.1 mg/kg, which was similar to that of 0.1 mg/kg of prazosin. DL-017 was able to block the pressor response to phenylephrine but not to angiotensin II. Regional cerebral blood flow of the right parietal cortex decreased by 14 +/- 4% 10 min after bolus injection and then rapidly returned to control levels while the arterial pressure was still low. These results indicate that blockade of the alpha 1 -adrenoceptor by DL-017 contributes to reduction of arterial pressure. The antihypertensive effect without reflex tachycardia and loss of autoregulation of cerebral blood flow makes DL-017 suitable for chronic long-term treatment of hypertension. |
2,332,357 | Differential regulation of the orphan nuclear receptor small heterodimer partner (SHP) gene promoter by orphan nuclear receptor ERR isoforms. | The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) interacts with a wide array of nuclear receptors and represses their transcriptional activity. SHP expression is regulated by several other members of the nuclear receptor superfamily, including the orphan receptors SF-1 and LRH-1, and the bile acid receptor FXR. We have found that the SHP promoter is also activated by the estrogen receptor-related receptor gamma (ERRgamma) but not the related ERRalpha and ERRbeta isoforms. SHP and ERRgamma mRNAs are coexpressed in several tissues, including pancreas, kidney, and heart, confirming the potential relevance of this transactivation. ERRgamma transactivation is dependent on only one of five previously characterized DNA-binding sites for SF-1, and this element differs from previously reported ERR response elements. However, treatment with the histone deacetylase inhibitor trichostatin A significantly increased ERRalpha and ERRbeta activity on this element indicating that the lack of activity of ERRalpha and -beta may depend on their association with co-repressor in vivo. Furthermore, using protease sensitivity assays on DNA bound receptors it was demonstrated that DNA sequence of different response elements may cause allosteric modulation of ERR proteins, which in turn may be responsible for the differential activities of these receptors on different response elements. SHP inhibits ERRgamma transactivation and physically interacts with all three members of ERR subfamily, as demonstrated by both yeast two-hybrid and biochemical assays. As with other SHP targets, this interaction is dependent on the AF-2 coactivator-binding site of ERRgamma and the previously described N-terminal receptor interaction domain of SHP. Several recently described SHP mutations associated with moderate obesity in humans block the inhibition of ERRgamma activity. Overall, these results identify a new autoregulatory loop controlling SHP gene expression and significantly extend the potential functional roles of the three ERRs. |
2,332,358 | Physiological patterns during practice of the Transcendental Meditation technique compared with patterns while reading Sanskrit and a modern language. | This study tested the prediction that reading Vedic Sanskrit texts, without knowledge of their meaning, produces a distinct physiological state. We measured EEG, breath rate, heart rate, and skin conductance during: (1) 15-min Transcendental Meditation (TM) practice; (2) 15-min reading verses of the Bhagavad Gita in Sanskrit; and (3) 15-min reading the same verses translated in German, Spanish, or French. The two reading conditions were randomly counterbalanced, and subjects filled out experience forms between each block to reduce carryover effects. Skin conductance levels significantly decreased during both reading Sanskrit and TM practice, and increased slightly during reading a modern language. Alpha power and coherence were significantly higher when reading Sanskrit and during TM practice, compared to reading modern languages. Similar physiological patterns when reading Sanskrit and during practice of the TM technique suggests that the state gained during TM practice may be integrated with active mental processes by reading Sanskrit. |
2,332,359 | Dexamethasone modulates hypotension induced by opioids in anaesthetised rats. | The effect of dexamethasone on hypotension induced by mu-, kappa- and delta-opioid receptor agonists was investigated in pentobarbital-anaesthetised rats. Morphine (nonselective opioid receptor agonist), DAGO (D-Ala2-N-methyl-[Phe4-Gly5-ol]enkephalin; mu-opioid receptor-selective agonist), U50-488H (trans(+/-)-3,4-dichloro-N-methyl-N-(2[1pyrrolidynyl]cyclohexyl)-benzeneacetamide; kappa-opioid receptor-selective agonist) and deltorphin II (delta-opioid receptor-selective agonist), given intravenously, 5 micromol/kg, induced hypotension in rats. This hypotension was characterised by a fall in mean arterial blood pressure in 1-2 min that recovered in 30 min for morphine and U50-488H and in 5 or 20 min for DAGO and deltorphin II, respectively. Dexamethasone per se at a dose of 7.5 micromol/kg, i.v. did not significantly modify the mean arterial blood pressure of animals. Dexamethasone administration 90 min, but not 30 or 60 min, before the opioid agonists injection, prevented the hypotension induced by morphine or U50-488H, but not that induced by DAGO or deltorphin II. Pretreatment with RU-38486 (mifepristone; 7.5 micromol/kg, i.v.), a glucocorticoid receptor antagonist, 15 min before the steroid, prevented dexamethasone inhibition of hypotension induced by morphine and U50-488H. Furthermore, pretreatment with cycloheximide, a protein synthesis inhibitor (3.5 micromol/kg, i.v.), was also able to abolish the effects of dexamethasone on morphine- and U50-488H-induced hypotension. Results of the present study indicate that dexamethasone inhibited kappa-opioid receptor-mediated hypotension in rats, indicating a further important functional interaction between corticosteroids and the opioid system at kappa receptors. The ability of cycloheximide and RU-38486 to block dexamethasone effects indicates that steroid interference with kappa-opioid receptor-mediated hypotension involves a protein synthesis-dependent mechanism via glucocorticoid receptors. |
2,332,360 | Effects of morphine withdrawal on catecholaminergic neurons on heart right ventricle; implication of dopamine receptors. | The purpose of our study was to examine the effects of D1-and D2-dopamine receptors blockade on the changes in the ventricular content of catecholamines in rats withdrawn from morphine. Rats were given morphine by subcutaneous (s.c.) implantation of morphine pellets for 5 days. On the eighth day, morphine withdrawal was induced by s.c. administration of naloxone (1 mg/kg), and rats were killed 30 min later. Pretreatment with SCH 23390 (dopamine D1, D5 receptor antagonist) 15 min prior to naloxone administration suppressed some the behavioural signs of morphine withdrawal, whereas eticlopride (dopamine D2, D3, D4 receptor antagonist) did not. In addition, biochemical analysis indicate that SCH 23390 completely abolished the withdrawal-induced increase in noradrenaline and dopamine turnover in the right ventricle. By contrast, eticlopride did not block the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal. These data suggest that the hyperactivity of catecholaminergic neurons in the heart during morphine withdrawal is dependent upon D1 dopamine receptor activation. In addition, our results exclude the involvement of D2 dopamine receptors. |
2,332,361 | Transvenous demand Pacemaker Treatment for intermittent complete Heart Block in a Cat. | A 13-year-old male neutered domestic shorthaired cat had repeated syncopal episodes over a 6 month period, which had variable duration and continued to increase in frequency. Intermittent ventricular asystole, due to complete heart block, and hyperthyroidism were documented. As the syncopal episodes did not respond to a 4-week medical treatment and symptoms became severe, a transvenous ventricular demand pacemaker system (VVIM) was implanted via the external jugular vein. The unipolar lead was tunneled subcutaneously and connected with the generator in a preformed ventral abdominal muscle pocket. During follow up of 18-months there were no recurrences of the syncopal episodes. |
2,332,362 | Heart block in dextrocardia and situs inversus: a case report. | The authors report a case of a 39-year-old woman with dextrocardia and situs inversus who presented with episodes of complete heart block, managed successfully with a permanent dual chamber endocardial pacemaker. |
2,332,363 | Amiloride derivatives are potent blockers of KATP channels. | In cardiomyocytes sarcolemmal KATP channels open massively when the cytosolic [ATP] drops into the range of tens of micromolar, as during acute ischemia. The diuretic drug amiloride and related derivatives are well established as drugs blocking the Na+/H+- and the Na+/Ca2+-exchange, protecting the ischemic heart. Herein, the blocking action of amiloride and its derivatives 2',4'-dichlorobenzamil (DCB) and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) on KATP channels was tested. In inside-out patches of mouse cardiac myocytes, amiloride, DCB, and EIPA reversibly blocked the KATP channels with the IC50 values 102, 1.80, and 2.14 micromol/l (-80 mV), respectively. Similar IC50 values were obtained in recombinant channels when coexpressing the KIR6.2 subunit with one of the sulfonylurea receptors SUR1 and SUR2A. All three drugs also blocked currents generated by the C-terminus deletion mutant KIR6.2delta26 in the absence of SUR. Amiloride blocked outward currents more effectively than inward currents whereas the block by DCB and EIPA was voltage independent. In cardiomyocytes, also whole-cell IKATP was blocked by the three drugs. In conclusion, amiloride, EIPA, and DCB block the pore-forming KIR6.2 subunit of cardiac KATP channels with higher potency than the Na+/H+- and the Na+/Ca2+-exchange, precluding a specific block of the exchanges under ischemic conditions. |
