title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Copper catalysts for soot oxidation: alumina versus perovskite supports. | Copper catalysts prepared using four supports (Mg- and Sr-modified Al2O3 and MgTiO3 and SrTiO3 perovskites) have been tested for soot oxidation by 02 and NOx/O2. Among the catalysts studied, Cu/SrTiO3 is the most active for soot oxidation by NOx/O2 and the support affects positively copper activity. With this catalyst, and under the experimental conditions used, the soot combustion by NOx/O2 presents a considerable rate from 500 degrees C (100 degrees C below the uncatalysed reaction). The Cu/ SrTiO3 catalyst is also the most effective for NOx chemisorption around 425 degrees C. The best activity of Cu/SrTiO3 can be attributed to the improved redox properties of copper originated by Cu-support interactions. This seems to be related to the presence of weakly bound oxygen on this sample. The copper species present in the catalyst Cu/SrTiO3 can be reduced more easily than those in other supports, and for this reason, this catalyst seems to be the most effective to convert NO into NO2, which explains its highest activity for soot oxidation. | 18,983,091 |
Validation of dietary intake of dichlorodiphenyltrichloroethane and metabolites in two populations from Beijing and Shenyang, China based on the residuals in human milk. | This paper presents the results of an investigation on association between dietary intakes and human milk concentrations of dichlorodiphenyltrichloroethane and metabolites (DDTs) of two populations from Beijing and Shenyang, China. We analyzed human milk samples from 76 women and 287 composite food samples covering major food categories for concentrations of DDTs. We also collected information on food consumptions and calculated dietary intakes of DDTs of the participants on individual basis. The median values of the measured DDTs in human milk were 125 ng/g lipid and 132 ng/g lipid for the samples from Beijing and Shenyang, respectively. The mean (+/-standard deviation) daily dietary intakes of DDTs by the two groups were 32.0 +/- 14.2 ng/kg day and 27.9 +/- 11.3 ng/kg day, respectively. The temporal trends of decreasing in DDTs and increasing in DDE/DDT ratio suggested that the residuals were primarily from historical application. We found a significant correlation between human milk concentration and daily dietary intake of DDTs, while the dietary intake could explain 22% of the variation in the DDTs in human milk. In addition to dietary exposure, we also found that maternal body mass index (body weight divided by the squared height), body weight, body height, and mother's age contributed significantly to the variation of DDTs in human milk after intake normalization. The result of a probabilistic risk assessment indicated that the exposure of infants to DDTs through breast feeding would be a public health concern for years to come, although breast feeding is still recommended. | 18,983,097 |
Factors associated with advance care planning among older women in Southwest Florida. | As the nation's population continues to age, many older women will face care needs that can be anticipated in advance. However, little is known about the advance care plans of older women and the characteristics of those who plan. This study utilized a stratified random sampling design to survey older women (n = 124) in the state of Florida regarding their attitudes toward future care and planning behavior in social-environmental, health, and financial domains. Regression analyses were conducted to determine factors most predictive of attitudes toward future care and planning behavior by domain. Results suggest that advanced age predicts greater planning behavior, while living alone is associated with less advance care planning behavior. Other factors associated with less planning by domains of care needs include income status, chronic health conditions, educational attainment, and religious status. Nonaccepting attitudes toward planning were associated with a decreased likelihood to have advance care planning documents. | 18,983,110 |
Rehabilitation programs for elderly women inpatients with schizophrenia. | This study aims to describe rehabilitation and resocialization methods we believe to be appropriate for application to female patients with schizophrenia, in a psychiatric unit with a predominantly older population. We briefly describe the unit and the interventions used as an example of the proposed rehabilitation and resocialization methods applied. The article provides an overview to guide accurate intervention, particularly in inpatient women, in different types of cognitive impairment under the broad category of schizophrenia. Our clinical approach includes a token economy approach, cognitive remediation therapy, and social skills training. The token economy intervention is particularly directed to patients that present with a high mental deterioration and/or debility. Cognitive remediation training is applicable to subjects with both cognitive and social dysfunction, but that do not possess signs of an organic cerebral illness or of substance abuse. Social skills training can be the third step to resocialization, training verbal and nonverbal communication competencies. | 18,983,112 |
Temperature-induced route to chaos in the H2O2-HSO3(-)-S2O3(2-) flow reaction system. | Low-frequency, high-amplitude pH-oscillations observed experimentally in the H2O2-HSO3(-)-S2O3(-) flow reaction system at 21.0 degrees C undergo period-doubling cascades to chemical chaos upon decreasing the temperature to 19.0 degrees C in small steps. Period-4 oscillations are observed at 20.0 degrees C and can be calculated on the basis of a simple model. A reverse transition from chaos to high-frequency limit cycle oscillations is also observable in the reaction system upon decreasing further the temperature step by step to 15.0 degrees C. Period-2 oscillations are measured at 18.0 degrees C. Such a temperature-change-induced transition between periodic and chaotic oscillatory states can be understood by taking into account the different effects of temperature on the rates of composite reactions in the oscillatory system. Small differences in the activation energies of the composite reactions are responsible for the observed transitions. Temperature-change-induced period doubling is suggested as a simple tool for determining whether an experimentally observed random behavior in chemical systems is of deterministic origin or due to experimental noise. | 18,983,129 |
New lipophilic tyrosyl esters. Comparative antioxidant evaluation with hydroxytyrosyl esters. | New lipophilic esters of tyrosol, a naturally occurring phenol with interesting biological properties, have been synthesized in good yields by a chemoselective procedure, using lipase from Candida antarctica or p-toluenesulfonic acid as catalysts. Their antioxidant activities have been evaluated by the Rancimat test in lipophilic food matrices, as well as by FRAP and ABTS assays in methanolic solutions, and compared with those of previously synthesized hydroxytyrosyl esters. Free tyrosol, hydroxytyrosol, butylhydroxytoluene, and alpha-tocopherol were used as standards. All methods used for the antioxidant activity evaluation emphasized the high influence of the ortho-diphenolic structure on the antioxidant capacity, tyrosol and its derivatives being less active than hydroxytyrosol and its analogues and even less than BHT and alpha-tocopherol. In addition, the Rancimat test revealed a lower activity for ester derivatives than for their respective reference compounds (HTy or Ty), in agreement with the polar paradox. On the other hand, FRAP and ABTS methods reported an opposite behavior between the synthetic esters and their respective references. Thus, hydroxytyrosyl esters were more active than HTy, whereas tyrosyl esters were less active than Ty. The length and nature of the acyl side chain did not seem to play an important role in the antioxidant activity of either the hydroxytyrosyl or tyrosyl ester series, since no significant differences were observed among them. | 18,983,160 |
Optimization of lipase-catalyzed synthesis of ginsenoside Rb1 esters using response surface methodology. | In the lipase (Novozyme 435)-catalyzed synthesis of ginsenoside Rb1 esters, different acyl donors were found to affect not only the degree of conversion but also the regioselectivity. The reaction of acyl donors with short carbon chain was more effective, showing higher conversion than those with long carbon chain. Among the three solvent systems, the reaction in tert-amyl alcohol showed the highest conversion rate, while the reaction in the mixed solvent of t-BuOH and pyridine (1:1) had the lowest conversion rate. To allow the increase of GRb1 lipophilicity, we decided to further study the optimal condition of synthesis of GRb1 with vinyl decanoate with 10 carbon chain fatty acids in tert-amyl alcohol. Response surface methodology (RSM) was employed to optimize the synthesis condition. From the ridge analysis with maximum responses, the maximum GRb1 conversion was predicted to be 61.51% in a combination of factors (40.2 h, 52.95 degrees C, substrate mole ratio 275.57, and enzyme amount 39.81 mg/mL). Further, the adequacy of the predicted model was examined by additional independent experiments at the predicted maximum synthesis conditions. Results showed that the RSM was effective to optimize a combination of factors for lipase-catalyzed synthesis of ginsenoside Rb1 with vinyl decanoate. | 18,983,161 |
Loss of ripening capacity of pawpaw fruit with extended cold storage. | The fruit ripening traits of pawpaw [ Asimina triloba (L.) Dunal] were examined after harvest and after cold storage at -2, 2, 4, and 6 degrees C for up to 12 weeks. Generally, fruits stored at 2-4 degrees C for 4 weeks ripened normally, but those stored at -2 degrees C did not ripen normally, those stored at 6 degrees C were overripe, and by 6-8 weeks those stored at 2-4 degrees C had a lower respiration rate and ethylene production, lower firmness, and lower pH than fruit cold-stored for 4 weeks or less. These changes, and the occasional development of brown discoloration in the pulp once the fruits were moved back to room temperature, were evidence of chilling injury by 6 weeks. After harvest and through 4 weeks of cold storage, the main volatile compounds produced by fruit were methyl and ethyl octanoates and hexanoates. Volatile production significantly increased >5-fold in fruit ripened for 72 h after harvest or after removal from up to 4 weeks of cold storage. Fruit cold-stored for 6 weeks or more produced fewer total volatiles and esters but increased levels of such off-flavor compounds as ethyl acetate, ethyl propionate, and hexanoic and decanoic acids. Alcohol acyltransferase (AAT) activity declined in cold-stored fruit but was not correlated with either total volatile production or total ester production. Alcohol dehydrogenase activity did not change during ripening after harvest or cold storage. Lipoxygenase activity was highest just after harvest or after 2 weeks of cold storage, but was low by 4 weeks. Thus, ripening of pawpaw fruit seems to be limited to 4 weeks at 2-4 degrees C with loss of ability to continue ripening and chilling injury symptoms evident at colder temperatures and after longer periods of cold storage. | 18,983,162 |
Pseudoirreversible inhibition of prostate-specific membrane antigen by phosphoramidate peptidomimetics. | The mode of inhibition for phosphoramidate peptidomimetic inhibitors of prostate-specific membrane antigen was determined by inhibition reversibility experiments. The results revealed that these inhibitors can be classified into three types: pseudoirreversible (compounds 1-3), moderately reversible (compounds 4-9), and rapidly reversible inhibitors (compounds 10 and 11). Representative compounds from each class were further evaluated for their ability to induce cellular internalization of PSMA. Results from these experiments revealed that the pseudoirreversible inhibitor 1 induced the greatest PSMA internalization. The discovery of pseudoirreversible PSMA inhibitors is expected to provide a new avenue of investigation and therapeutic applications for prostate cancer and neurological disorders. | 18,983,168 |
Shedding new light on the molecular architecture of oocytes using a combination of synchrotron Fourier transform-infrared and Raman spectroscopic mapping. | Synchrotron Fourier transform-infrared (FT-IR) and Raman microspectroscopy were applied to investigate changes in the molecular architecture of mouse oocytes and demonstrate the overall morphology of the maturing oocyte. Here we show that differences were identified between immature mouse oocytes at the germinal vesicle (GV) and mature metaphase II (MII) stage when using this technology, without the introduction of any extrinsic markers, labels, or dyes. GV mouse oocytes were found to have a small, centrally located lipid deposit and another larger polar deposit of similar composition. MII oocytes have very large, centrally located lipid deposits. Each lipid deposit for both cell types contains an inner and outer lipid environment that differs in composition. To assess interoocyte variability, line scans were recorded across the diameter of the oocytes and compared from three independent trials (GV, n = 91; MII, n = 172), and the data were analyzed with principal component analysis (PCA). The average spectra and PCA loading plots show distinct and reproducible changes in the CH stretching region that can be used as molecular maturation markers. The method paves the way for developing an independent assay to assess oocyte status during maturation providing new insights into lipid distribution at the single cell level. | 18,983,174 |
Aprotinin and renal dysfunction. | Aprotinin is a polypeptide serine protease inhibitor used to prevent bleeding and need for transfusions in patients having heart surgery. A recent analysis of an observational study data set suggested the use of aprotinin was associated with an increased risk of developing renal failure. The present article reviews the data from basic science studies in tissues, animals and man together with the data from observational studies and randomised controlled trials. The interpretation of the data is hampered owing to the use of different endpoints to describe mild/moderate renal impairment. Nonetheless, the evidence points to aprotinin use being associated with a transient small rise in plasma creatinine concentration in certain patients. There is no evidence for an increased risk of developing new renal failure requiring dialysis/renal replacement therapy. | 18,983,214 |
Smoking cessation in pregnancy. | Pregnant women who continue to smoke expose their developing fetus to a wide range of risks. Assisting these patients to stop smoking can be an important intervention for the health of the baby and the mother. The management of pregnant smokers can be challenging, due to the potential risks of pharmacotherapy. There are a number of options available to the clinician to aid smoking cessation in non pregnant women. These include nicotine replacement therapy (NRT), bupropion, varenicline, and a range of non-drug therapies. To provide guidance to prescribers on the best way to manage smoking cessation in the pregnant patient, reviewing the risks and efficacy of the different approaches. An extensive literature search was carried out to find original studies which examined issues surrounding the safety and efficacy of methods of smoking cessation in pregnancy. NRT is the agent of choice for smoking cessation in pregnancy as the safety of other therapies in pregnancy have not yet been proved. | 18,983,219 |
