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2,331,900 | Allograft tolerance induced by donor apoptotic lymphocytes requires phagocytosis in the recipient. | Cell death through apoptosis plays a critical role in regulating cellular homeostasis. Whether the disposal of apoptotic cells through phagocytosis can actively induce immune tolerance in vivo, however, remains controversial. Here, we report in a rat model that without using immunosuppressants, transfusion of apoptotic splenocytes from the donor strain prior to transplant dramatically prolonged survival of heart allografts. Histological analysis verified that rejection signs were significantly ameliorated. Splenocytes from rats transfused with donor apoptotic cells showed a dramatically decreased response to donor lymphocyte stimulation. Most importantly, blockade of phagocytosis in vivo, either with gadolinium chloride to disrupt phagocyte function or with annexin V to block binding of exposed phosphotidylserine to its receptor on phagocytes, abolished the beneficial effect of transfused apoptotic cells on heart allograft survival. Our results demonstrate that donor apoptotic cells promote specific allograft acceptance and that phagocytosis of apoptotic cells in vivo plays a crucial role in maintaining immune tolerance. |
2,331,901 | Comparison of 0.2% ropivacaine, 0.125% bupivacaine, and 0.25% bupivacaine for duration and magnitude of action in peripheral arterial blood flow induced by sympathetic block in dogs. | The aim of this study is to compare 0.2% ropivacaine with 0.125% bupivacaine or 0.25% bupivacaine for the duration and magnitude of the vasodilation effect induced by sympathetic block.</AbstractText>We measured mean arterial pressure, heart rate, and right and left brachial artery blood flow (BABF) before and after cervicothoracic sympathetic block in 24 dogs. The experimental protocol was designed as follows: (1) left cervicothoracic sympathetic block with 1.0 mL 0.2% ropivacaine (n =8), (2) left cervicothoracic sympathetic block with 1.0 mL 0.125% bupivacaine (n=8), and (3) left cervicothoracic sympathetic block with 1.0 mL 0.25% bupivacaine (n=8).</AbstractText>Mean arterial pressure and heart rate did not change significantly throughout the study in either group. Left cervicothoracic sympathetic block with 0.2% ropivacaine increased left BABF significantly from 5 to 100 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 254 +/- 38%; P <.01). Left cervicothoracic sympathetic block with 0.125% bupivacaine increased left BABF significantly from 5 to 80 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 144 +/- 9%; P <.01). Left cervicothoracic sympathetic block with 0.25% bupivacaine increased left BABF significantly from 5 to 100 minutes after the block (baseline, 100%; peak at 10 minutes after the block, 235 +/- 61%; P <.01).</AbstractText>Ropivacaine may be equally potent to bupivacaine at equal concentrations in sympathetic block in dogs.</AbstractText> |
2,331,902 | [Power spectral analysis on heart rate variability of hypoxaemia in fetal lambs]. | To analyze the effect of hypoxaemia on heart rate variability (HRV) in fetal lambs by means of power spectrum, the intrauterine surgical operations were performed at 116-125 gestational days in 7 lambs. Arterial catheter was inserted in the fetal femoral artery and sent to aorta abdominalis, and blood pressure was recorded continually on tape recorder. The microspheres were injected via the arterial catheter to block the micrangium of placenta, thus making an animal model of fetal hypoxaemia. The fetal blood sample was drawn through the catheter for blood gas analysis. In terms of the heart beat variability power spectral density, there were four consistent components, namely very low (VL, 0.01-0.025 cycle/beat), low (L, 0.025-0.125 cycle/beat), middle (M, 0.125-0.2 cycle/beat), and high (H, 0.2-0.5 cycle/beat). Integrated peaks in the power spectrum were compared before and after administration of microsphere. The spectral power in the L frequency components was significantly increased (0.07 +/- 0.01 vs. 0.21 +/- 0.03, P<0.01), and the spectral power in the H frequency components was significantly reduced (0.53 +/- 0.1 vs. 0.27 +/- 0.05, P<0.05). There was no significant difference in M and VL. The times of microsphere injection were related to fetal blood pH (r=0.585, p<0.01), PCO2 (r=0.5, p<0.05) and PO2 (r=0.75, P<0.01). The results clearly demonstrate the association between change of power spectrum of heart rate variability and the effect of hypoxia of the fetus in labour. |
2,331,903 | The microextraction of RNA from archival cardiac allografts embedded in paraffin. | One of the difficulties encountered in studying rejection in patients is the availability of tissue. The goal of our study was to isolate RNA from archival allograft tissue, and to demonstrate that it is of suitable quality for further molecular experimentation. Thirty-two paraffin embedded cardiac and five renal allograft archival samples were obtained after IRB approval, from a total of 18 transplant patients (13 cardiac/five renal transplant patients) from a search of the University of Tennessee's teaching hospitals. RNA was extracted from the paraffin blocks and amplified by reverse transcription-polymerase chain reaction (RT-PCR). Grade 3A and higher and non-rejection samples were tested. In addition, normal mouse liver tissue was isolated for comparison. Negative control samples were also included. RT-PCR amplification of 18s RNA, 324 bp target sequences, revealed readily detectable bands. Only one block that was 3 years old did not yield detectable RNA secondary to presumed degradation. The negative control showed no bands at 324 bp. We conclude that RNA from archived allograft tissue can be used for further experiments. The use of this tissue offers some distinct advantages when studying correlation of gene expression with clinical outcome and therapeutic response. |
2,331,904 | Demonstration of reverse fatty acid transport from rat cardiomyocytes. | Fatty acids flow from adipocytes to nonadipose tissues during fasting and exercise and normally are fully oxidized. To determine if nonadipose tissues can export unoxidized FA when FA influx exceeds oxidation, neonatal cardiomyocytes were cultured in 1 microCi (14)C-palmitate in the presence of etomoxir to block oxidation. The cells took up and stored 25% of the radioactivity as (14)C-triacylglycerol in 12 h, but 4.5% of the label was released in 3 h and comigrated with (14)C-palmitate. Both uptake and release of radioactivity were increased by insulin and reduced by the nonspecific inhibitors of FA transporters phloretin and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Perfused hearts from etomoxir-treated lean rats released 221 +/- 59 nmol/10 min of FA. Hearts from high-fat-fed lean rats released 366 +/- 172 nmol/10 min (P < 0.05). Hearts from obese rats released 744 +/- 260 and 1,578 +/- 630 nmol/10 min at 8 and 12 weeks of age, respectively. Perfusion with insulin increased FA release by 32%. In vitro and ex vivo findings suggest that nonadipose tissues such as myocardium can export FA when the unoxidized lipid content is excessive. |
2,331,905 | Effects of thoracic epidural anaesthesia on intestinal microvascular perfusion in a rodent model of normotensive endotoxaemia. | To investigate whether sympathetic blockade by means of thoracic epidural anaesthesia (TEA) increases intestinal perfusion during normotensive endotoxaemia.</AbstractText>A prospective, randomised and controlled animal study.</AbstractText>Animal laboratory in a university hospital.</AbstractText>Sprague-Dawley male rats.</AbstractText>The rats were anaesthetised with urethane and ketamine, mechanically ventilated and haemodynamically monitored. Lidocaine or saline were infused continuously via thoracic epidural catheters followed by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (1.5 mg/kg per h). Densities of perfused and non-perfused capillaries (i.e., with and without erythrocyte perfusion, respectively) as well as erythrocyte velocity in both the mucosa and the muscularis of the terminal ileum were determined using intravital microscopy.</AbstractText>Measurements were performed at baseline, after 30 min of epidural infusion as well as after 60 and 120 min of lipopolysaccharide infusion. In animals receiving TEA, mean arterial pressure and heart rate were significantly reduced throughout the experiment. In the muscularis the endotoxaemia-induced increase in non-perfused capillaries was absent with epidural lidocaine (0 [0/0] versus 39 [36/137] cm(-1), median [25(th)/75(th) percentile]), whereas in the mucosa perfused capillary density declined to a greater extent than in controls (-47 [-53/-23]%) versus -19 [-34/+10]%, p<0.05). Erythrocyte velocity decreased with endotoxaemia and was not influenced by epidural lidocaine.</AbstractText>Microvascular perfusion data during endotoxaemia show a redistribution of blood flow towards the mucosa. TEA seems to impede this redistribution resulting in improved muscularis and worsened mucosal microvascular perfusion.</AbstractText> |
2,331,906 | A randomised controlled trial of fluid pre-loading before low dose epidural analgesia for labour. | Preloading with fluid is recommended before regional block in labour. Low dose epidurals may produce less haemodynamic disturbance than traditional stronger solutions of local anaesthetics. Our aim was to compare the incidence of hypotension in normal labouring women who received a low dose epidural (0.1% bupivacaine 15 mL with fentanyl 2 microg microg.mL(-1)) with and without an i.v. crystalloid preload. Women with normal labours were randomised to the intervention group: no i.v. crystalloid preload (n = 85) and the control group: 7 mL mL.kg(-1) i.v. crystalloid solution before epidural injection (n = 83). Mean arterial pressure was recorded every 5 min for 30 min. There was no difference between the groups in mean decrease in mean arterial pressure and similar proportions of women showed falls in mean arterial pressure of 20% or greater (13% vs. 11%, risk ratio 1.2, 95% CI 0.54 to 2.8, P = 0.6). Blinded analysis by independent obstetricians revealed no differences in the fetal heart rate abnormalities (20% vs. 15%, risk ratio 1.3, 95% CI 0.67 to 2.7). A scientifically valid conclusion whether preloading is useful cannot be drawn from this study. This study suggests that about 350 participants in each group would be necessary to exclude a type 2 error in a future study. |
2,331,907 | Patient-controlled epidural analgesia for labor pain: effect on labor, delivery and neonatal outcome of 0.125% bupivacaine vs 0.2% ropivacaine. | The objective was to evaluate the influence of patient-controlled epidural analgesia (PCEA) using low doses of bupivacaine vs. ropivacaine, on labor pain, motor blockade, progression of labor, delivery and neonatal outcome. This randomized double blind study included 565 parturients. All received a 5-mL/h infusion and PCEA (5-mL boluses with a 20-min lockout, maximum volume 20 mL/h) of either 0.125% bupivacaine (n = 313: 165 nulliparous, 148 parous) or 0.2% ropivacaine (n = 252: 113 nulliparous, 139 parous). Pain score, lower limb motor block, sensory levels, local analgesic doses required, hemodynamic parameters, side effects and complications were assessed. Obstetric variables included cervical dilation at epidural insertion, incidence of ruptured membranes and their duration, use of oxytocin, fetal heart rate changes, duration of labor, mode and outcome of delivery, and use of invasive and non-invasive fetal monitoring. Neonatal characteristics included birth weight, Apgar scores, umbilical artery pH, serum bilirubin, hypoglycemia, need for assisted ventilation, sepsis or sepsis study, feeding difficulties and respiratory distress syndrome. Ropivacaine 0.2% was equianalgesic with 0.125% bupivacaine, but produced less motor block (P < 0.0001). There were no significant differences, however, in duration of labor, delivery type or neonatal outcome. |
2,331,908 | Is continuous spinal analgesia via an epidural catheter appropriate after accidental subarachnoid administration of 15 mL of bupivacaine 0.1% containing fentanyl 2 micrograms/mL? | We report a case of accidental insertion of an epidural catheter into the subarachnoid space and accidental administration of 15 mL of bupivacaine 0.1% with fentanyl 2 micrograms/mL, in the sitting position, during labour. Within 5 min, the patient was unable to move her lower limbs. Although the upper level of the sensory block using ethyl chloride was found to be T5, there was no cardiovascular depression. The catheter was left in situ and used for continuous spinal analgesia. Further administration of the bupivacaine-fentanyl solution was not required until after 315 min. The patient was given five further 2- to 3-mL top-up doses of bupivacaine-fentanyl at intervals of 105 to 145 min. After 16 h, caesarean section was performed for failure to progress in the first stage of labour. This was conducted under spinal anaesthesia using 2 mL of hyperbaric bupivacaine 0.5% with fentanyl 20 micrograms. A healthy baby was delivered with Apgar scores of 10 and 10, at 1 and 5 min, respectively. There was no postdural puncture headache or any neurological complications. |
2,331,909 | Anaesthetic management of caesarean section in a patient with a permanent pacemaker and severe bilateral ventricular dilatation. | A 33-year-old primigravida presented at 32 weeks gestation with increasing shortness of breath related to left ventricular failure. She had severe bilateral ventricular dilatation of unknown aetiology. An urgent caesarean section was required when she failed to improve on medical therapy, and for this she requested general anaesthesia. The patient had a permanent pacemaker for congenital complete heart block and Harrington rods for kyphoscoliosis. In view of the cardiac problems we transferred the patient to our cardiac unit and performed the procedure with full invasive haemodynamic monitoring. An alfentanil based modified rapid sequence induction resulted in stable maternal haemodynamics. The 2.2 kg male neonate initially required ventilation for 12 h, but then made a good recovery along with his mother. |
2,331,910 | Molecular characterization of an inward rectifier channel (IKir) found in avian vestibular hair cells: cloning and expression of pKir2.1. | A fast inwardly rectifying current has been observed in some of the sensory cells (hair cells) of the inner ear of several species. While the current was presumed to be an IKir current, contradictory evidence existed as to whether the cloned channel actually belonged to the Kir2.0 subfamily of potassium inward rectifiers. In this paper, we report for the first time converging evidence from electrophysiological, biochemical, immunohistochemical, and genetic studies that show that the Kir2.1 channel carries the fast inwardly rectifying currents found in pigeon vestibular hair cells. Following cytoplasm extraction from single type II and multiple pigeon vestibular hair cells, mRNA was reverse transcribed, amplified, and sequenced. The open reading frame (ORF), consisting of a 1,284-bp nucleotide sequence, showed 94, 85, and 83% identity with Kir2.1 subunit sequences from chick lens, Kir2 sequences from human heart, and a mouse macrophage cell line, respectively. Phylogenetic analyses revealed that pKir2.1 formed an immediate node with hKir2.1 but not with hKir2.2-2.4. Hair cells (type I and type II) and supporting cells in the sensory epithelium reacted positively with a Kir2.1 antibody. The whole cell current recorded in oocytes and CHO cells, transfected with pigeon hair cell Kir2.1 (pKir2.1), demonstrated blockage by Ba2+ and sensitivity to changing K+ concentration. The mean single-channel linear slope conductance in transfected CHO cells was 29 pS. The open dwell time was long (approximately 300 ms at -100 mV), and the closed dwell time was short (approximately 34 ms at -100 mV). Multistates ranging from 3-6 were noted in some single-channel responses. All of the above features have been described for other Kir2.1 channels. Current clamp studies of native pigeon vestibular hair cells illustrated possible physiological roles of the channel and showed that blockage of the channel by Ba2+ depolarized the resting membrane potential by approximately 30 mV. Negative currents hyperpolarized the membrane approximately 20 mV before block but approximately 60 mV following block. RT-PCR studies revealed that the pKir2.1 channels found in pigeon vestibular hair cells were also present in pigeon vestibular nerve, vestibular ganglion, lens, neck muscle, brain (brain stem, cerebellum and optic tectum), liver, and heart. |
2,331,911 | Slowing the progression of diabetic nephropathy and its cardiovascular consequences. | This paper incorporates the findings from a multidisciplinary meeting on diabetic nephropathy and its renal and cardiovascular complications into a review article. The epidemic of obesity and the growing elderly population in the United States are primary drivers of a secondary epidemic of incipient type 2 diabetes mellitus and diabetic nephropathy. Current therapies aim to treat blood pressure, particularly with agents that block the renin-angiotensin system, to a target of 130/80 mm Hg. However, even lower blood pressure targets may be optimal. Control of hyperglycemia and dyslipidemia, smoking cessation, exercise, and weight loss all compliment blood pressure control and are achieved most effectively when the patient, provider, and health system are aligned with these goals. Once end-stage renal disease (ESRD) is reached, patients enter the highest cardiovascular risk-state appreciated in human medicine. Because of uniform access to care in the United States, advanced data systems, and circulatory system (intravascular) access in most patients, the ESRD population should be the future sampling frame for newer treatments tested in both prospective cohort and randomized trials. Cardiorenal risk, or the degree of excess cardiovascular risk incurred by patients with chronic kidney disease and ESRD, is a state offering considerable research opportunities for novel cardiovascular risk factors. Future studies should fully consider the possibility that improved outcomes would be achieved at a greater cost; thus, cost-effectiveness studies are essential for understanding the economic aspects of implementation. The goal of an ideal clinical trial would be ESRD prevention; however, pragmatic objectives such as a greater understanding of therapeutic toxicities should also be explored in this population. |
2,331,912 | Addition of dexmedetomidine prolongs duration of vasodilation induced by sympathetic block with mepivacaine in dogs. | The aim of this study was to examine the duration of vasodilation induced by sympathetic block with the addition of dexmedetomidine to mepivacaine.</AbstractText>We measured right and left brachial artery blood flow (BABF) before and after stellate ganglion block used as a sympathetic block in dogs. The experimental protocol was designed as follows: (1) left stellate ganglion block using 1.0 mL 0.5% mepivacaine (n = 8), (2) left stellate ganglion block using the addition of dexmedetomidine 0.5 microg to 1.0 mL 0.5% mepivacaine (n = 8), and (3) left stellate ganglion block using the addition of dexmedetomidine 0.5 microg to 1.0 mL physiological saline solution (n = 8).</AbstractText>Left stellate ganglion block with mepivacaine alone increased left BABF significantly from 5 minutes through 50 minutes after the block (baseline, 100%; peak at 10 minutes after SGB, 181 +/- 27%; P <.01). Left stellate ganglion block with the addition of dexmedetomidine to mepivacaine induced a significant increase of left BABF from 5 minutes through 90 minutes after the block (baseline, 100%; peak at 10 minutes after SGB, 174 +/- 36%; P <.01). Left and right BABF did not change significantly after stellate ganglion block with dexmedetomidine only. Right BABF decreased significantly after left stellate ganglion block with mepivacaine alone or the addition of dexmedetomidine to mepivacaine throughout the study.</AbstractText>The addition of dexmedetomidine prolongs the duration of vasodilation induced by stellate ganglion block with mepivacaine used for sympathetic block in dogs.</AbstractText> |
2,331,913 | A novel zebrafish kelchlike gene klhl and its human ortholog KLHL display conserved expression patterns in skeletal and cardiac muscles. | In this study, a novel gene, kelchlike (klhl) was identified in zebrafish by whole-mount in situ hybridization screen for important genes involved in embryogenesis. A full-length klhl cDNA was cloned and characterized. We found that klhl was a member of the kelch-repeat superfamily, containing two evolutionary conserved domains--broad-complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domain, and kelch motif. Database mining revealed the presence of putative orthologs of klhl in human, mouse, rat, and pufferfish. klhl was determined to map to zebrafish linkage group (LG) 13 and was found to be syntenic with the proposed orthologs of klhl in human, mouse, and rat. In an effort to elucidate the function of klhl, klhl expression was investigated by Northern blot analysis and in situ hybridization. klhl is specifically expressed in the fast skeletal and cardiac muscle. Northern blot analyses show that the human ortholog, KLHL, is also specifically expressed in the skeletal muscles and heart. In silico analyses of rat expressed sequence tag (EST) clones corresponding to rat Klhl ortholog also indicate that its expression is also restricted to rat muscle tissues, suggesting a conserved role of klhl in vertebrates. The expression pattern of klhl, as well as the presence of the kelch repeats indicates a possible role for Klhl in the organization of striated muscle cytoarchitecture. |
