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Nonspecific
Terms modified by Nonspecific Selected AbstractsChange in Psychotherapy: A Plea for No More "Nonspecific" and False DichotomiesCLINICAL PSYCHOLOGY: SCIENCE AND PRACTICE, Issue 2 2005Louis G. Castonguay What factors are responsible for change in psychotherapy? We welcome those who question the primacy frequently given to relationship variables in explaining client improvement, as well as the delineation of cognitive-behavioral oriented treatments found to be effective for several disorders. However, we are also concerned about the terminology used (i.e., "nonspecific variables"), as well as with the dichotomy of variables (techniques vs. relationship) that was emphasized. Although such ways of defining and categorizing process variables are predominant in the field, we argue that they may fail to do justice to the complexity of the process of change. [source] Child sexual abuse in the etiology of depression: A systematic review of reviewsDEPRESSION AND ANXIETY, Issue 7 2010Roberto Maniglio Psy.D. Ph.D. Abstract Background: Despite a large amount of research, there is considerable controversy about the role that child sexual abuse plays in the etiology of depression. To prevent interpretative difficulties, mistaken beliefs, or confusion among professionals who turn to this literature for guidance, this article addresses the best available scientific evidence on the topic, by providing a systematic review of the several reviews that have investigated the literature on the issue. Methods: Seven databases were searched, supplemented with hand search of reference lists from retrieved papers. The author and a psychiatrist independently evaluated the eligibility of all studies identified, abstracted data, and assessed study quality. Disagreements were resolved by consensus. Results: Four reviews, including about 60,000 subjects from 160 studies and having no limitations that could invalidate their results, were analyzed. There is evidence that child sexual abuse is a significant, although general and nonspecific, risk factor for depression. The relationship ranges from small-to-medium in magnitude and is moderated by sample source. Additional variables may either act independently to promote depression in people with a history of sexual abuse or interact with such traumatic experience to increase the likelihood of depression in child abuse survivors. Conclusions: For all victims of abuse, programs should focus not only on treating symptoms, but also on reducing additional risk factors. Depressed adults who seek psychiatric treatment should be enquired about early abuse within admission procedures. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source] The use of neuroimaging in the diagnosis of mitochondrial diseaseDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2010Seth D. Friedman Abstract Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:129,135. [source] Temperature perception and nociceptionDEVELOPMENTAL NEUROBIOLOGY, Issue 1 2004Barry G. Green Abstract The specificity theory of somesthesis holds that perceptions of warmth, cold, and pain are served by separate senses. Although no longer accepted in all its details, the theory's basic assumptions of anatomical and functional specificity have remained guiding principles in research on temperature perception and its relationship to pain. This article reviews the response characteristics of thermoreceptors, temperature-sensitive nociceptors, and their associated pathways in the context of old and new perceptual phenomena, most of which cannot be satisfactorily explained by the specificity theory. The evidence indicates that throughout most of the perceptual range, temperature sensitivity depends upon coactivation of, and interactions among, thermal and nociceptive pathways that are composed of both specific "labeled lines" and nonspecific, multimodal fibers. Adding to this complexity is evidence that tactile stimulation can influence the way in which thermal stimulation is perceived. It is argued that thermoreception is best defined as a functional subsystem of somesthesis that serves the very different and sometimes conflicting demands of thermoregulation, protection from thermal injury, and haptic perception. © 2004 Wiley Periodicals, Inc. J Neurobiol 61: 13,29, 2004 [source] Pancreatic mucinous lesions: A retrospective analysis with cytohistological correlationDIAGNOSTIC CYTOPATHOLOGY, Issue 11 2006Jing Zhai M.D., Ph.D. Abstract The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples. A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation. The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions. Diagn. Cytopathol. 