Targeting important pathways in head and neck cancer: from the bench to the clinic. | Radiation therapy as single or combined modality (concurrent chemoradiotherapy) has been the cornerstone of treatment for squamous cell carcinoma of the head and neck for a long time. Fortunately, advances in tumor biology have provided new insights of tumor proliferation, metastases, migration and cell cycle regulation. The success seen with the use of cetuximab alone or in combination with conventional treatments has led the roadmap to discover other potential target mechanisms which may translate into better response rate with less local and systemic toxicity and improved overall survival. In this review, we discuss other cellular pathways that have shown to be involved in the carcinogenesis of squamous cell carcinoma of the head and neck and the actual efforts to target these mechanisms. | 18,983,242 |
Imbalanced distribution of GM immunoglobulin allotypes according to the clinical presentation of Plasmodium falciparum malaria in Beninese children. | Selection pressure exerted by pathogens contributes to the persistence of polymorphisms in GM and KM allotypes, which are antigenic determinants of immunoglobulins. This study investigated the impact of GM and KM allotypes on the clinical response to Plasmodium falciparum infection among Beninese children, including 65 with severe malaria, 37 with uncomplicated malaria, and 53 with asymptomatic carriage. An inverse relationship was found between the GM 5,6,13,14; 1,17 phenotype and uncomplicated malaria. Genetic markers implicated in the composition and activity of immunoglobulins may be associated with the genetic control of both malaria infection and morbidity. | 18,983,245 |
Cardiac differentiation is driven by NKX2.5 and GATA4 nuclear translocation in tissue-specific mesenchymal stem cells. | Myocardial infarction is a major public health problem that causes significant mortality despite recent advances in its prevention and treatment. Therefore, approaches based on adult stem cells represent a promising alternative to conventional therapies for this life-threatening condition. Mesenchymal stem cells (MSCs) are self-renewing pluripotent cells that have been isolated from multiple tissues and differentiate to various cell types. Here we have analyzed the capacity of MSCs from human bone marrow (BMSC), adipose tissue (ATSC), and dental pulp (DPSC) to differentiate to cells with a cardiac phenotype. Differentiation of MSCs was induced by long-term co-culture with neonatal rat cardiomyocytes (CMs). Shortly after the establishment of MSC-CM co-cultures, expression of connexin 43 and the cardiac-specific markers troponin I, beta-myosin heavy chain, atrial natriuretic peptide, and alpha-sarcomeric actinin was detected in BMSCs, ATSCs, and DPSCs. Expression of differentiation markers increased over time in the co-cultures, reaching the highest levels at 4 weeks. Translocation of the transcription factors NKX2.5 and GATA4 to the nucleus was observed in all three cultures of MSCs during the differentiation process; moreover, nuclear localization of NKX2.5 and GATA4 correlated with expression of alpha-sarcomeric actinin. These changes were accompanied by an increase in myofibril organization in the resulting CM-like cells as analyzed by electron microscopy. Thus, our results provide novel information regarding the differentiation of tissue-specific MSCs to cardiomyocytes and support the potential use of MSCs in cell-based cardiac therapies. | 18,983,250 |
A novel telemedicine system for monitoring congestive heart failure patients. | Congestive heart failure is a widespread cardiac disease in western countries. At present, the main measure for monitoring the level of pulmonary edema in telemedicine systems is weight, which is not a reliable indicator. The authors propose a novel bioimpedance telemedical system to monitor these patients. The system measures the resistivity of each lung using optimization methods and transmits the measurements via a modem to a call center. Preliminary results show that the measured resistivity values among healthy young patients are consistent and reproducible within 48 hours. The mean resistivity values in patients with pulmonary congestion were lower than those of the healthy patients: 887 [Omega*cm]+/-117 vs 1244 [Omega*cm]+/-87 (P<.01). The system is noninvasive, safe, and portable. It retrieves unique information correlated with the amount of fluid in the lungs and transmits the data to a medical call center in order to improve the diagnostics and treatment of congestive heart failure. | 18,983,286 |
Ten-year secular trends for congestive heart failure hospitalizations: an analysis of regional differences in the United States. | This study used data from the National Hospital Discharge Survey to examine secular trends and regional variation in hospitalization rates for congestive heart failure. The hospitalization rate for congestive heart failure rose significantly between 1995 and 2004 for adults aged 35 to 64 years. This trend was particularly marked in the West region (from 10.3 per 10,000 population in 1995 to 17.0 per 10,000 population in 2004; P<.001) and the South region (from 21.9 per 10,000 population in 1995 to 27.6 per 10,000 population in 2004; P<.001). The regional variations for congestive heart failure hospitalization among adults aged 35 to 64 years were associated with primary care physicians per 10,000 population, regional income level, and the proportion of Medicare payment. | 18,983,290 |
Lupus syndrome with neutropenia following minocycline therapy - a case report. | An 18-year-old patient is described who presented with febrile neutropenia and hepatitis caused by minocycline therapy. This rare complication of minocycline-induced lupus syndrome is discussed here. | 18,983,308 |
Trichosporon mucoides fungemia in a liver transplant recipient: case report and review. | Four months after receiving an orthotopic liver transplant, a 51-year-old man was admitted for progressive liver failure and severe hepatocellular necrosis thought to be due to tacrolimus. During his hospitalization he experienced bloodstream infections including fungemia due to Trichosporon mucoides and prolonged undulating fever despite antifungal and antibacterial treatment. He underwent removal of the allograft and implantation of another liver. Fever continued postoperatively until therapy with posaconazole was initiated. Initiation of posaconazole led to clinical improvement until the patient's demise from bacteremic vancomycin-resistant enterococcal peritonitis. Trichosporonosis appears to be an emerging fungal infection among immunocompromised individuals (including both hematological and solid organ transplant recipients). T. mucoides is a rare cause of systemic infection. When it occurs, trichosporonosis usually is associated with hematological malignancies and, to the best of our knowledge, has not been previously reported in a liver transplant recipient. The optimal treatment is not well defined. We report here the first case using posaconazole for treatment of trichosporonosis in a liver transplant recipient caused by T. mucoides. | 18,983,414 |
Morphological, biochemical and molecular characterisation of the first Italian Candida africana isolate. | One atypical isolate of the pathogenic yeast Candida albicans was isolated from an Italian patient with vulvovaginitis. The strain, germ tube positive and chlamydospore-negative showed white-thin turquoise colonies on Candida ID 2 medium. The yeast was identified as Candida africana by using morphological and biochemical tests. On the basis of the molecular results obtained in this study as well as in other studies, C. africana cannot be yet considered as a new species of Candida. It is possible that C. africana represents a new variant of C. albicans like the well-known Candida stellatoidea. To our knowledge, this is the first isolation of C. africana in Italy. | 18,983,430 |
Hyperzincemia and hypercalprotectinemia: unsuccessful treatment with tacrolimus. | We report on a 5-year-old boy with hyperzincemia and hypercalprotectinemia. Treatment began with Tacrolimus at the age of 4 years and 6 months. Despite an initial correction of clinical and biological symptoms, zincemia and calprotectinemia progressively worsened with secondary reappearance of symptoms. Tacrolimus seems to have a transient effect in the treatment of Hyperzincemia and hyperprolactinemia. | 18,983,438 |
Blood volume, blood pressure and total body sodium: internal signalling and output control. | Total body sodium and arterial blood pressure (ABP) are mutually dependent variables regulated by complex control systems. This review addresses the role of ABP in the normal control of sodium excretion (NaEx), and the physiological control of renin secretion. NaEx is a pivotal determinant of ABP, and under experimental conditions, ABP is a powerful, independent controller of NaEx. Blood volume is a function of dietary salt intake; however, ABP is not, at least not in steady states. A transient increase in ABP after a step-up in sodium intake could provide a causal relationship between ABP and the regulation of NaEx via a hypothetical integrative control system. However, recent data show that subtle sodium loading (simulating salty meals) causes robust natriuresis without changes in ABP. Changes in ABP are not necessary for natriuresis. Normal sodium excretion is not regulated by pressure. Plasma renin is log-linearly related to salt intake, and normally, decreases in renin secretion are a precondition of natriuresis after increases in total body sodium. Renin secretion is controlled by renal ABP, renal nerve activity and the tubular chloride concentrations at the macula densa (MD). Renal nerve activity is related to blood volume, also at constant ABP, and elevates renin secretion by means of beta(1)-adrenoceptors. Recent results indicate that renal denervation reduces ABP and renin activity, and that sodium loading may decrease renin without changes in ABP, glomerular filtration rate or beta(1)-mediated nerve activity. The latter indicates an essential role of the MD mechanism and/or a fourth mediator of the physiological control of renin secretion. | 18,983,442 |
Oxygen-dependent ion transport in erythrocytes. | The present contribution reviews current knowledge of apparently oxygen-dependent ion transport in erythrocytes and presents modern hypotheses on their regulatory mechanisms and physiological roles. In addition to molecular oxygen as such, reactive oxygen species, nitric oxide, carbon monoxide, regional variations of cellular ATP and hydrogen sulphide may play a role in the regulation of transport, provided that they are affected by oxygen tension. It appears that the transporter molecules themselves do not have direct oxygen sensors. Thus, the oxygen level must be sensed elsewhere, and the effect transduced to the transporter. The possible pathways involved in the regulation of transport, including haemoglobin as a sensor, and phosphorylation/dephosphorylation reactions both in the transporter and its upstream effectors, are discussed. | 18,983,458 |
Renal medullary effects of transient prehypertensive treatment in young spontaneously hypertensive rats. | Transient angiotensin II receptor blockade (ARB) leads to prolonged blood pressure (BP) lowering, but the underlying mechanism remains uncertain. Long-term BP control is regulated by the medullary microcirculation with the pericyte as contractile cell. We hypothesize that the prolonged BP effect is caused by increased medullary blood flow (MBF) associated with structural alterations based on reduced medullary pericyte number. Four-week-old spontaneously hypertensive rats (SHR) were treated for 4 weeks with losartan (SHR-Los: 20 mg kg(-1) day(-1)), hydralazine (SHR-Hyd: 15 mg kg(-1) day(-1)), losartan and pan-caspase inhibitor zVAD (SHR-Los + 1 mg kg(-1) day(-1) zVAD), losartan and glycogen synthase kinase-3beta (GSK) inhibitor valproate (SHR-Los + 10 mg kg(-1) day(-1) Val) or placebo. BP, MBF and pericyte number were determined under and after treatment (8 and 12 weeks). Apoptotic pericytes were determined with alpha-actin and TUNEL double staining. Sodium concentration was determined in renal medulla and urine. Antihypertensive treatment equipotently reduced BP at 8 weeks of age. After drug withdrawal (12 weeks of age) BP reduction was restricted to SHR-Los (SHR-Los: 153 +/- 5, SHR-Hyd: 177 +/- 2, SHR: 184 +/- 3 mmHg). Simultaneously, MBF was increased and pericyte number reduced, while medullary and urinary sodium concentration increased. Transient ARB in combination with zVAD or valproate resulted in more medullary pericytes and higher BP (SHR-Los/zVAD: 164 +/- 7; SHR-Los/Val: 168 +/- 6 mmHg) compared with transient ARB alone. After drug withdrawal, transient ARB leads to increased MBF and is associated with a reduction in medullary pericytes. This may be associated with pericyte apoptosis as anti-apoptosis during transient ARB increases pericyte number and BP. | 18,983,459 |
Can morphology predict 1p/19q loss in oligodendroglial tumours? | To investigate the relationship between phenotype and genotype in oligodendroglial tumours and evaluate whether 1p/19q status can be reliably predicted from histological findings. Three neuropathologists reviewed the association between 10 histological variables, location and genetic losses at 1p, 19q and 17p13 in 63 oligodendroglial tumours (cohort 1). Based on these findings, a multiple logistic regression model for prediction of 1p/19q status was constructed. The ability of this model to predict 1p/19q status was tested on cohort 2, comprising 20 oligodendroglial tumours. Loss of heterozygosity at 1p, 19q and 17p13 was analysed using polymerase chain reaction. Combined 1p/19q loss and losses at 17p13 were mutually exclusive (P < 0.001). The variable H1a (more or <50% of cells with round, uniform nuclei and perinuclear halos) demonstrated the strongest association with 1p/19q status (odds ratio 11.9, 95% confidence interval 3.6, 39.6, P < 0.001). Calcifications, absence of gemistocytic cells and a non-temporal/non-insular location were also associated. The correct 1p/19q status was predicted in 80% of cases in cohort 2. There is a strong association between phenotype and genotype in oligodendroglial tumours. However, even when all significant variables are accounted for, perfect prediction (100%) of 1p/19q status cannot be obtained. | 18,983,467 |
Development of targeted angiogenic medicine. | Strategies to alter angiogenesis have been successfully translated from the bench to bedside. With an estimated number of more than 500 million patients worldwide potentially benefiting from it, it is a prime example of targeted therapy that is increasingly changing the face of clinical medicine. Most efforts to stimulate or inhibit angiogenesis in the past were focused on the key angiogenic factor vascular endothelial growth factor (VEGF), resulting in the approval by the Food and Drug Administration of several drugs for the treatment of cancer and ocular disease. However, mounting clinical evidence reveals that inhibition of VEGF causes resistance and class-specific side effects, while therapeutic angiogenesis by delivering VEGF protein is more challenging than anticipated in human patients. Hence, alternatives are needed, and modulation of oxygen-sensitive enzymes (prolyl hydroxylase domain proteins) and of hypoxia induced transcription factors has recently emerged as a potential novel strategy to treat cancer and ischemic diseases. Furthermore, placental growth factor is a disease-specific angiogenic target, whose inhibition reduces cancer growth without causing major side effects, while its delivery induces revascularization of ischemic tissues. In this review, we summarize recent developments and discuss questions that arise in the exciting, rapidly developing field of angiogenic medicine, including a brief description of its possible implications in neurodegenerative diseases. | 18,983,480 |