2,331,914 | A unique pathway of cardiac myocyte death caused by hypoxia-acidosis. | Chronic hypoxia in the presence of high glucose leads to progressive acidosis of cardiac myocytes in culture. The condition parallels myocardial ischemia in vivo, where ischemic tissue becomes rapidly hypoxic and acidotic. Cardiac myocytes are resistant to chronic hypoxia at neutral pH but undergo extensive death when the extracellular pH (pH[o]) drops below 6.5. A microarray analysis of 20 000 genes (cDNAs and expressed sequence tags) screened with cDNAs from aerobic and hypoxic cardiac myocytes identified >100 genes that were induced by >2-fold and approximately 20 genes that were induced by >5-fold. One of the most strongly induced transcripts was identified as the gene encoding the pro-apoptotic Bcl-2 family member BNIP3. Northern and western blot analyses confirmed that BNIP3 was induced by 12-fold (mRNA) and 6-fold (protein) during 24 h of hypoxia. BNIP3 protein, but not the mRNA, accumulated 3.5-fold more rapidly under hypoxia-acidosis. Cell fractionation experiments indicated that BNIP3 was loosely bound to mitochondria under conditions of neutral hypoxia but was translocated into the membrane when the myocytes were acidotic. Translocation of BNIP3 coincided with opening of the mitochondrial permeability pore (MPTP). Paradoxically, mitochondrial pore opening did not promote caspase activation, and broad-range caspase inhibitors do not block this cell death pathway. The pathway was blocked by antisense BNIP3 oligonucleotides and MPTP inhibitors. Therefore, cardiac myocyte death during hypoxia-acidosis involves two distinct steps: (1) hypoxia activates transcription of the death-promoting BNIP3 gene through a hypoxia-inducible factor-1 (HIF-1) site in the promoter and (2) acidosis activates BNIP3 by promoting membrane translocation. This is an atypical programmed death pathway involving a combination of the features of apoptosis and necrosis. In this article, we will review the evidence for this unique pathway of cell death and discuss its relevance to ischemic heart disease. The article also contains new evidence that chronic hypoxia at neutral pH does not promote apoptosis or activate caspases in neonatal cardiac myocytes. |
2,331,915 | HERG binding specificity and binding site structure: evidence from a fragment-based evolutionary computing SAR study. | We describe the application of genetic programming, an evolutionary computing method, to predicting whether small molecules will block the HERG cardiac potassium channel. Models based on a molecular fragment-based descriptor set achieve an accuracy of 85-90% in predicting whether the IC(50) of a 'blind' set of compounds is <1 microM. Analysis of the models provides a 'meta-SAR', which predicts a pharmacophore of two hydrophobic features, one preferably aromatic and one preferably nitrogen-containing, with a protonatable nitrogen asymmetrically situated between them. Our experience of the approach suggests that it is robust, and requires limited scientist input to generate valuable predictive results and structural understanding of the target. |
2,331,916 | Neuromuscular pharmacodynamics of rocuronium in patients with major burns. | Rocuronium, which has a short onset time and is free of hyperkalemic effects, could be considered for rapid-sequence induction of anesthesia in patients with burns. In this study, we assessed the neuromuscular pharmacodynamics of rocuronium in patients with major burns. Adults aged 18-59 yr who had a major burn injury (n = 56) and a control group of 44 nonburned patients were included. Rocuronium was used at 3 times (0.9 mg/kg) or 4 times (1.2 mg/kg) the 95% effective dose. Anesthesia consisted of propofol and fentanyl with nitrous oxide and oxygen. Neuromuscular block was monitored with an acceleromyograph by using train-of-four stimulation. The onset time to 95% neuromuscular block was prolonged in burned compared with nonburned patients (115 +/- 58 s versus 68 +/- 16 s for 0.9 mg/kg; 86 +/- 20 s versus 57 +/- 11 s for 1.2 mg/kg). Dose escalation shortened the onset time, prolonged the duration of action, and improved intubating conditions in burned patients. All recovery profiles were significantly shorter in burned versus nonburned groups with both doses. Resistance to the neuromuscular effects of rocuronium was partially overcome by increasing the dose. A dose up to 1.2 mg/kg provides good tracheal intubating conditions after major burns. |
2,331,917 | Developmental changes of Ni(2+) sensitivity and automaticity in Nkx2.5-positive cardiac precursor cells from murine embryonic stem cell. | It is controversial which subtypes of T type Ca(2+) channels are implicated in automaticity of cardiac cells during the embryonic period.</AbstractText>The effect of Ni(2+) on the automaticity of Nkx2.5-positive cardiac precursor cells sorted from embryonic stem cells during their differentiation was examined using patch clamp techniques. Although 40 micromol/L Ni(2+), which is enough to block Ni(2+)sensitive T type-Ca(2+) channels, decreased the spontaneous beating rate in all cells in the early and intermediate stage, Ni(2+) did not show any effects on the automaticity of 50% of the cells in the late stage.</AbstractText>These results indicate that Ni(2+)-sensitive T-type Ca(2+) channels expressed in the Nkx2.5-positive cardiac precursor cells are developmentally regulated.</AbstractText> |
2,331,918 | Injuries associated with regional anesthesia in the 1980s and 1990s: a closed claims analysis. | The authors used the American Society of Anesthesiologists Closed Claims Project database to identify specific patterns of injury and legal liability associated with regional anesthesia. Because obstetrics represents a unique subset of patients, claims with neuraxial blockade were divided into obstetric and nonobstetric groups for comparison.</AbstractText>The American Society of Anesthesiologists Closed Claims Project is a structured evaluation of adverse anesthetic outcomes collected from closed anesthesia malpractice insurance claims of professional liability companies. An in-depth analysis of 1980-1999 regional anesthesia claims was performed with a subset comparison between obstetric and nonobstetric neuraxial anesthesia claims.</AbstractText>Of the total 1,005 regional anesthesia claims, neuraxial blockade was used in 368 obstetric claims and 453 of 637 nonobstetric claims (71%). Damaging events in 51% of obstetric and 41% of nonobstetric neuraxial anesthesia claims were block related. Obstetrics had a higher proportion of neuraxial anesthesia claims with temporary and low-severity injuries (71%) compared with the nonobstetric group (38%; P <or=0.01) and a lower proportion of claims with death or brain damage and permanent nerve injury compared with the nonobstetric group (P <or= 0.01). Cardiac arrest associated with neuraxial block was the primary damaging event in 32% of obstetric and 38% of nonobstetric neuraxial anesthesia claims involving death or brain damage. Eye blocks accounted for 5% of regional anesthesia claims.</AbstractText>Obstetric claims were predominately associated with minor injuries. Permanent injury from eye blocks increased in the 1990s. Neuraxial cardiac arrest and neuraxial hematomas associated with coagulopathy remain sources of high-severity injury.</AbstractText> |
2,331,919 | Intraoperative and postoperative analgesia with subcutaneous ring block of the penis with levobupivacaine for circumcision in children. | The purpose of the study is to evaluate both the efficacy of ring block of the penis with levobupivacaine in preventing intraoperative and postoperative pain associated with circumcision in children and the quality of the recovery. Thirty boys aged 3 - 12 years who underwent circumcision under general anaesthesia as day case patients were allocated randomly to receive either a subcutaneous ring block with levobupivacaine or intravenous fentanyl (2 microg/kg) and paracetamol (30 mg/kg) rectally, after induction of anesthesia but before surgery. The efficacy of intraoperative analgesia was estimated using the heart rate and alterations in blood pressure. The quality of the recovery was assessed based on the Aldrete Scoring System (First Value and Time of Maximum Value were recorded). Postoperative pain was estimated using a four degree scale by nurses in the Postanaesthesia Care Unit and over the next 24 hours by the parents. Paracetamol was given depending on the pain score and the time of first dose given was recorded. The quality of postoperative analgesia was based on the children's activity and mobilisation. The ring block group showed intraoperative cardiovascular stability and a faster and better recovery (p < 0.0005) while the postoperative analgesia tended to be longer and more adequate, although that no statistically significant difference was noted (p < 0.1). |
2,331,920 | Diastolic mitral regurgitation: a borderline case in cardiovascular physiology.<Pagination><StartPage>161</StartPage><EndPage>170</EndPage><MedlinePgn>161-70</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Mitral regurgitation during diastole in 5 subjects, of whom 4 affected by cardiovascular disease and 1 healthy competitive athlete, was the aim of this work. The 4 patients are respectively affected by: 1st case: arterial hypertension, dyslipidemia and III degree AV block in NYHA class II heart failure (HF); 2nd case: NYHA III HF, prosthetic biologic aortic valve dysfunction; 3th case: NYHA III HF, ischemic dilated cardiomyopathy; 4th case: ischemic dilated cardiomyopathy waiting for heart transplantation.</AbstractText><AbstractText Label="METHODS AND RESULTS" NlmCategory="RESULTS">The above 4 patients showed, on transthoracic echocardiogram, mitral diastolic regurgitation. The authors deem as caused, in agreement with the literature, both by an atrio-ventricular pressure gradient inversion during long-lasting diastoles (III degree atrioventricular block, blocked atrial systole, aortic valve regurgitation), and by an inadequate ventricular remodelling/distensibility. The 5th case deals with a healthy highly trained competitive athlete who, at the fitness checkup, showed mitral diastolic regurgitation. The study was also extended to two healthy groups of subjects, in order to rule out mitral regurgitation during the diastolic interval of the cardiac cycle.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Such finding, after an accurate and critical analysis, led the authors to assume it may deal with a borderline physiological condition.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alessandri</LastName><ForeName>N</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Dipartimento Scienze Cardiovascolari e Respiratorie, University of Rome "La Sapienza", Rome, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mariani</LastName><ForeName>S</ForeName><Initials>S</Initials></Author><Author ValidYN="Y"><LastName>Messina</LastName><ForeName>F R</ForeName><Initials>FR</Initials></Author><Author ValidYN="Y"><LastName>Rondoni</LastName><ForeName>G</ForeName><Initials>G</Initials></Author><Author ValidYN="Y"><LastName>Gerbasi</LastName><ForeName>E</ForeName><Initials>E</Initials></Author><Author ValidYN="Y"><LastName>Battista</LastName><ForeName>L</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Gaudio</LastName><ForeName>C</ForeName><Initials>C</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D002363">Case Reports</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Italy</Country><MedlineTA>Eur Rev Med Pharmacol Sci</MedlineTA><NlmUniqueID>9717360</NlmUniqueID><ISSNLinking>1128-3602</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002320" MajorTopicYN="Y">Cardiovascular Physiological Phenomena</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D003971" MajorTopicYN="N">Diastole</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004452" MajorTopicYN="N">Echocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006439" MajorTopicYN="N">Hemodynamics</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008889" MajorTopicYN="N">Military Personnel</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008944" MajorTopicYN="N">Mitral Valve Insufficiency</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000503" MajorTopicYN="Y">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010807" MajorTopicYN="N">Physical Endurance</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D013177" MajorTopicYN="N">Sports</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="N">physiology</QualifierName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2004</Year><Month>6</Month><Day>23</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2004</Year><Month>7</Month><Day>9</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2004</Year><Month>6</Month><Day>23</Day><Hour>5</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">15206485</ArticleId></ArticleIdList></PubmedData></PubmedArticle><PubmedArticle><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">15206310</PMID><DateCompleted><Year>2004</Year><Month>09</Month><Day>03</Day></DateCompleted><DateRevised><Year>2007</Year><Month>11</Month><Day>15</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0201-7563</ISSN><JournalIssue CitedMedium="Print"><Issue>1</Issue><PubDate><Year>2004</Year><Season>Jan-Feb</Season></PubDate></JournalIssue><Title>Anesteziologiia i reanimatologiia</Title><ISOAbbreviation>Anesteziol Reanimatol</ISOAbbreviation></Journal>[Changes in hemodynamics during regional anesthesia and medicinal sedation in children traumatology]. | Thirty-nine patients, aged 8 to 15, who were operated for damaged bones in the upper lower limbs were examined. The parameters of central hemodynamics, heart rate and arterial pressure were studied (monitor HP "Viridia m3", USA). Strike volume was determined automatically (rheography monitor NCCOM-3"Boomed Co.", USA). Cardiac output, body area, stroke index and the peripheral vascular resistance were calculated by the routine formulae. Group 1 comprised 20 children who were operated on with the halothane-oxide-oxygen narcosis. Group 2 comprised 19 patients who received regional anesthesia combined with drug sedation (midazolam). A 1% lydokain solution with adrenalin was used as a local anesthetic. The block of the brachial plexus with auxiliary approach and the "3 in 1" block were in use. The changes of hemodynamics detected in the children of group 1 revealed an insufficient analgetic and antistress efficiency of halothane. The data obtained for group 2 are indicative of insignificant hemodynamic changes observed at all examination stages and related with the impact exerted by drugs, used for sedation and regional anesthesia, on the vascular tonus of the original undetected hypovolemia. A lack of complications, a fast awakening and recovery of an adequate consciousness after combined regional anesthesia as well as comfort and a lack of need in extra analgetics that are normally used in the immediate postoperative period make it possible to refer to the discussed anesthesia variation as to the preferential one in cases of surgeries for damaged bones in children. |
2,331,921 | [Clinical effects and pharmacokinetics of ropivacaine and bupivacaine for epidural analgesia during labor]. | To compare the analgesic efficacy, pharmacokinetics and histamine release of ropivacaine and bupivacaine with fentanyl in continuous epidural perfusion during labor and childbirth.</AbstractText>Prospective study of 40 women at full-term pregnancy who requested epidural analgesia. The patients were randomly assigned to 2 groups of 20: group R received an initial bolus dose of 10 mL of 0.25% ropivacaine and group B received 0.25% bupivacaine, followed in both groups by epidural infusion of the assigned drugs at a concentration of 0.125% plus 0.30 mg of fentanyl at a rate of 5 mL/h through a patient-controlled analgesia device that allowed additional bolus doses. The studied variables were age, weight, height, sensory and motor block, mean blood pressure and maternal-fetal heart rates, number of bolus doses, total local anesthetic administered, duration and type of delivery, oxytocin increase, Apgar at 1 and 5 minutes, plasma levels of local anesthetic (30 minutes after the initial dose, at the end of dilation, in the umbilical vein, and 30 minutes after switching off the perfusion pump), time to clearance, elimination half-life, and a test of histamine release by radioimmunoassay.</AbstractText>No significant differences were observed in the course of labor or in Apgar scores. The plasma concentrations of ropivacaine were higher than those of bupivacaine (p<0.03). Clearance of both drugs was similar. The elimination half-life of ropivacaine was significantly less than that of bupivacaine (5.2 +/- 0.7 h vs. 10.8 +/- 1.06 h).</AbstractText>Analgesia was equally effective in both groups, without adverse maternal-fetal effects, with spontaneous micturition and absence of motor blockade in both groups. The plasma concentrations were higher with ropivacaine but were not toxic.</AbstractText> |
2,331,922 | The selection of the regional anaesthesia in the transurethral resection of the prostate (TURP) operation. | The aim of our study was to compare the three different regional anaesthesia methods in patients who underwent transurethral resection of the prostate (TURP) and to determine the ideal anaesthesia method for TURP operation.</AbstractText>Totally 77 ASA II-III patients were preloaded with 500 ml 0.9% NaCl solution before regional anaesthesia. In group E (n:27) epidural anaesthesia were achieved by applying 75 mg bupivacaine heavy + 50 microg fentanyl in the L3-L4 intervertebral space. In group SP (n:28) 15 mg bupivacaine heavy + 50 microg fentanyl were used for spinal anaesthesia (L3-L4 intervertebral space) while in group SA (n:30) 10 mg bupivacaine heavy + 50 microg fentanyl were used with saddle blockade. Systolic arterial pressure (SAP), heart rate (HR), peripheral oxygen saturation (SpO2), serum sodium measurement was recorded before and after hydration and during operation. The motor block and sensory level have been measured.</AbstractText>Intraoperative SAP values were more stable than the other groups in group SA. The decrease in HR values were significant 15 minutes after prehydration in three groups (p < 0.05). SpO2 values of the groups were stable during the operation. The time to reach the maximum block was very short in patients in Group SA (p < 0.0001). There was a statistically significant difference between the groups in terms of motor block values (p < 0.0001). No fully paralysed sample was seen in Group SA even though there was a sufficient surgical anaesthesia.</AbstractText>Saddle block has some advantages compared to spinal and epidural anaesthesia methods such as achieving adequate anaesthesia, stable haemodynami, the lower degree of motor blockage and no full blockage in patients. Saddle block is an the most optimal anaesthesia method for TURP operation.</AbstractText> |
2,331,923 | Comparison of two treatment techniques for breast irradiation including internal mammary nodes. | Techniques to treat breast cancer inclusive of the internal mammary lymph node chain (IMC) vary. This study compared a presently accepted technique implemented at the Radiation Oncology Department at Barnes-Jewish Hospital/Washington University School of Medicine (BJ/WU) to a proposed technique for irradiation of breast tissue and the IMC. The present technique consists of parallel-opposed breast tangential beams in combination with photon and electron IMC fields angled along the chest wall. The proposed method involves a wide medial tangent field covering the IMC, with an angled electron IMC field for a portion of the treatment regimen and an opposed lateral breast-only tangent. This technique uses a multileaf collimation (MLC) reduction to treat the IMC aspect following the wide medial tangent, to supplement the IMC to a tumorcidal dose. These techniques were compared by reviewing isodoses with subsequent isodensity confirmation. Computerized tomography imaging sets of patients with various body types (chest wall, small and large breasts) for left-sided tumors were planned using a three-dimensional treatment planning system (FOCUS, Computerized Medical Systems). The plans were evaluated by comparing irradiated heart and lung volumes and the respective dose distribution at the IMC field/medial tangent junction. Specific treatment aids and photon/electron energies were employed to produce desirable isodose distributions, with a dose prescription of 4680-cGy total dose. The efficiency of the radiation treatments itself was also evaluated. The proposed technique decreases treatment time by eliminating an additional IMC field that involves repositioning and placement of a block. Phantom-based film isodensity measurements were evaluated to validate the calculated dosimetry for these techniques. |