2006;34: 724,730. © 2006 Wiley-Liss, Inc. [source] Cadmium tolerance in the Nile tilapia (Oreochromis niloticus) following acute exposure: Assessment of some ionoregulatory parametersENVIRONMENTAL TOXICOLOGY, Issue 1 2006Sofia Garcia-Santos Abstract The Nile tilapia (Oreochromis niloticus) can tolerate very high levels of waterborne cadmium. It has one of the highest 96 h LC50 recorded for a freshwater teleost fish (14.8 mg/L Cd; hardness 50 mg/L CaCO3). Cadmium is known to perturb ion balance in teleost fishes. However, in an acute time course experiment, plasma Na+ concentrations were unaffected, and plasma Ca2+ values only decreased after 96 h exposure in a dose-independent manner. Branchial Na+/K+ -ATPase activity and ,-subunit protein level expression in crude gill homogenates were not affected by Cd exposure during this period. Branchial chloride cell numbers, identified as Na+/K+ -ATPase immunoreactive cells using immunohistochemistry, decreased 24 h after exposure but recovered thereafter. Histopathological changes did not follow a consistent pattern of variation with exposure time, and the alterations noted in gill epithelium were basically nonspecific to cadmium. Because of its tolerance, it can be concluded that the tilapia O. niloticus would not be a suitable test organism to evaluate sublethal toxicity of cadmium and the realistic impact of this pollutant in the environment. However, it certainly could contribute significantly to our understanding of the toxic mechanism of cadmium exposure in aquatic organisms. This is the first work to investigate the effect of waterborne pollutants on Na+/K+ -ATPase ,-subunit protein expression in fish gills. © 2006 Wiley Periodicals, Inc. Environ Toxicol 21: 33,46, 2006. [source] Detection of EHV-1 and EHV-4 in placental sections of naturally occurring EHV-1- and EHV-4-related abortions in the UK: use of the placenta in diagnosisEQUINE VETERINARY JOURNAL, Issue 5 2003S. GERST Summary Reasons for performing study: EHV-1 and EHV-4 abortion diagnosis is based upon detailed examination of the aborted fetus. However, in some cases, only the placenta is available for examination. Furthermore, the contribution of lesions in the placenta to pathogenesis and diagnosis of EHV-1 and EHV-4 abortion has been neglected. Objectives: To assess the utility of placental examination in equine herpesvirus-1 (EHV-1) and EHV-4 abortion diagnosis. Methods: Sections of allantochorion from 49 herpesvirus abortions were analysed by PCR, in situ hybridisation and immunostaining. Results: Virus-specific nested PCR confirmed the presence of viral DNA in 46 cases; 41 cases were EHV-1-positive and 5 EHV-4-positive. Microscopic changes were nonspecific. Examination of the PCR-positive sections of allantochorion revealed EHV-1 DNA by in situ hybridisation (ISH) in 21 cases and EHV-4 in 4 cases. In 2 samples, DNA of both viruses was present on PCR and ISH. Viral antigen was found by immunohistology in 15 cases. Regarding the localisation of virus in the placentae, both viral DNA and antigen of EHV-1 and EHV-4 were found in endothelial cells of chorionic villi and, occasionally, in trophoblast epithelium. In the stromal endothelium, only EHV-1 was found. Conclusions: The data indicate that examination of placentae is a useful diagnostic aid in EHV-1 and EHV-4 abortion diagnosis. Potential relevance: Virological examination of the placenta should be come standard practice in equine abortion investigations, particularly in those cases where the fetus is not available for examination. [source] Gemcitabine-induced severe pulmonary toxicityFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2004Fabrice Barlési Abstract Gemcitabine is a relatively new deoxycytidine analog (2,,2,-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C). Activity of gemcitabine is demonstrated in the treatment of many solid tumors, like pancreas, ovarian and nonsmall cell lung cancer (NSCLC). Although gemcitabine is considered as a drug with a good safety profile, cases of gemcitabine-induced severe pulmonary toxicity (GISPT) were reported as for Ara-C. We performed a systematic review of reported cases on the GISPT. Twenty-nine clinical trials especially interesting NSCLC patients (21) and 21 reported cases recording 40 patients were analyzed. The incidence of the GISPT varies from 0 to 5%. The clinical presentation is a subacute clinical syndrome and is frequently nonspecific. The predominant radiographic pattern on chest X-ray are reticulo-nodular interstitial infiltrates. It was postulated that the physio-pathological mechanism of the GISPT was an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which created an abnormal permeability of its membrane. After the differential diagnosis were ruled out, the discontinuation of the drug and the early initiation of steroids and diuretics are the most frequently performed treatments. Under these conditions, the outcome was favorable in a delay of few days generally for a majority of patients but 20% of patients died. Some risk factors, as a previous pulmonary disease or a previous thoracic irradiation, for the occurrence of the GISPT were proposed. GISPT is rare but sometimes fatal. Its a necessity to increase awareness about it to enhanced an early and suitable management of patients developing such a toxicity after gemcitabine administration. [source] Hypnic Headache Associated With Stage 3 Slow Wave SleepHEADACHE, Issue 9 2000José Antonio Molina Arjona MD We describe the polysomnographic data of a 79-year-old woman with an 11-year history of nocturnal headaches that were clinically consistent with hypnic headache. A polysomnographic