Nitric oxide specifically inhibits integrin-mediated platelet adhesion and spreading on collagen. | Nitric oxide (NO) inhibits platelet adhesion to collagen, although the precise molecular mechanisms underlying this process are unclear. Collagen-mediated adhesion is a multifaceted event requiring multiple receptors and platelet-derived soluble agonists. We investigated the influence of NO on these processes. S-nitrosoglutathione (GSNO) induced a concentration-dependent inhibition of platelet adhesion to immobilized collagen. Maximal adhesion to collagen required platelet-derived ADP and TxA(2). GSNO-mediated inhibition was lost in the presence of apyrase and indomethacin, suggesting that NO reduced the availability of, or signaling by, ADP and TxA(2). Exogenous ADP, but not the TxA(2) analogue U46619, reversed the inhibitory actions of GSNO on adhesion. Under adhesive conditions NO inhibited dense granule secretion but did not influence TxA(2) generation. These data indicated that NO may block signaling by TxA(2) required for dense granule secretion, thereby reducing the availability of ADP. Indeed, we found TxA(2)-mediated activation of PKC was required to drive dense granule secretion, a pathway that was inhibited by NO. Because our data demonstrated that NO only inhibited the activation-dependent component of adhesion, we investigated the effects of NO on individual collagen receptors. GSNO inhibited platelet adhesion and spreading on alpha(2)beta(1) specific peptide ligand GFOGER. In contrast, GSNO did not inhibit GPVI-mediated adhesion to collagen, or adhesion to the GPVI specific ligand, collagen related peptide (CRP). NO targets activation-dependent adhesion mediated by alpha(2)beta(1), possibly by reducing bioavailability of platelet-derived ADP, but has no effect on activation-independent adhesion mediated by GPVI. Thus, NO regulates platelet spreading and stable adhesion to collagen. | 18,983,487 |
Elevated platelet and leukocyte response to oral bacteria in periodontitis. | Periodontitis is associated with an increased risk for cardiovascular diseases (CVD), but the underlying mechanisms are poorly understood. Recently, we showed that platelets from periodontitis patients are more activated than those from controls. Given the regularly occurring bacteremic episodes in periodontitis patients, we hypothesized that platelets and/or leukocytes from periodontitis patients are more sensitive to stimulation by oral bacteria, in particular the known periodontal pathogens, than platelets from control subjects. Three-color flow cytometry analysis was performed to quantify activation of platelets (P-selectin, PAC-1, CD63) and leukocytes (CD11b) in whole blood from patients with periodontitis (n = 19) and controls (n = 18), with and without stimulation by oral bacteria. Phagocytosis was assessed by using green-fluorescent protein (GFP)-expressing Aggregatibacter actinomycetemcomitans (Aa). Neutrophils and monocytes were activated by all species of oral bacteria tested, but no differences were observed between patients and controls. In response to several species of oral bacteria, platelets from periodontitis patients showed, compared with controls, increased exposure of P-selectin (P = 0.027) and increased formation of platelet-monocyte complexes (P = 0.040). Platelet-leukocyte complexes bound and/or phagocytosed more GFP-Aa than platelet-free leukocytes (for neutrophils and monocytes, in both patients and controls, P < 0.001). In periodontitis, increased platelet response to oral bacteria is paralleled by increased formation of platelet-leukocyte complexes with elevated capacity for bacterial clearance. We speculate that activated platelets and leukocytes might contribute to increased atherothrombotic activity. | 18,983,491 |
Guidelines and the use of inferior vena cava filters: a review of an institutional experience. | Based on the American College of Chest Physicians 2004 antithrombotic therapy for venous thromboembolism (VTE) and the Eastern Association for the Surgery of Trauma 2002 guidelines, placement of an inferior vena cava (IVC) filter is indicated in patients who either have, or are at high risk for, VTE, but have a contraindication or failure of anticoagulation. Our aim is to compare clinical characteristics and outcomes of patients receiving IVC filters within-guidelines (WG) and outside-of-guidelines (OOG). The 558 patients who received an IVC filter were divided into two groups called WG or OOG. The WG group met the criteria described above and the OOG group did not have a contraindication to or a failure of anticoagulation. The WG group had 362 patients and the OOG group had 196 patients. The OOG group had one (0.5%) patient with post-filter pulmonary embolism (PE), two (1%) with IVC thrombosis, and seven (3.6%) with deep vein thrombosis (DVT). The WG group had five (1.4%) patients with post-filter PE, 13 (3.6%) with IVC thrombosis, and 34 (9.4%) with DVT. All patients who developed post-filter PE had a DVT before filter placement, and patients who did not have a prior VTE event were at a significantly lower risk of developing post-filter IVC thrombosis and PE. Our data do not support the use of an IVC filter outside of guidelines in patients without prior VTE who can tolerate anticoagulation because of the low risk of developing PE. | 18,983,493 |
Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model. | Atherothrombosis is a major cause of cardiovascular events. However, animal models to study this process are scarce. We describe the first murine model of acute thrombus formation upon plaque rupture to study atherothrombosis by intravital fluorescence microscopy. Localized rupture of an atherosclerotic plaque in a carotid artery from Apoe(-/-) mice was induced in vivo using ultrasound. Rupture of the plaque and formation of localized thrombi were verified by two-photon laser scanning microscopy (TPLSM) in isolated arteries, and by immunohistochemistry. The thrombotic reaction was quantified by intravital fluorescence microscopy. Inspection of the ultrasound-treated plaques by histochemistry and TPLSM demonstrated local damage, collagen exposure, luminal thrombus formation as well as intra-plaque intrusion of erythrocytes and fibrin. Ultrasound treatment of healthy carotid arteries resulted in endothelial damage and limited platelet adhesion. Real-time intravital fluorescence microscopy demonstrated rapid platelet deposition on plaques and formation of a single thrombus that remained subocclusive. The thrombotic process was antagonized by thrombin inhibition, or by blocking of collagen or adenosine diphosphate receptor pathways. Multiple thrombi were formed in 70% of mice lacking CD40L. Targeted rupture of murine plaques results in collagen exposure and non-occlusive thrombus formation. The thrombotic process relies on platelet activation as well as on thrombin generation and coagulation, and is sensitive to established and novel antithrombotic medication. This model provides new possibilities to study atherothrombosis in vivo. | 18,983,512 |
Heparin-induced thrombocytopenia--therapeutic concentrations of danaparoid, unlike fondaparinux and direct thrombin inhibitors, inhibit formation of platelet factor 4-heparin complexes. | Treatment of heparin-induced thrombocytopenia (HIT), a disorder in which anti-platelet factor 4 (PF4)-heparin antibodies cause platelet activation and hypercoagulability, requires alternative (non-heparin) anticoagulation. Treatment options include direct thrombin inhibitors [lepirudin and argatroban (approved), and bivalirudin], danaparoid (approved) (mixture of anticoagulant glycosaminoglycans), or fondaparinux (synthetic heparin-mimicking pentasaccharide). PF4-heparin complexes form at optimal stoichiometric ratios. To compare the effects of these various non-heparin anticoagulants in disrupting the formation of PF4-heparin complexes, and PF4-containing immune complexes. Sera were obtained from patients with serologically confirmed HIT. The effects of the alternative anticoagulants on PF4 and PF4-heparin complex interactions with platelets, as well as HIT antibody binding and platelet activation, were investigated. Danaparoid at very low concentrations increased PF4 binding to platelets. In therapeutic concentrations, however, it decreased PF4 binding to platelets (P = 0.0004), displaced PF4-heparin complexes from platelets (P = 0.0033) and PF4 from the surface of a PF4-transfected HEK-293 EBNA cell line expressing the PF4 receptor CXCR3-B (P = 0.0408), reduced PF4-heparin complex size (P = 0.025), inhibited HIT antibody binding to PF4-heparin complexes (P = 0.001), and prevented platelet activation by HIT antibodies (P = 0.046). Although fondaparinux also interfered with PF4 binding to platelets, HIT antibody binding to PF4-heparin complexes, and activation of platelets by HIT antibodies, these effects occurred only at supratherapeutic concentrations. The direct thrombin inhibitors had no effect at any concentrations. Danaparoid uniquely interferes with the pathogenesis of HIT by disrupting PF4-containing immune complexes at therapeutic dose concentrations. It is possible that these effects contribute to its therapeutic efficacy. | 18,983,520 |
Ida Mann Lecture 2007: Planet eye. | The concept for this lecture arose as a consequence of the invitation from the College to give the 'Ida Mann Lecture' arriving recently after I had enjoyed the beautiful David Attenborough series 'Planet Earth' on television. It struck me as not too fanciful an idea at the time to make an analogy between 'Planet Earth' and the eye and thus the idea of giving an Attenborough-like tour of the ocular microenvironments and making the analogy between various immune cells in the eye and wildlife on planet Earth was born. I could only hope that in some small measure my presentation would inspire and educate an audience of ophthalmologists on the amazing world of ocular immune cells in the way that David Attenborough enraptures millions of television viewers with his beautiful series. | 18,983,543 |
Nucleus extraction in sutureless surgery: getting hooked! | Simple modifications to a readily available disposable 25 gauge cannula facilitate nucleus extraction in sutureless extracapsular cataract surgery. A case series using the modified cannula, and a temporal incision approach, are presented. Outcomes and complications attributable to the use of the cannula are discussed. | 18,983,544 |
Methods for studying the physiology of kidney oxygenation. | 1. An improved understanding of the regulation of kidney oxygenation has the potential to advance preventative, diagnostic and therapeutic strategies for kidney disease. Here, we review the strengths and limitations of available and emerging methods for studying kidney oxygen status. 2. To fully characterize kidney oxygen handling, we must quantify multiple parameters, including renal oxygen delivery (DO2) and consumption (VO2), as well as oxygen tension (Po2). Ideally, these parameters should be quantified both at the whole-organ level and within specific vascular, tubular and interstitial compartments. 3. Much of our current knowledge of kidney oxygen physiology comes from established techniques that allow measurement of global kidney DO2 and VO2, or local tissue Po2. When used in tandem, these techniques can help us understand oxygen mass balance in the kidney. Po2 can be resolved to specific tissue compartments in the superficial cortex, but not deep below the kidney surface. We have limited ability to measure local kidney tissue DO2 and VO2. 4. Mathematical modelling has the potential to provide new insights into the physiology of kidney oxygenation, but is limited by the quality of the information such models are based on. 5. Various imaging techniques and other emerging technologies have the potential to allow Po2 mapping throughout the kidney and/or spatial resolution of Po2 in specific renal tissues, even in humans. All currently available methods have serious limitations, but with further refinement should provide a pathway through which data obtained from experimental animal models can be related to humans in the clinical setting. | 18,983,577 |
Effects of in utero exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) on somatic growth and endocrine status in rat offspring. | Exposure to polychlorobiphenyl (PCB) mixtures at an early stage of development has been reported to affect endocrine glands; however, little is known about the precise toxicological properties of individual PCB. The present study was undertaken to determine whether prenatal exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153), a di-ortho-substituted non-coplanar congener, affects postnatal development in rat offspring. Pregnant Sprague-Dawley rats (Crj: CD (SD) IGS) were given PCB 153 (0, 16, or 64 mg/kg/day) orally from gestational day (GD) 10 through GD 16, and developmental parameters in the male and female offspring were examined. We found no dose-dependent changes in body weight, body length (nose-anus length), tail length, or the weights of kidneys, testes, ovaries and uterus in offspring at 1 or 3 weeks of age. Liver weights were increased in the PCB 153-treated groups, although we observed a significant difference only in males. Anogenital distance was unaffected in the PCB 153-treated groups. We observed a significant dose-dependent decrease in the plasma concentrations of thyroxine and tri-iodothyronine, whereas those of thyroid-stimulating hormone were not significantly changed. In addition, there were no dose-dependent changes in plasma concentrations of growth hormone and insulin-like growth factor-I in any dose group. These findings suggest that prenatal exposure to PCB 153 (GD 10-16, 16-64 mg/kg/day) may alter the thyroid status in rat offspring to some extent without affecting somatic growth or its related hormonal parameters. | 18,983,581 |
Reliability and repeatability of the Pentacam on corneal curvatures. | The purpose of this study was to assess the intra-observer reliability and inter-session repeatability of the Pentacam system (Oculus, Inc.) on the simulated keratometry readings (Sim K) and peripheral corneal curvatures (PCC) at both the anterior and posterior corneal surfaces. One eye was randomly selected from each of the 39 normal subjects from the School of Optometry at The Hong Kong Polytechnic University. In the first session, three readings were taken for reliability analysis. Measurements were repeated in a second session scheduled one to two weeks later for repeatability analysis. Two approaches were used, comparing the first reading between the two sessions and comparing the average from three readings between the two sessions. Both the anterior and posterior Sim K and PCC were calculated from the tangential and axial maps. The inter-session repeatability was reported as the coefficient of repeatability (COR = +/- 1.96 x standard deviation of differences). Relative repeatability (RR) was a percentage of the ratio of COR to the mean. All parameters showed good intra-observer reliability (Cronbach's alpha > or = 0.925; intra-class correlation coefficient, ICC > or = 0.804), except for the posterior power vector J45 (= 0.896; ICC = 0.742) and tangential PCC at the superior region (= 0.891; ICC = 0.732). The inter-session repeatability on anterior Sim K (COR < or = +/-0.21 D; RR < or = 0.48 per cent) and posterior Sim K (COR < or = +/-0.09 D; RR < or = 1.39 per cent) was good. Axial PCC showed better repeatability than the tangential PCC. The COR from using the first approach for all the posterior PCC was within 0.23 D, while the COR reduced to within 0.16 D from using the second approach. The Pentacam showed good intra-observer reliability on Sim K and PCC measurements. Averaging three readings from one visit could improve repeatability between visits. | 18,983,633 |