2,331,924 | Deterministic nonlinear characteristics of in vivo blood flow velocity and arteriolar diameter fluctuations. | We have performed a nonlinear analysis of fluctuations in red cell velocity and arteriolar calibre in the mesenteric bed of the anaesthetized rat. Measurements were obtained under control conditions and during local superfusion with NG-nitro-L-arginine (L-NNA, 30 microM) and tetrabutylammonium (TBA, 0.1 mM), which suppress NO synthesis and block Ca2+ activated K+ channels (KCa), respectively. Time series were analysed by calculating correlation dimensions and largest Lyapunov exponents. Both statistics were higher for red cell velocity than diameter fluctuations, thereby potentially differentiating between global and local mechanisms that regulate microvascular flow. Evidence for underlying nonlinear structure was provided by analysis of surrogate time series generated from the experimental data following randomization of Fourier phase. Complexity indices characterizing time series under control conditions were in general higher than those derived from data obtained during superfusion with L-NNA and TBA. |
2,331,925 | [Modern differential therapy with diuretics]. | Diuretics block different electrolyte transporters in renal tubular cells. Their predominant action is inhibition of renal sodium chloride reabsorption, however, and achievement of a negative body sodium balance is the principal goal of diuretic therapy in patients with hypertension and edema. Several classes of diuretics can be distinguished with respect to the sites of sodium reabsorption along the nephron, but loop diuretics and distal-tubular diuretics (incl. thiazides) are the most widely used. The latter have a less potent natriuretic effect than loop diuretics, but their long duration of action predispose them for treatment of patients with uncomplicated hypertension. In conditions of gross edema, e.g. heart and/or renal failure, distal-tubular diuretics lose their efficacy and must be replaced by or combined with loop diuretics ("sequential nephron blockade"). Aldosterone antagonists are unique among diuretics because they improve survival in patients with heart failure independently of their effect on sodium metabolism. |
2,331,926 | The effectiveness of continuous epidural infusion of low-dose fentanyl and mepivacaine in perioperative analgesia and hemodynamic control in mastectomy patients. | To investigate, in mastectomy patients, the effectiveness of continuous cervical epidural block using a low-dose fentanyl infusion in combination with local anesthetics.</AbstractText>Prospective, observational study.</AbstractText>450-bed, university-affiliated hospital.</AbstractText>21 ASA physical status I and II female patients undergoing modified radical mastectomy.</AbstractText>An epidural catheter was inserted at the C(7)-Th(1) interspace before the induction of anesthesia. Anesthesia was maintained using a low concentration of sevoflurane with nitrous oxide-oxygen (N(2)O-O(2)). A mixture of 100 microg fentanyl and 49 mL of 1% mepivacaine was prepared, and 7 mL of this solution was epidurally injected before the initial incision. This same solution was continuously infused at a rate of 7 mL/hr (fentanyl 17.5 microg/hr) throughout the anesthesia, and at 2 mL/hr (fentanyl 5 microg/hr) postoperatively.</AbstractText>Intraoperative mean arterial pressure (MAP) and heart rate (HR), postoperative pain and analgesic use, and the frequency of postoperative side effects of anesthesia, including nausea, dizziness, and respiratory depression, were recorded. The protocol described provided stable intraoperative hemodynamic control with no or low-dose nicardipine infusion. Sufficient postoperative analgesia was achieved in 18 of 21 patients. One patient reported postoperative nausea, and no other side effects were reported.</AbstractText>Continuous epidural infusion of the low-dose fentanyl mixture described above provides adequate intraoperative hemodynamic control and postoperative pain relief, with a low rate of side effects in mastectomy patients.</AbstractText> |
2,331,927 | Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. | Human ether-a-go-go-related gene (HERG) potassium channels are expressed in multiple tissues including the heart and adenocarcinomas. In cardiomyocytes, HERG encodes the alpha-subunit underlying the rapid component of the delayed rectifier potassium current, I(Kr), and pharmacological reduction of HERG currents may cause acquired long QT syndrome. In addition, HERG currents have been shown to be involved in the regulation of cell proliferation and apoptosis. Selective alpha 1-adrenoceptor antagonists are commonly used in the treatment of hypertension and benign prostatic hyperplasia. Recently, doxazosin has been associated with an increased risk of heart failure. Moreover, quinazoline-derived alpha 1-inhibitors induce apoptosis in cardiomyocytes and prostate tumor cells independently of alpha1-adrenoceptor blockade. To assess the action of the effects of prazosin, doxazosin, and terazosin on HERG currents, we investigated their acute electrophysiological effects on cloned HERG potassium channels heterologously expressed in Xenopus oocytes and HEK 293 cells.Prazosin, doxazosin, and terazosin blocked HERG currents in Xenopus oocytes with IC(50) values of 10.1, 18.2, and 113.2 microM respectively, whereas the IC(50) values for HERG channel inhibition in human HEK 293 cells were 1.57 microM, 585.1 nM, and 17.7 microM. Detailed biophysical studies revealed that inhibition by the prototype alpha 1-blocker prazosin occurred in closed, open, and inactivated channels. Analysis of the voltage-dependence of block displayed a reduction of inhibition at positive membrane potentials. Frequency-dependence was not observed. Prazosin caused a negative shift in the voltage-dependence of both activation (-3.8 mV) and inactivation (-9.4 mV). The S6 mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) HERG current blockade, indicating that prazosin binds to a common drug receptor within the pore-S6 region. In conclusion, this study demonstrates that HERG potassium channels are blocked by prazosin, doxazosin, and terazosin. These data may provide a hypothetical molecular explanation for the apoptotic effect of quinazoline-derived alpha1-adrenoceptor antagonists. |
2,331,928 | Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure. | Traditional risk factors of a poor clinical outcome and mortality in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcome in patients with chronic heart failure (CHF), but in an opposite direction. Obesity, hypercholesterolemia, and high values of BP have been demonstrated to be associated with greater survival among CHF patients. These findings are in contrast to the well-known associations of over-nutrition, hypercholesterolemia, and hypertension with a poor outcome in the general population. The association between traditional cardiovascular risk factors and an adverse clinical outcome in CHF patients is referred to as "reverse epidemiology." The mechanisms for this inverse association in CHF is not clear. There are other populations with a similar risk factor reversal phenomenon, including patients with end-stage renal disease receiving dialysis, those with advanced malignancies, and individuals with advanced age. Several possible causes are hypothesized: the time discrepancy of the competing risk factors may play a role; the presence of the "malnutrition-inflammation complex syndrome" in CHF patients may explain the existence of reverse epidemiology; and a decreased level of lipoprotein molecules may distort their endotoxin-scavenging role, predisposing CHF patients with a low serum cholesterol level to inflammatory consequences of endotoxemia. It is possible that new goals for such traditional risk factors as BMI, serum cholesterol, and BP should be developed for CHF. Reverse epidemiology of conventional cardiovascular risk factors is observed in CHF and may have a bearing on the management of these patients; thus, it deserves further investigation. |
2,331,929 | Preclinical pharmacology of GW280430A (AV430A) in the rhesus monkey and in the cat: a comparison with mivacurium. | No replacement for succinylcholine is yet available. GW280430A (AV430A) is a representative of a new class of nondepolarizing neuromuscular blocking drugs called asymmetric mixed-onium chlorofumarates. It undergoes rapid degradation in plasma by chemical hydrolysis and inactivation by cysteine adduction, resulting in a very short duration of effect. The neuromuscular, cardiovascular, and autonomic pharmacology of GW280430A is compared herein with that of mivacurium.</AbstractText>Adult male rhesus monkeys and adult male cats were anesthetized with nitrous oxide-oxygen-halothane and chloralose-pentobarbital, respectively. The neuromuscular blocking properties of GW280430A and mivacurium were compared at a stimulation rate of 0.15 Hz in the extensor digitorum of the foot (monkey) and the tibialis anterior (cat). Sympathetic responses were assayed in the cat in the nictitating membrane preparation, and vagal effects were evaluated in the cat via observation of bradycardic responses after stimulation of the cervical right vagus nerve.</AbstractText>GW280430A and mivacurium were equipotent in the monkey (ED95 was 0.06 mg/kg in each case). GW280430A was half as potent as mivacurium in the cat. The total duration of action of GW280430A was less than half that of mivacurium in the monkey; recovery slopes were more than twice as rapid. The 25-75% recovery index of GW280430A did not vary significantly after various bolus doses or infusions, averaging 1.4-1.8 min in the monkey, significantly shorter than the same time interval (4.8-5.7 min) for mivacurium. Dose ratios for autonomic versus neuromuscular blocking properties in the cat were greater than 25 for both GW280430A and mivacurium. The ratio ED Hist:ED95 Neuromuscular Block in the monkey was significantly greater (approximately 53 vs. 13) for GW280430A, indicating approximately four times less relative prominence of the side effects of skin flushing and decrease of blood pressure, which are associated with release of histamine.</AbstractText>These experiments show a much shorter neuromuscular blocking effect and much-reduced side effects in the case of GW280430A vis-à-vis mivacurium. These results, together with the novel chemical degradation of GW280430A, suggest further evaluation in human subjects.</AbstractText> |
2,331,930 | Clinical pharmacology of GW280430A in humans. | An ultrashort-acting nondepolarizing neuromuscular blocking agent that could be an alternative to succinylcholine has been the focus of a concerted effort in the field of muscle relaxants. GW280430A showed a promising pharmacodynamic profile in preclinical work and a wide margin of safety and so was selected for study in humans.</AbstractText>Thirty-one volunteers participated in this study, which determined the dose producing 95% block (ED95) and the safety and pharmacodynamics of increasing ED95 multiples. Anesthesia was induced and maintained with propofol, midazolam, and fentanyl. Neuromuscular transmission was measured at the adductor pollicis using ulnar nerve stimulation, and responses were recorded continuously by standard mechanomyographic monitoring.</AbstractText>The ED95 for GW280430A is 0.19 mg/kg. The time to onset of 90% block ranged from 1.3 to 2.1 min, depending on the dose. Clinical durations ranged from 4.7 to 10.1 min and increased with increasing dose. Five to 95% and 25-75% recovery rates were approximately 7 and 3 min, respectively, and were independent of the dose administered. Transient cardiovascular side effects were observed at doses beginning at 3 x ED95 and above and were suggestive of histamine release. Most volunteers receiving 4 x ED95 exhibited plasma histamine concentrations indicative of significant histamine release.</AbstractText>GW280430A has a rapid onset and ultrashort duration of action. The recovery rate is rapid, predictable, and independent of dose. Doses at least up to 2.5 x ED95 seem to be free of side effects and seem to be able to provide relaxation within 60-90 s.</AbstractText> |
2,331,931 | An evaluation of the use of cottonseed cake in the diet of growing pigs. | An experiment was conducted to determine the effects of including cottonseed cake in rations for weaned growing pigs. Thirty-two Landrace x Large White pigs, weighing 20-24 kg, were included in four blocks formed on the basis of initial weight within sex in an otherwise completely randomized block design. The pigs were killed when they reached a live weight of 75.0 +/- 2.0 kg and the half carcases were analysed into cuts and the weights of the organs were recorded. An estimate of the productivity of the pigs on each diet was calculated. Cottonseed cake reduced the voluntary feed intake (p < 0.001) and live weight gains p < 0.001) and increased the heart, kidney and liver weights (p < 0.01). The pigs on the soya bean-based control diet took the shortest time to reach slaughter weight. The result was probably in part due to lysine deficiency and in part to the effect of free gossypol. It was found that it is at present cost-effective to include cottonseed cake in pig weaner-grower diets up to 300 g/kg in Cameroon. |
2,331,932 | The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: a potent sodium-channel blocker. | Bufonid anurans of the genus Atelopus contain both steroidal bufadienolides and various guanidinium alkaloids of the tetrodotoxin class. The former inhibit sodium-potassium ATPases, whereas the latter block voltage-dependent sodium channels. The structure of one guanidinium alkaloid, zetekitoxin AB, has remained a mystery for over 30 years. The structure of this alkaloid now has been investigated with a sample of approximately 0.3 mg, purified from extracts obtained decades ago from the Panamanian golden frog Atelopus zeteki. Detailed NMR and mass spectral analyses have provided the structure and relative stereochemistry of zetekitoxin AB and have revealed that it is an analog of saxitoxin. The proposed structure is characterized by richness of heteroatoms (C16H25N8O12S) and contains a unique 1,2-oxazolidine ring-fused lactam, a sulfate ester, and an N-hydroxycarbamate moiety. Zetekitoxin AB proved to be an extremely potent blocker of voltage-dependent sodium channels expressed in Xenopus oocytes. The IC50 values were 280 pM for human heart channels, 6.1 pM for rat brain IIa channels, and 65 pM for rat skeletal muscle channels, thus being roughly 580-, 160-, and 63-fold more potent at these channels than saxitoxin. |
2,331,933 | Systemic autonomic function in subjects with primary angle-closure glaucoma: a comparative study of symptomatic and asymptomatic disease presentation. | Autonomic dysfunction is thought to be a contributory factor in primary angle-closure glaucoma (PACG) by precipitating pupil block in anatomically predisposed eyes. This study aimed to compare systemic autonomic function between subjects who had suffered a previous episode of acute angle closure (symptomatic PACG), those who had asymptomatic PACG, and age and sex-matched controls.</AbstractText>Tests for systemic parasympathetic function included the heart-rate response to standing (30:15 ratio), heart-rate variation during deep breathing, and the ratio of the heart rate at phases IV and II of the Valsalva manoeuvre (Valsalva ratio). For assessment of the sympathetic nervous system, blood pressure was recorded supine and then after 2 and 5 min of standing. A modified sweat test, the sympathetic skin response, was recorded on the palm and sole.</AbstractText>A total of 30 subjects were examined: eight previous symptomatic PACG, eight asymptomatic PACG and 14 control subjects. The mean ages were similar, and all except one subject were Chinese. None of the subjects had evidence of systemic dysautonomia. There was no significant difference found between the groups for the 30:15 ratio, heart-rate variation during deep respiration and the Valsalva ratio. No significant orthostatic hypotension was detected in subjects with PACG. Abnormal sympathetic skin response was not more common in PACG subjects compared to control subjects.</AbstractText>This study identified no systemic autonomic dysfunction in people with PACG.</AbstractText> |
2,331,934 | [Prolongation of Bupivacaine spinal anaesthesia by oral and intramuscular Clonidine]. | The effect of oral and intramuscular clonidine premedication on the duration of sensory and motor blockade and postoperative analgesia during bupivacaine spinal anaesthesia was studied in 102 ASA physical status I-II patients scheduled for lower limbs orthopaedic surgery. In all cases one hour before anaesthesia midazolam (0.1-0.15 mg/kg) was applied orally and isotonic saline solution (10 ml/kg) was infused intravenously. The patients were randomly allocated into one of the following groups: oral (A) or intramuscular (B) clonidine premedication (0.15 mg) (n = 33) and oral or intramuscular premedication by placebo (C) (n = 36). All patients received 10-20 mg of 0.5% hyperbaric bupivacaine intrathecally. Sensory blockade (SB) was evaluated by pinprick and motor blockade (MB) according to Bromage's scale. The following parameters were measured: duration of motor and sensory block, requirement for postoperative analgesia (buprenorfine); systolic, diastolic and mean blood pressures; heart rate; oxyhemoglobin saturation (SpO2) and adverse events. As far as sex, body weight, age, height, ASA grade, dose of midazolam and bupivacaine, the onset of sensory and motor blockade, level of sensory analgesia, type of surgery and its average duration between groups were concerned, no differences were observed (p > 0.05). Both oral and intramuscular premedication with clonidine increased significantly the duration of motor (A--185.9 +/- 59.3; B--190.9 +/- 66.3 min) and sensory (A--216.2 +/- 69.4; B--254.2 +/- 76.8 min) blockade in comparison with placebo (MB--141.9 +/- 56.6; SB--156.7 +/- 62.9 min) (p < 0.01). The effect was more pronounced at the parenteral vs oral administration (p < 0.05). The intramuscular premedication with clonidine intensified the sedative effect of midazolam (p < 0.01). Hypotension, bradycardia and the decrease of SpO2 were significantly greater in B compared to C group (p < 0.05). Dose of buprenorfine applied in the first 24 postoperative hours was in both groups receiving clonidine (A--0.6 +/- 0.2; B--0.5 +/- 0.2 mg) nearly twice as small as than in a control group (1.1 +/- 0.2 mg) (p < 0.01). The authors conclude that prolongation of bupivacaine sensory analgesia may be produced by premedication with 0.15 mg of oral and intramuscular clonidine. The application of clonidine reduces the early postoperative analgesic requirements. The side effects are more pronounced with the intramuscular route of administration. |
2,331,935 | Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism in healthy volunteers. | The addition of clonidine to local anaesthetics enhances pain relief after peripheral nerve block, but the site of action is unproven.</AbstractText>Seven healthy volunteers underwent three brachial block procedures using bupivacaine 0.25% 1 mg kg(-1) + epinephrine 1:200,000 (=local analgesic) in a randomized, double-blind cross-over fashion: (a) control treatment: local analgesic with 0.9% sodium chloride solution for the block and an intramuscular injection of saline; (b) intramuscular treatment: local analgesic with 0.9% NaCl for block and an intramuscular injection of clonidine 2 microg kg(-1) and (c) block treatment: local analgesic with clonidine 2 microg kg(-1) for block and an intramuscular injection of saline.</AbstractText>The onset and duration of complete blockade (sensory/motor/temperature) was evaluated in the four nerve regions of the hand and forearm. Additionally, sedation score, blood pressure, heart rate and plasma clonidine concentrations were determined. The median duration of complete sensory blockade was 270 min (range 0-600) for block treatment compared to 0 min (range 0-480) for intramuscular treatment (P < 0.05) and 0 min (range 0-180) for control treatment (P < 0.05). Motor and temperature blockade exhibited similar results. Administration of clonidine was associated with sedation and a decrease in heart rate and blood pressure independent of the route of administration. Plasma clonidine concentrations were lower for block compared to the intramuscular treatment.</AbstractText>The admixture of clonidine to bupivacaine plus epinephrine prolongs and enhances brachial plexus blockade. Lower clonidine plasma concentrations for block treatment strongly suggest a local effect.</AbstractText> |