study showed arousal at stage 3 slow wave sleep because of a headache episode. Although this finding could be nonspecific, it suggests the possible relationship between stage 3 slow wave sleep and hypnic headache. [source] Melatonin and ulcerative colitis: Evidence, biological mechanisms, and future researchINFLAMMATORY BOWEL DISEASES, Issue 1 2009Paul D. Terry PhD Abstract Ulcerative colitis (UC) is an inflammatory bowel disease that afflicts up to 1 million people in the US. Current treatments for UC are mostly nonspecific, not always effective, and often accompanied by serious side effects. Therefore, there is considerable interest in finding alternative and more tolerable treatments for this disease. Physiologic data suggest that melatonin is an important regulator of both inflammation and motility in the gastrointestinal tract, and data from in vitro studies, animal experiments, and limited studies in humans suggest that supplemental melatonin may have an ameliorative effect on colitis. In this review we summarize the evidence regarding melatonin as a possible therapeutic agent in UC and discuss possible biological mechanisms and directions for future research. (Inflamm Bowel Dis 2008) [source] Small bowel adenocarcinoma in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 8 2008Richard C. Feldstein MD Abstract Small bowel neoplastic disease is a rare but dreaded occurrence in Crohn's disease (CD) and the diagnosis is often disguised by nonspecific and varied presenting symptoms mimicking active or obstructive CD. As such, the diagnosis is all too often delayed, typically detected at a late stage, and with a poor prognosis. CD has become a well-recognized risk factor for the development of small bowel adenocarcinoma. The data, however, are limited and based on case reports, retrospective studies, and review of the literature. (Inflamm Bowel Dis 2008) [source] Oxidation of substituted benzaldehydes by quinolinium chlorochromate: A structure and solvent dependent kinetic studyINTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2003G. Fatima Jeyanthi The kinetics of oxidation of several para-substituted benzaldehydes by quinolinium chlorochromate was studied under pseudo-first-order conditions in different (hydrogen bond donor and hydrogen bond acceptor) neat organic solvents. The operation of nonspecific and specific solvent,solvent,solute interactions was explored by correlating the rate data with solvent parameters through correlation analysis. Both electron-releasing and electron-withdrawing substituents enhanced the rate and the Hammett plot showed a break in the reactivity order indicating applicability of dual mechanism. An explanation in conformity with structure and solvent effects on reactivity has been proposed. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 35: 154,158, 2003 [source] Fabry Disease: Treatment and diagnosisIUBMB LIFE, Issue 11 2009Paula A. Rozenfeld Abstract Fabry disease is an X-linked lysosomal disorder that results from a deficiency of the lysosomal enzyme ,-galactosidase A leading to accumulation of glycolipids, mainly globotriaosylceramide in the cells from different tissues. Classical Fabry disease affects various organs. Clinical manifestations start at early age and include angiokeratoma, acroparesthesia, hypohydrosis, heat/exercise intolerance, gastrointestinal pain, diarrhea, and fever. The main complications of Fabry disease are more prominent after the age of 30 when kidney, heart, and/or cerebrovascular disorders appear. Most of the heterozygous females are symptomatic. Enzyme replacement therapy (ERT) is the only specific treatment for Fabry disease. The beneficial effect of ERT on different organs/systems has been extensively evaluated. Quality of life of patients receiving ERT is improved. Enzyme replacement stabilizes or slows the decline in renal function and reduces left ventricular hypertrophy. Fabry disease may be underdiagnosed because of nonspecific and multiorgan symptoms. Different screening strategies have been carried out in different at-risk populations in order to detect undiagnosed Fabry patients. An increasing knowledge about Fabry disease within the medical community increases the chances of patients to receive a timely diagnosis and, consequently, to access the appropriate therapy. © 2009 IUBMB IUBMB Life, 61(11): 1043,1050, 2009 [source] Placebo psychotherapy: Synonym or oxymoron?JOURNAL OF CLINICAL PSYCHOLOGY, Issue 7 2005Irving Kirsch Contrary to some recent claims, the placebo effect is real and in some cases very substantial. Placebo effects can be produced or enhanced by classical conditioning, but consistent with virtually all contemporary conditioning theories, these effects are generally mediated by expectancy. Expectancy can also produce placebo effects that are inconsistent with conditioning history. Although expectancy also plays an important role in psychotherapy outcome, the logic of placebo-controlled trials does not map well onto psychotherapy research. The idea of evaluating the efficacy of psychotherapy by controlling for nonspecific or placebo factors is based on a flawed analogy and should be abandoned. © 2005 Wiley