2,332,364 | Calcium as a modulator of photosensitized killing of H9c2 cardiac cells. | Illumination of H9c2 rat heart cells in the presence of Rose Bengal resulted in dose-dependent cell killing (assessed by trypan blue staining) and modification of ionic currents flowing through the heart cell membrane. Inhibitors of voltage-gated ionic currents were shown to have little effect on cell killing. Ionic current measurements were used to assess the increase in leak conductance of these cells, which has been suggested to be a causal factor in killing of other cell types (1). Inhibitors of voltage-gated ionic currents, including the sodium channel blocker tetrodotoxin (100 microM) and the calcium channel blocker lanthanum (10 microM) were shown to have little effect on cell killing. The potassium channel inhibitor tetraethylammonium (20 mM) inhibited cell killing, but the effect is viewed as being caused by an inhibition of leak current. The time course of block of voltage-activated ionic currents during illumination, in the presence of Rose Bengal, was rapid compared with that for induction of leak current and for cell killing. These observations are consistent with a role for leak current in photosensitized killing of cardiac cells. They are interpreted with respect to calcium influx through the leak current pathway as a trigger for the cellular response. |
2,332,365 | The Otsego-Schoharie healthy heart program: prevention of cardiovascular disease in the rural US. | To describe a rural, hospital-based public health intervention program and to evaluate its effectiveness in cardiovascular disease (CVD) risk reduction using cross-sectional studies and a panel study.</AbstractText>A rural population of 158,000 located in New York state comprised the intervention population. A similar but separate population was used for reference. A multifaceted, multimedia 5-year program provided health promotion and education initiatives to increase physical activity, decrease smoking, improve nutrition, and identify hypercholesterolemia and hypertension. To evaluate the effectiveness of the intervention, surveys were conducted at baseline in 1989 (cross-sectional) and at follow-up in 1994-95 (cross-sectional and panel). For cross-sectional studies, a random sample of adults was obtained using a three-stage cluster design. Self-reported and objective risk factor measurements were obtained. Comparison of pre- to post- changes in intervention versus reference populations was done using 2 x 2 randomized block ANOVA, 2 x 2 mixed ANOVA. and extension of the McNemar test.</AbstractText>Smoking prevalence declined (from 27.9% to 17.6%) in the intervention population. Significant adverse trends were observed for high-density lipoprotein cholesterol and triglycerides. Systolic blood pressure was reduced while diastolic blood pressure remained stable. Body mass index increased significantly in both populations.</AbstractText>This rural. 5-year CVD community intervention program decreased smoking. The risk reduction may be attributable to tailoring of a multifaceted approach (multiple risk factors, multiple messages, and multiple population subgroups) to a target rural population. The study period was too short to identify changes in CVD morbidity and mortality.</AbstractText> |
2,332,366 | Subconductance states of the cardiac K(ATP) channel revealed by partial block with glybenclamide. | Currents carried by single ATP-sensitive potassium channels (K(ATP) channels) were recorded in membrane patches isolated from adult rat ventricular myocytes. Channel currents were blocked completely by ATP at millimolar concentrations and by glybenclamide at micromolar concentrations. However, at lower glybenclamide concentrations (1-1000 nM), a partial block, manifest as a subconductance state, was often seen. At concentrations of 100-300 nM the mean size of the subconductance state was 33+/-2.7 pS (175 mM potassium in the pipette; n=13). The size of the conductance substate varied slightly with the concentration of glybenclamide, (42 pS at 1 nM, 34 pS at 100 nM and 31 pS at 1 microM), while the open time of the subconductance state decreased with increasing glybenclamide concentration (n=4). ATP (4 mM) completely blocked both the main conductance state of the channel and the subconductance state induced by glybenclamide. Submaximal concentrations of ATP also appeared to induce subconductance states, but these could not be resolved into discrete conductance levels. The observation that subconductance states can be induced by low concentrations of glybenclamide may have implications for models of how the binding of glybenclamide is translated into closure of the Kir6.2 pore. |
2,332,367 | The Newfoundland and Labrador Heart Health Program dissemination story: the formation and functioning of effective coalitions. | Newfoundland and Labrador is the most easterly province of Canada (O'Loughlin et al., Figure 1) with a population of 537,000. Rural in nature, 50% of the population resides in widely-dispersed communities of less than 2500 people. The economy traditionally relied on the fishing industry, but with the closure of the once lucrative cod fishery in 1991, the poorest province in Canada faced a difficult economic climate with up to 20% unemployment rates. With little funding available to supplement or sustain expensive initiatives, the Demonstration Phase of the Newfoundland and Labrador Heart Health Program (1990-1996) focused on how community-based programs are developed and sustained, with a view to diffusion throughout the province. The whole province was defined as the demonstration site for the project, and a community mobilization strategy was used with extensive reliance on community health professionals and volunteer contributions. |
2,332,368 | Oral glucose solution for analgesia in infant circumcision. | Our objectives were to determine if a 50% dextrose solution would reduce the percentage of circumcision procedure time a neonate spent crying by 50% compared with water and whether it would be similar to a dorsal penile nerve block (DPNB).</AbstractText>This was a randomized placebo-controlled blinded clinical trial.</AbstractText>We included 71 patients who were recruited from the inpatient nursery of a military community hospital over a 5-month period.</AbstractText>The primary outcome was the percentage of the procedure time neonates spent crying. Secondary outcomes were the percentage change in heart rate from baseline, the percentage of oxygen saturation, and the score from the modified behavioral pain scale.</AbstractText>There were no significant differences between the oral glucose and water groups among any of the pain-related measurements. The DPNB group had significantly lower pain-related measurements (P &lt.05).</AbstractText>Concentrated glucose administered orally does not provide significant analgesia in neonatal circumcision. The use of DPNB significantly reduced objective measurements of pain and physiologic stress in infants undergoing circumcision.</AbstractText> |
2,332,369 | Clathrin exchange during clathrin-mediated endocytosis. | During clathrin-mediated endocytosis, clathrin-coated pits invaginate to form clathrin-coated vesicles (CVs). Since clathrin-coated pits are planar structures, whereas CVs are spherical, there must be a structural rearrangement of clathrin as invagination occurs. This could occur through simple addition of clathrin triskelions to the edges of growing clathrin-coated pits with very little exchange occurring between clathrin in the pits and free clathrin in the cytosol, or it could occur through large scale exchange of free and bound clathrin. In the present study, we investigated this question by studying clathrin exchange both in vitro and in vivo. We found that in vitro clathrin in CVs and clathrin baskets do not exchange with free clathrin even in the presence of Hsc70 and ATP where partial uncoating occurs. However, surprisingly FRAP studies on clathrin-coated pits labeled with green fluorescent protein-clathrin light chains in HeLa cells show that even when endocytosis is blocked by expression of a dynamin mutant or depletion of cholesterol from the membrane, replacement of photobleached clathrin in coated pits on the membrane occurs at almost the same rate and magnitude as when endocytosis is occurring. Furthermore, very little of this replacement is due to dissolution of old pits and reformation of new ones; rather, it is caused by a rapid ATP-dependent exchange of clathrin in the pits with free clathrin in the cytosol. On the other hand, consistent with the in vitro data both potassium depletion and hypertonic sucrose, which have been reported to transform clathrin-coated pits into clathrin cages just below the surface of the plasma membrane, not only block endocytosis but also block exchange of clathrin. Taken together, these data show that ATP-dependent exchange of free and bound clathrin is a fundamental property of clathrin-coated pits, but not clathrin baskets, and may be involved in a structural rearrangement of clathrin as clathrin-coated pits invaginate. |