Cardiogenic shock as a complication of acute mitral valve regurgitation following posteromedial papillary muscle infarction in the absence of coronary artery disease. | A 48 year old man was transferred to our department with cardiogenic shock, pyrexia, a high white cell count and significant serum troponin T level. Clinical evaluation revealed severe mitral regurgitation secondary to a flail of both mitral valve leaflets. An emergency cardiac catheterisation did not reveal any significant coronary artery disease. Left ventricular angiogram and echocardiography demonstrated a good left ventricular function and massive mitral regurgitation. Blood cultures were negative for aerobics, anaerobics and fungi. The patient underwent emergency mitral valve replacement with a mechanical valve. Intraoperatively, the posteromedial papillary muscle was found to be ruptured. Histology of the papillary muscle revealed myocardial necrosis with no signs of infection. Cultures obtained from a mitral valve specimen were negative. The patient's recovery was uneventful and he was discharged on the 6th postoperative day. | 18,983,645 |
Empowering employees with chronic diseases; development of an intervention aimed at job retention and design of a randomised controlled trial. | Persons with a chronic disease are less often employed than healthy persons. If employed, many of them experience problems at work. Therefore, we developed a training programme aimed at job retention. The objective of this paper is to describe this intervention and to present the design of a study to evaluate its effectiveness. DEVELOPMENT AND DESCRIPTION OF INTERVENTION: A systematic review, a needs assessment and discussions with Dutch experts led to a pilot group training, tested in a pilot study. The evaluation resulted in the development of a seven-session group training combined with three individual counselling sessions. The training is based on an empowerment perspective that aims to help individuals enhance knowledge, skills and self-awareness. These advances are deemed necessary for problem solving in three stages: exploration and clarification of work related problems, communication at the workplace, and development and implementation of solutions. Seven themes are discussed and practised in the group sessions: 1) Consequences of a chronic disease in the workplace, 2) Insight into feelings and thoughts about having a chronic disease, 3) Communication in daily work situations, 4) Facilities for disabled employees and work disability legislation, 5) How to stand up for oneself, 6) A plan to solve problems, 7) Follow-up. Participants are recruited via occupational health services, patient organisations, employers, and a yearly national conference on chronic diseases. They are eligible when they have a chronic physical medical condition, have a paid job, and experience problems at work. Workers on long-term, 100% sick leave that is expected to continue during the training are excluded. After filling in the baseline questionnaire, the participants are randomised to either the control or the intervention group. The control group will receive no care or care as usual. Post-test mail questionnaires will be sent after 4, 8, 12 and 24 months. Primary outcome measures are job retention, self efficacy, fatigue and work pleasure. Secondary outcome measures are work-related problems, sick leave, quality of life, acquired work accommodations, burnout, and several quality of work measures. A process evaluation will be conducted and satisfaction with the training, its components and the training methods will be assessed. Many employees with a chronic condition experience problems in performing tasks and in managing social relations at work. We developed an innovative intervention that addresses practical as well as psychosocial problems. The results of the study will be relevant for employees, employers, occupational health professionals and human resource professionals (HRM). ISRCTN77240155. | 18,983,652 |
The incidence of interstitial lung disease 1995-2005: a Danish nationwide population-based study. | Current data on incidence of interstitial lung diseases (ILDs) are sparse and concerns about an increasing trend have been raised. We examined incidence rates (IRs) of ILDs and changes in IRs between 1995 and 2005. All persons with a first-time hospital discharge or outpatient diagnosis of ILD were identified through the Danish National Registry of Patients, which covers all Danish hospitals. Crude and age-standardised IRs were computed for ILD overall, as well as stratified by ILD subcategories. A total of 21,765 patients with ILD were identified. Between 1995 and 1998 the overall standardised IR of ILD decreased from 27.14 (95% CI 25.82-28.46) per 100,000 person-years to 19.36 (95% CI 18.26-20.46) per 100,000 person-years. After 1998 the IR increased considerably, peaking at 34.34 (95% CI 32.84-35.85) per 100,000 person-years in 2002. Subsequently there was a slight decrease. The highest IR was observed in the non-specific category "Respiratory disorders in diseases classified elsewhere". By ILD subcategory, the greatest average increase during the study period was observed in "Respiratory disorders in diseases classified elsewhere". The incidence rate of ILD in Denmark increased during the study period, most pronounced for ILDs associated with systemic diseases. | 18,983,653 |
Geographic disparities in the risk of perforated appendicitis among children in Ohio: 2001-2003. | Rural-urban disparities in health and healthcare are often attributed to differences in geographic access to care and health seeking behavior. Less is known about the differences between rural locations in health care seeking and outcomes. This study examines how commuting patterns in different rural areas are associated with perforated appendicitis. Controlling for age, sex, insurance type, comorbid conditions, socioeconomic status, appendectomy rates, hospital type, and hospital location, we found that patient residence in a rural ZIP code with significant levels of commuting to metropolitan areas was associated with higher risk of perforation compared to residence in rural areas with commuting to smaller urban clusters. The former group was more likely to seek care in an urbanized area, and was more likely to receive care in a Children's Hospital. To our knowledge, this is the first study to differentiate rural dwellers with respect to outcomes associated with appendicitis as opposed to simply comparing "rural" to "urban". Risk of perforated appendicitis associated with commuting patterns is larger than that posed by several individual indicators including some age-sex cohort effects. Future studies linking the activity spaces of rural dwellers to individual patterns of seeking care will further our understanding of perforated appendicitis and ambulatory care sensitive conditions in general. | 18,983,666 |
Networks for all. | A report on the Cold Spring Harbor Laboratory/Wellcome Trust conference on Network Biology, Hinxton, UK, 27-31 August 2008. | 18,983,700 |
X-chromosome inactivation: the molecular basis of silencing. | X-chromosome inactivation occurs randomly for one of the two X chromosomes in female cells during development. Inactivation occurs when RNA transcribed from the Xist gene on the X chromosome from which it is expressed spreads to coat the whole X chromosome. In the first issue of Epigenetics and Chromatin, Nesterova and colleagues investigate the role of the RNA interference pathway enzyme Dicer in DNA methylation of the Xist promoter. | 18,983,701 |
Barbiturates for the treatment of intracranial hypertension after traumatic brain injury. | In their article on the use of barbiturates for the treatment of intracranial hypertension after traumatic brain injury, Perez-Barcena and colleagues conclude that thiopental was more effective than pentobarbital in decreasing intracranial pressure. Here we discuss the limitations of this study and review areas of controversy surrounding barbiturate use in neurocritical care. | 18,983,702 |
Year in review 2007: Critical Care--intensive care unit management. | With the development of new technologies and drugs, health care is becoming increasingly complex and expensive. Governments and health care providers around the world devote a large proportion of their budgets to maintaining quality of care. During 2007, Critical Care published several papers that highlight important aspects of critical care management, which can be subdivided into structure, processes and outcomes, including costs. Great emphasis was given to quality of life after intensive care unit stay, especially the impact of post-traumatic stress disorder. Significant attention was also given to staffing level, optimization of intensive care unit capacity, and drug cost-effectiveness, particularly that of recombinant human activated protein C. Managing costs and providing high-quality care simultaneously are emerging challenges that we must understand and meet. | 18,983,704 |
Year in review 2007: Critical Care--multiple organ failure and sepsis. | Several research papers published in Critical Care throughout 2007 examined the pathogenesis, diagnosis, treatment and prognosis of sepsis and multiorgan failure. The present review summarizes the findings and implications of the papers published on sepsis and multiorgan failure and places the research in the context of other work in the field. | 18,983,708 |
Antimicrobial resistance in swine production. | Large amounts of antimicrobial agents are still being used in modern swine production in many countries around the world. This facilitates the emergence and development of antimicrobial resistance. Bacteria causing infections in swine have in several cases acquired resistance to a number of the agents most commonly used for treatment, making it difficult to predict the efficacy of different antimicrobial agents without prior susceptibility testing. This review gives an overview of recent susceptibility data from different parts of the world and discusses the importance of the development of resistance not only in the treatment of infections in swine but also taking into account the human health implications of antimicrobial resistance. | 18,983,723 |
Assisted reproductive technology: perspectives in Halakha (Jewish religious law). | The Jewish religion is characterized by a strict association between faith and practical precepts. In principle, Jewish law has two divisions, the Written and the Oral traditions. The foundation of the Written Law and the origin of authority is the Torah, the first five books of the Scripture. This paper presents the attitude of Jewish religion to assisted reproductive therapeutic procedures such as IVF-embryo transfer, spermatozoa, oocytes, embryo donation, cryopreservation of genetic material, surrogacy, posthumous reproduction, gender preselection and reproductive and therapeutic cloning. | 18,983,733 |
The Greek Orthodox position on the ethics of assisted reproduction. | In dealing with reproduction, the Church believes that every human being has a beginning but has no end; this is why conception constitutes an event of unique importance. The exact moment of the beginning of life is unknown to man, but the logic of sexual intercourse without reproduction and of reproduction without sexual intercourse must be seen with concern. Irrespective of the way it is conceived, the embryo has both a human beginning and a human perspective and in it, along with cellular multiplication, another process takes place, the beginning and development of its soul. Although modern technology has greatly contributed to health research, its irrational use threatens to desacralize man and to treat him as a machine. For this reason, all modern techniques of artificial fertilization have ethical and spiritual parameters that compel the Church to state Her reservations. The Church cannot recommend assisted reproduction as the solution to infertility; instead, She proposes a non-secularized perception on life that guarantees simplicity, peace, abstinence and mutual trust between spouses. She does not oppose resorting to medical help, but, at the same time, suggests that men and women render their life into the hands of God. | 18,983,734 |
A Catholic ethical approach to human reproductive technology. | This article presents the Catholic Christian tradition and teaching on the moral respect due to human life from conception, supported by natural law moral philosophical reasoning. This approach contrasts with the ethical views of secular philosophers on human embryo research for therapeutic purposes. The challenges for Catholic healthcare institutions is to find ethical ways of using suitable pluripotent stem cells for therapies without creating or destroying human embryos. Catholic teaching on infertility treatment and reproductive technology are presented with emphasis given to the ethical need for children to be conceived and born of the marriage union compared with alterative ethical approaches for the use of infertility treatment and reproductive technology. | 18,983,736 |
Magnetic resonance and diffusion-weighted imaging findings of herpes simplex encephalitis. | Herpes simplex encephalitis (HSE) is a rare, life-threatening disease. This paper draws attention to the role of imaging in early HSE diagnosis. Five consecutive patients diagnosed with HSE (type 1) between June 2005 and June 2006 (three males, two females, mean age 44 [range 16-68] years) were included in this retrospective study. Computed tomography, conventional magnetic resonance imaging (MRI) sequences and diffusion-weighted imaging (DWI) were obtained for each patient. Apparent diffusion coefficient values were calculated in diseased and normal tissue. Therefore, we propose that MRI scan with DWI should be performed when HSE is suspected, although in disease follow-up DWI is not superior to conventional sequences. There is no need for contrast media to be administered at any disease stage. Fluid-attenuated inversion recovery is superior to T2 sequencing in showing cortical lesions at all disease stages. | 18,983,763 |
[Effect of beta-elemene on the proliferation, migration and RhoA expression of hepatic stellate cells induced by angiotensin II]. | To explore the influence of beta-elemene on the proliferation, migration and RhoA expression of hepatic stellate cells (HSC) induced by angiotensin II (ANG II). HSC were incubated in vitro. Proliferation and migration of the HSC were induced by ANG II. The effect on the proliferation of HSC was determined by MTT colorimetry. The migration ability was detected by transwell chamber cultures. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Protein levels were determined by Western blot. Different concentrations (from 1 to 10 micromol/L) of ANG II markedly promoted the growth of the HSC in a concentration dependent way (0 micromol/L ANG II, F = 112.640, P less than 0.01). 10, 8, 4 micromol/L ANGII significantly induced HSC migration, F = 117.496, P less than 0.01. Compared with the 4 micromol/L ANG II group, 10 mg/L, 5 mg/L, 2.5 mg/L beta-elemene markedly inhibited HSC proliferation and migration induced by 4 micromol/L ANG II (F values were 95.706 and 55.600 and P less than 0.01). 4 micromol/L ANG II markedly promoted the protein and mRNA expressions of RhoA in HSC. 10 mg/L, 5 mg/L and 2.5 mg/L beta-elemene notably inhibited the expressions of RhoA protein and mRNA (F values were 217.119 and 18.010). ANG II can significantly induce the proliferation and migration of HSC. Beta-elemene can inhibit the proliferation and migration of HSC induced by ANG II. The effects of beta-elemene are mediated through inhibiting the RhoA signal transduction pathway and are associated with RhoA. | 18,983,771 |
Emergency thyroidectomy in infected thyroid cyst due to spontaneous gas forming organisms. | We are reporting a case of a young female, who presented to emergency room with sudden increase in thyroid swelling, high fever and acute respiratory distress. Clinical diagnosis of spontaneous infection of thyroid cyst was made. Operative finding was infection of thyroid cyst with gas formation. Systemic antibiotics and operative intervention by subtotal thyroidectomy led to recovery of the patient. | 18,983,798 |