Periodicals, Inc. J Clin Psychol 61: 791,803, 2005. [source] Fever of unknown origin in the elderlyJOURNAL OF INTERNAL MEDICINE, Issue 4 2002S. Tal Fever of unknown origin (FUO) means fever that does not resolve itself in the period expected for self-limited infection and whose cause cannot be ascertained despite considerable diagnostic efforts. The differential diagnosis is often different in older patients, and presentation of disease is frequently nonspecific and symptoms are difficult to interpret. Multisystem disease has emerged as the most frequent cause of FUO in the elderly, and temporal arteritis is the most frequent specific diagnosis. Infections, particular tuberculosis, remain an important group. FUO is often associated with treatable conditions in this age group. Early recognition and prompt initiation of appropriate empirical therapy are cornerstones of the strategy. [source] Lactate Detection by MRS in Mitochondrial Encephalopathy: Optimization of Technical ParametersJOURNAL OF NEUROIMAGING, Issue 1 2008Antônio José da Rocha MD ABSTRACT Mitochondriopathies are a heterogeneous group of diseases with variable phenotypic presentation, which can range from subclinical to lethal forms. They are related either to DNA mutations or nuclear-encoded mitochondrial genes that affect the integrity and function of these organelles, compromising adenosine triphosphate (ATP) synthesis. Magnetic resonance (MR) is the most important imaging technique to detect structural and metabolic brain abnormalities in mitochondriopathies, although in some cases these studies may present normal results, or the identified brain abnormalities may be nonspecific. Magnetic resonance spectroscopy (MRS) enables the detection of high cerebral lactate levels, even when the brain has normal appearance by conventional MR scans. MRS is a useful tool for the diagnosis of mitochondriopathies, but must be correlated with clinical, neurophysiological, biochemical, histological, and molecular data to corroborate the diagnosis. Our aim is to clarify the most relevant issues related to the use of MRS in order to optimize its technical parameters, improving its use in the diagnosis of mitochondriopathies, which is often a challenge. [source] A combinatorial approach to studying protein complex composition by employing size-exclusion chromatography and proteome analysisJOURNAL OF SEPARATION SCIENCE, JSS, Issue 10 2007Shi-Sheng Li Abstract The genome sequences of numerous organisms are available now, but gene sequences alone do not provide sufficient information to accurately deduce protein functions. Protein function is largely dependent on the association of multiple polypeptide chains into large structures with interacting subunits that regulate and support each other. Therefore, the mapping of protein interaction networks in a physiological context is conducive to deciphering protein functions, including those of hypothetical proteins. Although several high-throughput methods to globally identify protein interactions have been reported in recent years, these approaches often have a high rate of nonspecific or artificial interactions detected. For instance, the fraction of false positives of the protein interactions identified by yeast two-hybrid assay has been predicted to be of the order of 50%. We have developed a strategy to globally map Bacillus subtilis protein,protein interactions in a physiological context by fractionating the cell lysates using size-exclusion chromatography (SEC), followed by proteome analysis. Components of both known and unknown protein complexes, multisubunits and multiproteins, have been identified using this strategy. In one case, the partners of the B. subtilis protein complex have been coexpressed in Escherichia coli, and the formation of the overexpressed protein complex has been further confirmed by a pull-down assay. [source] Evaluation and Treatment of Hyperthyroidism and HypothyroidismJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 10 2004ANP-C, FAANP, Mary Jo Goolsby EdD ABSTRACT This month's clinical practice guideline (CPG) review is on the diagnosis and treatment of hyperthyroidism and hypothyroidism as provided by the American Association of Clinical Endocrinologists. An estimated 27 million Americans have thyroid disease, and about 13 million of them are undiagnosed. The risk of thyroid disease increases with age, and women are seven times more likely than men to develop thyroid problems. Unfortunately, thyroid symptoms are usually very nonspecific and should be kept in the differential diagnosis of many clinical complaints. The format of this month's column is a little different because we received two independent manuscripts, each of which had merit. We made a decision to present both points of view and deleted repetitive material. This is an example of variable approaches one can take with reviewing and critiquing CPGs. [source] Dietary Bovine Lactoferrin Increases Resistance of Juvenile Channel Catfish, Ictalurus punctatus, to Enteric SepticemiaJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 2010Thomas L. Welker Juvenile channel catfish, Ictalurus punctatus, were fed nutritionally