2,332,370 | Effects of short-term citicoline treatment on acute cocaine intoxication and cardiovascular effects. | The majority of pharmacotherapies proposed for cocaine dependence have been marginally effective and frequently have undesirable side effects. We recently demonstrated that short-term treatment with citicoline decreased self-reported desire to use cocaine in crack cocaine users.</AbstractText>The present study was conducted to assess the safety of citicoline in combination with cocaine by investigating whether cocaine-induced cardiovascular and behavioral effects and cocaine plasma levels are altered by citicoline pretreatment.</AbstractText>Eight healthy male and female volunteers who used cocaine on an occasional basis participated in this randomized, placebo-controlled, three-visit study. During all three visits, subjects received an acute intranasal dose of cocaine (0.9 mg/kg) and were continuously monitored for the ensuing 3.5 h. The first visit involved no pretreatment, and visits 2 and 3 were preceded by a 4-day pretreatment period of either citicoline (1 g/day) or placebo.</AbstractText>Citicoline pretreatment did not alter the cardiovascular, physiologic, or subjective effects of acute cocaine.</AbstractText>Although citicoline did not block the acute subjective effects of cocaine in a laboratory environment, the combined use of citicoline and a moderate dose of intranasal cocaine presented no added risk of cardiovascular effects. Further study is necessary to determine whether this medication (which is currently used to treat strokes) will be a useful adjunct to treat cocaine dependence.</AbstractText> |
2,332,371 | Heart block in patients after bariatric surgery accompanying sleep apnea. | Heart block and bradycardia during sleep has been reported in patients with obesity. The occurrence of bradyarrhythmias in patients after undergoing bariatric surgery has not been reported.</AbstractText>Over a period of 6 months, 3 patients who underwent laparoscopic weight reduction surgery developed prolonged heart block during sleep. Clinical course and follow-up are presented.</AbstractText>All 3 patients were diagnosed with sleep apnea. For 2 of these patients this was a new diagnosis. The episodes of heart block coincided with their episodes of sleep apnea. During follow-up of at least 6 months, no patient has had any adverse consequences related to their nocturnal heart block.</AbstractText>Heart block during sleep is sometimes seen in patients undergoing bariatric surgery. The cause is sleep apnea, which often is worsened in the postoperative state due to narcotic analgesics. These patients require treatment of their sleep apnea, not pacemakers.</AbstractText> |
2,332,372 | [The influence of baricity on differential blockade with 0.5% bupivacaine spinal anesthesia]. | We evaluated the influence of baricity on differential blockade during spinal anesthesia using isobaric or hyperbaric 0.5% bupivacaine. Forty ASA-PS I-II patients scheduled for elective surgery (orthopedic, lower abdominal and urologic) were divided into two groups; group H, using hyperbaric 0.5% bupivacaine, and group I, using isobaric 0.5% bupivacaine. Spinal anesthesia was performed in lateral decubitus position, using a 25-gauge Quincke needle at L2-3 interspace, and 0.5% bupivacaine 2.0 ml was injected for 10 seconds. Patients were turned to supine position soon after the spinal anesthesia and the block levels were examined every 5 min for 30 min. Sympathetic blockade was detected by observer's hand, the loss of cold sensation by alcohol sponge and the loss of pain sensation by pinprick. Complete motor blockade was detected by modified Bromage scale. Significant higher sensory blockade and large number of complete motor block were observed in group H. Differential blockade between sympathetic and sensory was significant and lasted 30 min in group I, but lasted only 15 min in group H. |
2,332,373 | Fetal congenital complete heart block: prophylaxis with intravenous gammaglobulin and treatment with dexamethasone. | We report a case of complete fetal heart block in a 35-year-old Chinese woman known to be positive for anti-SSA/Ro and anti-SSB/La antibodies. She had fetal hydrops leading to intrauterine death in her first pregnancy Prophylactic intravenous immunoglobulin, given at 14 and 18 weeks' gestation, as well as oral dexamethasone, commenced at 24 weeks' gestation, allowed continuation of the pregnancy until 34 completed weeks of gestation. An external pacemaker was inserted in the baby on the first day of life. Two-and-a-half months later, a permanent pacemaker was inserted. |
2,332,374 | Acute myocardial injury caused presumably by coronary spasm after magnesium fluoro-silicate ingestion. | A patient who developed magnesium fluoro-silicate poisoning is described. This condition was manifest by the findings of acute chest pain, dysphagia, diarrhea, metabolic acidosis, hypocalcemia and hypomagnesemia and was complicated by acute myocardial injury-a phenomenon not previously described. Coronary cineangiography showed normal coronary arteries. The physiopathologic mechanisms of this electrocardiographic finding are discussed. |
2,332,375 | Both right and left cervical cordotomies depress sympathetic indexes derived from heart rate variability in humans. | Unilateral percutaneous cervical cordotomy, performed in humans to relieve intractable cancer pain, elicits signs of ipsilateral sympathetic block. In patients undergoing right or left percutaneous cervical cordotomy (9 per group), changes in sympathovagal balance were evaluated by spectral analysis of heart rate to confirm the sympatholytic effect of this surgical procedure and to investigate the lateralization of sympathetic cardiac control. For these purposes, heart rate variability was recorded 1 hour before cordotomy and 24 hours later. Cordotomy significantly depressed the low frequency peak (LF) of heart rate variability and increased the high frequency component (HF), when measured as a percentage of total power. As a consequence, the LF/HF ratio decreased significantly (P =.001), particularly during standing. The effects of right or left cordotomies were not significantly different. In conclusion, in humans unilateral percutaneous cervical cordotomy depresses some sympathetic indexes (LF/total power ratio and LF/HF ratio) derived from heart rate variability, irrespective of side. |
2,332,376 | [Stroke of cardioembolic origin in Chagas disease].<Pagination><StartPage>311</StartPage><EndPage>315</EndPage><MedlinePgn>311-5</MedlinePgn></Pagination><Abstract><AbstractText Label="INTRODUCTION" NlmCategory="BACKGROUND">American trypanosomiasis, Chagas disease is caused by Trypanosoma cruzi. Between 10% and 30% of infected persons develop the chronic form, with predominance of the cardiac and gastrointestinal forms. Chagas myocardiopathy leads to congestive heart failure, dysrhythmias and thromboembolic phenomena, and may cause strokes.</AbstractText><AbstractText Label="PATIENTS AND METHODS" NlmCategory="METHODS">We report two patients, a 57 year old woman and a 52 year old man, carriers of the chronic cardiac form of Chagas disease, with cardioembolic strokes. In both persons, serology was positive for Chagas disease (indirect hemagglutination and indirect immunofluorescence). The causes of atherothrombotic stroke were ruled out on carotid and transcranial Doppler studies.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">The woman had previously had an infarct of the left middle cerebral artery. She was admitted with a stroke involving the vertebrobasilar territory. On Holter studies there was second degree atrioventricular block and the electrocardiogram showed severe dilated myocardiopathy. On magnetic resonance studies there was an old left temporoparietal infarct and recent ischaemia of the pons and cerebral peduncle. She was anticoagulated and a pacemaker implanted. The man had a right middle cerebral artery infarct. His electrocardiogram showed atrial fibrillation and left anterosuperior block. The echocardiogram showed left ventricular dysfunction and concentric ventricular hypertrophy.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">The chronic cardiac form of Chagas disease should be included in the differential diagnosis of stroke of cardioembolic origin both in endemic areas and in countries to which persons exposed to infection during the early years of life emigrate.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Carod Artal</LastName><ForeName>F J</ForeName><Initials>FJ</Initials><AffiliationInfo><Affiliation>Servicio de Neurología; Hospital Sarah. Red Sarah de Hospitales del aparato Locomontor, Brasilia DF, 70330-901, Brasil. javier@bsb.sarah.br</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Melo</LastName><ForeName>M</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Vargas</LastName><ForeName>A P</ForeName><Initials>AP</Initials></Author></AuthorList><Language>spa</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><VernacularTitle>Ictus cardioembólico en la enfermedad de Chagas.