2,331,936 | Effects of S(+) ketamine added to bupivacaine for spinal anaesthesia for prostate surgery in elderly patients. | Intrathecal ketamine as the sole anaesthetic agent has demonstrated a lack of cardiovascular depression that should be of advantage in an elderly population. S(+) ketamine has three-times the analgesic potency of R(-) ketamine and its antinociceptive effects after intrathecal administration in rats are known. We decided to evaluate the effects of intrathecal S(+) ketamine added to a small dose of spinal bupivacaine in elderly patients undergoing transurethral prostate surgery.</AbstractText>Forty males over 60 yr old, scheduled for transurethral prostate resection under spinal anaesthesia, were studied in a prospective, double-blinded, randomized way. Patients were allocated to receive either bupivacaine 10 mg or bupivacaine 7.5 mg combined with S(+) ketamine 0.1 mg kg(-1). Spinal block onset time, maximum sensory level, duration of blockade, haemodynamic variables, postoperative analgesic requirements and adverse events were recorded.</AbstractText>Onset times of motor and sensory block were shorter in the bupivacaine plus S(+) ketamine group. Incomplete motor block of the lower extremities was seen in 80% of the patients in bupivacaine plus S(+) ketamine group. Duration of complete motor block and spinal analgesia was shorter in the bupivacaine plus S(+) ketamine group. There was no significant difference in arterial pressure. Heart rate decreased after spinal anaesthesia in the bupivacaine plus S(+) ketamine group and was significantly lower until the end of anaesthesia. The incidence of adverse effects was not different between groups.</AbstractText>Intrathecal S(+) ketamine administered with a low dose of bupivacaine provides shorter motor and sensory block onset time, shorter duration of action and less motor blockade in elderly males.</AbstractText> |
2,331,937 | Primary prevention of coronary heart disease in general practice: a cross sectional population study. | The aim of this study was to assess the interventions by general practitioners on cardiovascular risk factors among persons without a history of cardiovascular disease attending for a cardiovascular check-up. All inhabitants of three Belgian towns aged between 45 and 64 years were invited for a cardiovascular check-up and blood test. Of all the attending persons without a history of cardiovascular disease (n = 898), 51% received at least one prescription, diet or health advice: 28% for hyperlipidaemia, 23% for physical activity, 22% for caloric intake, 9% for blood sugar, 5% for blood pressure and 4% for smoking. Interventions on lipoproteins, blood sugar and smoking habits were significantly more often proposed to persons with a medium or high cardiovascular risk compared to those at low cardiovascular risk. For persons at low cardiovascular risk, therapeutic lifestyle changes are often not advised, and isolated risk factors often remain untreated. |
2,331,938 | Cardiac arrest after interscalene brachial plexus block in the sitting position for shoulder arthroscopy: a case report. | The authors report a case of cardiac arrest following interscalene brachial plexus block in the sitting position for shoulder arthroscopy. The cardiac arrest occurred 45 minutes after interscalene brachial plexus block. It seems that it resulted from the activation of Bezold-Jarisch's reflex and a related vasovagal syncope. |
2,331,939 | Cardiovascular and endocrine responses to cutaneous electrical stimulation after fentanyl in the ovine fetus. | The purpose of this study was to determine whether physical stimulation is stressful to the ovine fetus, as judged from physiologic changes that are similar to those reported for other stressors (such as hypoxia); whether any stress response could be blocked by clinically used doses of fentanyl; and whether fentanyl alone had any potentially deleterious physiologic effects in the fetus.</AbstractText>We investigated the effect of fentanyl analgesia on the cardiovascular and endocrine response to cutaneous electrical stimulation in the late gestation (>125 days) ovine fetus (n=7 fetuses). Chronically implanted catheters and blood flow probes were used to measure fetal arterial blood pressure, heart rate, carotid and femoral blood flow, pH, Po(2), Pco(2), lactate, cortisol, and beta-endorphin levels before, during, and for 1 hour after 5 minutes of cutaneous electrical stimulation to the lip, forelimb, and abdomen, in a crossover design. Clinically used 30 or 150 microg doses of fentanyl (which approximated 10 or 50 microg/kg estimated fetal weight) or saline solution were given intravenously to the fetus 2 minutes before stimulation.</AbstractText>When compared with the control, stimulation caused a significant rise in fetal heart rate (P=.003; mean maximal rise, 48.6+/-14.0 beats/min, 0-10 minutes after the start of stimulation) but caused no change in any other parameters studied. Neither dose of fentanyl attenuated the changes in heart rate that were observed in response to stimulation alone. Fentanyl alone significantly increased fetal heart rate, carotid blood flow, and lactate and cortisol levels and significantly decreased pH and Po(2).</AbstractText>Cutaneous electrical stimulation in the fetal sheep causes an increase in heart rate, which fentanyl does not block. Fentanyl itself has significant effects on the cardiovascular and endocrine system, which might adversely affect the fetus.</AbstractText> |
2,331,940 | Intrathecal sufentanil and fetal heart rate abnormalities: a double-blind, double placebo-controlled trial comparing two forms of combined spinal epidural analgesia with epidural analgesia in labor. | Combined spinal epidural analgesia (CSE) for labor pain relief has become increasingly popular. However, the effect of intrathecal sufentanil on the incidence of uterine hyperactivity and fetal heart rate (FHR) abnormalities remains controversial. We hypothesized that the use of intrathecal sufentanil in a dose of 7.5 microg is more likely to induce a nonreassuring FHR tracing than a small dose of spinal sufentanil combined with bupivacaine or epidural analgesia. Three-hundred parturients were randomized into three groups. In the first group, epidural analgesia was initiated with 12.5 mg of bupivacaine, 12.5 microg of epinephrine, and 7.5 microg of sufentanil in a volume of 10 mL (EPD group). In Group 2, initial intrathecal analgesia consisted of 2.5 mg of bupivacaine, 2.5 microg of epinephrine, and 1.5 microg of sufentanil (BSE group); in Group 3, spinal analgesia consisted of 7.5 microg of sufentanil (SUF group). Analgesia was maintained in all groups with patient-controlled epidural analgesia using bupivacaine 0.125%, 1.25 microg/mL of epinephrine, and 0.75 microg/mL of sufentanil (bolus, 4 mL; lockout, 15 min). Cardiotocography was monitored continuously 15 min before analgesia and for 60 min after the start of analgesia. The quality of analgesia, labor, and neonatal outcome and side effects were recorded. Twenty-four percent of patients in the SUF group developed FHR abnormalities (bradycardia or late decelerations) during the first hour after initiation of analgesia compared with 12% in the BSE group and 11% in the EPD group. Uterine hyperactivity occurred in 12% of parturients in the SUF group but in only 2% in the other groups. Onset of analgesia was more rapid in both CSE groups as compared with the EPD group. However, 29% of patients in the BSE group developed severe hypotension, requiring IV ephedrine (29% in the BSE group versus 7% and 12% in the EPD and SUF groups, respectively). All these differences reached statistical significance. The present data corroborate previous recommendations of caution when performing CSE using a large dose (7.5 microg or more) of spinal sufentanil because of the risk of uterine hyperactivity and FHR abnormalities.</AbstractText>Combined spinal epidural analgesia (CSE) produces pain relief during labor. Fetal heart rate changes after CSE using intrathecal sufentanil have been reported. We performed a randomized, blinded trial confirming that fetal heart rate changes are more frequent after CSE using 7.5 micro g of intrathecal sufentanil as compared with other forms of neuraxial labor analgesia.</AbstractText> |
2,331,941 | Identification in human airways smooth muscle cells of the prostanoid receptor and signalling pathway through which PGE2 inhibits the release of GM-CSF. | 1. The prostanoid receptor(s) on human airways smooth muscle (HASM) cells that mediates the inhibitory effect of PGE(2) on interleukin (IL)-1 beta-induced granulocyte/macrophage colony-stimulating factor (GM-CSF) release has been classified. 2. IL-1 beta evoked the release of GM-CSF from HASM cells, which was suppressed by PGE(2), 16,16-dimethyl PGE(2) (nonselective), misoprostol (EP(2)/EP(3)-selective), ONO-AE1-259 and butaprost (both EP(2)-selective) with pIC(50) values of 8.61, 7.13, 5.64, 8.79 and 5.43, respectively. EP-receptor agonists that have selectivity for the EP(1)-(17-phenyl-omega-trinor PGE(2)) and EP(3)-receptor (sulprostone) subtypes as well as cicaprost (IP-selective), PGD(2), PGF(2 alpha) and U-46619 (TP-selective) were poorly active or inactive at concentrations up to 10 microM. 3. AH 6809, a drug that can be used to selectively block EP(2)-receptors in HASM cells, antagonised the inhibitory effect of PGE(2), 16,16-dimethyl PGE(2) and ONO-AE1-259 with apparent pA(2) values of 5.85, 6.09 and 6.1 respectively. In contrast, the EP(4)-receptor antagonists, AH 23848B and L-161,982, failed to displace to the right the concentration-response curves that described the inhibition of GM-CSF release evoked by PGE(2) and ONO-AE1-259. 4. Inhibition of GM-CSF release by PGE(2) and 8-Br-cAMP was abolished in cells infected with an adenovirus vector encoding an inhibitor protein of cAMP-dependent protein kinase (PKA) but not by H-89, a purported small molecule inhibitor of PKA. 5. We conclude that prostanoid receptors of the EP(2)-subtype mediate the inhibitory effect of PGE(2) on GM-CSF release from HASM cells by recruiting a PKA-dependent pathway. In addition, the data illustrate that caution should be exercised when using H-89 in studies designed to assess the role of PKA in biological processes. |
2,331,942 | Protective and anti-protective effects of acute ethanol exposure in myocardial ischemia/reperfusion. | Epidemiological data suggest that a cardioprotective effect of acute alcohol exposure exists in humans. Recent studies in animal models indicate that transient alcohol exposure can indeed reduce myocardial infarct size and exert a preconditioning-like protective effect akin to ischemic preconditioning (IPC). Moreover, the mechanism of alcohol-induced cardioprotection in part resembles the signaling cascade triggered by ischemic preconditioning, with adenosine receptors, PKC, protein tyrosine kinases, and mitochondrial K(ATP) channels all being implicated as key components. However, it was also seen, at least in the rabbit, that if alcohol were present during the ischemic insult, it could block its own protection. The primary protective effect of alcohol use is probably in the chronic setting where alcohol exposure causes a second window type of protection that persists for many days thereafter. Regular moderate drinking should keep the heart in a second window state indefinitely. |
2,331,943 | Cue reactivity and regulation of food intake. | A robust finding in eating research is the so-called counterregulation in restrained eaters. This means that while normal subjects eat less during a taste test, after they consumed a preload, restrained eaters consume more. An explanation is that food exposure causes stronger physiological preparatory reactivity in the restrained eaters. This reactivity is experienced as craving and leads to an increased food intake. To test this theory, 46 high and low restrained eaters were exposed to food or soap, while physiological measurements were made. Afterwards, the subjects performed a taste test, during which food intake was secretly measured. Unrestrained eaters showed an increase in heart rate, gastric activity, and saliva during food exposure; however, restrained eaters did not. Gastric activity significantly correlated with food intake. Group or exposure type did not influence food intake. It can be concluded that unrestrained eaters prepared for food intake, whereas the restrained eaters did not. A possible explanation is that restrained eaters used cognitive suppression to block physiological responding, thereby controlling their food intake. |
2,331,944 | Spinal anaesthesia using hyperbaric 0.75% vs hyperbaric 1% bupivacaine: a double blind comparison. | The aim of this study was to compare the anesthetic effects, potency and postoperative outcome of 0.75% and 1% concentrations of hyperbaric bupivacaine in selective spinal anesthesia.</AbstractText>We enrolled 40 patients in a double blind fashion in 2 groups (A= 0.75% bupivacaine; B= 1% bupivacaine). Demographic data were respectively for Groups A and B: age 40.6+/-16 and 67+/-16, weight 74+/-14.4 and 68+/-10.2; sex 10M/10F and 6M/14F; ASA I-II 11/9 and 14/6. All patients received 11.25 mg bupivacaine. In all cases a 27G Whitacre needle was introduced at L1-L2, L2- L3, L3-L4 introduced with a midline approach. Time to onset and offset of sensitive and motor block, dermatomeric extension non invasive blood pressure, heart rate, ephedrine dose, deambulation time, diuresis time and request for supplemental analgesia were recorded.</AbstractText>No statistically significant differences between the 2 groups for demographic data were found. Group B revealed a faster onset and a more adequate dermatomeric extension (4.1+/-0.8 min vs 6.5+/-1.2 min). Both concentrations guaranteed good hemodynamic stability. Motor offset times were 115.8+/-145 min and 142+/-4.8 min respectively in groups A and B. Sensitive offset times were 197.5+/-12 min and 168+/-5.2 min respectively in groups A and B. No statistically relevant differences were noticed for intraoperative Bromage, sensitive block or for postoperative motor and sensitive offset time, diuresis time and deambulation time. There are no advantages of 1% hyperbaric bupivacaine over 0.75% for selective spinal anesthesia, while several disadvantages presented shorter duration of postoperative analgesia and higher incidence of headache.</AbstractText> |
2,331,945 | The effect of fluid consumption on the forest workers' performance strategy. | The heart rate development and time consumption of four Zimbabwean forest workers engaged in manual harvesting were studied to assess their performance strategy and whether this strategy was affected by differences in fluid consumption. Each worker was studied during 8 consecutive working days and produced 2.4 m3 pulpwood/day. They consumed either 0.17 l or 0.6 l of water each 1/2 hour with one fluid scheme assigned to each day according to a randomised block (person) design with four replicates (days). All workers were found to harvest large trees at the start of the working day and small trees at the end. All workers took longer to complete their task when on the low fluid scheme, however, the effect on the heart rate development varied for the individual workers as the strategies adopted to accommodate the stress inflicted by the low fluid scheme, varied for the individual workers. It is recommended that sufficient fluid supply during work be accompanied by training of the workers to convey the need and benefits of sufficient fluid consumption. |
2,331,946 | Transmission of arterial baroreflex signals depends on neuronal nitric oxide synthase. | Because inhibition of neuronal nitric oxide synthase in the nucleus tractus solitarii blocks cardiovascular responses to activation of local glutamate receptors, and because glutamate is a neurotransmitter of baroreceptor afferent nerves, we sought to test the hypothesis that neuronal nitric oxide synthase inhibition would block baroreflex transmission and cause hypertension. We determined reflex heart rate responses to intravenous phenylephrine and sodium nitroprusside in 5 anesthetized rats before and after bilateral microinjection (100 nL) of the neuronal nitric oxide synthase inhibitor AR-R 17477 (7.5 nmol) into the nucleus tractus solitarii. The inhibitor significantly increased mean arterial pressure without affecting heart rate, and it significantly reduced the gain of the baroreflex. After administration of the inhibitor, reflex responses of heart rate to changes in mean arterial pressure were always less than those responses to the same, or less, change in mean arterial pressure in the same animal without administration of the inhibitor. Microinjection of saline (100 nL) bilaterally into the nucleus tractus solitarii did not lead to hypertension or change baroreflex responses. These data support the hypothesis and suggest that neuronal nitric oxide synthase is critical to transmission of baroreflex signals through the nucleus tractus solitarii. |
2,331,947 | [Emotional stimuli: sensory processing and motor responses]. | Emotion can be functionally considered as action dispositions preparing the organism for either avoidance- or approach- related behaviors. In order to prepare an appropriate behavioral output, the organism has to be efficient in the encoding of relevant stimuli. We herein present evidence from neuroimaging studies that seeing emotional and arousing pictures leads to greater activation in visual cortex than seeing neutral ones. In addition to this facilitation of sensory processing, emotional stimuli prompt somatic and vegetative reactions. Recordings of postural oscillations and heart rate while participants visualized a block of unpleasant pictures, revealed a significant reduction of body sway and bradycardia. A parallel investigation showed that reaction time also slows down after the visualization of negative pictures. Taken together, immobility, bradycardia and slower reaction time in the laboratory experimental set may reflect the engagement of the defensive system, resembling the defensive reactions to distant threatening stimuli in natural contexts. In summary, the affective system operates at an early level of sensory encoding and at the motor output favoring dispositions for appropriate actions. |
2,331,948 | NF-kappaB action in sepsis: the innate immune system and the heart. | Sepsis is the clinical syndrome that results from a host's inflammatory response to infection via activation of the innate immune system. This response involves a complex network of inflammatory mediators that is self-reinforcing. When this immune response progresses uncontrollably, it can ultimately result in cardiovascular collapse and death. This complex inflammatory response is comprised of multiple mediators including cytokines such as TNF-alpha and IL-1beta, that are synthesized and secreted in response to signaling by receptors of the Toll-like receptor (TLR) family of pattern recognition receptors (PRR) that bind to pathogen associated molecules. A central downstream element of TLR-dependent signaling is the pleiotropic transcription factor NF-kappaB. NF-kappaB has been implicated in the regulation of multiple biological phenomena and disease states, including apoptosis, cell growth, stress response, innate immunity and septic shock. NF-kappaB-dependent genes are numerous and several have been implicated in the pathogenesis of sepsis and associated with cardiac dysfunction in sepsis. NF-kappaB activation occurs in multiple organs and cell types, and may be primarily protective in one tissue but injurious in another. Thus, a detailed understanding of the molecular basis of the pathophysiology of sepsis is needed in order to specifically block pro-inflammatory and pro-apoptotic signaling in the heart, while avoiding adverse effects in other organs. |
2,331,949 | Effects of chrysin on urinary testosterone levels in human males. | The equilibrium of sexual hormones in both sexes is controlled in vertebrates by the enzyme aromatase, a member of the cytochrome P450 superfamily, which catalyzes the conversion of androstenedione and testosterone into estrone and estradiol, respectively. Flavonoids are diphenolic compounds present in whole grains, legumes, fruits, and vegetables that are strongly implicated as protective in coronary heart disease, stroke, and cancer. One flavonoid, chrysin, found in high concentrations in honey and propolis, has been shown to be an inhibitor of aromatase enzyme activity. These foods are often used as supplements, particulary by sportsmen for their energetic and antioxidant properties. The aim of this study was to verify if daily treatment for 21 days with propolis and honey, containing chrysin, would modify urinary concentrations of testosterone in volunteer male subjects. In fact, aromatase inhibition by chrysin could block the conversion of androgens into estrogens with a consequent increase of testosterone, eventually measurable in urine samples. The obtained data did not show alterations of the levels of testosterone in the volunteers after 7, 14, and 21 days of treatment in comparison with baseline values and compared with measurements on the control subjects at the same time. In conclusion, the use of these foods for 21 days at the doses usually taken as oral supplementation does not have effects on the equilibrium of testosterone in human males. |