complete, practical basal diets supplemented with bovine lactoferrin (Lf) at 0, 200, 400, 800, or 1600 mg/kg diet for 5 wk. Feed intake was significantly higher in fish-fed diets supplemented with Lf compared to the control diet, but the increased feed intake did not translate to significant increases in growth performance. Hemoglobin, white and red blood cell counts, and resistance to low-water stress also were not different among dietary groups (P > 0.05). Levels of Lf in diets had a significant effect on survival of channel catfish following challenge with Edwardsiella ictaluri: catfish fed 800 or 1600 mg/kg Lf had higher survival than the groups fed the control or 200 mg Lf diet. We established the break point minimum concentration of Lf for resistance to E. ictaluri infection as 1136 mg/kg. There was not a corresponding increase in activity of nonspecific or specific immune parameters with addition of Lf to diets, but plasma iron decreased significantly in channel catfish fed bovine Lf compared to the control group. However, no clear trend for level of dietary Lf, iron status, and resistance to E. ictaluri infection could be established. [source] Airway Mucus in Recurrent Airway Obstruction, Short-Term Response to Environmental ChallengeJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2004V. Gerber Mucus accumulation and neutrophilic inflammation in the airways are hallmarks of heaves. Endoscopically visible mucus accumulations, however, have not been studied during exposure to dusty hay and allergens (ie, environmental challenge). We hypothesized that (1) heaves-affected horses have increased mucus accumulation compared with controls, (2) mucus accumulations increase in heaves-affected horses during environmental challenge, and (3) environmental challenge also induces neutrophilic inflammation and mucus accumulation in control horses. Mucus accumulation was graded endoscopically (mucus grades [MGs] 1,5), and airway inflammation was evaluated by bronchoalveolar lavage fluid (BALF) cytology before (0 hours) and during (6, 24, 48 hours) environmental challenge. Large amounts of mucus (MG 4,5) were specific for heaves-affected horses in this study. Variation among controls was considerable, however, and intermediate grades (MG 2,3) were nonspecific, showing complete overlap between the 2 groups. Median mucus accumulations (25th, 75th percentiles) increased in heaves-affected horses from MG 2.5 (1.5, 3.5) at baseline to MG 3.5 (2.0, 4.0), 4.0 (3.0, 4.0), and 4.0 (4.0, 4.0) at 6, 24, and 48 hours, respectively. MG values did not increase in controls,overall MG 1.0 (1.0, 2.0),even though controls also showed a moderate increase of BALF neutro-phils. Mucus accumulations before and especially after exposure to dust and allergens are increased in heaves-affected horses compared with controls. Healthy controls show considerable variability in mucus accumulation but, despite an influx of neutrophils into the airways, no increase of mucus accumulation after exposure to hay dust. [source] Evaluation of Naranjo Adverse Drug Reactions Probability Scale in causality assessment of drug-induced liver injuryALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 9 2008M. GARCÍA-CORTÉS Summary Background, Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. Aim, To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Methods, Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (,w) test. Results, A total of 249 ratings were generated. Between-observer agreement was 45% with a ,w value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, ,w: 0.71). Concordance between the two scales was 24% (,w: 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. Conclusion, The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity. [source] Lipid bilayers: an essential environment for the understanding of membrane proteinsMAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2007Richard C. Page Abstract Membrane protein structure and function is critically dependent on the surrounding environment. Consequently, utilizing a membrane mimetic that adequately models the native membrane environment is essential. A range of membrane mimetics are available but none generates a better model of native aqueous, interfacial, and hydrocarbon core environments than synthetic lipid bilayers. Transmembrane ,-helices are very stable in lipid bilayers because of the low water content and low dielectric environment within the bilayer hydrocarbon core that strengthens intrahelical hydrogen bonds and hinders structural rearrangements within the transmembrane helices. Recent evidence from solid-state NMR spectroscopy illustrates that transmembrane ,-helices, both in peptides and full-length proteins, appear to be highly uniform based on the observation of resonance patterns in PISEMA spectra. Here, we quantitate for the first time through simulations what we mean by highly uniform structures. Indeed, helices in transmembrane peptides appear to have backbone torsion angles that are uniform within ± 4° . While individual helices can be structurally stable due to intrahelical hydrogen bonds, interhelical interactions within helical bundles can be weak and