</VernacularTitle></Article><MedlineJournalInfo><Country>Spain</Country><MedlineTA>Rev Neurol</MedlineTA><NlmUniqueID>7706841</NlmUniqueID><ISSNLinking>0210-0010</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000098" MajorTopicYN="N">blood supply</QualifierName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D014355" MajorTopicYN="N">Chagas Disease</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000469" MajorTopicYN="N">parasitology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003937" MajorTopicYN="N">Diagnosis, Differential</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004617" MajorTopicYN="N">Embolism</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006331" MajorTopicYN="N">Heart Diseases</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006386" MajorTopicYN="N">Hemagglutination Tests</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D020244" MajorTopicYN="N">Infarction, Middle Cerebral Artery</DescriptorName><QualifierName UI="Q000150" MajorTopicYN="Y">complications</QualifierName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008279" MajorTopicYN="N">Magnetic Resonance Imaging</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014057" MajorTopicYN="N">Tomography, X-Ray Computed</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014349" MajorTopicYN="N">Trypanosoma cruzi</DescriptorName><QualifierName UI="Q000302" MajorTopicYN="N">isolation & purification</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>10</Month><Day>6</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2002</Year><Month>1</Month><Day>30</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>10</Month><Day>6</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11588721</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11586620</PMID><DateCompleted><Year>2002</Year><Month>04</Month><Day>19</Day></DateCompleted><DateRevised><Year>2015</Year><Month>11</Month><Day>19</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>4</Issue><PubDate><Year>2001</Year><Season>Jul-Aug</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Ganglion block in cardiopulmonary bypass surgery]. | Ganglion blockers increase the antinociceptive defense in anesthesiological support of cardiopulmonary bypass operations for mitral and aortic valve failure. Benzohexonium decreased total peripheral vascular resistance, increased cardiac and stroke indexes, and increased systolic potency of the heart. Ganglionar blocking was associated with an increase of systemic oxygen transport, arrhythmias developed rarely, blood concentrations of epinephrine, norepinephrine, ACTH, vasopressin, and leukinferon were lower. |
2,332,377 | Type III heart block with peripheral use of the Angiojet thrombectomy system. | The authors describe the occurrence of type III heart block in a patient undergoing a transjugular intrahepatic portosystemic shunt recanalization with use of the AngioJet thrombectomy system. |
2,332,378 | Nuclear factor-kappa B decoy attenuates neuronal damage after global brain ischemia: a future strategy for brain protection during circulatory arrest. | Recent studies have reported that cis element decoy oligodeoxynucleotides against nuclear factor-kappa B block the activation of genes that mediate ischemic injury. To improve brain protection during circulatory arrest in cardiac surgery, we evaluated the efficacy of nuclear factor-kappa B decoy oligodeoxynucleotides in preventing neuronal damage after global brain ischemia.</AbstractText>Hemagglutinating virus of Japan-liposome complex with fluorescein isothiocyanate-labeled nuclear factor-kappa B decoy oligodeoxynucleotides was injected through the carotid artery during 20 minutes of global brain ischemia in rats to evaluate the efficacy of transfecting the decoy oligodeoxynucleotides. The messenger RNA levels of several factors related to ischemia-reperfusion injury in the hippocampus were estimated by a real-time polymerase chain reaction method 1 hour after reperfusion. Neuronal damage was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and by using immunohistochemical study of microtubule-associated protein 2 in the hippocampus CA-1 region 7 days after ischemia.</AbstractText>Introduction of the nuclear factor-kappa B decoy oligodeoxynucleotides into rat brain neurons through the carotid artery during global brain ischemia was markedly successful. The polymerase chain reaction study showed that the transfected nuclear factor-kappa B decoy oligodeoxynucleotides effectively inhibited the expression of tumor necrosis factor alpha interleukin 1 beta and intracellular adhesion molecule 1 messenger RNA 1 hour after global brain ischemia. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and microtubule-associated protein 2 immunohistochemistry showed that the transfected nuclear factor-kappa B decoy oligodeoxynucleotides significantly attenuated the neuronal damage 7 days after global brain ischemia.</AbstractText>Therapeutic transfection of nuclear factor-kappa B decoy oligodeoxynucleotides during brain ischemia may be useful for attenuating neuronal damage, suggesting a strategy for cerebral protection against global ischemia.</AbstractText> |
2,332,379 | A comparison of propofol and remifentanil for sedation and limitation of movement during periretrobulbar block. | To compare clinical conditions in patients sedated with propofol or remifentanil during combined peri-bulbar and retrobulbar block (PRBB) for cataract surgery.</AbstractText>Prospective, randomized, double-blind study.</AbstractText>Private clinic.</AbstractText>106 ASA physical status I and II patients scheduled for cataract surgery.</AbstractText>Patients were randomized to receive either 0.5 mg/kg propofol (Group P) or 0.3 microg/kg remifentanil (Group R) as an intravenous (IV) bolus 1 minute prior to PRBB. At the same time, patients in both groups also received 0.5 to 1 mg midazolam IV. Movement of the hands, arms, head, and eyes were counted during each stage of the procedure by an observer who was blinded to the sedation used. Heart rate (HR), blood pressure (BP), respiratory rate (RR), expiratory CO(2) (PECO(2)), and hemoglobin oxygen saturation (SaO(2)) were recorded every minute for 10 minutes after the PRBB. Anesthetic complications, recall, and the pain experienced with the block and surgery were compared between the two groups. Means and variance of the results were compared with one-way analysis of variance and Fisher's exact test.</AbstractText>Movements of the hands, arms, and head were significantly greater in Group P during all stages of the block. Almost no movements were recorded in the remifentanil group. Immediately after the PRBB (1 to 6 min), HRs were higher in Group P (73 +/- 11 bpm vs. 67 +/- 10 bpm; p = 0.0075), whereas the RRs were slower in Group R for the period 1 to 5 minutes after the PRBB (16 +/- 5 breaths/min vs.14 +/- 4 breaths/min; p = 0.0206). At these times, the mean PECO(2) was higher in Group R (36 +/- 7 mmHgvs. 32 +/- 9 mmHg; p = 0.0125). Nineteen patients in the propofol group sneezed during the medial peribulbar injection compared with none in the remifentanil group. Anesthetic and surgical complications were unremarkable and similar for the two groups.</AbstractText>Respiratory depression with remifentanil was mild and not clinically significant. Remifentanil sedation for this application was superior to sedation with propofol.</AbstractText> |
2,332,380 | [Therapeutic plasmapheresis for the prevention of congenital complete heart block associated with anti-SS-A/Ro antibody and anti-SS-B/La antibody]. | Neonatal lupus erythematosus is characterized by transient lupus abnormalities, various systemic and hematological abnormalities, and congenital complete heart block (CCHB). It is well known that anti-SS-A/Ro antibody (52 kD/60 kD) and anti-SS-B/La antibody are associated with CCHB. This study was conducted to evaluate the effects of the removal of anti-SS-A/Ro antibody (52 kD/60 kD) and anti-SS-B/La antibody from plasma in pregnant women whose fetuses are at a high risk of developing CCHB.</AbstractText><AbstractText Label="MATERIALS & METHODS" NlmCategory="METHODS">Fifteen pregnant patients positive for anti-SS-A/Ro antibody and anti-SS-B/Laantibody were subjected weekly to double filtration plasmapheresis to remove both antibodies. Antibody titers were measured by double immunodiffusion (DID) and ELISA.</AbstractText>As a result, all women gave birth to live babies, but CCHB was recognized in one baby. No transient lupus abnormalities were recognized in any of the babies. Fourteen patients showed decreased antibody titers by ELISA during plasmapheresis. However, the patient who was delivered of a baby with CCHB showed an increase of antibody titers by ELISA while the DID method showed a decrease of antibody titers.</AbstractText>Our study suggested that plasmapheresis prevents CCHB associated with anti-SS-A/Ro and anti-SS-B/La antibody. Also, it is important to monitor the antibody titer regularly during the course of pregnancy, because it may increase due to worsening of the mother's primary disease.</AbstractText> |
2,332,381 | Effects of pharmacological adrenergic and vagal modulation on fractal heart rate dynamics. | Breakdown of short-term fractal-like behaviour of HR indicates an increased risk for adverse cardiovascular events and mortality, but the pathophysiological background for altered fractal HR dynamics is not known. Our aim was to study the effects of pharmacological modulation of autonomic function on fractal correlation properties of heart rate (HR) variability in healthy subjects. Short-term fractal scaling exponent (alpha1) along with spectral components of HR variability were analysed during the following pharmacological interventions in healthy subjects: (i) noradrenaline (NE) infusion (n=22), (ii) NE infusion after phentolamine (PHE) (n=8), (iii) combined NE + adrenaline (EPI) infusion (n=12), (iv) vagal blockade with high dose of atropine (n=10), (v) and vagal activation by low dose of atropine (n=10). Then alpha1 decreased progressively during the incremental doses of NE (from 0.85 +/- 0.250 to 0.55 +/- 0.23, P<0.0001). NE also decreased the average HR (P<0.001) and increased the high frequency spectral power (P<0.001). Vagal blockade with atropine increased the alpha1 value (from 0.82 +/- 0.22 to 1.24 +/- 0.41, P<0.05). Combined NE + EPI infusion and vagal activation with a low dose atropine did not result in any changes in alpha1, and alpha-adrenergic blockade by PHE did not completely reverse the effects of NE on alpha1. Increased levels of circulating NE result in reduction of short-term correlation properties of HR dynamics. The results suggest that coactivation of cardiac vagal outflow at the time of high levels of a circulating sympathetic transmitter explains the breakdown of fractal-like behaviour of human HR dynamics. |