2,331,950 | Plastid lysophosphatidyl acyltransferase is essential for embryo development in Arabidopsis. | Lysophosphatidyl acyltransferase (LPAAT) is a pivotal enzyme controlling the metabolic flow of lysophosphatidic acid into different phosphatidic acids in diverse tissues. A search of the Arabidopsis genome database revealed five genes that could encode LPAAT-like proteins. We identified one of them, LPAAT1, to be the lone gene that encodes the plastid LPAAT. LPAAT1 could functionally complement a bacterial mutant that has defective LPAAT. Bacteria transformed with LPAAT1 produced LPAAT that had in vitro enzyme activity much higher on 16:0-coenzyme A than on 18:1-coenzyme A in the presence of 18:1-lysophosphatidic acid. LPAAT1 transcript was present in diverse organs, with the highest level in green leaves. A mutant having a T-DNA inserted into LPAAT1 was identified. The heterozygous mutant has no overt phenotype, and its leaf acyl composition is similar to that of the wild type. Selfing of a heterozygous mutant produced normal-sized and shrunken seeds in the Mendelian ratio of 3:1, and the shrunken seeds could not germinate. The shrunken seeds apparently were homozygous of the T-DNA-inserted LPAAT1, and development of the embryo within them was arrested at the heart-torpedo stage. This embryo lethality could be rescued by transformation of the heterozygous mutant with a 35S:LPAAT1 construct. The current findings of embryo death in the homozygous knockout mutant of the plastid LPAAT contrasts with earlier findings of a normal phenotype in the homozygous mutant deficient of the plastid glycerol-3-phosphate acyltransferase; both mutations block the synthesis of plastid phosphatidic acid. Reasons for the discrepancy between the contrasting phenotypes of the two mutants are discussed. |
2,331,951 | Caspase-dependent cytochrome c release and cell death in chick cardiomyocytes after simulated ischemia-reperfusion. | We recently demonstrated that reperfusion rapidly induces the mitochondrial pathway of apoptosis in chick cardiomyocytes after 1 h of simulated ischemia. Here we tested whether ischemia-reperfusion (I/R)-induced apoptosis could be initiated by caspase-dependent cytochrome c release in this model of cardiomyocyte injury. Fluorometric assays of caspase activity showed little, if any, activation of caspases above baseline levels induced by 1 h of ischemia alone. However, these assays revealed rapid activation of caspase-2, yielding a 2.95 +/- 0.52-fold increase (over ischemia only) within the 1st h of reperfusion, whereas activities of caspases-3, -8, and -9 increased only slightly from their baseline levels. The rapid and prominent activation of caspase-2 suggested that it could be an important initiator caspase in this model, and using specific caspase inhibitors given only at the point of reperfusion, we tested this hypothesis. The caspase-2 inhibitor benzyloxycarbonyl-Val-Asp(Ome)-Val-Ala-Asp(Ome)-CH(2)F was the only caspase inhibitor that significantly inhibited cytochrome c release from mitochondria. This inhibitor also completely blocked activation of caspases-3, -8, and -9. The caspase-3/7 inhibitor transiently and only partially blocked caspase-2 activity and was less effective in blocking the activities of caspases-8 and -9. The caspase-8 inhibitor failed to significantly block caspase-2 or -3, and the caspase-9 inhibitor blocked only caspase-9. Furthermore, the caspase-2 inhibitor protected against I/R-induced cell death, but the caspase-8 inhibitor failed to do so. These data suggest that active caspase-2 initiates cytochrome c release after reperfusion and that it is critical for the I/R-induced apoptosis in this model. |
2,331,952 | PKC-epsilon regulation of extracellular signal-regulated kinase: a potential role in phenylephrine-induced cardiocyte growth. | Hypertrophic growth of cardiac muscle is dependent on activation of the PKC-epsilon isoform. To define the effectors of PKC-epsilon involved in growth regulation, recombinant adenoviruses were used to overexpress either wild-type PKC-epsilon (PKC-epsilon/WT) or dominant negative PKC-epsilon (PKC-epsilon/DN) in neonatal rat cardiocytes. PKC-epsilon/DN inhibited acute activation of PKC-epsilon produced in response to phorbol ester and reduced ERK1/2 activity as measured by the phosphorylation of p42 and p44 isoforms. The inhibitory effects were specific to PKC-epsilon because PKC-epsilon/DN did not prevent translocation of either PKC-alpha or PKC-delta. Overexpression of PKC-epsilon/DN blunted the acute increase in ERK1/2 phorphorylation induced by the alpha(1)-adrenergic agonist phenylephrine (PE ). Inhibition of PKC-delta with rottlerin potentiated the effects of PE on ERK1/2 phosphorylation. PKC-epsilon/DN adenovirus also blocked cardiocyte growth as measured after 48 h of PE treatment, although the multiplicity of infection was lower than that required to block acute ERK1/2 activation. PE activated p38 mitogen-activated protein kinase as measured by its phosphorylation, but the response was not blocked by PKC inhibitors or by overexpression of PKC-epsilon/DN. Taken together, these studies show that the hypertrophic agonist PE regulates ERK1/2 activity in cardiocytes by a pathway dependent on PKC-epsilon and that PE-induced growth is mediated by PKC-epsilon. |
2,331,953 | Buspirone raises blood pressure through activation of sympathetic nervous system and by direct activation of alpha1-adrenergic receptors after severe hemorrhage. | 5-Hydroxytryptamine 1A (5-HT1A) receptor agonists reverse the hypotensive and sympathoinhibitory responses to severe hemorrhage in rats. To determine whether 5-HT1A receptor-mediated pressor responses in hypovolemic animals are due to sympathoexcitation and/or direct vasoconstriction, blood pressure (BP), heart rate (HR), and renal sympathetic nerve activity (RSNA) responses to the partial 5-HT1A receptor agonist buspirone or the more selective, full 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were compared in intact and ganglionic blocked, hemorrhaged Sprague-Dawley rats. Buspirone produced dose-dependent increases in BP (110 +/- 4(**), 86 +/- 4(**), 65 +/- 7 mm Hg), HR [369 +/- 10(**), 337 +/- 14, 277 +/- 16 beats per minute (bpm)], and RSNA (114 +/- 36(**), 34 +/- 21, -23 +/- 25% baseline for 0.2, 0.1, and 0 mg/kg; (**)p < 0.01 versus 0 mg/kg, 3 min after injection). Ganglionic blockade with hexamethonium chloride blocked the pressor effect of 9.9 microg/kg 8-OH-DPAT and attenuated, but did not block, the pressor response to 0.2 mg/kg buspirone (85 +/- 7 versus 46 +/- 6 mm Hg for buspirone + ganglionic blockade versus saline + ganglionic blockade; p < 0.01). In subsequent tests, rats treated with the selective alpha1-adrenergic receptor antagonist prazosin (25 microg/kg) continued to show extensive tachycardic (+73 +/- 26 bpm) and sympathoexcitatory (128 +/- 55% baseline) responses to 0.2 mg/kg buspirone. Ganglionic blockade combined with prazosin completely blocked all responses to buspirone. Buspirone (0.2 mg/kg) produced significant bradycardic (-89 +/- 12 bpm; p < 0.01) and sympathoinhibitory (-72 +/- 7% baseline; p < 0.01) responses in euvolemic rats 3 min after injection. It is concluded that the pressor effect of buspirone is unique to hypovolemic animals and is mediated by sympathetic activation as well as direct activation of vascular alpha1-adrenergic receptors. |
2,331,954 | A multicentre trial comparing different concentrations of ropivacaine plus sufentanil with bupivacaine plus sufentanil for patient-controlled epidural analgesia in labour. | To determine the optimal concentration of ropivacaine for bolus-only patient-controlled epidural labour analgesia, three different doses of ropivacaine were evaluated in comparison with bupivacaine in a double-blinded multicentre study.</AbstractText>Four hundred-and-fifty labouring parturients at term in three different academic institutions were randomized to four groups receiving bupivacaine 0.125% with sufentanil 0.75 microg mL(-1), ropivacaine 0.125% or 0.175% with sufentanil 0.75 microg mL(-1), or ropivacaine 0.2%. After an initial bolus of 10 mL of the study solution, and once visual analogue scores (VAS) were below 30 mm, patient-controlled epidural analgesia was initiated with a bolus of 4 mL, a lockout interval of 15 min and without a background infusion. Variables studied were the quality of analgesia, incidence of side-effects, the degree of motor blockade, and the mode of delivery.</AbstractText>Bupivacaine 0.125% and ropivacaine 0.125% with sufentanil proved equally effective in providing labour analgesia without a difference in local anaesthetic consumption (48.6 +/- 23 mg bupivacaine vs. 52.1 +/- 38 mg ropivacaine), motor blockade or mode of delivery. Ropivacaine 0.175% plus sufentanil enhanced the quality of analgesia of the initial loading dose, whereas ropivacaine 0.2% without sufentanil increased the consumption of local anaesthetics (80.2 +/- 34 mg; P < 0.05) and the degree of motor blockade.</AbstractText>Despite recent studies indicating that bupivacaine and ropivacaine may not be equipotent, both local anaesthetics provided equi-effective analgesia at equal doses without a difference in side-effects.</AbstractText> |
2,331,955 | Evidence of sustained forearm vasodilatation after brief isocapnic hypoxia. | Healthy subjects exposed to 20 min of hypoxia increase ventilation and muscle sympathetic nerve activity (MSNA). After return to normoxia, although ventilation returns to baseline, MSNA remains elevated for up to an hour. Because forearm vascular resistance is not elevated after hypoxic exposure, we speculated that the increased MSNA might be a compensatory response to sustained release of endogenous vasodilators. We studied the effect of isocapnic hypoxia (mean arterial oxygen saturation 81.6 +/- 4.1%, end-tidal Pco2 44.7 +/- 6.3 Torr) on plethysmographic forearm blood flow (FBF) in eight healthy volunteers while infusing intra-arterial phentolamine to block local alpha-receptors. The dominant arm served as control. Forearm arterial vascular resistance (FVR) was calculated as the mean arterial pressure (MAP)-to-FBF ratio. MAP, heart rate (HR), and FVR were reported at 5-min intervals at baseline, then while infusing phentolamine during room air, isocapnic hypoxia, and recovery. Despite increases in HR during hypoxia, there was no change in MAP throughout the study. By design, FVR decreased during phentolamine infusion. Hypoxia further decreased FVR in both forearms. With continued phentolamine infusion, FVR after termination of the exposure (17.47 +/- 6.3 mmHg x min x ml(-1) x 100 ml of tissue) remained lower than preexposure baseline value (23.05 +/- 8.51 mmHg x min x ml(-1) x 100 ml of tissue; P < 0.05). We conclude that, unmasked by phentolamine, the vasodilation occurring during hypoxia persists for at least 30 min after the stimulus. This vasodilation may contribute to the sustained MSNA rise observed after hypoxia. |
2,331,956 | Effects of perioperative alpha1 block on haemodynamic control during laparoscopic surgery for phaeochromocytoma. | Laparoscopic surgery for phaeochromocytoma can cause excessive catechol amine release with severe hypertension and sinus tachycardia. i.v. calcium antagonists may be used to prevent increases in blood pressure during phaeochromocytoma resection. We investigated the effects of perioperative alpha(1) adrenergic block with urapidil on intraoperative haemodynamic events. The aim was to block the alpha(1) adrenergic receptors before any acute catecholamine release, to prevent any severe rise in blood pressure.</AbstractText>Eighteen patients with a phaeochromocytoma received a continuous i.v. infusion of urapidil 10-15 mg h(-1) for 3 days before surgery and until the adrenal gland had been removed. Plasma catecholamine concentrations were measured before surgery, after induction of anaesthesia, at the end of pneumoperitoneal insufflation, during gland manipulation, after gland resection, and in the recovery room after extubation. Arterial pressure was recorded concomitantly. Hypertensive events were treated with boluses of nicardipine with or without esmolol.</AbstractText>All patients had the adrenal tumour removed without any severe rise in blood pressure or other complication. Creation of a pneumoperitoneum and adrenal gland manipulation induced significant catecholamine release associated with hypertension in 6 and 12 patients, respectively. No correlation was found between hypertensive events and plasma catecholamine levels suggesting alpha(1) receptor block with urapidil is efficacious.</AbstractText>Perioperative alpha(1) block using i.v. urapidil is a safe and efficient alternative during surgical management of phaeochromocytoma.</AbstractText> |
2,331,957 | Effect of caudal epidural xylazine on intraoperative distress and post-operative pain in Holstein heifers. | To compare the effects of caudal epidural xylazine versus saline on tolerance of paravertebral nerve block and flank surgery and on post-operative pain in heifers used for a veterinary student training laboratory.</AbstractText>Randomized controlled prospective study.</AbstractText>Fourteen one-year-old, nongravid, healthy Holstein heifers, weighing 360 +/- 5 kg.</AbstractText>Xylazine (0.05 mg kg(-1)) or 0.9% saline (5 mL) was injected using a caudal epidural technique to seven heifers undergoing a flank surgery. Nerve block of the right paravertebral fossa was performed using equal parts of lidocaine 2% and bupivacaine 0.5%. Heart and respiratory rates, rectal temperature, rumination frequency, and appetite were recorded before and at 4, 8, and 24 hours after surgery. Scores were recorded for: tolerance of local anesthesia injections (pre-operatively), sedation, ataxia and distress (intraoperatively, every 30 minutes), and pain (4, 8, and 24 hours post-operatively).</AbstractText>The animals reaction to local anesthetic injection was judged to be less in the xylazine group by both an experienced observer (p<0.001) and student surgeons (p<0.01). The xylazine group required less local anesthetic (82.9 +/- 13.8 mL) versus the saline group (108.4 +/- 19.6 mL, p=0.035). Intraoperatively, xylazine heifers were more sedated at all times (p-values from <0.001 to 0.017), were more ataxic for the first 1.5 hours (p-values from <0.001 to 0.026), and lower in distress at all times (p-values from <0.001 to 0.007). No difference in post-operative pain or physiologic variables was found, except immediately post-operatively, rectal temperature was higher in the xylazine group (39.5 +/- 0.3 degrees C) than in the saline group (38.6 +/- 0.2 degrees C, p<0.001).</AbstractText>Compared with epidural saline, caudal epidural xylazine reduced distress of anesthetic injection and surgical manipulation in heifers and an improvement in animal well-being was apparent. This effect may have been as a result of sedation. Pre-operative epidural xylazine did not appear to improve post-surgical analgesia in our study.</AbstractText> |
2,331,958 | Cardioprotection of interleukin-2 is mediated via kappa-opioid receptors. | We examined whether interleukin-2 (IL-2) protects the myocardium against injury induced by ischemia and reperfusion via the kappa-opioid receptor (OR). The cardioprotective effect of IL-2 was evaluated by measuring infarct size and lactate dehydrogenase (LDH) release in response to ischemia and reperfusion in the isolated rat heart. IL-2 at an optimal dose of 50 U/ml mimicked the effect of ischemic preconditioning by reducing infarct size and LDH release. The infarct and LDH-reducing effects of IL-2 were blocked by nor-binaltorphimine (5 microM), a kappa-OR antagonist, but not naltrindole (5 microM), a delta-OR antagonist known to block the action of its stimulation. Moreover, blockade of the mitochondrial ATP-sensitive potassium (mito-K(ATP)) channel with a selective antagonist, 5-hydroxydecanoate (100 microM), or a nonselective antagonist of K(ATP) channels, glybenclamide (100 microM), or blockade of protein kinase C (PKC) with its inhibitors chelerythrine (5 microM) or GF 109203X (10 microM) [3-[1-[3-(dimethylaminopropyl]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione monohydrochloride] abolished the protective effect of IL-2. Administration of free radical scavengers N-acetylcysteine (4 mM) or N-(2-mercaptopropionyl)-glycine (1 mM) also abolished the protective effects of IL-2 and U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide], a selective kappa-OR agonist. This study provides the first evidence that IL-2 confers cardioprotection against injury induced by ischemia/reperfusion. The effect of IL-2 is mediated via kappa-OR as evidenced by kappa-OR antagonism and similar signaling mechanisms, mito-K(ATP), PKC, and reactive oxygen species involved in the cardioprotective effects of both IL-2 and kappa-OR stimulation. |
2,331,959 | Epidural block with ropivacaine and bupivacaine for elective caesarean section: maternal cardiovascular parameters, comfort and neonatal well-being. | To determine cardiovascular effects and neonatal outcome of ropivacaine 0.75% and bupivacaine 0.5% for elective epidural caesarean section.</AbstractText>Healthy pregnant women, scheduled for elective caesarean section, were enrolled in this randomised, double-blind study. Epidural block was obtained with 20-30 ml of ropivacaine 0.75% (Group R) or bupivacaine 0.5% (Group B) and surgery did not commence until anaesthesia was achieved bilaterally to T6.</AbstractText>Maternal heart rate and blood pressure were assessed before the main dose of local anaesthetic and at 5-min intervals until 35 min. Neonatal umbilical pH and Apgar scores were determined after delivery. Ten, twenty and thirty minutes after the main dose, sensory and motor block characteristics were determined. Quality of analgesia was assessed by the anaesthetist, surgeon and the patient. Adverse events were recorded.</AbstractText>Sixty-two patients were enrolled and the data of 60 of them were eligible for analysis: 31 in Group R and 29 in Group B. The area under the curve (AUC) for maternal heart rate decreased significantly less in Group B than in Group R (p = 0.038). Twenty-five and thirty minutes after administration of the main local anaesthetic dose, heart rate decreased significantly less in Group B than in Group R (p = 0.006 and p = 0.007). There was no difference in AUC for maternal blood pressure (p = 0.32). Repeated measurement analysis showed no difference between groups in motor block (p = 0.78) and in spread of the sensory block (lower level: p = 0.83, upper level: p = 0.88). There was no statistical difference in neonatal umbilical pH (p = 0.22) and Apgar score (p = 0.59). Multiple linear regression analysis showed a significant influence of maternal body mass index on neonatal pH (p = 0.004), but not of maternal blood pressure (p = 0.323), nor of maternal heart rate (p = 0.12). The quality of analgesia and incidence of adverse events were similar in both groups.</AbstractText>Both drugs produced equally satisfactory epidural block. Although ropivacaine 0.75% resulted in a greater decrease of maternal heart rate, this effect did not influence neonatal well-being. Both ropivacaine 0.75% and bupivacaine 0.5% can therefore be recommended for epidural anaesthesia in elective caesarean section.</AbstractText> |
2,331,960 | Bilateral interpleural versus lumbar epidural bupivacaine-morphine analgesia for upper abdominal surgery. | This randomized study was designed to compare the effectiveness of bilateral interpleural analgesia with lumbar epidural analgesia, on postoperative pain relief in upper abdominal surgery. The studied patients were randomely allocated into either interpleural group "IP" (n = 15) or epidural group "EP" (n = 15). In "IP" group, preanesthetic bilateral interpleural block was done using a mixture of bupivacaine 0.5% (0.8 mg/kg) and 2 mg morphine diluted to 50 ml saline for each side. In "EP" group, the same mixture-diluted in 20 ml saline-was injected in the epidural space (L2-3). The general anesthetic technique was the same in both groups. Hemodynamic, gasometric, verbal pain score (VPS) values and complications were compared in both techniques. Heart rate (HR) and mean arterial pressure (MAP) readings were in the accepted normal range in the perioperative period although significant lower readings were detected in "EP" group. No significant differences were displayed in blood gasometric variables between the two groups. There were considerable level of analgesia in both groups in the postoperative period although "EP" analgesia was superior to "IP". More pain free patients (9 versus 4) and significant lower consumption of nalbuphine were detected in "EP" group. The results of this study indicate that bilateral "IP" analgesia may offer a satisfactory analgesia for upper abdominal surgery when the use of other analgesic techniques may be contraindicated. |