nonspecific, resulting in multiple packing arrangements. Some helical bundles have the capacity through their amino acid composition for hydrogen bonding and electrostatic interactions to stabilize the interhelical conformations and solid-state NMR data is shown here for both of these situations. Solid-state NMR spectroscopy is unique among the techniques capable of determining three-dimensional structures of proteins in that it provides the ability to characterize structurally the membrane proteins at very high resolution in liquid crystalline lipid bilayers. Copyright © 2007 John Wiley & Sons, Ltd. [source] Pulmonary arterial hypertension in childrenPEDIATRIC PULMONOLOGY, Issue 1 2004Erika Berman Rosenzweig MD Abstract Pulmonary arterial hypertension is a serious progressive condition with a poor prognosis if not identified and treated early. Because the symptoms are nonspecific and the physical findings can be subtle, the disease is often diagnosed in its later stages. Remarkable progress has been made in the field of pulmonary arterial hypertension over the past several decades. The pathology is now better defined, and significant advances have occurred in understanding the pathobiologic mechanisms. Risk factors have been identified, and the genetics have been characterized. Advances in technology allow earlier diagnosis as well as better assessment of disease severity. Therapeutic modalities such as new drugs, e.g., epoprostenol, treprostinil, and bosentan, and surgical/interventional options, e.g., transplantation and atrial septostomy, which were unavailable several decades ago, have had a significant impact on prognosis and outcome. Thus, despite our inability to cure pulmonary arterial hypertension, advances in medical treatments over the past two decades have resulted in significant improvement in outcomes for children with various forms of pulmonary arterial hypertension. This report is a review the current state of the art for pulmonary arterial hypertension in 2004, with an emphasis on childhood pulmonary arterial hypertension and specific recommendations for current practice and future directions. Pediatr Pulmonol. 2004; 38:2,22. © 2004 Wiley-Liss, Inc. [source] Erosive pustular dermatosis of the scalp: a successful treatment with photodynamic therapyPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2010Teresa Meyer Erosive pustular dermatosis of the scalp (EPDS) is a rare inflammatory disease of unknown aetiology that usually occurs in the elderly. It is characterized by sterile pustules, chronic crusted erosions, cicatricial alopecia, and skin atrophy. The histopathology is nonspecific, and its pathophysiology remains undetermined, with various types of local trauma possibly acting as the triggering factor. We describe a case of EPDS in a 75-year-old female in whom there was a marked response to photodynamic therapy with methyl 5-aminolaevulinic acid. [source] Multiple diverse ligands binding at a single protein site: A matter of pre-existing populationsPROTEIN SCIENCE, Issue 2 2002Buyong Ma Abstract Here, we comment on the steadily increasing body of data showing that proteins with specificity actually bind ligands of diverse shapes, sizes, and composition. Such a phenomenon is not surprising when one considers that binding is a dynamic process with populations in equilibrium and that the shape of the binding site is strongly influenced by the molecular partner. It derives implicitly from the concept of populations. All proteins, specific and nonspecific, exist in ensembles of substates. If the library of ligands in solution is large enough, favorably matching ligands with altered shapes and sizes can be expected to bind, with a redistribution of the protein populations. Point mutations at spatially distant sites may exert large conformational rearrangements and hinge effects, consistent with mutations away from the binding site leading to population shifts and (cross-)drug resistance. A similar effect is observed in protein superfamilies, in which different sequences with similar topologies display similar large-scale dynamic motions. The hinges are frequently at analogous sites, yet with different substrate specificity. Similar topologies yield similar conformational isomers, although with different distributions of population times, owing to the change in the conditions, that is, the change in the sequences. In turn, different distributions relate to binding of different sizes and shapes. Hence, the binding site shape and size are defined by the ligand. They are not independent entities of fixed proportions and cannot be analyzed independently of the binding partner. Such a proposition derives from viewing proteins as dynamic distributions, presenting to the incoming ligands a range of binding site shapes. It illustrates how presumably specific binding molecules can bind multiple ligands. In terms of drug design, the ability of a single receptor to recognize many dissimilar ligands shows the need to consider more diverse molecules. It provides a rationale for higher affinity inhibitors that are not derived from substrates at their transition states and indicates flexible docking