2,332,382 | Comparison of effects of remifentanil and alfentanil on cardiovascular response to tracheal intubation in hypertensive patients. | In a randomized double-blind study, we compared the effect of remifentanil and alfentanil on the cardiovascular response to laryngoscopy and tracheal intubation in patients on long-term treatment for hypertension. Forty ASA II-III patients were allocated to receive (i) remifentanil 0.5 microg kg(-1) followed by an infusion of 0.1 microg kg min(-1) or (ii) alfentanil 10 microg kg(-1) followed by an infusion of saline; all patients received glycopyrrolate 200 microg before the study drug. Anaesthesia was induced with propofol and rocuronium and maintained with 1% isoflurane and 66% nitrous oxide in oxygen. Laryngoscopy and tracheal intubation were performed after establishment of neuromuscular block. Arterial pressure and heart rate (HR) were measured non-invasively at 1 min intervals from 3 min before induction until 5 min after intubation. Systolic (SAP), diastolic and mean arterial pressure decreased significantly after induction in both groups (P<0.05). Maximum increases in mean SAP after laryngoscopy and intubation were 35 and 41 mm Hg in the remifentanil and alfentanil groups, respectively. After intubation, arterial pressure did not increase above baseline values in either group. HR remained stable after induction of anaesthesia, but increased above baseline values after intubation. Mean maximum HR was 87 beats min(-1) for the remifentanil group (12 beats min(-1) above baseline; P=0.065) and 89 beats min(-1) for the alfentanil group (15 beats min(-1) above baseline; P<0.05). There were no significant differences between groups in HR or arterial pressure at any time. There were no incidences of bradycardia. Seven patients in the remifentanil group and four in the alfentanil group received ephedrine for hypotension (i.e. SAP<100 mm Hg). |
2,332,383 | Levobupivacaine combined with sufentanil and epinephrine for intrathecal labor analgesia: a comparison with racemic bupivacaine. | We performed a randomized, double-blinded study to compare levobupivacaine with racemic bupivacaine for labor analgesia. Eighty term parturients received either levobupivacaine 0.125% or racemic bupivacaine 0.125%, to which was added sufentanil 0.75 microg/mL and epinephrine 1.25 microg/mL. As part of a combined spinal-epidural procedure, 2 mL of this mixture was initially injected intrathecally, and the same solutions were subsequently administered epidurally. For both combinations, onset until the first painless contraction was 4 to 5 min. Most patients were pain free during the second contraction. The duration of initial spinal analgesia was 93.5 +/- 20 min and 94.7 +/- 31 min for levobupivacaine and racemic bupivacaine, respectively. The duration of analgesia for the first epidural top-up dose was also similar in the two groups. Total local anesthetic requirements during labor were not different. The only major difference observed was the absence of motor impairment in levobupivacaine-treated parturients as compared with the Racemic Bupivacaine group, in which the incidence of a Bromage-1 motor block was 34%. Other side effects and obstetric or neonatal outcomes were not different between groups. Intrathecal levobupivacaine has a similar clinical profile as racemic bupivacaine, but at equal doses it produced less motor block.</AbstractText>When used intrathecally and epidurally for labor analgesia, levobupivacaine had the same clinical profile as racemic bupivacaine, but at equal doses it produced less motor block.</AbstractText> |
2,332,384 | Flecainide widens the excitable gap at pivot points of premature turning wavefronts in rabbit ventricular myocardium. | The mechanisms by which Class IC drugs slow the rate of functional reentrant arrhythmias are not completely understood. We hypothesized that flecainide widens the excitable gap beyond the pivot point of premature turning wavefronts.</AbstractText>In eight perfused subepicardial layers of rabbit left ventricle, a linear lesion was made by radiofrequency (RF) ablation parallel to the fiber orientation. One end of the RF lesion was extended by a short incision. Pacing next to the lesion induced a wavefront propagating with a sharp U-turn around the end of the lesion in either the clockwise or counterclockwise direction. A high-density mapping electrode (240 electrodes, 350-microm resolution) was used to record unipolar electrograms at the pivot point. During control, the shortest V1-V2 interval proximal to the pivot point was 162 +/- 12 msec compared with 173 +/- 13 msec distal to the pivot point (difference 11 +/- 8 msec; P < 0.01). After infusion of flecainide 2 mg/L, the shortest V1-V2 interval proximal and distal to the pivot point were 217 +/- 29 msec and 244 +/- 36 msec (difference 27 +/- 16 msec; P < 0.01). Due to the increase in V1-V2 interval at the pivot point, flecainide widened the temporal excitable gap in the returning limb of the turning wavefront from 30 +/- 11 msec to 55 +/- 22 msec (P < 0.01). High-density mapping at the pivot point revealed that this widening of the excitable gap was due to both macroscopic discontinuous conduction and functional conduction block at the pivot point.</AbstractText>Flecainide widens the excitable gap in the returning limb of premature U-turning wavefronts by causing macroscopic discontinuous conduction and functional conduction block at the pivot point.</AbstractText> |
2,332,385 | Influence of dynamic gap junction resistance on impulse propagation in ventricular myocardium: a computer simulation study. | The gap junction connecting cardiac myocytes is voltage and time dependent. This simulation study investigated the effects of dynamic gap junctions on both the shape and conduction velocity of a propagating action potential. The dynamic gap junction model is based on that described by Vogel and Weingart (J. Physiol. (Lond.). 1998, 510:177-189) for the voltage- and time-dependent conductance changes measured in cell pairs. The model assumes that the conductive gap junction channels have four conformational states. The gap junction model was used to couple 300 cells in a linear strand with membrane dynamics of the cells defined by the Luo-Rudy I model. The results show that, when the cells are tightly coupled (6700 channels), little change occurs in the gap junction resistance during propagation. Thus, for tight coupling, there are negligible differences in the waveshape and propagation velocity when comparing the dynamic and static gap junction representations. For poor coupling (85 channels), the gap junction resistance increases 33 MOmega during propagation. This transient change in resistance resulted in increased transjunctional conduction delays, changes in action potential upstroke, and block of conduction at a lower junction resting resistance relative to a static gap junction model. The results suggest that the dynamics of the gap junction enhance cellular decoupling as a possible protective mechanism of isolating injured cells from their neighbors. |
2,332,386 | Neonatal lupus: clinical features, therapy, and pathogenesis. | Neonatal lupus is a disease characterized by one or more of the following findings: congenital heart block, cardiomyopathy, cutaneous lupus lesions, hepatobiliary disease, and thrombocytopenia. Accumulating evidence indicates that the disease is probably caused by maternal autoantibodies, particularly autoantibodies of the Ro family. While often initially asymptomatic, mothers tend to develop symptoms of connective tissue disease. This review discusses the recent advances in the understanding of neonatal lupus, its clinical features, therapy, and pathogenesis. |
2,332,387 | Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1/minK and HERG. | Mefloquine is a quinoline antimalarial drug that is structurally related to the antiarrhythmic agent quinidine. Mefloquine is widely used in both the treatment and prophylaxis of Plasmodium falciparum malaria. Mefloquine can prolong cardiac repolarization, especially when coadministered with halofantrine, an antagonist of the human ether-a-go-go-related gene (HERG) cardiac K+ channel. For these reasons we examined the effects of mefloquine on the slow delayed rectifier K+ channel (KvQT1/minK) and HERG, the K+ channels that underlie the slow (I(Ks)) and rapid (I(Kr)) components of repolarization in the human myocardium, respectively. Using patch-clamp electrophysiology we found that mefloquine inhibited KvLQT1/minK channel currents with an IC50 value of approximately 1 microM. Mefloquine slowed the activation rate of KvLQT1/minK and more block was evident at lower membrane potentials compared with higher ones. When channels were held in the closed state during drug application, block was immediate and complete with the first depolarizing step. HERG channel currents were about 6-fold less sensitive to block by mefloquine (IC50 = 5.6 microM). Block of HERG displayed a positive voltage dependence with maximal inhibition obtained at more depolarized potentials. In contrast to structurally related drugs such as quinidine, mefloquine is a more effective antagonist of KvLQT1/minK compared with HERG. Block of KvLQT1/minK by mefloquine may involve an interaction with the closed state of the channel. Inhibition by mefloquine of KvLQT1/minK in the human heart may in part explain the synergistic prolongation of QT interval observed when this drug is coadministered with the HERG antagonist halofantrine. |