2,331,961 | Differential susceptibility of cells expressing allogeneic MHC or viral antigen to killing by antigen-specific CTL. | CD8(+) cytotoxic T lymphocytes (CTLs) generated by immunization with allogeneic cells or viral infection are able to lyse allogeneic or virally infected in vitro cells (e.g., lymphoma and mastocytoma). In contrast, it is reported that CD8(+) T cells are not essential for allograft rejection (e.g., heart and skin), and that clearance of influenza or the Sendai virus from virus-infected respiratory epithelium is normal or only slightly delayed after a primary viral challenge of CD8-knockout mice. To address this controversy, we generated H-2(d)-specific CD8(+) CTLs by a mixed lymphocyte culture and examined the susceptibility of a panel of H-2(d) cells to CTL lysis. KLN205 squamous cell carcinoma, Meth A fibrosarcoma, and BALB/c skin components were found to be resistant to CTL-mediated lysis. This resistance did not appear to be related to a reduced expression of MHC class I molecules, and all these cells could block the recognition of H-2(d) targets by CTLs in cold target inhibition assays. We extended our observation by persistently infecting the same panel of cell lines with defective-interfering Sendai virus particles. The Meth A and KLN205 lines infected with a variant Sendai virus were resistant to lysis by Sendai virus-specific CTLs. The Sendai virus-infected Meth A and KLN205 lines were able to block the lysis of Sendai virus-infected targets by CTLs in cold target inhibition assays. Taken together, these results suggest that not all in vivo tissues may be sensitive to CTL lysis. |
2,331,962 | Retinoids and TIMP1 prevent radiation-induced apoptosis of capillary endothelial cells. | Radiation-induced changes in capillaries constitute a basic injury in the pathogenesis of chronic radiation damage to the heart, lung, liver, kidney and brain. It is important to identify new radioprotectors for capillary endothelial cells for use during radiotherapy to minimize normal tissue damage and possibly to increase the deliverable dose. Previously we demonstrated that exposure to ionizing radiation (10 Gy) results in death of bovine adrenal capillary endothelial cells in confluent monolayers by apoptosis. We also showed that retinoids inhibit the growth of endothelial cells, induce their differentiation, down-regulate matrix metalloproteinase (MMP) production, and up-regulate tissue inhibitors of matrix metalloproteinases (TIMPs). In the present studies, we demonstrated that radiation (10 Gy) induced an immediate increase in the amounts and activation of MMP1 and MMP2 in the cell fraction and medium of bovine capillary endothelial cells followed by an incidence of apoptosis. We also obtained data indicating that radiation-induced apoptosis can be inhibited by exposing bovine capillary endothelial cells to all-trans-retinol or all-trans-retinoic acid for 6 days before irradiation, even when the vitamins were removed 24 h before irradiation. Finally, we determined that inhibition of MMPs by TIMP was sufficient to block radiation-induced apoptosis, suggesting that the mechanism of protection by retinoids is through the alteration of levels of MMPs and TIMPs produced by the cells. |
2,331,963 | Vasopressin receptor antagonists. Therapeutic potential in the management of acute and chronic heart failure. | Despite the use of ACE inhibitors and beta-blockers, the morbidity and mortality of patients with chronic heart failure remains quite high. This has stimulated the development of new therapies, many based on the neurohormonal hypothesis. There are now multiple agents being developed for the treatment of heart failure designed to block many of the neurohormones that are increased in these patients. One of the hormones that is increased in chronic heart failure is vasopressin. Vasopressin reduces free water secretion and at high concentrations, causes vasoconstriction in the peripheral vasculature. Antagonists to vasopressin will promote free water excretion (aquaresis) and vasodilatation with a subsequent reduction in afterload. In theory, these agents would be beneficial for both acute exacerbations of heart failure (free water excretion) and chronic heart failure (neurohormonal blockade). We review the potential uses of these antagonists for these two conditions and the promising results of small, hemodynamic trials with the new vasopressin antagonists that have already been performed. |
2,331,964 | [Application of combined epidural-spinal anesthesia in pediatric surgery and postoperative analgesia]. | To compare the anesthetic and analgesic efficacy of ropivacaine and bupivacaine and their side reactions in combined spinal-epidural anesthesia (CSEA) and postoperative analgesia in pediatric surgery.</AbstractText>Fifty children for lower abdominal surgery, aged 6-14 years, were randomly assigned to receive either ropivacaine (Group R, n=25) or bupivacaine (Group B, n=25) for CSEA. Spinal injection for Group R was a mixture of 1.5 ml of 10 g x L(-1) ropivacaine, 0.5 ml distilled water and 1ml of 100 g x L(-1) dextrose. The injection for Group B was the same as that for Group R except 0.5 ml of 7.5 g x L(-1) bupivacaine. The terminal concentrations of anesthetics were 5 g x L(-1) for the two groups. The injection volume was calculated as: ml=(age x 0.2 + weight x 0.5) divided by 2. When operations prolonged to 1.5 h, epidural infusion at the rate of 1 mg x (kg(-1) x h(-1)) started with 2.5 g x L(-1) ropivacaine for Group R and 2.5 g x L(-1) bupivacaine for Group B. The observed variables were the changes in blood pressure, heart rate, SpO(2), block level, visual analogue scores, and motor block. Epidural postoperative analgesia was performed for Group R with 100 ml of 0.75 g x L(-1) ropivacaine to which 100 mg tramadol and 5 mg were added, and for Group B with 100 ml of 0.75 g/L(-1) bupivacaine instead. Backgroup infusion was 3 ml x h(-1) for the children aged 6-9 years or 4 ml x h(-1) for the children aged 10-14 years, bolus was 2 ml controlled by children or their parents when necessary, and locktime was 15 min. The observed variables were the efficacy of postoperative analgesia, recession of motor block of legs, and the incidence of headache, nausea and vomiting, leg numbness, and urinary retention within 24 h after operation.</AbstractText>There was no significant difference between the two groups in block level. Motor block was much milder in Group R than that in Group B during operation, and recessed faster after operation. Only one case of nausea occurred in each group, and one case of urinary retention in Group B without statistical significance.</AbstractText>Either ropivacaine or bupivacaine can be satisfactorily used in CSEA for analgesia during and after operation. However, ropivacaine has a weaker motor block than bupivacaine, which benefits early walking after operation and recovery of bowl movement.</AbstractText> |
2,331,965 | The effect of caudal bupivacaine versus tramadol in post-operative analgesia for paediatric patients. | In this study 20 paediatric surgical patients were randomized to two groups after induction of general anaesthesia. Group 1 received 0.25% bupivacaine (2 mg/kg) and group 2 received 5% tramadol (2 mg/kg) both as a caudal block. Heart rate, mean arterial pressure, arterial oxygen saturation, respiratory rate and pain and sedation scores were recorded at 1, 2, 4, 6, 12 and 24 h post-operatively. Acetaminophen was administered rectally (20 mg/kg) if the pain score was > 3/10. The pain and sedation scores in group 2 were significantly lower compared with group 1. There were no significant differences in heart rate, mean arterial pressure, arterial oxygen saturation and respiratory rate between the two groups. In conclusion, caudal tramadol was superior to bupivacaine in analgesic efficacy and in reducing the need for additional analgesia during the post-operative period in paediatric patients. |
2,331,966 | Autoimmune response in mothers of children with congenital and postnatally diagnosed isolated heart block: a population based study. | To study the autoimmune response in mothers of children with isolated congenital heart block (CHB) and heart block (HB) diagnosed postnatally.</AbstractText>We reviewed the Finnish hospital registries for patients born between 1950 and 2000 and diagnosed with isolated HB before the age of 16 years. Clinical data and sera for the determination of autoantibodies were available from 67 mothers of children with CHB and from 37 mothers of children with postnatally diagnosed HB 9.9 years and 22.6 years (mean) after the index delivery, respectively. Maternal antibodies to 52 kDa and 60 kDa SSA and 48 kDa SSB were determined by time-resolved fluoroimmunoassay (TR-FIA) and by immunoblotting. Other marker antibodies for connective tissue diseases (CTD) were determined by immunoblot and/or by immunofluorescence. The control group comprised 136 mothers with primary Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), or other CTD with healthy children.</AbstractText>Sixty of our 67 mothers (90%) of children with CHB had antibodies to SSA or SSB by the methods initially used in this study. When retests and tests performed previously were taken into account, only 3 (4%) of the 67 mothers did not have any autoantibodies. Two (3%) of the 67 mothers had antibodies to dsDNA and one (1%) each to Jo-1/HRS, RNP-70 kDa, and histone proteins. Of 37 mothers of children with postnatally diagnosed HB, only 3 (8%) had any autoantibodies. Increased risk of having a child with CHB was indicated by maternal primary SS and high levels of anti-SSA and anti-SSB by all assays, whereas low risk was indicated by maternal SLE or other CTD and undetectable or low levels of the antibodies. No single anti-SSA or anti-SSB test was clearly superior to others, but in general, immunoblots were more specific than TR-FIA.</AbstractText>Maternal autoimmune disorder is almost always associated with CHB but only rarely with postnatally diagnosed HB. Anti-SSA and anti-SSB are marker antibodies for mothers of children with CHB, and an increased risk of having an affected child is indicated by maternal primary SS and high titer antibodies to SSA and SSB.</AbstractText> |
2,331,967 | Pro-nucleotide inhibitors of adenylyl cyclases in intact cells. | 9-substituted adenine derivatives with protected phosphoryl groups were synthesized and tested as inhibitors of adenylyl cyclase in isolated enzyme and intact cell systems. Protected 3'-phosphoryl derivatives of 2',5'-dideoxyadenosine (2',5'-dd-Ado) and beta-l-2',5'-dd-Ado, protected 5'-phosphoryl derivatives of beta-l-2',3'-dd-Ado, and protected phosphoryl derivatives of two 9-(2-phosphonomethoxy-acyl)-adenines were synthesized. Protection was afforded by two cyclosaligenyl- or three S-acyl-2-thioethyl-substituents. These pro-nucleotides were tested for their capacity to block forskolin-induced increases in [(3)H]cAMP in OB1771 and F442A preadipocytes and human macrophages prelabeled with [(3)H]adenine. A striking selectivity for 2',5'-dd-Ado-3'-phosphoryl derivatives was observed. Cyclosaligenyl-derivatives (IC(50) approximately 2 microm) were much less potent than S-acyl-2-thioethyl-derivatives. Best studied of these was 2',5'-dd-Ado-3'-O-bis(S-pivaloyl-2-thioethyl)-phosphate, which blocked [(3)H]cAMP formation in preadipocytes (IC(50) approximately 30 nm) and suppressed opening of cAMP-dependent Cl(-) channels in cardiac myocytes (IC(50) approximately 800 nm). None of the pro-nucleotides inhibited adenylyl cyclase per se, whether isolated from rat brain or OB1771 cells. These compounds exhibit the hallmarks of prodrugs. Data suggest they are taken up, are deprotected, and are converted to a potent inhibitory form to inhibit adenylyl cyclase, but only by intact cells. The availability and characteristics of these prodrugs should make them useful for blocking cAMP-mediated pathways in intact cell systems, in biochemical, pharmacological, and potentially therapeutic contexts. |
2,331,968 | Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts. | Co-stimulatory blockade combined with donor bone marrow transfusion engenders stable mixed chimerism and robust tolerance to various organ and cell transplants. However, repeated administration of costly agents to block the co-stimulatory pathway and the high doses of donor bone marrow cells (BMCs) used in most protocols are impeding clinical development of this strategy. To circumvent these shortcomings, we developed a plan in which repeated administration of costly agents was replaced by a single injection of adenovirus containing the gene of interest, and the high dose of donor BMCs replaced by a mixture of low-dose donor BMCs and splenocytes (SPLCs). Cardiac allografts from DA(RT-1(a)) rats were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. A cocktail of adenovirus containing CTLA4Ig gene (AdCTLA4Ig), donor BMCs (100 x 10(6)), and SPLCs (50 x 10(6)) was administered to recipients via the portal vein immediately after grafting (n = 6). Treatment with regimens, including AdCTLA4Ig only, AdCTLA4Ig plus donor BMCs, and AdCTLA4Ig plus donor SPLCs, significantly prolonged cardiac allograft survival in recipient rats, while animals that received no treatment or treatment with control adenovirus (AdLacZ) promptly rejected their allografts. Nevertheless, LEW recipients treated with AdCTLA4Ig and the mixture of a low dose of donor BMCs and SPLCs developed stable mixed chimerism, rendering them long-term survivors of cardiac allografts that also accepted skin grafts from the donor but not the third-party strain. We conclude that blockade of CD28-B7 pathway with AdCTLA4Ig plus a mixture of low doses of donor BMCs and SPLCs is a feasible strategy to induce long-term mixed chimerism with a potential application for clinical development. |
2,331,969 | The effects of three different approaches on the onset time of sciatic nerve blocks with 0.75% ropivacaine. | We studied three different injection techniques of sciatic nerve block in terms of block onset time and efficacy with 0.75% ropivacaine. A total of 75 patients undergoing foot surgery were randomly allocated to receive sciatic nerve blockade by means of the classic posterior approach (group classic; n = 25), a modified subgluteus posterior approach (group subgluteus; n = 25), or a lateral popliteal approach (group popliteal; n = 25). All blocks were performed with the use of a nerve stimulator (stimulation frequency, 2 Hz; intensity, 2-0.5 mA) and 30 mL of 0.75% ropivacaine. Onset of nerve block was defined as complete loss of pinprick sensation in the sciatic nerve distribution with concomitant inability to perform plantar or dorsal flexion of the foot. In the three groups, an appropriate sciatic stimulation was elicited at <0.5 mA. The failure rate was similar in the three groups (group popliteal: 4% versus group classic: 4% versus group subgluteus: 8%). The onset of nerve block was slower in group popliteal (25 +/- 5 min) compared with group classic (16 +/- 4 min) and group subgluteus (17 +/- 4 min; P < 0.001). There was no significant difference in the onset of nerve block between group classic and group subgluteus. No differences in the degree of pain measured at the first postoperative administration of pain medication were observed among the three groups. We conclude that the three approaches resulted in clinically acceptable anesthesia in the distribution of the sciatic nerve. The subgluteus and classic posterior approaches generated a significantly faster onset of anesthesia than the lateral popliteal approach.</AbstractText>Comparing three different approaches to the sciatic nerve with 0.75% ropivacaine, the classic and subgluteal approaches exhibited a faster onset time of sensory and motor blockade than the lateral popliteal approach.</AbstractText> |
2,331,970 | Single-dose dexmedetomidine reduces agitation after sevoflurane anesthesia in children. | Emergence agitation is a common side effect of sevoflurane anesthesia in children. Dexmedetomidine, because of its sedative and analgesic properties, might be useful for the management of this adverse effect. We studied the effect of dexmedetomidine on recovery characteristics in 90 children aged 1 to 10 yr scheduled to undergo superficial lower abdominal and genital surgery. After inhaled induction with sevoflurane, patients were randomly assigned to receive saline (Group 1, n = 30), dexmedetomidine 0.15 micro g/kg (Group 2, n = 30), or dexmedetomidine 0.30 micro g/kg (Group 3, n = 30). After a laryngeal mask airway insertion a caudal block was performed in all patients. Maintenance of anesthesia was with 1% end-tidal sevoflurane and 50% nitrous oxide and spontaneous ventilation. Intraoperative hemodynamic and respiratory variables were recorded every 5 min. At the end of anesthesia time to eyes opening (TEO) and characteristics of emergence were recorded. General and intraoperative variables were similar in the 3 groups. The TEO was 7.5 +/- 5.0 min in Group 1, 8.2 +/- 5.0 min in Group 2, and 9.8 +/- 4.0 min in Group 3 (NS). The incidence (95% confidence interval) of agitation was 37% (20%-54%) in Group 1, 17% (4%-30%) in Group 2, and 10% (0%-21%) in Group 3 (P < 0.05). Paired comparisons showed a significant difference for Group 1 versus Group 3 (P < 0.05, 95% confidence interval of the difference: 7%-47%). The time to discharge from the postanesthesia care unit was similar for the 3 groups. We conclude that a dose of dexmedetomidine 0.3 micro g/kg administered after induction of anesthesia reduces the postsevoflurane agitation in children and with no adverse effects.</AbstractText>In children undergoing surgery using sevoflurane anesthesia, dexmedetomidine 0.3 micro g/kg administered in 10 min after induction reduced the incidence of emergence agitation from 37% in the control group to 10%. No adverse effects attributable to dexmedetomidine were observed.</AbstractText> |
2,331,971 | Clonidine prolongs spinal anesthesia in newborns: a prospective dose-ranging study. | Spinal anesthesia may reduce the incidence of morbidity that follows general anesthesia in neonates and in former preterm infants. However, bupivacaine alone provides a block too short for complete surgery in up to 40% of the patients. Clonidine lengthens spinal anesthesia in adults and caudal block in children without significant side effects. We conducted a controlled, prospective, dose-ranging study of clonidine in spinal anesthesia in 75 neonates, including 50% of former preterm infants, undergoing elective inguinal herniorrhaphy. Patients were given a spinal anesthetic with either 0.5% plain isobaric bupivacaine (1 mg/kg), or bupivacaine plus 0.25, 0.5, 1, or 2 micro g/kg clonidine. Mean arterial blood pressure, heart rate, SpO(2), sensory block extension and duration were the main data recorded. Mean arterial blood pressure, heart rate, SpO(2), and block extension were similar in the five groups. Duration of spinal block increased from 67 (58-82) min in the control group up to 111 (93-125) min in the group receiving 1 micro g/kg clonidine (P < 0.003). Transient hypotension occurred more often (P < 0.05), and caffeine was given more often, when 2 micro g/kg clonidine was given. We conclude that 1 micro g/kg clonidine provides a significant improvement in spinal anesthesia duration in newborns without significant side effects.</AbstractText>Spinal anesthesia is suitable but often too short for complete surgery in newborns. This controlled, randomized, prospective, dose-ranging study was conducted in 75 neonates to test the hypothesis that clonidine could significantly lengthen bupivacaine spinal block. Clonidine 1 micro g/kg, added to spinal isobaric bupivacaine, doubles the duration of the block without significant deleterious hemodynamic or respiratory side effects.</AbstractText> |
2,331,972 | Insulin-induced improvement of postischemic recovery is abolished by inhibition of protein kinase C in rat heart. | We demonstrated earlier that postischemic addition of insulin improves recovery of function in isolated rat heart by phosphatidylinositol 3-kinase. Activation of phosphatidylinositol 3-kinase before ischemia improves recovery of the heart after ischemia through protein kinase C. We tested whether protein kinase C activation is required for the positive inotropic effect of insulin during reperfusion.</AbstractText>Isolated working rat hearts were perfused with Krebs-Henseleit buffer containing [2-(3)H]glucose (5 mmol/L, 0.05 microCi/mL) plus oleate (0.4 mmol/L) and were subjected to 15 minutes of global ischemia followed by 35 minutes of reperfusion with or without insulin (1 mU/mL). We measured cardiac power, glucose uptake, and tissue metabolites. The protein kinase C inhibitor chelerythrine (5 micromol/L) was added either at the beginning of the experiment or together with insulin. Experiments were repeated under normoxic conditions.</AbstractText>Cardiac power before ischemia was 9.63 to 12.4 mW. Insulin improved recovery of power after ischemia (96.3% +/- 10.8% versus 65.7% +/- 3.79%, P <.05). This effect was abolished by chelerythrine (55.3% +/- 6.49%). However, chelerythrine given at reperfusion did not block insulin's effect on recovery (101.0% +/- 4.25%, P <.05). Postischemic glucose uptake was not increased by insulin (3.07 +/- 0.32 before, 3.45 +/- 0.34 micromol/min/gdw after ischemia, not significant) and was not affected by chelerythrine (3.01 +/- 0.26 before, 3.29 +/- 0.32 micromol/min/gdw after ischemia, not significant). Under normoxic conditions, chelerythrine did not influence insulin's effects on glucose uptake or power.</AbstractText>The results suggest that (1) insulin's effect on recovery is dependent on ischemia-induced protein kinase C activation, (2) the activity of protein kinase C during reperfusion may not be important for this effect of insulin, and (3) protein kinase C plays no role in insulin's effect on glucose uptake under normoxic or postischemic conditions.</AbstractText> |