schemes. [source] Differences among techniques for high-abundant protein depletionPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 13 2005Nina Zolotarjova Abstract The need to identify protein or peptide biomarkers via readily available biological samples like serum, plasma, or cerebrospinal fluid is often hindered by a few particular proteins present at relatively high concentrations. The ability to remove these proteins specifically, reproducibly, and with high selectivity is increasingly important in proteomic studies, and success in this procedure is leading to an ever-increasing list of lower abundant proteins being identified in these biological fluids. The current work addresses some of the potential problems in depleting proteins in typical biomarker studies, including nonspecific binding during depletion procedures and whether low molecular weight (LMW) species bind to the column in a so-called "sponge" effect caused by the ability of albumin or other high-abundant proteins to bind peptides or protein fragments. LC-MS/MS methods were applied to the comparative analysis of an IgG-based immunodepletion method and a Cibacron blue (CB)-dye-based method, for specificity of removing targeted proteins (binding fraction), as well as for assessing efficiency of target removal. This analysis was extended to examine the effects of repeated use of materials (cycles of binding and elution), in order to assess potential for carryover of one sample to the next. Capacity studies and efficiency of protein removal from the serum samples were followed for the IgG-based system using both immunochemical assays (ELISA) as well as LC-MS/MS methods. Additionally, the IgG-based system was further characterized for the removal of LMW polypeptides by nonspecific binding. We conclude that the IgG-based system provided effective removal of targeted proteins, with minimal carryover, high longevity, and minimal nonspecific binding. Significant differences are noted between the depletion techniques employed, and this should be considered based on the expectations set during experimental design. [source] Double child burial from sunghir (Russia): Pathology and inferences for upper paleolithic funerary practicesAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2004Vincenzo Formicola Abstract The double child burial from Sunghir (Russia) is a spectacular Mid Upper Palaeolithic funerary example dated to about 24,000 BP. A boy (Sunghir 2) and a girl (Sunghir 3), about 12,13 and 9,10 years old, respectively, were buried at the same time, head to head, covered by red ocher and ornamented with extraordinarily rich grave goods. Examination of the two skeletons reveals that the Sunghir 3 femora are short and exhibit marked antero-posterior bowing. The two femora do not show any asymmetry in the degree of shortening and bowing. Bowing affects the whole diaphysis and shows a regularly incurved profile, with the highest point at midshaft. Pathology is confined to the femora, and no other part of this well-preserved specimen shows abnormality. The isolated nature of the Sunghir 3 anomalies points to cases reported in the medical literature under the label of "congenital bowing of long bones" (CBLB). These are a group of rare conditions exhibiting localized, sometimes bilateral, bowing and shortening which are nonspecific and may result from different causes, including abnormalities of the primary cartilaginous anlage (i.e., the aggregation of cells representing the first trace of an organ). Localized ossification disturbances, possibly linked to a diabetic maternal condition, might explain the shortening and the coincidence of maximum midshaft curvature with the position of the primary ossification center, as well as the lack of involvement of other skeletal parts. This scenario, rather than other possibilities (early bilateral midshaft fracture, acute plastic bowing deformities, or faulty fetal posture), provides the most likely explanation for the Sunghir 3 femoral deformities. The intriguing combination of a pathological condition apparent since birth with a spectacular burial of unusually positioned young individuals of different sexes recalls significant aspects of the triple burial from the contemporary site of Dolní V,stonice (Moravia), evoking a patterned relationship between physical abnormality and extraordinary Upper Paleolithic funerary behavior. Am J Phys Anthropol, 2003. © 2003 Wiley-Liss, Inc. [source] Response to novel food and the role of social influences in common marmosets (Callithrix jacchus) and Goeldi's monkeys (Callimico goeldii)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 11 2007Elsa Addessi Abstract Neophobia, defined as showing caution toward novel features of the environment, is widespread in birds and mammals; it can be affected by ecology, early experience, and social context. In this study, we aimed to (i) investigate the response to novel food in adult common marmosets and Goeldi's monkeys and (ii) assess the role of social influences. We used an experimental paradigm employed previously with capuchin monkeys and children, in which a subject (observer) was presented with a novel food under three conditions: (i) Presence: group members did not have food; (ii) Different color: group members received familiar food whose color differed from that of the observer's novel food; (iii) Same color: group members received familiar food of the same color as the observer's novel food. Although most common marmosets tasted and/or ate the novel food, none of the Goeldi's monkeys ate it and only two sampled it. Differences in home range size and early social experience might explain the divergent behavior of the two species. Observers of both species similarly attended to group members and their visual attention increased with the number of group members eating, especially when the observer's and group members' foods were perceptually similar. However, we observed social influences on explorative behavior in Goeldi's monkeys but not on explorative or eating behavior in common marmosets. This result might be explained by the different pattern of response to novel food observed in the two species. Moreover, social influences on Goeldi's monkeys' behavior were nonspecific, i.e. they were not based on an appreciation that the food is safe because eaten by group members. Am. J. Primatol. 69:1210,1222, 2007. © 2007 Wiley-Liss, Inc. [source] Hydrodynamics-based procedure involves transient hyperpermeability in the hepatic cellular membrane: implication of a nonspecific process in efficient intracellular gene deliveryTHE JOURNAL OF GENE MEDICINE, Issue 5 2004Naoki Kobayashi Abstract Background The mechanisms underlying the efficient gene transfer by a large-volume and high-speed intravenous injection of naked plasmid DNA (pDNA), a so-called hydrodynamics-based procedure, remain unclear and require further investigation. In this report, we have investigated possible mechanisms for the intracellular transport of naked pDNA by this procedure. Methods Propidium iodide (PI), a fluorescent indicator for cell membrane integrity, and luciferase- or green fluorescent protein (GFP)-expressing pDNA were injected into mice by the hydrodynamics-based procedure. Results PI was efficiently taken up by hepatocytes which appeared to be viable following the hydrodynamics-based procedure. Pre-expressed GFP in the cytosol was rapidly eliminated from the hepatocytes by a large-volume injection of saline. The profiles of plasma ALT and AST showed a steady decline with the highest values observed immediately after the hydrodynamics-based procedure. These results suggest that the hydrodynamics-based procedure produces a transient increase in the permeability of the cell membrane. The cellular uptake process appeared nonspecific, since simultaneous injection of an excess of empty vector did not affect the transgene expression. Sequential injections of a large volume of pDNA-free saline followed by naked pDNA in a normal volume revealed that the increase in membrane permeability was transient, with a return to normal conditions within 30 min. Transgene expression was observed in hepatocyte cultures isolated 10 min after pDNA delivery and in the liver as early as 10 min after luciferase-expressing RNA delivery, indicating that pDNA delivered immediately by the hydrodynamics-based procedure has the potential to produce successful transgene expression. Conclusions These findings suggest that the mechanism for the hydrodynamics-based gene transfer would involve in part the direct cytosolic delivery of pDNA through the cell membrane due to transiently increased permeability. Copyright © 2004 John Wiley & Sons, Ltd. [source] Two Subgroups of Stapes Fixation: Otosclerosis and Pseudo-Otosclerosis,THE LARYNGOSCOPE, Issue 11 2005Tamás Karosi MD Abstract Hypothesis: Stapes ankylosis is a disease with variable histopathology and can be caused by otosclerosis or pseudo-otosclerosis. Viral pathogenesis of otosclerosis could be established only by correlative analysis: histologic examination of the stapes footplate and reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of the viral RNA. Background: Presence of the RNA genome of measles virus was demonstrated in the footplates of clinically otosclerotic patients by RT-PCR, and also viral proteins were detected by immunohistochemistry. Methods: Nucleic acids were extracted from ankylotic stapes footplates of clinically stapes fixation patients (n = 104). Measles virus genomic nucleoprotein (NP) RNA was amplified by seminested RT-PCR. Amplification results were correlated to postoperative histologic and audiologic findings. Results: Measles virus RNA was detectable only in histologically otosclerotic stapes footplates (n = 67). Histology for virus negative footplates (n = 37) excluded otosclerosis. Virus negative stapes footplates showed nonotosclerotic, degenerative disorders. Conclusions: Stapes ankylosis is a heterogeneous disease causing conductive hearing loss with different etiologies. Nonotosclerotic stapes fixations could be established as pseudo-otosclerosis and may belong to nonspecific, degenerative disorders with variable and noncharacteristic histopathology. Otosclerosis is an inflammatory disease caused by persisting measles virus infection of the otic cap-sule. [source] | ||||||||||||||||||||||||||||||||||||||||