2,332,388 | Markers of myocardial damage in acute coronary syndromes--therapeutic implications.<Pagination><StartPage>27</StartPage><EndPage>32</EndPage><MedlinePgn>27-32</MedlinePgn></Pagination><Abstract><AbstractText>Patients admitted with suspicion of an acute coronary syndrome (ACS) still constitute a diagnostic, prognostic and therapeutic challenge for the treating physician. The final diagnosis ranges from a noncardiac diagnosis to a full-blown myocardial infarction (MI). Biochemical markers of myocardial damage are essential for diagnosis and, especially troponin T and troponin I, have been shown to be valuable for early risk stratification and for selection of treatment in ACS. Patients identified to be at low risk of future cardiac events might be discharged early, and unnecessary investigations and treatments avoided. On the contrary, a more intense treatment can be started in patients identified to be at high risk. Unstable angina patients with, compared to without, elevation of troponin, have a more activated coagulation system and more frequently complex lesions and visible thrombus in their coronary arteries. Accordingly, antithrombotic and antiplatelet therapies, i.e. l.m.w heparin and GP IIb/IIIa receptor antagonists, have been proved to have beneficial effects in troponin positive patients, but little or no beneficial effects in troponin negative patients. Also, the beneficial effects of an invasive compared to a noninvasive approach seem to be much more pronounced in troponin positive patients. In patients with ST-elevation MI, an elevated troponin T level at admission are associated with an increased mortality. However, the therapeutic implications of this finding remain speculative. Patients admitted with chest pain and left bundle branch block (LBBB) and who develop an MI have a poor prognosis. Current guidelines in acute myocardial infarction state that these patients should receive thrombolysis. Despite that, only a minority of these patients do receive thrombolysis, most probably because of the great diagnostic uncertainty. Rapid testing with a cardiac marker, e.g. myoglobin, would most probably increase the proportion of patients with chest pain and LBBB who receive appropriate reperfusion treatment.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lindahl</LastName><ForeName>B</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Cardiology, Uppsala Cardiothoracic Centre, University Hospital, Uppsala, Sweden. Bertil.Lindahl@Card.Uas.Se</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>Clin Chim Acta</MedlineTA><NlmUniqueID>1302422</NlmUniqueID><ISSNLinking>0009-8981</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000208" MajorTopicYN="N">Acute Disease</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D015415" MajorTopicYN="Y">Biomarkers</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002037" MajorTopicYN="N">Bundle-Branch Block</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003327" MajorTopicYN="N">Coronary Disease</DescriptorName><QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="Y">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009206" MajorTopicYN="N">Myocardium</DescriptorName><QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName></MeshHeading></MeshHeadingList><NumberOfReferences>29</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>9</Month><Day>15</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>11</Month><Day>3</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>9</Month><Day>15</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11557249</ArticleId><ArticleId IdType="doi">10.1016/s0009-8981(01)00554-x</ArticleId><ArticleId IdType="pii">S000989810100554X</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11555996</PMID><DateCompleted><Year>2001</Year><Month>12</Month><Day>04</Day></DateCompleted><DateRevised><Year>2005</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><JournalIssue CitedMedium="Print"><Issue>35</Issue><PubDate><Year>2001</Year></PubDate></JournalIssue><Title>Ryoikibetsu shokogun shirizu</Title><ISOAbbreviation>Ryoikibetsu Shokogun Shirizu</ISOAbbreviation></Journal>[LGMD1D].<Pagination><StartPage>76</StartPage><EndPage>78</EndPage><MedlinePgn>76-8</MedlinePgn></Pagination><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Sunada</LastName><ForeName>Y</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Neurology, Kawasaki Medical School.</Affiliation></AffiliationInfo></Author></AuthorList><Language>jpn</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016454">Review</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Japan</Country><MedlineTA>Ryoikibetsu Shokogun Shirizu</MedlineTA><NlmUniqueID>9501926</NlmUniqueID></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D002312" MajorTopicYN="N">Cardiomyopathy, Hypertrophic</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002874" MajorTopicYN="N">Chromosome Mapping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002896" MajorTopicYN="N">Chromosomes, Human, Pair 6</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003937" MajorTopicYN="N">Diagnosis, Differential</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D005799" MajorTopicYN="N">Genes, Dominant</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006327" MajorTopicYN="N">Heart Block</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName><QualifierName UI="Q000628" MajorTopicYN="N">therapy</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009136" MajorTopicYN="Y">Muscular Dystrophies</DescriptorName><QualifierName UI="Q000145" MajorTopicYN="N">classification</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D011379" MajorTopicYN="N">Prognosis</DescriptorName></MeshHeading></MeshHeadingList><NumberOfReferences>11</NumberOfReferences></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2001</Year><Month>9</Month><Day>15</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2002</Year><Month>1</Month><Day>5</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2001</Year><Month>9</Month><Day>15</Day><Hour>10</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11555996</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">11555994</PMID><DateCompleted><Year>2001</Year><Month>12</Month><Day>04</Day></DateCompleted><DateRevised><Year>2005</Year><Month>11</Month><Day>16</Day></DateRevised><Article PubModel="Print"><Journal><JournalIssue CitedMedium="Print"><Issue>35</Issue><PubDate><Year>2001</Year></PubDate></JournalIssue><Title>Ryoikibetsu shokogun shirizu</Title><ISOAbbreviation>Ryoikibetsu Shokogun Shirizu</ISOAbbreviation></Journal>[LGMD1B(lamin A/C)]. | Patients admitted with suspicion of an acute coronary syndrome (ACS) still constitute a diagnostic, prognostic and therapeutic challenge for the treating physician. The final diagnosis ranges from a noncardiac diagnosis to a full-blown myocardial infarction (MI). Biochemical markers of myocardial damage are essential for diagnosis and, especially troponin T and troponin I, have been shown to be valuable for early risk stratification and for selection of treatment in ACS. Patients identified to be at low risk of future cardiac events might be discharged early, and unnecessary investigations and treatments avoided. On the contrary, a more intense treatment can be started in patients identified to be at high risk. Unstable angina patients with, compared to without, elevation of troponin, have a more activated coagulation system and more frequently complex lesions and visible thrombus in their coronary arteries. Accordingly, antithrombotic and antiplatelet therapies, i.e. l.m.w heparin and GP IIb/IIIa receptor antagonists, have been proved to have beneficial effects in troponin positive patients, but little or no beneficial effects in troponin negative patients. Also, the beneficial effects of an invasive compared to a noninvasive approach seem to be much more pronounced in troponin positive patients. In patients with ST-elevation MI, an elevated troponin T level at admission are associated with an increased mortality. However, the therapeutic implications of this finding remain speculative. Patients admitted with chest pain and left bundle branch block (LBBB) and who develop an MI have a poor prognosis. Current guidelines in acute myocardial infarction state that these patients should receive thrombolysis. Despite that, only a minority of these patients do receive thrombolysis, most probably because of the great diagnostic uncertainty. Rapid testing with a cardiac marker, e.g. myoglobin, would most probably increase the proportion of patients with chest pain and LBBB who receive appropriate reperfusion treatment. |