Prevalence of antibodies and cell mediated immune response against Leishmania major in feral nonhuman primates from Kenya. | In Kenya, Leishmania major is responsible for human cutaneous leishmaniasis (CL). Natural infection with L. major of a vervet monkey and experimental susceptibility of some nonhuman primates (NHPs) from Kenya has been established. However, there has been no comprehensive study of the prevalence of zoonotic CL in Kenya. And also, no investigation has been done to assess whether NHPs could be potential reservoir hosts of L. major even when the involvement of reservoir animals is obligatory in transmission of this parasite. To achieve this, wild caught Chlorocebus aethiops (Vervet monkeys n=213), Papio cynocephalus anubis (olive baboons n=101) and Cercopithecus mitis (Syke's monkeys n=64) from five geographical locations in Kenya were screened for antibodies against L. major using enzyme linked immunosorbent assay (ELISA) and Western blot (WB) analysis. From the population of C. aethiops (n=213) captured, 57 were used in lymphocyte proliferation assay. ELISA revealed a high prevalence of leishmaniasis sero conversion in olive baboons 78/101 (77.2%), vervet monkeys 129/213 (60.6%) and Sykes' monkeys 43/64 (67.2%). WB detected anti-L. major antibodies in 48.5% (49/101) of the baboons, 48% (102/213) of vervet monkeys and 37.5% (24/64) of Sykes' monkey sera. Specific proliferation of peripheral blood mononuclear cells to L. major antigen was demonstrated in 17 of the 57 (29.8%) vervet monkeys. In conclusion, the results of serological assays provide strong circumstantial evidence that CL is prevalent in five Provinces of Kenya and that Kenyan NHPs could be could be a potential reservoir hosts of L. major. | 18,983,806 |
Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery. | The epithelial and endothelial barriers of the human body are major obstacles for drug delivery to the systemic circulation and to organs with unique environment and homeostasis, like the central nervous system. Several transport routes exist in these barriers, which potentially can be exploited for enhancing drug permeability. Beside the transcellular pathways via transporters, adsorptive and receptor-mediated transcytosis, the paracellular flux for cells and molecules is very limited. While lipophilic molecules can diffuse across the cellular plasma membranes, the junctional complexes restrict or completely block the free passage of hydrophilic molecules through the paracellular clefts. Absorption or permeability enhancers developed in the last 40 years for modifying intercellular junctions and paracellular permeability have unspecific mode of action and the effective and toxic doses are very close. Recent advances in barrier research led to the discovery of an increasing number of integral membrane, adaptor, regulator and signalling proteins in tight and adherens junctions. New tight junction modulators are under development, which can directly target tight or adherens junction proteins, the signalling pathways regulating junctional function, or tight junction associated lipid raft microdomains. Modulators acting directly on tight junctions include peptides derived from zonula occludens toxin, or Clostridium perfringens enterotoxin, peptides selected by phage display that bind to integral membrane tight junction proteins, and lipid modulators. They can reversibly increase paracellular transport and drug delivery with less toxicity than previous absorption enhancers, and have a potential to be used as pharmaceutical excipients to improve drug delivery across epithelial barriers and the blood-brain barrier. | 18,983,815 |
Bisnaphthalimidopropyl spermidine induces apoptosis within colon carcinoma cells. | Bisnaphthalimido compounds bisintercalate to DNA via the major groove and are potentially potent cancer therapeutics. We incorporated natural polyamines as linkers connecting the two-naphthalimido ring moieties to create a series of novel soluble cytotoxic bisnaphthalimidopropyl polyamines (BNIPPs). Here, we determined the cytotoxicity of bisnaphthalimidopropyl spermidine (BNIPSpd) towards Caco-2 and HT-29 colon adenocarcinoma cells revealing an IC(50) value of 0.15 and 1.64 microM after 48h exposure within Caco-2 and HT-29 cells, respectively. After 4h, >/=0.5 microM BNIPSpd treatment-induced significant DNA damage. After 24h exposure a concentration-dependent increase in active caspase-3 expression, chromatin condensation and internucleosomal DNA fragmentation identified apoptosis as the principal manifestation for the cytotoxicity within both cell lines. By 24h exposure, there was also a significant decline in cellular spermine and spermidine levels. It is concluded that bisnaphthalimidopropyl spermidine (BNIPSpd) toxicity primarily results from apoptosis and that BNISpd has potential to be further developed as an anti-tumour agent. | 18,983,836 |
Paclitaxel-octreotide conjugates in tumor growth inhibition of A549 human non-small cell lung cancer xenografted into nude mice. | Targeted chemotherapy is a novel approach to cancer therapies. This study evaluated the anti-tumor effects of conjugates made by coupling cytotoxic paclitaxel to the somatostatin analog octreotide in A549 human non-small-cell lung cancer (NSCLC) cells xenografted into nude mice. Two cytotoxic somatostatin analogs, paclitaxel-octreotide and 2paclitaxel-octreotide, were prepared by the coupling of one or two paclitaxel molecules with an octreotide molecule. A549 xenografts expressed mRNAs for type 1, 2, 4, and 5 somatostatin receptors. Immunohistology revealed that type 2 somatostatin receptors were mainly located in tumor cell membrane but type 5 somatostatin receptors were found in tumor cell membrane and cytoplasm. Significant tumor growth inhibition was achieved by 2paclitaxel-octreotide at 150 nM/kg and 300 nM/kg. 2paclitaxel-octreotide also significantly extended the tumor doubling time and significantly reduced tumor microvessel density at these doses. Moreover, there was more fragmented DNA in the 2paclitaxel-octreotide single and double dose groups than in the controls. Paclitaxel was ineffective and more toxic than the conjugate as shown by the significant decline of body weight in Paclitaxel group on Days 6, 12, and 26 compared to those treated with 2paclitaxel-octreotide (P<0.05). White blood cell counts in the paclitaxel single and double dose groups were also significantly less than in the controls (P<0.05). In conclusion, the targeting conjugate 2paclitaxel-octreotide made by coupling two molecules of cytotoxic paclitaxel to one somatostatin analog octreotide could enhance tumor growth inhibition and reduce toxicity in comparison to using the cytotoxic paclitaxel alone. | 18,983,839 |
Unfolding thermodynamics of the Delta-domain in the prohead I subunit of phage HK97: determination by factor analysis of Raman spectra. | An early step in the morphogenesis of the double-stranded DNA (dsDNA) bacteriophage HK97 is the assembly of a precursor shell (prohead I) from 420 copies of a 384-residue subunit (gp5). Although formation of prohead I requires direct participation of gp5 residues 2-103 (Delta-domain), this domain is eliminated by viral protease prior to subsequent shell maturation and DNA packaging. The prohead I Delta-domain is thought to resemble a phage scaffolding protein, by virtue of its highly alpha-helical secondary structure and a tertiary fold that projects inward from the interior surface of the shell. Here, we employ factor analysis of temperature-dependent Raman spectra to characterize the thermostability of the Delta-domain secondary structure and to quantify the thermodynamic parameters of Delta-domain unfolding. The results are compared for the Delta-domain within the prohead I architecture (in situ) and for a recombinantly expressed 111-residue peptide (in vitro). We find that the alpha-helicity (approximately 70%), median melting temperature (T(m)=58 degrees C), enthalpy (DeltaH(m)=50+/-5 kcal mol(-1)), entropy (DeltaS(m)=150+/-10 cal mol(-1) K(-1)), and average cooperative melting unit (n(c) approximately 3.5) of the in situ Delta-domain are altered in vitro, indicating specific interdomain interactions within prohead I. Thus, the in vitro Delta-domain, despite an enhanced helical secondary structure ( approximately 90% alpha-helix), exhibits diminished thermostability (T(m)=40 degrees C; DeltaH(m)=27+/-2 kcal mol(-1); DeltaS(m)=86+/-6 cal mol(-1) K(-1)) and noncooperative unfolding (<n(c)> approximately 1) vis-à-vis the in situ Delta-domain. Temperature-dependent Raman markers of subunit side chains, particularly those of Phe and Trp residues, also confirm different local interactions for the in situ and in vitro Delta-domains. The present results clarify the key role of the gp5 Delta-domain in prohead I architecture by providing direct evidence of domain structure stabilization and interdomain interactions within the assembled shell. | 18,983,851 |
Testing a counter-intuitive prediction of optimal cue combination. | Weighted averaging is said to be optimal when the weights assigned to the cues minimize the variance of the final estimate. Since the variance of this optimal percept only depends on the variances of the individual cues, irrespective of their values, judgments about a cue conflict stimulus should have the same variance as ones about a cue consistent stimulus. We tested this counter-intuitive prediction with a slant matching experiment using monocular and binocular slant cues. We found that the slant was indeed matched with about the same variance when the cues indicated slants that differed by 15 degrees as when they indicated the same slant. | 18,983,869 |
Identification of a minimal peptide derived from heptad repeat (HR) 2 of spike protein of SARS-CoV and combination of HR1-derived peptides as fusion inhibitors. | The heptad repeats (HR1 and HR2) of the spike protein of SARS-CoV are highly conserved regions forming a critical 6-helix bundle during the fusion step of virus entry and are attractive targets of entry inhibitors. In this study, we report that a minimal HR2 peptide, P6 of 23-mer, can block the fusion of SARS-CoV with an IC(50) of 1.04+/-0.22 microM. This finding supports the structural prediction of the deep groove of HR1 trimer as a target for fusion inhibitors, and suggests P6 as a potential lead peptide for future drug development. Moreover, combination of an HR-1 peptide, N46, and its mutated version, N46eg, shows synergistic inhibition with an IC(50) of 1.39+/-0.05 microM and combination index of 0.75+/-0.15, suggesting a common strategy to achieve promising inhibition by HR1 peptide for other class I envelope viruses. | 18,983,873 |
Pre-surgical training ameliorates orbitofrontal-mediated impairments in spatial reversal learning. | We recently reported that orbitofrontal cortical (OFC) lesions impaired reversal learning of an instrumental two-lever spatial discrimination task, a deficit manifested as increased perseveration on the pre-potent response. Here we examine whether exposure to reversal learning test pre-operatively may have a beneficial effect for future reversal learning of OFC-lesioned animals. Rats were trained on a novel instrumental two-lever spatial discrimination and reversal learning task, measuring both 'cognitive flexibility' and constituent processes including response inhibition. Both levers were presented, only one of which was reinforced. The rat was required to respond on the reinforced lever under a fixed ratio 3 schedule of reinforcement. Following attainment of criterion, two reversals were introduced. Rats were then matched according to their reversal performance and subjected to bilateral excitotoxic OFC lesions. Following recovery, a series of four reversals was presented. OFC lesions impaired neither retention nor reversal phases. These data, together with the previously reported reversal deficit following OFC lesions, suggest that OFC is not needed when task experience has been gained but it is necessary when task demands are relatively high. | 18,983,877 |
Neem leaf glycoprotein directs T-bet-associated type 1 immune commitment. | Neem leaf glycoprotein (NLGP)-mediated immune activation and associated immune polarization was studied. NLGP-induced activation is reflected in upregulation of early activation marker CD69 on lymphocytes, monocytes, and dendritic cells. Activation is also denoted by CD45RO enhancement, with a decrease in CD45RA phenotype and CD62L (L-selectin). NLGP-activated T cells secrete greater amount of signature T-helper (Th)1 cytokines interferon-gamma and a lower amount of the Th2 cytokine interleukin (IL)-4. Similar type 1 directiveness is also observed in antigen-presenting monocytes and dendritic cells by upregulation of IL-12, tumor necrosis factor -alpha and downregulation of IL-10. Creation of the type 1 microenvironment is also assisted by NLGP-induced downregulation of FoxP3(+) T-Reg cells. A type 1-specific transcription factor, T-bet, is upregulated in circulating immune cells after their stimulation with NLGP. In the creation of type 1 immune network, increased phosphorylation of STAT1 and STAT4 with decreased phosphorylation of STAT3 might have significance. We conclude that NLGP may be effective in maintaining normal immune homeostasis by upregulating type 1 response in immunosuppressed hosts, which may have significant role in the induction of host protective antitumor functions. | 18,983,881 |
The mechanism of vasorelaxation induced by Schisandra chinensis extract in rat thoracic aorta. | Schisandra chinensis (SC) is a known medical herb for the treatment of cardiovascular symptoms associated with menopausal symptoms in Korea. However, the pharmacological action mechanisms involved have not been well studied. This study was aimed to investigate the vascular effects of SC in rat thoracic aorta. We isolated the hexane, chloroform, and methanol extracts from SC and evaluated their vasodilatory effects in the rat thoracic aorta. Hexane extracts of SC (SCHE, 5 x 10(-5) to 10(-3) g/L) caused a concentration-dependent relaxation in both endothelium-intact and -denuded aortas. The relaxant effect of SCHE on the endothelium-intact aorta was more prominent than on the endothelium-denuded aorta. The former was significantly attenuated by L-NAME, a nitric oxide synthase inhibitor, and ODQ, a soluble guanyl cyclase inhibitor, but not by tetraethylammonium, a nonselective blocker of K(+) channels, and indomethacin, a cyclooxygenase inhibitor. Furthermore, SCHE caused nitrite production as well as eNOS activation in aortic segments, suggesting implication of NO signal pathway in SCHE-induced relaxation. In endothelium-denuded aorta, SCHE-induced vasorelaxation was also attenuated by calyculin A, an inhibitor of myosin light chain (MLC) phosphatase, but not by ML-9, a MLC kinase inhibitor, suggestive of implication of MLC phosphatase activation. Phenylephrine-enhanced MLC phosphorylation ratio was significantly attenuated by SCHE, which was recovered to the control level by pretreatment with calyculin A. Taken collectively, these findings suggest that the vascular relaxation evoked by SCHE was mediated by not only endothelium dependent NO pathway but also direct effect on vascular smooth muscle cell via dephosphorylation of MLC. | 18,983,904 |
Aggregation of Escherichia coli proteins during stationary phase depends on glucose and oxygen availability. | In natural environments, bacteria are often challenged by nutrient starvation and other stresses. As a consequence, cell growth is arrested and bacteria enter stationary phase. In this report, we demonstrate that during stationary phase, Escherichia coli cells accumulate aggregates of misfolded proteins and complexes of Dps (starvation-induced protein) with chromosomal DNA. We found that the formation of multicomponent protein aggregates and insoluble Dps-DNA complexes depended on growth conditions and was influenced by the availability of oxygen and glucose in a medium. Aerobic stationary cells grown in unbuffered medium supplemented with glucose contained insoluble Dps-DNA, whereas multicomponent protein aggregates were accumulated under glucose starvation. On the contrary, under oxygen depletion, Dps-DNA complexes were formed in the absence of glucose, whereas multicomponent protein aggregates appeared in the presence of glucose. The mechanisms responsible for this phenomenon remain to be elucidated; however, we demonstrated that in MOPS-buffered cultures the level of insoluble Dps and protein aggregates was decreased. | 18,983,914 |