2,331,973 | Simulate heart rate variability in different physiological conditions. | Heart rate variability is assumed to result from a multiplicative or cascade mechanism based on its multifractal property. Numerical results on the perturbation of the cascade are given to compare HRV under parasympathetic (PNS) and sympathetic (SNS) autonomic blockades. It was found that qualitative change of the HRV multifractal, which was observed in PNS blockade, is due to the change from a multiplicative to an additive mechanism. |
2,331,974 | Use of a subcutaneous beta-sympathomimetic pump for the treatment of fetal congenital complete heart block. A case report. | Complete heart block is the most common congenital heart block diagnosed in the fetalneonatal period. Maternal administration of beta-sympathomimetic agents has been used to treat this condition in the fetus. We know of no previous reports of the delivery of beta-sympathomimetics via a continuous subcutaneous pump for management of this condition.</AbstractText>An intrauterine gestation at 28 5/7 weeks complicated by fetal congenital complete heart block was successfully managed to term with maternal administration of a beta-sympathomimetic agent via a continuous subcutaneous pump.</AbstractText>Maternal administration of beta-sympathomimetic agents by a continuous subcutaneous pump in cases of fetal congenital complete heart block may help prolong pregnancy by preventing hydrops fetalis and avoiding confounding problems of prematurity. However, it should be used with caution due to the potential for dilated cardiomyopathy in the infant.</AbstractText> |
2,331,975 | Mice lacking connexin45 conditionally in cardiac myocytes display embryonic lethality similar to that of germline knockout mice without endocardial cushion defect. | The gap junction protein connexin45-deficient (Cx45-KO) mice die shortly after the hearts begin to beat. In addition to the heart defect, they also show defective vascular development which may be closely related with the cardiac phenotype. Therefore, we created mice whose floxed-Cx45 locus could be removed conditionally. We utilized cardiac alpha-actin-Cre transgenic mice to investigate the specific cardiac muscular function of Cx45 in vivo. The resultant conditional mutants were lethal, showing conduction block similar to that of the Cx45-KO mice. Unlike Cx45-KO, development of the endocardial cushion was not disrupted in the conditional mutants. X-gal staining was detected in the embryonic cardiac myocytes as a hallmark of Cre-loxP mediated floxed-Cx45 deletion. These results reconfirm the requirement of Cx45 for developing cardiac myocytes. These also indicate that establishing the first contractions is a crucial task for the early hearts. |
2,331,976 | Psychoneurological applications of endoscopic sympathetic blocks (ESB). | In addition to more widely and longer known indications of ETS, various neurological disorders and psychologically stressful situations in their worst expressions might be alleviated by the reversible ESB procedure. The patients with social phobia, especially those who have also blushing and/or stage fright type of heart racing, benefit from the ESB. The disturbances of the sympathetic nervous system, e. g. in Parkinson's disease and multiple system atrophy might be alleviated with sympathetic block, especially the extrapyramidal symptoms in these diseases. In migraine, sympathetic surgery has been noted to give some help. The unilateral left-sided block has been effective in long QT-syndrome type arrhythmias. In schizophrenia, the phobic, paranoic or confusional reactions have been tentatively treated by the sympathetic block. |
2,331,977 | Single and multiple early afterdepolarization caused by nickel in rat atrial muscle. | We examined the possible role of the Na-Ca exchange (NCX) in the arrhythmogenesis in rat atrial preparations applying microelectrode technique. In control Tyrode solution preparations isolated from the sinoatrial area contracted with frequency of 48+/-4 min(-1) (group I) or 84+/-7 min(-1) (group II). In preparation beating with low frequency partial inhibition of NCX by administration of Ni2+ (0.3 mmol/l) to the bath solution caused single early afterdepolarization (EAD) on the 15th min. During the following five minutes they were transformed into multiple EADs from 4 to 47 (action potentials) with general duration of 1-12 s. The effects were reversible. Ni2+ (0.3 mmol/l) in the preparations beating with higher rate (group II) did not cause multiple EADs, but after higher Ni2+ concentration (0.5 mmol/l) single EAD was observed more often. It was concluded that Ca2+ overload due to partial block of the NCX can contribute to the development of atrial tachyarrhythmias. |
2,331,978 | Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. | Feedback inhibition is a fundamental principle in signal transduction allowing rapid adaptation to different stimuli. In mammalian cells, the major feedback inhibitor for G-protein-coupled receptors (GPCR) is G-protein-coupled receptor kinase 2 (GRK-2), which phosphorylates activated receptors, uncouples them from G proteins and initiates their internalization. The functions of GRK-2 are indispensable and need to be tightly controlled. Dysregulation promotes disorders such as hypertension or heart failure. In our search for a control mechanism for this vital kinase, here we show that the Raf kinase inhibitor protein (RKIP) is a physiological inhibitor of GRK-2. After stimulation of GPCR, RKIP dissociates from its known target, Raf-1 (refs 6-8), to associate with GRK-2 and block its activity. This switch is triggered by protein kinase C (PKC)-dependent phosphorylation of the RKIP on serine 153. The data delineate a new principle in signal transduction: by activating PKC, the incoming receptor signal is enhanced both by removing an inhibitor from Raf-1 and by blocking receptor internalization. A physiological role for this mechanism is shown in cardiomyocytes in which the downregulation of RKIP restrains beta-adrenergic signalling and contractile activity. |
2,331,979 | The use of benzodiazepines in the treatment of chest pain: a review of the literature. | Benzodiazepines, although not listed in the American Heart Association's guidelines for the treatment of chest pain, are often used to provide symptomatic relief to patients who experience chest pain. To investigate the utility of benzodiazepines in the treatment of chest pain, the pharmacologic actions and cardiovascular effects of benzodiazepines were reviewed. In addition, a literature search regarding the use of benzodiazepines to treat patients with chest pain was conducted. The results indicated that benzodiazepines reduce anxiety, pain, and cardiovascular activation. Benzodiazepines amplify gamma-aminobutyric acid (GABA) throughout the central nervous system, and act more peripherally to reduce catecholamines. In addition, preliminary evidence indicates that benzodiazepines may cause coronary vasodilatation, prevent dysrhythmias, and block platelet aggregation, though further study is needed. Both non-cardiac chest pain (associated with musculoskeletal, esophageal, neurologic, and psychiatric conditions) and cardiac chest pain (associated with acute and chronic myocardial ischemia) seem to be effectively treated with benzodiazepines. Benzodiazepines are safe and well tolerated when administered alone or in combination with other medications. Moreover, the risk of dependence is minimal when benzodiazepines are prescribed on a short-term basis. Further study of benzodiazepines in the treatment of acute chest pain is needed to confirm these favorable actions and better define their use in the acute medical setting. |
2,331,980 | Pneumocystis carinii mimicking neonatal lupus erythematosus-related pneumonitis. | Neonatal lupus erythematosus (LE) is a rare disease associated with the transplacental passage of maternal autoantibodies to infants who manifest congenital heart block, skin disease, and less commonly, hematologic and hepatic disease. Pulmonary disease is a rare manifestation of neonatal LE and has presented as transient pneumonitis. In this report we describe an infant with neonatal LE who had the classic skin and hematologic findings of the disease in addition to pulmonary disease which might be attributed to neonatal LE-related pneumonitis, but in fact was caused by a concomitant Pneumocystis carinii infection. This case demonstrates the importance of looking for other causes of pulmonary disease in neonatal LE patients. |
2,331,981 | Patient controlled intravenous analgesia with tramadol for labor pain relief. | To evaluate the safety and analgesic efficacy of patient controlled intravenous analgesia (PCIA) with tramadol, and to compare its benefits and risks with combined spinal-epidural analgesia (CSEA)+ patient controlled epidural analgesia (PCEA).</AbstractText>Eighty American Society of Anesthesiologist (ASA) I-II at term parturients in active labor were randomly divided into 3 groups: the control group (n = 30) received no analgesia; group A (n = 30) received spinal administration with ropivacaine 2.5 mg and fentanyl 5 microg, then with PCEA; group B (n = 20) received 1 mg/kg tramadol loading dose i.v. PCIA with 0.75% tramadol and it included: PCA dose 2 ml, lockout time 10 minutes, background infusion 2 ml/h, total dose no more than 400 mg. The intensity of pain was evaluated using Visual Analogue Scale (VAS).</AbstractText>Both group A and B showed good pain relief. VAS pain scores were significantly decreased in group A and B compared with those in the control group (P < 0.01). In comparison with group B, the VAS pain scores decreased in group A (P < 0.05). The onset times of analgesia in group A were shorter than those in group B (P < 0.05). Apgar scores in group B were lower than those in group A (P < 0.05). The periods of second stage of labor in group A were longer than those in the control group and group B (P < 0.05). The cesarean delivery rate was significantly higher in the control group (16.7%) than in group A (3.3%) and group B (5.0%), but it did not differ between group A and B. There were no significant differences in vital signs, fetal heart rate, degree of motor block, and uterine contractions among the 3 groups.</AbstractText>PCIA with tramadol is now a useful alternative when patients are not candidates for CSEA for labor, or do not want to have a neuraxial block anesthesia. However, sometimes it may not provide satisfactory analgesic effect.</AbstractText> |
2,331,982 | An overview on systemic lupus erythematosus pregnancy. | Abstract A systemic lupus erythematosus (SLE) pregnancy is no longer regarded as unacceptable, with an early diagnosis, a mild disease condition, and good interdisciplinary collaboration ensuring intense surveillance of pregnant SLE patients. The key point is a sufficiently long period of disease quiescence before conception. A low dose of prednisone is preferable during pregnancy. Nevertheless, 20% of disease flare-up still happens interpartum or postpartum, even in such well-planned pregnancies, although usually with only mild severity. Pregnancy during an active disease stage, especially active nephritis, should always be avoided. Substantial renal function damage may occur, and there is a relatively high prevalence of preeclampsia, which may further compromise the mother as well as the fetus. It is well documented that antiphospholipid syndrome and antiphospholipid antibodies are strongly associated with fetal wastage. Low-dose aspirin or heparin is indicated for a favorable fetal outcome. Women with positive anti-SSA and/or anti-SSB should be aware of the danger of congenital heart block in their infants. Cytotoxic drugs applied in the early stage of pregnancy are dangerous to the fetus. A rather long-term follow-up is required to make a precise evaluation of the maternal SLE influence on the offspring. |
2,331,983 | A preoperative retrobulbar block in patients undergoing scleral buckling reduces pain, endogenous stress response, and improves vigilance. | This study aims to test postoperative analgesia by using retrobulbar block in patients with retinal detachment surgery.</AbstractText>Twenty-nine patients scheduled for scleral buckling were included in this double-blind, randomized, prospective study. After induction of general anesthesia and opening of the conjunctiva, patients received either 4 mL bupivacaine 0.5% or 4 mL saline 0.9% injected into the retrobulbar space preoperatively. Heart rate and blood pressure were documented before the start of anesthesia, 10 and 50 minutes later, and 60 minutes after completion of surgery. At the same time points, 10 mL of blood were withdrawn for measurement of glucose and cortisol levels to evaluate the efficacy of retrobulbar block in eliminating humoral response. Postoperative scores for pain and vigilance were recorded 1, 6, and 24 hours after completion of surgery. The application of analgesic and antiemetic drugs was documented, as well as occurrence of nausea and vomiting.</AbstractText>A preoperative retrobulbar block in patients undergoing scleral buckling reduces pain, endogenous stress response, and improves vigilance.</AbstractText>Because the analgesic effect of the retrobulbar block was considerably longer than pharmacologically expected, the combined retrobulbar and general anesthesia "protects" against postoperative pain and is recommended for patients undergoing scleral buckling.</AbstractText> |
2,331,984 | Thoracic epidural anesthesia increases tissue oxygenation during major abdominal surgery. | Intraoperative surgical stress may markedly increase adrenergic nerve activity and plasma catecholamine concentrations, which causes peripheral vasoconstriction and decreased tissue oxygen partial pressure possibly leading to tissue hypoxia. Tissue hypoxia is associated with an increased incidence of surgical wound infections. Thoracic epidural anesthesia blocks afferent neural stimuli and inhibits efferent sympathetic outflow in response to painful stimuli. Consequently, we tested the hypothesis that supplemental thoracic epidural anesthesia during major abdominal surgery improves tissue perfusion and subcutaneous oxygen tension. Thirty patients were randomly assigned to two groups: general (n = 15) or combined general and epidural anesthesia (n = 15). Anesthesia technique and fluid management were standardized. Subcutaneous tissue oxygen tension was measured continuously in the upper arm with a Clark type electrode. Data were compared with unpaired, two-tailed t-tests, Wilcoxon's ranked sum test, or repeated-measures analysis of variance and Scheffé F tests as appropriate; P < 0.05 was considered statistically significant. After 60 min, intraoperative tissue oxygen tension was significantly larger during combined anesthesia than during general anesthesia (54.3 +/- 7.4 mm Hg versus 42.1 +/- 8.6 mm Hg; P = 0.0002). Subcutaneous tissue oxygen tension remained significantly higher in the combined general/epidural anesthesia group throughout the observation period. Hemodynamic responses and global oxygen variables were similar in the groups. Thoracic epidural anesthesia improved intraoperative tissue oxygen tension outside the area of the epidural block. Thus, our results give evidence that supplemental neural nociceptive block blunts generalized vasoconstriction caused by surgical stress and adrenergic responses.</AbstractText>Thoracic epidural anesthesia blunts the decrease of subcutaneous tissue oxygen tension caused by surgical stress and adrenergic vasoconstriction during major abdominal surgery. Consequently, combined general and epidural anesthesia helps to provide sufficient tissue oxygenation.</AbstractText> |
2,331,985 | Ropivacaine and fentanyl concentrations in patient-controlled epidural analgesia during labor: a volume-range study. | We enrolled nulliparous women in induced labor in a randomized study to determine whether increasing the concentration of the solution used in a patient-controlled epidural analgesia (PCEA) device was required as labor progressed. Patients were assigned to 6 groups (n = 25 in each group), receiving ropivacaine/fentanyl in concentrations of either 0.1%/0.5 microg/mL or 0.2%/1 microg/mL via a PCEA pump. Three groups received boluses of 12, 16, or 20 mL dilute solution in early labor (uterine contractions every 3 min and 4-cm cervical dilation) then 6, 8, and 10 mL concentrated solution in late labor. Three other groups received boluses of 12, 16, or 20 mL dilute solution during both periods. The lockout interval was 25 min. The primary outcome was time until the first request for staff-administered analgesia supplement. Hourly assessments included pain scores on a visual analog scale (VAS) graded from 0 to 10, satisfaction scores, arterial blood pressure, motor block intensity, and the upper sensory level of epidural anesthesia. Patients, midwives, and the observer were unaware of study solutions and PCEA settings. The maximum pain score was defined as the highest score experienced by each patient during each period. Duration of analgesia was defined as the time from the start of each period to the first injection of rescue analgesia and was compared using a survival analysis. There were no differences among the groups with regard to demographic and obstetric variables, arterial blood pressure, motor block intensity, upper sensory level, or satisfaction scores. At least 75% of the women rated their satisfaction as either good or excellent during each period. During late labor, the maximum pain score was lower in the group receiving 20 mL dilute solution compared with the group receiving 6 mL concentrated solution. Maximum pain score was not significantly different between 20 mL dilute solution and 10 mL concentrated solution (difference between VAS values = -0.4; 95% confidence limits, -1.599 and 0.799; P = 0.5055). During late labor, the duration of analgesia was longer in groups receiving 20 mL dilute solution (99 +/- 4 min) (mean +/- SD) than in those receiving 12 mL (77 +/- 30 min) and 16 mL (80 +/- 23 min). Duration of analgesia did not differ between groups receiving 20 mL and 10 mL (92 +/- 23 min) or between groups receiving 12 mL and 6 mL (78 +/- 30 min) of each respective solution. Duration of analgesia was longer in the groups receiving 8 mL concentrated solution (94 +/- 16 min) than in those receiving 16 mL dilute solution. We concluded that 0.1%/0.5 microg/mL ropivacaine/fentanyl was effective throughout labor when 20 mL was injected with each PCEA demand. With 16 mg ropivacaine and 8 microg fentanyl, the duration of analgesia was prolonged by doubling the concentration when labor became active. When 12 mg ropivacaine and 6 microg fentanyl were injected at each demand, analgesia was less satisfactory and doubling the concentration was not clinically effective. These results suggest that the effectiveness of PCEA is dependent on drug mass rather than the volume or concentration administered with each successful pump demand.</AbstractText>There is no clinical reason for increasing the concentration of the patient-controlled epidural analgesia (PCEA) solution when labor becomes active provided that an effective dose is already being administered with each demand. The quality of PCEA depends on the drug mass given with each demand rather than the concentration of the pump solution.</AbstractText> |
2,331,986 | [Effect of wenxin capsule on myocyte apoptosis and expression of Bcl-2, Fas gene protein in rats of experimental myocardial ischemia]. | To explore the molecular mechanism of Wenxin Capsule (WXC, an effective Chinese composite drug) in preventing and treating myocardial ischemia of coronary heart disease.</AbstractText>Rat model of myocardial ischemia was established by subcutaneous multi-point injecting isoproterenol. Effect of WXC on cell apoptosis was observed by transmission electron microscopy and TUNEL method, and its effect on apoptotic related gene Bcl-2 and Fas gene protein expression was observed by immunohistochemical method.</AbstractText>Isoproterenol induced myocardial ischemic injury could cause evident cardial cell apoptosis, obvious enhance Fas gene protein expression and mild enhance Bcl-2 gene protein expression. WXC could significantly down-regulate Fas, up-regulate Bcl-2 gene protein expression, significantly inhibit and block the myocardial cell apoptosis.</AbstractText>To inhibit and block the event of cell apoptosis through regulating Bcl-2 and Fas gene protein expression in ischemic myocardium might be one of the mechanisms of WXT in preventing and treating myocardial ischemic injury of coronary heart disease.</AbstractText> |