2,332,389 | Nd-YAG laser damage to metal and silicone endobronchial stents: delineation of margins of safety using an in vitro experimental model. | To identify margins of safety within which bronchoscopic Nd-YAG laser resection can be performed without damaging indwelling tracheobronchial stents.</AbstractText>Experimental in vitro study simulating a patient-care environment.</AbstractText>Uncovered and covered metal Wallstent (Schneider; Zurich, Switzerland) and Dumon (Bryan Corporation; Woburn, MA) silicone stents were deployed in the tracheobronchial tree of a ventilated and oxygenated (fraction of inspired oxygen, 40%) heart-lung block of a dead canine. Rigid bronchoscopic Nd-YAG (1,064 nm) laser procedures were performed in order to deliver laser energy using fiber-to-target distances of 10 mm and 20 mm, and noncontact, continuous-mode, 1-s pulses at power settings of 10 W, 30 W, and 40 W. The major outcome measure was laser-induced stent damage, defined as discoloration, ignition, or breakage. This was assessed using six power densities: 75 W/cm(2), 172 W/cm(2), 225 W/cm(2), 300 W/cm(2), 518 W/cm(2), and 690 W/cm(2).</AbstractText>The uncovered Wallstent and the silicone stent remained intact at power densities of 75 W/cm(2) (10 W, 20 mm) and 172 W/cm(2) (10 W, 10 mm), but were damaged at power densities > 225 W/cm(2) (30 W, 20 mm). The covered Wallstent was damaged at all power densities tested.</AbstractText>Uncovered Wallstent and silicone stents are not damaged when Nd-YAG laser energy is delivered using power densities < or = 72 W/cm(2) (10 W, 10 mm). Covered Wallstents, however, had a high likelihood of ignition at all power densities studied.</AbstractText> |
2,332,390 | AlphaB crystallin translocation and phosphorylation: signal transduction pathways and preconditioning in the isolated rat heart. | In this program of studies we have characterized in detail the translocation (assessed by Triton-insolubility) and phosphorylation (using serine-45 or -59 phosphospecific antibodies) of alphaB crystallin during myocardial ischemia [both with or without ischemic preconditioning (IPC)]. Pharmacological activators and inhibitors allowed us to characterize the signaling pathways involved in alphaB crystallin phosphorylation during ischemia. Ischemic preconditioning alone caused 30% of the heart's alphaB crystallin pool to translocate, providing a significant translocation 'head-start' in protected tissue. This enhanced translocation is coupled with increased (3-fold) alphaB crystallin phosphorylation at both serine residues. The possible role of alphaB crystallin in the protection afforded by ischemic preconditioning is supported by the signal transduction data; which showed preconditioning-induced alphaB crystallin phosphorylation can be blocked by tyrosine kinase inhibition (using genistein) and by p38 MAP kinase or PKC inhibition (using SB203580 or bisindolylmaleimide, respectively). The activation of both p38 MAP kinase and PKC are recognized requirements for the induction of preconditioning and their inhibition is known to block protection. Western immunoblotting analysis after isoelectric focusing electrophoresis, confirmed the observations made with the phosphospecific antibodies; but also showed that 27+/-4% of total cardiac crystallin was phosphorylated after 30 min of ischemia. AlphaB crystallin exists as large polymeric aggregates in cardiac tissue under basal conditions (approximately 1 MDa as determined by gel filtration chromatography). We induced phosphorylation of alphaB crystallin during aerobic perfusion by the administration of phenylephrine. However this treatment did not alter the molecular aggregate size of alphaB crystallin. It appears that alphaB crystallin molecular aggregate size is not simply regulated by phosphorylation. AlphaB crystallin may have a role to play in the myocardial protection induced by ischemic preconditioning, as both translocation and phosphorylation are both accelerated and enhanced by ischemic preconditioning. |
2,332,391 | Thiopentone does not block ischemic preconditioning in the isolated rat heart. | Ischemic preconditioning protects the heart against subsequent prolonged ischemia by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. Thiopentone blocks K(ATP) channels in isolated cells. Therefore, we investigated the effects of thiopentone on ischemic preconditioning.</AbstractText>Isolated rat hearts (n=56) were subjected to 30 min of global no-flow ischemia, followed by 60 min of reperfusion. Thirteen hearts underwent the protocol without intervention (control, CON) and in 11 hearts (preconditioning, PC), ischemic preconditioning was elicited by two five-minute periods of ischemia. In three additional groups, hearts received 1 (Thio 1, n=11), 10 (Thio 10, n=11) or 100 microg x mL(-1) (Thio 100, n=10) thiopentone for five minutes before preconditioning. Left ventricular (LV) developed pressure and creatine kinase (CK) release were measured as variables of myocardial performance and cellular injury, respectively.</AbstractText>Recovery of LV developed pressure was improved by ischemic preconditioning (after 60 min of reperfusion, mean +/- SD: PC, 40 +/- 19% of baseline) compared with the control group (5 +/- 6%, P <0.01) and this improvement of myocardial function was not altered by administration of thiopentone (Thio 1, 37 +/- 15%; Thio 10, 36 +/- 16%; Thio 100, 38 +/- 16%, P=0.87-0.99 vs PC). Total CK release over 60 min of reperfusion was reduced by preconditioning (PC, 202 +/- 82 U x g(-1) dry weight) compared with controls (CON, 383 +/- 147 U x g(-1), P <0.01) and this reduction was not affected by thiopentone (Thio 1, 213 +/- 69 U x g(-1); Thio 10, 211 +/- 98 U x g(-1); Thio 100, 258 +/- 128 U x g(-1), P=0.62-1.0 vs PC).</AbstractText>These results indicate that thiopentone does not block the cardioprotective effects of ischemic preconditioning in an isolated rat heart preparation.</AbstractText> |
2,332,392 | Chronic inflammation in Alzheimer's disease offers therapeutic opportunities. | Postmortem studies have revealed a state of chronic inflammation in affected regions of the brain in Alzheimer's disease (AD). Chronic inflammation can be damaging to host cells and the brain may be particularly vulnerable as neurons are not replaced. Evidence suggests that the inflammation is killing neurons in AD brain, so anti-inflammatory agents might slow the process of the disease. More than 20 epidemiological studies have shown that persons taking nonsteroidal anti-inflammatory drugs (NSAIDs) have a greatly reduced incidence of AD. In one clinical trial, indomethacin appeared to halt the progression of memory loss in AD patients. NSAIDs inhibit synthesis of prostaglandins, which are fringe players in the inflammatory process. Agents that would block the more important actors, such as the complement system, activated microglia and inflammatory cytokines, might have important therapeutic benefits in AD as well as in other conditions, such as heart disease and stroke, where inflammation also plays a deleterious role. |
2,332,393 | Effect of fibre rotation on the initiation of re-entry in cardiac tissue. | Transmural rotation of cardiac fibres can have a big influence on the initiation of re-entry in the heart. However, owing to computational demands, this has not been fully explored in a three-dimensional model of cardiac tissue that has a microscopic description of membrane currents, such as the Luo-Rudy model. Using a previously described model that is computationally fast, re-entry in three-dimensional blocks of cardiac tissue is induced by a cross-shock protocol, and the activity is examined. In the study, the effect of the transmural fibre rotation is ascertained by examining differences between a tissue block with no rotation and ones with 1, 2 and 3 degrees of rotation per fibre layer. The direction of the re-entry is significant in establishing whether or not re-entry can be induced, with clockwise re-entry being easier to initiate. Owing to the rotating anisotropy that results in preferential propagation along the fibre axis, the timing of the second stimulus in the cross-shock protocol has to be changed for different rates of fibre rotation. The fibre rotation either increases or decreases the window of opportunity for re-entry, depending on whether the activation front is perpendicular or parallel to the fibre direction. By varying the transmural extent of the S2, it is found that a deeper stimulus has to be applied to the blocks with fibre rotation to create re-entry. Increasing the transmural resistance also tends to reduce the extent of the S2 required to induce re-entry. Results suggest that increasing fibre rotation reduces the susceptibility of the tissue to re-entry, but that more complex spatiotemporal patterns are possible, e.g. stable figure-of-eight re-entries and transient rotors. Three mechanisms of re-entry annihilation are identified: front catchup, filling of the excitable gap and core wander. |
2,332,394 | Monoclonal antibody detection of plasma membrane cholesterol microdomains responsive to cholesterol trafficking. | The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The cholesterol microdomains were visualized with a monoclonal antibody that specifically detects ordered cholesterol arrays. These unique cholesterol microdomains were induced on macrophages and fibroblasts when they were enriched with cholesterol in the presence of an ACAT inhibitor, to block esterification of excess cellular cholesterol. Induction of the plasma membrane cholesterol microdomains could be blocked by agents that inhibit trafficking of cholesterol to the plasma membrane and by cholesterol acceptors that remove cholesterol from the plasma membrane. In addition, plasma membrane cholesterol microdomains did not develop in mutant Niemann-Pick type C fibroblasts, consistent with the defect in cholesterol trafficking reported for these cells. The induction of plasma membrane cholesterol microdomains on inhibition of ACAT helps explain how ACAT inhibition promotes cholesterol efflux from cells in the presence of cholesterol acceptors such as HDL. The anti-cholesterol monoclonal antibody also detected extracellular cholesterol-containing particles that accumulated most prominently during cholesterol enrichment of less differentiated human monocyte-macrophages. For the first time, cholesterol microdomains have been visualized that function in cholesterol trafficking to and from the plasma membrane. |