Anti-inflammatory effects and clinical efficacy of theophylline and tulobuterol in mild-to-moderate chronic obstructive pulmonary disease. | The airway inflammation of chronic obstructive pulmonary disease (COPD) demonstrates a poor response to the anti-inflammatory actions of corticosteroids. However, long-acting beta(2)-agonists and low-dose theophylline are reported to have a possible anti-inflammatory effect in COPD. The aim of this study was to compare the effects of treatment between theophylline and the tulobuterol patch (transdermal patch preparation designed to yield sustained beta(2)-agonistic effects for 24h) on airway inflammation in addition to quality of life (QOL) and pulmonary function in mild-to-moderate COPD. The study subjects consisted of 26 patients with COPD who were treated with theophylline or tulobuterol for 8 weeks with a wash-out period of 4 weeks in a randomized open-label crossover study. We prospectively investigated the differential cell counts and levels of inflammatory markers in induced sputum before and after treatment with theophylline and tulobuterol. We also examined pulmonary function and quality of life (QOL) as assessed by St. George's Respiratory Questionnaire. In the induced sputum, the total inflammatory cell count and number of neutrophils were significantly reduced by treatment with low-dose theophylline. Neither of these parameters was significantly changed by treatment with tulobuterol. Pulmonary function measurements such as FEV(1), FEV(1) % pred, FVC, PEF, MEF(50), and MEF(25) were significantly improved by the treatment with low-dose theophylline but not tulobuterol. The total QOL scores, levels of interleukin 8 and myeloperoxidase in the supernatants of induced sputum, and serum levels of hypersensitive C-reactive protein were not significantly changed by either of the treatments. These results suggest that treatment with low-dose theophylline but not the tulobuterol patch may have anti-inflammatory effects and improve pulmonary function in mild-to-moderate COPD. | 18,983,928 |
Field preservation of monogenean parasites for molecular and morphological analyses. | In the present work we examined the efficacy of three different chemical solutions (EtOH 70%, DMSO-NaCl solution, and Longmire buffer) in field preservation of fish gills to be subsequently screened for monogenean specimens destined to morphological and molecular analyses. Degree of difficulty in collecting monogeneans from gills, morphological state of parasites, integrity of their DNA and reliability of sequence reading were observed and qualitatively compared to those of gills and parasites stored in 5% formalin and 99% ethanol. Data were collected over a period of 2 months. Storage in Longmire buffer resulted in dissociation of gills and parasites, while both DMSO and 70% ethanol provided a fine physical and molecular preservation of gills and monogeneans, allowing rapid collection of parasites from lamellae, and easy extraction, amplification and sequencing of parasitic DNA. | 18,983,938 |
Cyclin-dependent kinase-5 targeting for ischaemic stroke. | Recovery from ischaemic stroke is dependent on survival of neurones, particularly in peri-infarcted regions. Angiogenesis is critical for the development of new microvessels resulting in the re-formation of collateral circulation associated with enhanced neuronal survival and reduced morbidity and mortality. Recently, the identification of a neurovascular niche has been described, where the co-ordinated effects of angiogenesis and migration of neuroprogenitor cells to damaged stroke regions were shown to be vital in the process of tissue remodelling. Cdk5, a serine/threonine kinase is highly expressed in the central nervous system, particularly following ischaemic stroke and its aberrant activation is directly associated with neuronal apoptosis and death. In contrast, recent evidence suggests that increased expression of Cdk5 by endothelium might be protective against cell death and/or promote angiogenesis leading to increased vessel formation and reperfusion. Owing to its known interaction with over 20 substrates including caspase-3, MEF2, Tau and p53, Cdk5 could be a master switch controlling both neuronal survival and revascularisation. Therefore its cell-specific pharmacological or genetic modulation using novel nanotechnology-based delivery systems could be of benefit when considering future stroke therapies. | 18,983,942 |
SUMO1 polymorphisms are associated with non-syndromic cleft lip with or without cleft palate. | Small ubiquitin-like modifier 1 (SUMO1) haploinsufficiency results in cleft lip and palate in animal models. However, no studies have linked SUMO1 to non-syndromic cleft lip with or without cleft palate (NSCLP) in humans. In the present study, we investigated the potential association between SUMO1 single nucleotide polymorphisms (SNPs) and risk for human NSCLP. From 181 patients and 162 healthy controls, we found statistically significant correlations between a 4-SNP SUMO1 haplotype and NSCLP. These data are the first to suggest a role for SUMO1 gene variation in human NSCLP development. | 18,983,974 |
Chinese hamster monomeric carbonyl reductases of the short-chain dehydrogenase/reductase superfamily. | Chinese hamster monomeric carbonyl reductases (CHCRs) belong to the short-chain dehydrogenase/reductase (SDR) superfamily, which is a family of enzymes that metabolize many endogenous and xenobiotic compounds. We previously cloned three carbonyl reductase cDNAs-Chcr1, Chcr2, and Chcr3. By performing spectrophotometric analyses, we indicated that the enzymes CHCR1, CHCR2, and CHCR3 had similar specificities toward steroids; only CHCR3 did not show any reactivity with prostaglandins (PGs). In the present study, we investigated the characteristics of CHCRs in detail, that is, the differences in their expression patterns, physicochemical properties, and enzymatic activities. CHCR1 exhibited sex-dependent expression patterns. CHCRs showed multiple surface potentials in the zeta potential analysis and CHCR3 exhibited an isatin reductase activity with a high K(m) value. By the present HPLC-analysis, all the three enzymes exhibited PGF(2alpha) dehydrogenase activity and could oxidize PGF(2alpha) to PGE(2) and 15-keto-PGF(2alpha), i.e., the three enzymes exhibited 9- and 15-hydroxy PG dehydrogenase activities. Moreover, 15-keto-PGE(2) was detected in a comparatively higher amount in the dehydrogenase reaction products of CHCR2 than in those of CHCR1 and CHCR3, suggesting that CHCR2 can oxidize PGE(2) and/or 15-keto-PGF(2alpha) to 15-keto-PGE(2); however, these two PGs did not seem to be efficient substrates of CHCR1. Despite the differences in the dehydrogenase activities between CHCR1 and CHCR2, PGE(2) reductase activities of the two enzymes were similar, and PGF(2alpha) was predominantly produced from PGE(2) as a result of the PG 9-keto reductase activity. On the other hand, CHCR3 exhibited a reduced PGE(2) reductase activity. In conclusion, although the CHCRs share a high degree of sequence identity (>70%), they clearly differed in their enzymatic characteristics. | 18,983,989 |
Free radical fragmentation of cardiolipin by cytochrome c. | The effect of cytochrome c (cyt c) on degradation of cardiolipin in its polar part was investigated in cardiolipin/phosphatidylcholine (CL/PC) liposomes incubated with cyt c/H(2)O(2)/and (or) ascorbate by high-performance thin layer chromatography and MALDI-TOF mass spectrometry. It has been shown that phosphatidic acid (PA) and phosphatidylhydroxyacetone (PHA) were formed in the system under conditions where hydrogen peroxide favours a release of heme iron from cyt c. The formation of PA and PHA occurs via an OH-induced fragmentation taking place in the polar moiety of cardiolipin. Formation of fragmentation products correlated with the loss of CL in CL/PC liposomes incubated with cyt c/H(2)O(2)/ascorbate or with Cu(2+)/H(2)O(2)/ascorbate. | 18,983,994 |
Altering the regioselectivity of the subterminal fatty acid hydroxylase P450 BM-3 towards gamma- and delta-positions. | Cytochrome P450 BM-3 monooxygenase from Bacillus megaterium (CYP102A1) catalyzes the subterminal hydroxylation of fatty acids with a chain length of 12-22 carbons. Wild-type P450 BM-3 oxidizes saturated fatty acids at subterminal positions producing a mixture of omega-1, omega-2 and omega-3 hydroxylated products. Using a rational site-directed mutagenesis approach, three new elements have been introduced into the substrate binding pocket of the monooxygenase, which greatly changed the product pattern of lauric acid hydroxylation. Particularly, substitutions at positions S72, V78 and I263 had an effect on the enzyme regioselectivity. The P450 BM-3 mutants V78A F87A I263G and S72Y V78A F87A were able to oxidize lauric acid not only at delta-position (14% and 16%, respectively), but also produced gamma- and beta-hydroxylated products. delta-Hydroxy lauric and gamma-hydroxy lauric acid are important synthons for the production of the corresponding lactones. | 18,984,016 |
Differences in the injury/sprouting response of splenic noradrenergic nerves in Lewis rats with adjuvant-induced arthritis compared with rats treated with 6-hydroxydopamine. | Sympathetic nerves in the spleen undergo an injury and sprouting response with development of adjuvant-induced arthritis (AA), a model of rheumatoid arthritis (RA). The objective of the present study was to determine whether this injury and sprouting response is disease-specific or occurs in a non-specific manner similar to injury and sprouting responses following sympathectomy with specific neurotoxins. Changes in noradrenergic (NA) innervation in spleens from Lewis rats 28 days following adjuvant treatment to induce arthritis and/or local 6-hydroxydopamine (6-OHDA) treatment to destroy NA nerves were examined using immunocytochemistry for tyrosine hydroxylase (TH). We observed significant increases in sympathetic innervation of hilar regions, sites of nerve entry into the spleen, and a striking decline in innervation of splenic regions distant to the hilus in arthritic compared to non-arthritic rats. While increased hilar and decreased distal NA innervation in arthritic rats was strikingly similar to that of non-arthritic 6-OHDA-treated rats, there were differences in splenic compartments innervated by sympathetic nerves between these groups. In 6-OHDA-treated rats, NA nerves re-innervated splenic compartments normally innervated by sympathetic nerves. In arthritic rats, sympathetic nerves returned to normally innervated splenic compartments, but also abundantly innervated red pulp. These findings suggest that splenic sympathetic nerves undergo a disease-associated injury/sprouting response with disease development that alters the normal pattern and distribution of NA innervation. The altered sympathetic innervation pattern is likely to change NA signaling to immune cell targets, which could exert long-term regulatory influences on initiation, maintenance, and resolution of immune responses that impact disease pathology. | 18,984,038 |
Regulation of somatic firing dynamics by backpropagating dendritic spikes. | Pyramidal cells of the apteronotid ELL have been shown to display a characteristic mechanism of burst discharge, which has been shown to play an important role in sensory coding. This form of bursting depends on a reciprocal dendro-somatic interaction, in which discharge of a somatic spike causes a dendritic spike, which in turn contributes a dendro-somatic current flow to create a depolarizing afterpotential (DAP) in the soma. We review here our recent work showing how the timing of this DAP influences the somatic firing dynamics, and how the degree of inactivation of dendritic Na(+) currents can cause an increased delay between somatic and dendritic spikes. This ultimately allows the DAP to become more effective at increasing the excitability of the somatic spike generating mechanism. Further, this delay between dendritic and somatic spiking can be regulated by strongly hyperpolarizing GABA(B) mediated dendritic inhibition, allowing the burst dynamics to fall under synaptic regulation. In contrast, a weaker, shunting inhibition due to GABA(A) mediated dendritic inhibition can regulate the dendritic spike waveform to decrease the dendro-somatic current flow and the resulting DAP. We therefore show that the qualitative behaviour of an individual cell can depend on the degree of synaptic input, and the exact timing of events across the spatial extent of the neuron. Thus, our results serve to illustrate the complex dynamics that can be observed in cells with significant dendritic arborisation, a nearly ubiquitous adaptation amongst principal neurons. | 18,984,047 |
Discussion: 'Hypnotic analgesia during first-trimester termination' by Marc et al. | In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Marc I, Rainville P, Masse B, et al. Hypnotic analgesia intervention during first-trimester pregnancy termination: an open randomized trial. Am J Obstet Gynecol 2008;199:469.e1-469.e9. | 18,984,071 |
Infrared endoscopic system for bleeding-point detection after flushing with indocyanine green solution (with videos). | Infrared endoscopy is used to visualize vessels in the GI tract. By applying this system, we developed a new method to visualize a bleeding point during endoscopic resection. This study aimed to evaluate the ability of infrared endoscopy to detect a bleeding point during endoscopic resection and to elucidate the mechanism required for clear visualization of a bleeding point by in vitro color analysis. Observational case series. A cancer-referral center. A total of 10 bleeding sites were observed during endoscopic resection of upper-GI cancers by infrared endoscopy after flushing with indocyanine green (ICG) solution (0.125 mg/mL water). Detection of bleeding points. Bleeding points were identified in all bleeding sites by infrared endoscopic viewing. Bleeding points were displayed in white, whereas, an ulcer bed was in blue and pooled blood was a blue-to-gray color. By in vitro color analysis, blood was white, blood twice diluted with ICG solution was dark blue, and blood 4-times diluted with ICG solution was light blue on infrared endoscopic views. Color differences with blood dilution were more obvious in an infrared endoscopic view compared with a conventional endoscopic view. Blood thickness, movement, and clotting did not influence the color differences. Uncontrolled study. We reported a flushing method by which we could detect all bleeding points during endoscopic resection. Clear visualization of bleeding points comes from differences in blood and ICG concentration between spurting and pooled blood. | 18,984,104 |
Treatment of a completely obstructed colonic anastomotic stricture by using a prototype forward-array echoendoscope and facilitated by SpyGlass (with videos). | Colonic anastomotic strictures complicate colorectal resection in up to 7% of cases and are often managed with endoscopic dilation. Complete anastomotic obstructions are rare and have traditionally required surgical remediation. To demonstrate a novel endoscopic approach to treat complete colonic anastomotic obstruction. Case report. Tertiary-referral center. A 40-year-old woman with a completely obstructed colonic anastomosis after sigmoidectomy for a fibrotic Crohn's stricture. A prototype front-view and forward-array echoendoscope was used to recanalize the completely obstructed anastomotic stricture. Real-time EUS imaging guided puncture through the stenosis. Access into the proximal obstructed segment was confirmed by using SpyGlass fiberoptic probe visualization. Subsequent stricture dilation was performed by using wire-guided balloon dilators through the instrument channel of the prototype echoendoscope, and luminal continuity was reestablished. Technique success and complications. The completely obstructed anastomotic stricture was successfully recanalized and dilated by using a single, prototype, forward-array echoendoscope without complications. Single case report with a relatively short follow-up interval. EUS-guided puncture and dilation of completely obstructed anastomotic strictures is feasible when using a prototype forward-array echoendoscope. This novel technique appears to be an effective method to reestablish luminal continuity across completely obstructed strictures. | 18,984,106 |