2,331,987 | Clinical characteristics of 195 Japanese sarcoidosis patients treated with oral corticosteroids. | Questionnaires were sent to 46 hospitals of all over Japan in order to obtain the clinical data on sarcoidosis patients who were treated with oral corticosteroids. The number of female patients was greater than that of male patients (1.5:1), and the average age was 44.9 +/- 16.5 with peaks at 20 and at 50 to 60. The markers of disease activity were high in serum or bronchoalveolar lavage fluids (BALF): specifically, the serum angiotensin-converting enzyme (sACE) was 27.9 +/- 31.9 IU/ml (n.v. < 21.4), and the CD4/CD8 lymphocyte ratio was 6.5 +/- 5.7. Eye involvement was the most common reason for systemic steroid therapy, followed in order by lung and heart involvement. The main reasons for steroid therapy were the exacerbation of ocular symptoms, visual disturbance, respiratory symptoms, such as cough or exertional dyspnea, progression of chest radiographic findings, heart failure and severe arrhythmia, such as AV block. The initial corticosteroid dose was usually 30 mg of predinisolone per day, but for some refractory cases, a 40-60 mg per day was used. Immunosuppressive drugs, such as methotrexate, were also used in the small number of patients who responded poorly to the steroid. Overall, a good clinical response to the drug was found in 70-80% of the steroid treated patients, but in those with cardiac disease, the response rate was only 48%. |
2,331,988 | Anti-ICAM-1 antibody and CTLA-4Ig synergistically enhance immature dendritic cells to induce donor-specific immune tolerance in vivo. | Immature dendritic cells (DC) have been demonstrated to induce T-cell hyporesponsiveness in vitro and immune tolerance in vivo. However, immature DC (iDC) may become mature once infused in vivo, thus limiting the prolongation of the allograft survival. Considering that mature DC express high level of B7, intercellular adhesion molecule-1 (ICAM-1), and T-cell activation needs costimulation signals provided by DC, we selected anti-ICAM-1 mAb and cytotoxic T lymphocyte antigen-4Ig fusion protein (CTLA-4Ig) for in vivo administration to block costimulation pathways in order to further improve the efficacy of iDC to induce immune tolerance. Seven days before allogeneic cardiac transplantations, the recipients were intravenously (i.v.) pretreated of donor-derived iDC with or without simultaneous injections of anti-ICAM-1 mAb and CTLA-4Ig. CTLA-4Ig or anti-ICAM-1 mAb administration alone resulted in significant prolongation of cardiac allograft survival induced by iDC. When used simultaneously, CTLA-4Ig and anti-ICAM-1 mAb induced permanent allografts acceptance even in 90% recipients. The recipients could keep the skin alive for a longer time in the donor-specific second transplantation, but no effect was observed on the skin from C3H third-party mice. The efficient induction of donor-specific tolerance observed above may be related to the more potent inhibition of donor-specific T-cell responses including cytotoxicity activity, Th1 cytokines production, and alloantibody production by the combined use of anti-ICAM-1 mAb and CTLA-4Ig. Our data suggest that anti-ICAM-1 antibody and CTLA-4Ig can synergistically enhance iDC to induce donor-specific immune tolerance in vivo. |
2,331,989 | Immunosuppression and transplant vascular disease: benefits and adverse effects. | Cardiac allograft vasculopathy (CAV) occurs within 5 years of transplantation surgery and represents the main cause of death in long-term heart transplant survivors. The detailed pathogenesis of CAV is unknown, but there are strong indications that immunologic mechanisms, which are regulated by nonimmunologic factors, are the major cause of this phenomenon. Cyclosporine A (CsA) is a frequently used immunosuppressive agent in transplant medicine to prevent rejection. The mechanism of action of CsA involves initial binding to cyclophilin to form a complex that then inhibits calcineurin (CN), leading to reduced interleukin (IL)-2 production as part of the signal transduction pathway for the activation of B-lymphocytes and T-lymphocytes. Based on this proposed mechanism, it was expected that CsA should be an effective strategy in attenuating the host immune response against transplanted allograft tissue; however, CsA has not changed the outcome of CAV. Several mechanisms have been suggested for the ineffectiveness of CsA in long-term prevention of CAV. For example, routine therapeutic doses of CsA may block CN incompletely (50%), whereas complete blockade requires doses that are not clinically tolerable. Another explanation is the possible activation of T-cell receptors directly (CN independent) by the immune response, which induces protein kinase C theta (PKCtheta) and leads to IL-2 production and immune rejection. Moreover, there may be a role for nonimmunologic mechanisms, such as complement, which cannot be controlled by CsA, or CsA may cause hypercholesterolemia or induce overexpression of transforming growth factor-beta (TGF-beta). This review also compares the effect of CsA with other immunosuppressants in allograft artery preservation and their clinical efficacy. |
2,331,990 | Early stage-specific inhibitions of cardiomyocyte differentiation and expression of Csx/Nkx-2.5 and GATA-4 by phosphatidylinositol 3-kinase inhibitor LY294002. | Inhibition of phosphatidylinositol 3-kinase (PI3-kinase) has been reported to block cardiomyocyte differentiation. However, at which stage PI3-kinase plays this important role and what its molecular targets are remain unknown. To answer these questions, we induced cardiomyocyte differentiation of P19CL6 mouse embryonal carcinoma cells and investigated the activation of PI3-kinase by analyzing phospho-Akt. We also treated P19CL6 cells with the PI3-kinase-specific inhibitor LY294002 either continuously or at various time points and monitored the expression of cardiac contractile proteins and transcription factors. Most cells differentiated into sarcomeric myosin heavy chain (MHC)-positive cardiomyocytes on day 16 after induction. An increase in phospho-Akt was observed after induction and was maintained throughout the differentiation. LY294002 treatment restricted to the phase from days 0 to 4 was sufficient to inhibit cardiomyocyte differentiation in a dose-dependent manner. In contrast, LY294002 treatment either from days 4 to 8 or from days 8 to 12 did not cause significant changes in sarcomeric MHC expression. LY294002 treatment from days 0 to 4 also suppressed Csx/Nkx-2.5 and GATA-4 expression. These results demonstrate that PI3-kinase becomes activated and plays a pivotal role at a very early stage of cardiomyocyte differentiation, possibly by modulating the expression of the cardiac transcription factors. |
2,331,991 | Comparison of the haemodynamic effects of interscalene block combined with general anaesthesia and interscalene block alone for shoulder surgery. | Interscalene brachial plexus block (ISB) anaesthesia is widely used with or without general anaesthesia in patients undergoing shoulder surgery, which is generally done with the patient in a sitting position. This position affects haemodynamics, and supplementing ISB with general anaesthesia can exaggerate these haemodynamic changes. This study compared ISB combined with general anaesthesia, with ISB alone, in 29 patients undergoing elective shoulder surgery. Heart rate and oxygen saturation remained stable throughout the study in both groups. Mean arterial pressure was significantly decreased when the patient moved into the sitting position in those given combined anaesthesia, whereas in those given ISB alone mean arterial pressure did not change significantly. Neither pain scores nor patient satisfaction scores differed significantly between the two groups. All of the patients were either satisfied or entirely satisfied with their anaesthesia/analgesia. There were no significant differences in side-effects and no severe complications in either group. We advocate using ISB alone for patients undergoing shoulder surgery, but further larger studies are needed to confirm the present results. |
2,331,992 | Efficacy, safety, and pharmacokinetics of levobupivacaine with and without fentanyl after continuous epidural infusion in children: a multicenter trial. | Levobupivacaine, the levo-enantiomer of bupivacaine, is as potent as bupivacaine but less toxic. Therefore, the authors investigated the efficacy, safety, and pharmacokinetics of perioperative epidural levobupivacaine with and without fentanyl in children.</AbstractText>After Research Ethics Board approval and informed written consent, 120 healthy children aged 6 months to 12 yr who were scheduled to undergo urologic or abdominal surgery were randomized in a double-blinded and concealed manner to receive one of four epidural solutions as a continuous infusion for 24 h: 0.125% levobupivacaine; 0.0625% levobupivacaine; 1 mug/ml fentanyl; or the combination, 0.0625 levobupivacaine and 1 mug/ml fentanyl. After induction of anesthesia and tracheal intubation, a lumbar epidural catheter was sited, a loading dose was administered (0.75 ml/kg levobupivacaine, 0.175%), and the epidural infusion was commenced. The primary endpoint was the need for rescue analgesia (morphine) in the first 10 h after surgery. Pain, motor strength, and side effects were recorded for 24 h. Venous blood was collected from 18 children to determine the plasma concentrations of levobupivacaine and/or fentanyl before and 2, 4, 8, 16, 24, and 26 or 30 h after the start of the epidural infusion.</AbstractText>Of the 114 children who were analyzed for intention to treat, a similar number of children in each group reached the 10-h mark. The time to the first dose of morphine in the first 10 h was less in the plain fentanyl group (P < 0.044). All other effects were similar among the four groups. The plasma concentration of levobupivacaine increased during the infusion period, reaching a maximum of 0.76 +/- 0.11 mug/ml in the 0.125% group and 0.48 +/- 0.12 mug/ml in the 0.0625% group by 24 h. The plasma concentration of fentanyl also increased steadily, reaching a maximum concentration of 0.37 +/- 0.11 ng/ml by 24 h.</AbstractText>We conclude that 0.0625% levobupivacaine without fentanyl is an effective perioperative epidural solution in children when infused at a rate of 0.3 ml. kg-1. h-1. The plasma concentrations of 0.125% and 0.0625% levobupivacaine and fentanyl (1 mug/ml) at the end of a 24-h infusion are low.</AbstractText> |
2,331,993 | Sequential compression device with thigh-high sleeves supports mean arterial pressure during Caesarean section under spinal anaesthesia. | This study investigated the use of a Sequential Compression Device (SCD) with thigh-high sleeves and a preset pressure of 50 mm Hg that recruits blood from the lower limbs intermittently, as a method to prevent spinal hypotension during elective Caesarean section. Possible association of arterial pressure changes with maternal, fetal, haemodynamic, and anaesthetic factors were studied.</AbstractText>Fifty healthy parturients undergoing elective Caesarean section under spinal anaesthesia were randomly assigned to either SCD (n=25) or control (n=25) groups. A standardized protocol for pre-hydration and anaesthetic technique was followed. Hypotension was defined as a decrease in any mean arterial pressure (MAP) measurement by more than 20% of the baseline MAP. Systolic (SAP), MAP and diastolic (DAP) arterial pressure, pulse pressure (PP), and heart rate (HR) were noted at baseline and every minute after the spinal block until delivery.</AbstractText>A greater than 20% decrease in MAP occurred in 52% of patients in the SCD group vs 92% in the control group (P=0.004, odds ratio 0.094, 95% CI 0.018-0.488). There were no significant differences in SAP, DAP, HR, and PP between the groups.</AbstractText>SCD use in conjunction with vasopressor significantly reduced the incidence of a 20% reduction of MAP.</AbstractText> |
2,331,994 | The relative motor blocking potencies of bupivacaine and levobupivacaine in labor. | Minimum local analgesic concentrations (MLAC) have been used to determine the epidural analgesic potencies of bupivacaine and its levo- counterpart. There are no reports of the motor blocking potencies of these drugs. In this study we sought to determine the motor block MLAC of both drugs and determine the relative potency ratio. Sixty ASA physical status I-II parturients were randomized. The first woman in each group received 0.25% wt/vol. Up-down sequential allocation was used to determine subsequent concentrations at a testing interval of 0.025% wt/vol. Effective motor block was defined as a Bromage score <4 within 30 min. The up-down sequences were analyzed with the Dixon and Massey method and probit regression. Two-sided P < 0.05 defined significance. The motor block MLAC for bupivacaine was 0.27% wt/vol (95% confidence interval [CI], 0.25-0.30) and for levobupivacaine was 0.31% wt/vol (95% CI, 0.29-0.34) (P = 0.024), with a levobupivacaine/bupivacaine potency ratio of 0.87 (95% CI, 0.77-0.98). This is the first study to estimate the motor-blocking potency ratio of bupivacaine and levobupivacaine in labor. This study demonstrates that the S-enantiomer of bupivacaine is less potent at motor block than the racemate.</AbstractText>We estimated the motor-blocking potency ratio of bupivacaine and levobupivacaine in labor and demonstrated that the S-enantiomer of bupivacaine is less potent at motor block than the racemate.</AbstractText> |
2,331,995 | Topical treatment of pressure ulcers with nerve growth factor: a randomized clinical trial. | The prevalence of pressure ulcers of the foot is a major health care problem in frail elderly patients. A pressure sore dramatically increases the cost of medical and nursing care, and effective treatment has always been an essential nursing concern. Management options for pressure ulcers include local wound care; surgical repair; and, more recently, topical application of growth factors.</AbstractText>To examine the effects of topical treatment with nerve growth factor in patients with severe, noninfected pressure ulcers of the foot.</AbstractText>Randomized, double-blind, placebo-controlled trial.</AbstractText>Teaching nursing home of Catholic University of the Sacred Heart, Italy.</AbstractText>36 persons with pressure ulcers of the foot.</AbstractText>18 patients received nerve growth factor treatment, and 18 patients received only conventional topical treatment.</AbstractText>The course of the ulcers during follow-up was evaluated by tracing the perimeter of the wound onto sterile, transparent block paper and determining the stage.</AbstractText>At baseline, the treatment and control groups did not differ across demographic variables, clinical characteristics, and functional measures. The mean area (+/-SD) of the ulcers was 1012 +/- 633 mm2 in the treatment group and 1012 +/- 655 mm2 in the control group (P > 0.2). The average reduction in pressure ulcer area at 6 weeks was statistically significantly greater in the treatment group than in the control group (738 +/- 393 mm2 vs. 485 +/- 384 mm2; P = 0.034).</AbstractText>Topical application of nerve growth factor may be an effective therapy for patients with severe pressure ulcers.</AbstractText> |
2,331,996 | Reentrant waves in a ring of embryonic chick ventricular cells imaged with a Ca2+ sensitive dye. | According to the classic model initially formulated by Mines, reentrant cardiac arrhythmias may be associated with waves circulating in a ring geometry. This study was designed to study the dynamics of reentry in a ring geometry of cardiac tissue culture. Reentrant calcium waves in rings of cultured embryonic chick cardiac myocytes were imaged using a macroscope to monitor the fluorescence of intracellular Calcium Green-1 dye. The rings displayed a variety of stable rhythms including pacemaker activity and spontaneous reentry. Waves originating from a localized pacemaker could lead to reentry as a consequence of unidirectional block. In addition, more complex patterns were observed due to the interactions between reentrant and pacemaker rhythms. These rhythms included instances in which pacemakers accelerated the reentrant rhythm, and instances in which the excitation was blocked in the vicinity of pacemakers. During reentrant activity an appropriately timed electrical stimulus could induce resetting of activity or cause complete annihilation of the propagating waves. This experimental preparation reveals many spontaneously occuring complex rhythms. These complex rhythms are hypothesized to reflect interactions between spontaneous pacemakers, wave propagation, refractory period, and overdrive suppression. This preparation may serve as a useful model system to further investigate complex dynamics arising during reentrant rhythms in cardiac tissue. |
2,331,997 | Cardiovascular effects of nicotine, chlorisondamine, and mecamylamine in the pigeon. | Chlorisondamine and mecamylamine are nicotinic antagonists that produce both ganglionic and central blockade. Chlorisondamine, when administered as a large systemic dose, produces a persistent central block, despite being charged. The present study evaluated the cardiovascular effects of chlorisondamine. Shortly after administration, chlorisondamine (0.10, 1, and 10 mg/kg i.m.) lowered blood pressure significantly and decreased heart rate at the low dose (0.1 mg/kg i.m.) and increased heart rate at the high dose (10 mg/kg i.m.). Mecamylamine (1 and 10 mg/kg i.m.) also lowered blood pressure and heart rate. After both antagonists, heart rate returned to baseline values within 90 min and blood pressure within 24 h. Low doses of nicotine (0.01-0.03 mg/kg i.m.) lowered blood pressure but did not affect heart rate. Higher doses (0.10-3.2 mg/kg i.m.) transiently increased blood pressure and heart rate. Subsequent to antagonist administration, nicotine was administered to determine whether either drug blocked the cardiovascular effects of nicotine. Chlorisondamine (0.1, 1, and 10 mg/kg i.m.) administered 30 min before nicotine blocked the increases in blood pressure and heart rate. Only the high dose (10 mg/kg i.m.) of chlorisondamine administered 24 h before nicotine produced a blockade of nicotine's pressor effect. This block diminished within 3 days. Mecamylamine (1 mg/kg i.m.) antagonized only nicotine's tachycardic effect. Longer pretreatment with mecamylamine (10 mg/kg, 24 h before nicotine challenge) did not antagonize the cardiovascular effects of nicotine. Thus, chlorisondamine produces a longer lasting blockade of nicotine's cardiovascular effects than mecamylamine. |
2,331,998 | Cytokine-directed therapies for the treatment of chronic airway diseases. | Multiple cytokines play a critical role in orchestrating and perpetuating inflammation in asthma and chronic obstructive pulmonary disease (COPD) and several specific cytokine and chemokine inhibitors now in development as future therapy for these diseases. Anti-IL-5 antibody markedly reduces peripheral blood and airway eosinophils, but does not appear to be effective in symptomatic asthma. Inhibition of IL-4 despite promising early results in asthma has been discontinued and blocking IL-13 might be more effective. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, as systemic delivery produces side effects. Inhibition of TNF-alpha may be useful in severe asthma and for treating severe COPD with systemic features. Many chemokines are involved in the inflammatory response of asthma and COPD and several small molecule inhibitors of chemokine receptors (CCR) are in development. CCR3 antagonists (which block eosinophil chemotaxis) and CXCR2 antagonists (which block neutrophil and monocyte chemotaxis) are in clinical development for asthma and COPD, respectively. Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful; several such classes of drug are now in clinical development and any risk of side effects with these non-specific inhibitors may be reduced by the inhaled route. |
2,331,999 | Sox6 regulation of cardiac myocyte development. | A mouse mutation (p100H/p100H) has been identified that is associated with cardioskeletal myopathy, heart block, delayed growth and early postnatal death. The gene that is disrupted in this mutation encodes the transcription factor Sox6. P19CL6 cells were used as an in vitro cardiomyocyte differentiation system and revealed that Sox6 is expressed exclusively when the cells are committed to differentiate to beating cardiac myocytes. We used the yeast two-hybrid system to identify the Prtb (Proline-rich transcript of the brain) protein as a Sox6 interactor, and subsequently confirmed the interaction by co-immunoprecipitation. Prtb expression in P19CL6 cells increased with differentiation to beating cardiomyocytes. Using the P19CL6 cells stably transfected with noggin, an antagonist of BMP (Bone Morphogenic Protein), we found that BMP expression is required for Sox6 expression in cardiomyocyte differentiation. Surprisingly, the expression of the alpha1c-subunit gene of the L-type Ca2+ channel decreased in P19CL6 cells as they differentiated to beating cardiac cells. Ectopic expression of Sox6 or Prtb alone in P19CL6 cells caused down-regulation of L-type Ca2+ alpha1c expression, but when Sox6 and Prtb were co-transfected to the cells, L-type Ca2+ alpha1c remained at basal levels. A similar relationship of Sox6 and L-type Ca2+ alpha1c expression was seen in vivo (comparing wild-type and p(100H)/p(100H) mutant mice). Thus, Sox6 is within the BMP pathway in cardiac differentiation, interacts with Prtb and may play a critical role in the regulation of a cardiac L-type Ca2+ channel. |
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