2,332,395 | Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning. | The signal cascade that triggers and mediates ischemic preconditioning (IPC) remains unclear. The present study investigated the role of the Src family of tyrosine kinases in IPC. Isolated and buffer-perfused rat hearts underwent IPC with three cycles of 5-min ischemia and 5-min reperfusion, followed by 30-min ischemia and 120-min reperfusion. The Src tyrosine kinase family-selective inhibitor PP1 was administered between 45 and 30 min before ischemia (early PP1 treatment) or for 15 min before IPC [early PP1-preconditioning (PC) treatment]. PP1 was also administered for 5 min before the sustained ischemia (late PP1 treatment) or after IPC (late PP1-PC treatment). Src kinase was activated after 30 min of ischemia in both the membrane and cytosolic fractions. Src kinase was also activated by IPC but was attenuated after the sustained ischemia. Early and late PP1 treatment inhibited Src activation after the sustained ischemia and reduced infarct size. Early PP1-PC inhibited Src activation after IPC but not after the sustained ischemia and blocked cardioprotection afforded by IPC. Late PP1-PC treatment abrogated IPC-induced activation of Src and protein kinase C (PKC)-epsilon in the membrane but not in the cytosolic fraction. This treatment modality abrogated Src activation after the sustained ischemia and failed to block cardioprotection afforded by IPC. These results suggest that Src kinase activation mediates ischemic injury but triggers IPC in the position either upstream of or parallel to membrane-associated PKC-epsilon. |
2,332,396 | The antipsychotic drugs sertindole and pimozide block erg3, a human brain K(+) channel. | The antipsychotic drugs sertindole and pimozide are known to prolong the QT interval on the electrocardiogram via a high affinity block of the cardiac K(+) channel known as HERG (human ether-a-go-go-related gene; erg1). We wished to test whether these drugs also displayed high affinity for the related neuronal K(+) channel erg3. The cDNA encoding erg3 channel was cloned from a human brain library. Northern analysis confirmed that the channel was localized to brain relative to other tissues including heart, liver and lung. Within the brain, erg3 was expressed in higher amounts in the frontal lobe and cerebellum relative to the temporal, parietal and occipital lobes. Transient expression of erg3 in Chinese hamster ovary cells produced outwardly directed K(+) currents that activated at approximately -50 mV and produced a large transient component at positive membrane potentials. Inward tail currents measured at -100 mV were blocked in a dose-dependent fashion by sertindole resulting in an IC(50) value of 43 nM. Significant inhibition was observed at concentrations as low as 3 nM. Block of erg3 by sertindole also displayed a positive voltage-dependence. Pimozide blocked erg3 channel currents with an IC(50) of 103 nM and significant inhibition was noted at concentrations of 10 nM and higher. We conclude that erg3 can be blocked by certain antipsychotic drugs like sertindole and pimozide. Inhibition of erg3 or related K(+) channels in the brain may contribute to the efficacy/side effect profiles of some antipsychotic drugs. |
2,332,397 | Overalkylation of a protein digest with iodoacetamide. | Cystine linkages in proteins are often opened with reducing agents, sometimes to improve their digestion, often to eliminate disulfide linkages from complicating analysis of the digest. After reduction, the sulfhydryls are usually reacted with iodoacetamide (IAM), iodoacetic acid (IAA), or another electrophile to prevent reformation of disulfide linkages in a random manner. When the amount of protein may be reliably estimated, side reactions from excess IAM or IAA can be avoided. When this is not so, removal of excess iodoalkane can be accomplished by HPLC, by dialysis, or simply by allowing a reducing thiol to consume any excess. In mass spectrometric analysis of proteins isolated by 1D or 2D gels, removal of the excess iodoalkane is often accomplished simply by washing the gel prior to proteolytic digestion. During a recent study of the glutathionylation site mapping of actin, IAM was used to block any residual sulfhydryl groups remaining on the protein so that they would not displace glutathione from its initial site. In addition, to avoid losses due to actin polymerization during dialysis, the IAM was allowed to remain during the digestion. This further ensured that any sulfhydryl groups liberated during the digestion would be similarly blocked by the IAM. Under these conditions, we observed the peptides to undergo N- as well as S-carbamidomethylation. In examining a series of other peptides alkylated with IAM in this way, we have found N-alkylation to be the rule rather than the exception and even O-alkylation was detected. The main sites to which the carbamidomethyl group attaches to the peptides have been located with LC-MS2 using an ion trap mass spectrometer and found to be the N-terminal amino group. A simple expedient to prevent such reactions when an excess of reducing agent must be avoided is to run the alkylation in the presence of a thioether such as 2,2'-thiodiethanol rather than a thiol. |
2,332,398 | Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women. | To assess the true prevalence of congenital complete heart block (CCHB) in infants of anti-Ro/SSA-positive women known to have connective tissue disease (CTD) and, secondarily, to evaluate the prevalence of other electrocardiographic abnormalities in these newborns at birth.</AbstractText>A prospective study was conducted in 4 referral hospitals. One hundred anti-Ro/SSAA-positive mothers were followed up before they became pregnant and during the index pregnancy. Counterimmunoelectrophoresis and immunoblotting were used to test for antibodies to extractable nuclear antigens.</AbstractText>Of the 100 women with anti-Ro/SSA antibodies, 2 had infants who developed CCHB in utero (2%). The CCHB was detected at 22 weeks and 20 weeks, respectively. One of the 2 mothers had primary Sjögren's syndrome (SS), and the other had undifferentiated CTD (UCTD). No case of CCHB occurred among the infants of 53 mothers with systemic lupus erythematosus (SLE). No fetal death occurred due to CCHB. In 2 centers, electrocardiography was recorded in 24 unselected newborns, and 4 were found to have sinus bradycardia.</AbstractText>The prevalence of CCHB in newborns of prospectively followed up women already known to be anti-Ro/SSA positive and with known CTD was 2%. This finding is useful with regard to preconception counseling of these women. The risk of delivering an infant with CCHB may be higher in mothers with primary SS or UCTD than in those with SLE. Additional electrocardiographic abnormalities such as sinus bradycardia and prolongation of the QT interval may be present in their children.</AbstractText> |
2,332,399 | pH-dependent blocking actions of three novel antiarrhythmic compounds on K+ and Na+ currents in rat ventricular myocytes. | Three novel chemically related compounds were studied for their pH-dependent ion channel blocking actions on the transient outward K+ current (I(to)) and the Na+ current (I(Na)) in isolated rat ventricular myocytes. The (+/-)-trans-napthylethoxycyclohexylamines, RSD1108, RSD1070 and RSD1067, showed similar potencies in reducing the inactivation time course of I(to) at pH 7.4. However, RSD1108 (pK(a) 6.8) was a more potent blocker of I(to) at pH 6.4 than the other two compounds (pK(a) values near 8.0). The reduction of inactivation times induced by the RSD compounds was consistent with open channel blockade and in consequence an open channel block model was used in order to estimate blocking and unblocking rate constants. This analysis showed no apparent correlation between pK(a) and onward blocking rate constants for the compounds. However, the unblocking rate constant for the low pK(a) compound RSD1108 at acid pH decreased markedly from that found at normal pH. Both RSD1108 and RSD1070 showed an enhanced potency to block I(Na) at acid pH relative to pH 7.4. However, RSD1108 showed significantly less inhibition of I(Na) at both pH values compared to RSD1070 and RSD1067. Differences in channel block were also evident between RSD1070 and RSD1067, which could be attributed to the difference in napthyl groups between their chemical structures. The compounds exhibited use- and frequency-dependent blockade of I(Na) with the amount of use-dependent blockade greater for RSD1108 and RSD1067 than for RSD1070 at acid pH compared to neutral pH. Greater frequency-dependent inhibition was apparent for RSD1108 as compared to RSD1070 and RSD1067 at both pH 7.4 and 6.4. These results point out the importance of the magnitude of pK(a) and chemical structure in ion channel blocking actions of a series of structurally related compounds. |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.