[Paraplegia after interlaminar epidural steroid injection: a case report]. | We report the first case of paraplegia observed after epidural steroid injection in the upper spine. The patient was a 42-year-old male who underwent surgery two years earlier for stenosis of the lumbar spine from L2 to the sacrum leading to early manifestations of an equina cauda syndrome. This first operation provided satisfactory function with complete resolution of the objective neurological symptoms. The patient later developed bilateral radiculalgia involving the L3 and L4 territories and was treated by radio-guided epidural steroid injection (125 mg hydrocortancyl) delivered in the L1-L2 interlaminar space. The injection was achieved with no technical difficulty and there was no injury to the dural sac. Immediately after the injection, the patient developed complete motor and sensorial paraplegia from T12. CT and MRI performed 30 min and 4h, respectively, after the accident revealed a medium-sized discal herniation behind the L2 body. No other lesion was observed. Emergency surgery was performed for radicular release but to no avail. The patient's neurological status remained unchanged and four days later the T2 MRI sequence revealed a high-intensity intramedullar signal in the cone. The diagnosis of ischemia of the medullary cone was retained, hypothetically by injury to the dominant radiculomedullary artery via an undetermined mechanism. This complication has been previously described after upper foraminal steroid injections but not after intralaminar epidural steroid injection. | 18,984,128 |
It takes a (dysfunctional) village to raise a tumor. | The tumor microenvironment is known to play an important role in tumorigenesis. In this issue, Yang et al. (2008) demonstrate that mast cells heterozygous for the Nf1 gene promote the growth of neurofibromas in a mouse model of neurofibromatosis and that genetic and pharmacological inhibition of these cells is sufficient to block tumor growth. | 18,984,150 |
The MatP/matS site-specific system organizes the terminus region of the E. coli chromosome into a macrodomain. | The organization of the Escherichia coli chromosome into insulated macrodomains influences the segregation of sister chromatids and the mobility of chromosomal DNA. Here, we report that organization of the Terminus region (Ter) into a macrodomain relies on the presence of a 13 bp motif called matS repeated 23 times in the 800-kb-long domain. matS sites are the main targets in the E. coli chromosome of a newly identified protein designated MatP. MatP accumulates in the cell as a discrete focus that colocalizes with the Ter macrodomain. The effects of MatP inactivation reveal its role as main organizer of the Ter macrodomain: in the absence of MatP, DNA is less compacted, the mobility of markers is increased, and segregation of Ter macrodomain occurs early in the cell cycle. Our results indicate that a specific organizational system is required in the Terminus region for bacterial chromosome management during the cell cycle. | 18,984,159 |
Clinical characteristics of external auditory canal cholesteatoma in children. | The purpose of this study was to investigate the characteristics of pediatric external auditory canal cholesteatoma (EACC). Chart review of nine children with EACC between January 1, 2000 and December 31, 2007 was performed with subsequent analysis of etiologic factors, associated symptoms, otoscopic findings, imaging features, and treatment outcomes. The average age of patients was 10.3 years (range 6-15 years). Five patients were girls and four were boys. There was greater incidence of EACC on the right side (eight of nine patients). Otorrhea and hearing impairment were the most common presenting symptoms. The inferior wall of the external auditory canal was most commonly involved. Five patients underwent cholesteatoma removal under general anesthesia. Surgical procedures were performed in four patients. No recurrence except in one patient was found during the follow-up period. Pediatric EACC is reported as a rare condition, but its low occurrence may be due to underreporting. Early diagnosis and treatment is essential in the management of pediatric EACC. | 18,984,260 |
Relationship between voice quality and vocal nodule size. | To determine the effect of vocal nodule size on voice in pediatric patients. Vocal nodules were graded according to a validated grading scale by three pediatric otolaryngologists. Patients evaluated from 2003 to 2007 with a diagnosis of vocal nodules were included. Forty patients (21 female) with a mean age of 7.5 years were identified. Vocal nodules were rated as grade 1 (17 patients), grade 2 (15 patients), and grade 3 (8 patients). Pitch range was reduced in patients with larger nodules (P = 0.001). There was no statistical association between nodule grade and fundamental frequency abnormality, perturbation, shimmer, decreased respiratory support, air loss, or significant muscle tension. Voice characteristics in patients with vocal nodules were evaluated. Other than pitch reduction, objective and subjective voice measurements are not statistically different in varying vocal nodule sizes; however, many of the measures did show a trend towards significance. Vocal rehabilitation is complex in children with nodules and may not directly correlate with vocal nodule size. | 18,984,271 |
Foreign-body reaction to the Artelon CMC joint spacer: case report. | The Artelon CMC spacer (Small Bone Innovations, Inc., Morrisville, PA) is a relatively new device that was developed for the treatment of basal joint arthritis. It is composed of a biodegradable polycaprolactone-based polyurethane urea that acts to resurface the distal part of the trapezium and stabilize the trapeziometacarpal joint by augmenting the joint capsule. This is a case report of a foreign-body tissue reaction to the Artelon CMC spacer. | 18,984,346 |
Chronic Mycobacterium infection of first dorsal web space after accidental Bacilli Calmette-Guérin injection in a health worker: case report. | We present a case of inoculation of the first dorsal web space by a nurse practitioner who accidentally stuck herself while preparing Bacilli Calmette-Guérin vaccine for treatment of bladder tumor. We report the evolution and management of this resistant chronic Mycobacterium infection that ultimately required use of a vacuum wound management system followed by a microvascular free tissue transfer. | 18,984,347 |
Clinical considerations in the treatment of acne vulgaris and other inflammatory skin disorders: a status report. | This article reviews the anti-inflammatory and nonantimicrobial effects of antibiotics in acne and other diseases and examines issues relating to the emergence of decreased bacterial sensitivity to antibiotics and how these issues relate to clinical practice. It includes an overview of the inflammatory activities of some antibiotic agents and their potential for use in various dermatologic and nondermatologic diseases. It demonstrates that P. acnes-resistant organisms may be associated with therapeutic failure in some patients with acne, and that the prudent use of antibiotics is necessary to ensure that we can continue to use these drugs to combat disease effectively. It concludes that there are treatment strategies that can effectively minimize the potential for development of resistant P. acnes organisms. | 18,984,363 |
Use of antibiotics for noninfectious dermatologic disorders. | One fascinating element of medical dermatology is the diversity of available therapeutic agents, and dermatologists are well versed in applying the mechanism of action of a drug to modify a disease process. Oral antibiotics are the ideal example of pharmacologic agents that are effective against inflammatory processes and have obvious roles in infectious diseases. | 18,984,371 |
Medical management of hip fracture. | The United States population at the greatest risk for hip fracture, those aged 65 years and older, is steadily increasing in size. Today, the incidence of hip fracture is approximately 250,000 per year and it is expected to double in the next 30 years. Hip fracture patients are comorbid at baseline, and there are complications inherent to hip fractures that can occur in almost a predictable fashion. Overall, one in four hip fracture patients will die within one year of injury. Medical comanagement of hip fracture patients offers the best chance for successful outcome. | 18,984,382 |
Impact of orthodontic appliances on sleep quality. | Many young patients are asked to wear headgear or functional appliances during sleep as part of their orthodontic treatment. The objective of this clinical study was to assess the impact of these appliances on sleep quality. Twenty-two subjects (8 boys, 14 girls) between 10 and 15 years of age wearing either a headgear or a removable appliance for 3 to 12 months were enrolled in a sleep study. Each subject participated in 2 overnight sleep studies with and without the appliance. There was a 1-week interval after an adaptation night. The studies were performed at the Sleep Research Laboratory at Toronto Western Hospital in Canada. Each subject served as his or her own control. Twelve subjects had an extraoral headgear appliance, and 10 had intraoral functional (5 Fränkel, 5 Twin-block) appliances. No subject reported any sleep or medical disorder. The primary outcome variable was sleep efficiency. Sleep efficiencies were 90.7% (SD, 7.9) and 91.6% (SD, 4.3) with and without the appliances, respectively. When sleep quality was compared with and without appliances, analysis of variance (ANOVA) showed no significant difference in sleep efficiency or other sleep variables such as sleep onset latency, rapid eye movement onset latency, rapid eye movement percentage, short-wave sleep percentage, or respiratory disturbance index. Sex and body mass index were not confounding variables. In addition, the use of extraoral or intraoral appliances did not affect sleep quality. In young orthodontic patients, there appears to be no difference in sleep quality with or without the overnight use of these appliances after they have been worn for a minimum of 3 months. | 18,984,392 |
Comparison of treatment outcomes between skeletal anchorage and extraoral anchorage in adults with maxillary dentoalveolar protrusion. | The goal of this retrospective cephalometric study was to compare orthodontic outcomes in patients with maxillary dentoalveolar protrusion malocclusion treated with extraoral headgear or mini-implants for maximum anchorage. Forty-seven subjects with Angle Class II malocclusion or Class I bimaxillary dentoalveolar protrusion were treated by retracting the maxillary dentoalveolar process by using the extraction space of the bilateral maxillary first premolars. Two anchorage systems were used. Group 1 (n = 22) received traditional anchorage preparation with a transpalatal arch and headgear; group 2 (n = 25) received mini-implants (miniplates, miniscrews, or microscrews) for bony anchorage. Pretreatment and posttreatment lateral cephalograms were superimposed to compare the following parameters between groups: (1) amount of maxillary central incisor retraction, (2) reduction in maxillary central incisor angulation, (3) anchorage loss of the maxillary first molar, (4) movements of the maxillary central incisor and first molar in the vertical direction, and (5) changes in skeletal measurements representing the anteroposterior and vertical jaw relationships. The skeletal anchorage group had greater anterior tooth retraction (8.17 vs 6.73 mm) and less maxillary molar mesialization (0.88 vs 2.07 mm) than did the headgear group, with a shorter treatment duration (29.81 vs 32.29 months). Translational movement of the incisors was more common than tipping movement, and intrusion of the maxillary dentition was greater, in patients receiving miniplates than in those receiving screw-type bony anchorage, resulting in counterclockwise rotation of the mandible and a statistically significant decrease in the mandibular plane angle. Cephalometric analysis of skeletal measurements in patients with low to average mandibular plane angles showed no significant difference between groups, although greater maxillary incisor retraction and less mesial movement of the first molar were noted in the mini-implant group. In patients with a high mandibular plane angle, those receiving skeletal anchorage had genuine intrusion of the maxillary first molar and reduction in the mandibular plane angle, whereas those receiving headgear anchorage had extrusion of the maxillary first molar and an increase of mandibular plane angle. In contrast to the posterior movement in the headgear group, anterior movement of Point A was noted in the mini-implant group. In both the anteroposterior and vertical directions, skeletal anchorage achieved better control than did the traditional headgear appliance during the treatment of maxillary dentoalveolar protrusion. Greater retraction of the maxillary incisor, less anchorage loss of the maxillary first molar, and the possibility of counterclockwise mandibular rotation all facilitated the correction of the Class II malocclusion. | 18,984,393 |
Bicortical vs monocortical orthodontic skeletal anchorage. | Case reports have documented the use of titanium miniscrews in providing skeletal anchorage for orthodontic tooth movement. Success rates as low as 50% have been reported for screw retention in either the facial or the lingual cortical plates (monocortical placement). The purpose of this in-vitro study was to test the hypothesis that bicortical miniscrew placement (across the entire width of the alveolus) gives the orthodontist superior force resistance and stability (anchorage) compared with monocortical placement. Forty-four titanium alloy screws, 1.5 x 15.0 mm, were placed in 22 hemi-sected maxillae and mandibular specimens between the first and second premolars. Half were placed monocortically, half were placed bicortically, and all were subjected to tangential force loading perpendicular to the miniscrew through a lateral displacement of 1.5 mm. Bone samples were sectioned and bone thickness at the screw sites measured. Statistical analyses, consisting of paired samples t tests, 2-samples t tests, Spearman rank correlation tests, and Fisher exact tests, were used to compare monocortical with bicortical screw force-deflection characteristics and stability. Additionally, 2-dimensional plane-stress finite-element models of bicortical and monocortical screw placement subjected to similar loading were analyzed. As hypothesized, deflection force values were significantly greater for bicortical screws than for monocortical screws placed in both the maxilla and the mandible (P <0.01 in each instance). Furthermore, force values at mandibular sites were significantly greater than those at maxillary sites for both types of screws. No significant differences in deflection force values were found between the right and left sides of the jaws, or between coronal and apical alveolar-process screw positions. A significant increasing relationship was found between mandibular buccal bone thickness and deflection force for monocortical screws only, and no relationship was found between maxillary bone thickness and deflection force for monocortical or bicortical screws. Monocortical screws were significantly more mobile after force application than bicortical screws. Finite-element analysis indicated lower cortical bone stresses with bicortical placement than with monocortical placement, and these results were consistent with in-vitro experimental findings. Bicortical miniscrews provide the orthodontist superior anchorage resistance, reduced cortical bone stress, and superior stability compared with monocortical screws. | 18,984,394 |
Gingival recession in young adults: occurrence, severity, and relationship to past orthodontic treatment and oral piercing. | Gingival recession can be localized or generalized and associated with at least 1 tooth surface. As a result, gingival recession leads to root surface exposure, often causing esthetic impairment, fear of tooth loss, increased susceptibility for root caries, and dentin hypersensitivity. The prevalence, extent, and severity of gingival recession in a young adult Israeli population were evaluated, and the relationship between orthodontic therapy and other potential risk indicators and gingival recession was assessed. Our cohort included 303 consecutive healthy patients who had routine dental examinations at a military dental center. Information was collected regarding age, smoking habits, oral piercing, oral hygiene habits, and past orthodontic treatment. Clinical examination included visible gingival inflammation, visible dental plaque, and gingival recession on the facial aspects of all teeth. Gingival recession was found in 14.6% of the subjects and in 1.6% of all examined teeth. The prevalence, extent, and severity of recession correlated with past orthodontic treatment. A negative correlation was found between plaque on the buccal tooth aspect and gingival recession. There was no correlation between gingivitis or smoking habits and recession. Prevalence was related to oral piercing. Gingival recession is not uncommon in young adults and is related to past orthodontic treatment and oral piercing. Patients undergoing orthodontic treatment or about to pierce the tongue or lips should be advised regarding these findings. | 18,984,397 |
Growth and development of the cranial base in mice that spontaneously develop anterior transverse crossbite. | Homozygous brachymorphic (bm/bm) mice are characterized by disproportionately short stature. Anterior transverse crossbite sometimes develops spontaneously in inbred BALB/c-bm/bm mice that produce undersulfated glycosaminoglycans. The reason for inferior growth of the craniofacial structures of BALB/c-bm/bm mice has not been clarified. We focused on the spheno-occipital synchondrosis (SOS)-the growth site of the cranium-and investigated the growth pattern in the SOS of the BALB/c-bm/bm mice. The BALB/c-+/+ mice and BALB/c-bm/bm mice without malocclusion were used. Sagittal sections of the cranial bases were stained with hematoxylin and eosin, observed histologically, and used to measure the anteroposterior length and the percentage of active bone volume around the SOS. In the histologic study, compared with the cartilage in the BALB/c mice, a bipolar column was not seen in the cartilage of the SOS in the BALB/c-bm/bm mice. The histomorphometric study showed that the anteroposterior length of the posterior cranial base was significantly shorter and the percentage of active bone volume was significantly smaller in the BALB/c-bm/bm mice than in the BALB/c mice. The results suggested that normal endochondral growth is disturbed in the synchondrosis of the posterior base of the skull in BALB/c-bm/bm mice. | 18,984,401 |
Orthodontics in 3 millennia. Chapter 15: Skeletal anchorage. | For many years, orthodontists have searched for a form of anchorage that does not rely on patient cooperation, although the answer already lay in the implants dentists used to replace missing teeth and oral surgeons used to hold bone segments together. Now these divergent lines have come together in the form of stationary anchorage, and titanium is the most biocompatible material. State-of-the-art miniscrews and microscrews--temporary anchorage devices--now permit movements hitherto thought difficult or impossible. This article continues the series last published in April 2007. | 18,984,405 |
Role of nuclear scintigraphy in the characterization and management of the salivary component of Sjögren's syndrome. | The American-European Consensus Group, in its classification criteria of Sjögren's syndrome (SS), consigns dynamic salivary scintigraphy to providing objective evidence of xerostomia, a secondary role. In the current SS therapeutic environment, scintigraphy's ability to differentiate parenchymal damage from neuropathic or other derangements of the salivary apparatus may prove more valuable than its role as a diagnostic modality. The procedure itself is highly process-dependent and its discriminatory power task-dependent. A multiplicity of data collection protocols and interpretative approaches tends to corrode the validity of its diagnostic information. Salivary scintigraphy's clinical utility might be extended by standardization of its test protocol and uniformity in its interpretative algorithms. | 18,984,416 |
A risk score to predict intracranial hemorrhage after recombinant tissue plasminogen activator for acute ischemic stroke. | Ability to predict risk of postthrombolysis intracerebral hemorrhage (ICH) is currently limited. Using data from the Multicenter Recombinant Tissue Plasminogen Activator Stroke Survey Group, we developed a score to predict this risk. One point was assigned for the presence of each of 4 variables: age older than 60 years, baseline National Institutes of Health Stroke Scale score greater than 10, glucose greater than 8.325 mmol/L, and platelet count less than 150,000/mm(3). Rate of any ICH increased with higher scores: 0 points, 2.6%; 1 point, 9.7%; 2 points, 15.1%; and greater than or equal to 3 points, 37.9%. The model had reasonable discriminatory capability (C-statistic 0.69). A similar pattern was seen with symptomatic and asymptomatic ICH separately, and with radiographically defined parenchymal hemorrhage. A simple risk score may be useful for predicting postthrombolysis ICH. | 18,984,422 |
The effects of study participation in the Familial Intracranial Aneurysm Study on cigarette smoking. | Cigarette smoking is the most modifiable risk factor for the formation and rupture of intracranial aneurysm (IA). This study examined the impact of participation in the Familial IA study on smoking behavior. On entry into the study, a baseline smoking history was obtained. At follow-up visits, subjects were surveyed concerning their current smoking status. Risk reduction education was site specific and the study did not include a standard approach. Of participants, 66% had a history of cigarette smoking, with 33.1% being current smokers. There was a significant reduction in the proportion of current smokers by the third yearly follow-up visit (26.7%, P < .001). There was a significant reduction in the daily amount of cigarettes smoked (17.7-11.5, P < .001), with the most significant reduction at the first follow-up visit. Current smokers given the diagnosis of an IA before entry or during the course of the study were more likely to decrease their smoking (19.4-9.8 cigarettes/day, P < .001) than those not given a diagnosis of an IA (16.0-13.3, P = .002). Individuals older then 51 years had a greater reduction in the amount of cigarettes smoked per day compared with those younger than 51 years (2.3 cigarettes/day reduction v 1.5, P = .002). Subjects who entered into the Familial IA study had a significant decrease in their smoking by the end of 3 years. Factors associated with decreased smoking were diagnosis of IA and older age. | 18,984,429 |
Asymptomatic large T2 high-signal pontine lesions that are different from ischemic rarefaction. | We encountered asymptomatic large T2 high-signal pontine lesion (PL) with peachlike configurations on magnetic resonance imaging. The objective of this study was to determine the pathogenic factors for such PLs and to differentiate PL from ischemic rarefaction. We compared the clinical backgrounds of 37 patients with PL and 100 patients without PL, including conventional atherosclerotic risk factors, chronic kidney disease (CKD) defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(3), and the degree of supratentorial deep white matter hyperintensities (DWMH). The chronologic alternations in PL were also reviewed. Patients with PL had a much higher incidence of diabetes mellitus (DM) and CKD as compared with patients without PL: 54% versus 15% for DM (P < .001) and 57% versus 29% for CKD (P < .05). PL did not necessarily accompany DWMH and its degree did not correlate with PL. Further analyses showed that patients with PL without DWMH had a much higher incidence of DM and CKD as compared with patients with DWMH without PL: 85% versus 6% for DM (P < .0001) and 85% versus 50% for CKD (P < .05). Chronologically, PLs expanded, shrunk, or fluctuated in size in 5 patients with DM and CKD. We demonstrated that DM and CKD are important for PL and that the backgrounds of PL were inconsistent with DWMH. These results and the chronologic alternations in PL suggested that metabolic factors other than ischemic rarefaction played important roles in the development of PL. | 18,984,434 |
Erectile dysfunction as a coronary artery disease risk equivalent. | The conditions that predispose patients to erectile dysfunction are substantially similar to the coronary artery disease risk factors, including diabetes mellitus, hypertension, hyperlipidemia, obesity, sedentary lifestyle, depression, age, and smoking. Because of these shared risks and overlapping pathophysiologic mechanisms, we designed this pilot study to address the hypothesis that the presence of coronary artery calcium, a known indicator of increased cardiac risk, is associated with erectile dysfunction. A prospective registry enrolled 9150 men who underwent multidetector computed tomography. Subjects supplied baseline data regarding demographic variables, coronary risk factors, and erectile dysfunction symptoms or lack thereof. The 2 groups then underwent computed tomography to screen for the presence or absence of coronary artery calcium. Subjects with erectile dysfunction were older, had higher triglyceride levels, had higher blood pressures, and were more likely to have measurable coronary artery calcification than men without erectile dysfunction (79% vs 58%, P < .001). Erectile dysfunction is significantly associated with abnormal coronary artery calcification and, like peripheral arterial disease, might warrant consideration as a coronary artery disease risk equivalent. | 18,984,455 |
PET detection of the impact of dobutamine on myocardial glucose metabolism in women with type 1 diabetes mellitus. | Our objective was to determine, in the hearts of women with type 1 diabetes mellitus (T1DM), whether the fate of extracted glucose is altered and, if so, what the impact of dobutamine is on myocardial substrate metabolism. In experimental models of T1DM, myocardial glycolysis and glucose oxidation are reduced with the impairment becoming more pronounced with dobutamine. Whether similar changes occur in humans with T1DM is unclear. Myocardial perfusion, oxygen consumption, and glucose and fatty acid metabolism were measured with positron emission tomography in 19 women, 7 normal volunteers (NVs) and 12 with T1DM. The NVs and 6 T1DM (DM1) patients were studied under baseline metabolic conditions and 6 T1DM patients were studied during hyperinsulinemic-euglycemic clamp (DM1-C), both at rest and during dobutamine. At rest, myocardial glucose uptake, glycolysis, glycogen storage, and oxidation were reduced by similar levels in DM1 patients compared with NVs (P < .05). During dobutamine, although myocardial glucose uptake was not different from DM1 patients at rest, fractional glycolysis was lower compared with NVs or DM1-C patients and reflected a lower glucose oxidation rate (P < .001). Measurements of myocardial glucose metabolism at rest and during dobutamine were comparable between NVs and DM1-C patients. During dobutamine, myocardial fatty acid uptake and oxidation increased in all 3 groups. In women with T1DM, (1) myocardial glucose metabolism is impaired downstream from initial uptake, (2) these abnormalities become more pronounced with dobutamine and are paralleled by an increase in myocardial fatty acid metabolism, and (3) insulin restores glucose metabolism to levels observed in normal control subjects. | 18,984,454 |
Noninvasive assessment of liver fibrosis: serum markers, imaging, and other modalities. | Liver fibrosis is a common pathway of injury after chronic insult to the liver. The evolution of liver fibrosis to cirrhosis has many clinical implications, including bleeding, infection, hepatocellular carcinoma, and death. The reference standard for diagnosing liver fibrosis is currently histologic assessment of tissue obtained through liver biopsy. Although this provides valuable information, it has limitations, including its invasiveness, sampling error, observer variability, and the use of categorical scoring systems. This article outlines the various noninvasive markers, including blood tests, imaging, and novel technologies. It examines the principles behind their development, their diagnostic accuracy, and their evolution. | 18,984,472 |
Current and future anti-fibrotic therapies for chronic liver disease. | Chronic injury results in a wound healing response that eventually leads to fibrosis. The response is generalized, with features common among multiple organ systems. In the liver, various different types of injury lead to fibrogenesis, implying a common pathogenesis. Although several specific therapies for patients who have different liver diseases have been successfully developed, including antiviral therapies for those who have hepatitis B and hepatitis C virus infection, specific and effective antifibrotic therapy remains elusive. Over the past 2 decades, great advances in the understanding of fibrosis have been made and multiple mechanisms underlying hepatic fibrogenesis uncovered. Elucidation of these mechanisms has been of fundamental importance in highlighting novel potential therapies. Preclinical studies have indicated several putative therapies that might abrogate fibrogenesis. This article emphasizes mechanisms underlying fibrogenesis and reviews available and future therapeutics. | 18,984,475 |
Imported infectious diseases and surveillance in Japan. | Surveillance of imported infectious diseases is important because of the need for early detection of outbreaks of international concern as well as information of risk to the travelers. This paper attempts to review how the Japanese surveillance system deals with imported infectious diseases and reviews the trend of these diseases. The cases of acquired infection overseas were extracted from the surveillance data in 1999-2008. The incidence and rate of imported cases of a series of infectious diseases with more than one imported case were observed by the year of diagnosis and place of acquired infection. During the period 10,030 cases that could be considered to be imported infectious diseases were identified. Shigellosis ranked as the most common imported disease, followed by amebiasis, malaria, enterohemorrhagic Escherichia coli infection and the acquired immunodeficiency syndrome, typhoid fever, dengue fever, hepatitis A, giardiasis, cholera, and paratyphoid fever. The annual trends of these diseases always fluctuated but not every change was investigated. The study reveals that the situation of imported infectious diseases can be identified in the current Japanese surveillance system with epidemiologic features of both temporal and geographic distribution of cases of imported infectious diseases. However, further timely investigation for unusual increase in infectious diseases is needed. | 18,984,479 |
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