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PubMed1996

Mood-congruent vs. mood-incongruent psychotic symptoms in affective psychotic disorders.

This review of the literature on the importance of congruence of mood to identify nosological sub-categories among the affective disorders showed the limited value of this concept. The reported prevalence rates of affective psychoses with mood-congruent, mood-incongruent and a combination of these symptoms vary widely among the different studies. This categorization seems neither to identify sub-groups with distinct demographic and onset characteristics nor to predict course and outcome. Furthermore, the ambiguity of the guidelines and the different use of this concept in the studies increase the confusion. The only heuristic value of the use of this concept seems to be its prediction of change of diagnosis. The authors suggest eliminating the concept of mood congruence from the categorization of affective disorders and, if not, to state more concise and explicit guidelines for research and clinical use.

Affect↗

PubMed2002

First-episode schizophrenia, bipolar disorder and other psychoses in a rural Irish catchment area: incidence and gender in the Cavan-Monaghan study at 5 years.

BACKGROUND: The potential of first-episode studies in schizophrenia is maximised through systematic epidemiological, clinical and biological comparisons between homogeneous populations of the psychoses. AIMS: To conduct prolonged accrual of 'all' cases of non-affective and affective psychotic illness on an epidemiologically complete basis. METHOD: Within the region covered by Cavan-Monaghan psychiatric service (population 102,810), all putative cases of first-episode psychosis were diagnosed using DSM-IV. RESULTS: From 1995 to 2000, 69 cases of psychosis were ascertained, the incidence being 2.3-fold lower in females than in males. On resolving the 'core' diagnoses of schizophrenia and bipolar disorder, incidence of schizophrenia among women was 7.5-fold lower than among men whereas incidence of bipolar disorder among women was 6.6-fold lower than among men. CONCLUSIONS: This homogeneous population, which eliminates factors associated with urbanicity and minimises confounding factors such as socioeconomic, ethnic and geographical diversity, shows a markedly reduced incidence among females both of schizophrenia and of bipolar disorder.

Analysis of Variance↗

PubMedDate not supplied

Problems in the surgical treatment of motility disorders occurring after gastric surgery.

Delayed or accelerated gastric emptying and excessive reflux of upper intestinal contents into the stomach are the main disorders of motility occurring after gastric surgery. Most of these syndromes may be treated by conservative measures. When surgical therapy is needed attention must be paid to the possible specific side effects of remedial treatment. Interposition of a reversed jejunal loop in the treatment of dumping after Billroth I gastrectomy may be responsible for the development of an anastomotic ulcer. Roux-en-Y biliary diversion for the surgical treatment of postoperative reflux alkaline gastritis may result in a Roux-en-Y syndrome characterized by severe, delayed gastric emptying. Whenever possible, the pyloric sphincter should be preserved in gastric surgery as the elimination of the pylorus is the main cause of postoperative motility disorders.

Duodenogastric Reflux↗

PubMed1975

Cross-national study of diagnosis of the mental disorders: a comparative psychometric assessment of elderly patients admitted to mental hospitals serving Queens County, New York, and the former borough of Camberwell, London.

In a cross-national comparison of the frequency of occurrence of various diagnoses among elderly psychiatric patients admitted to public mental hospitals in London and New York, a short battery of psychological tests was administered to all patients independently of psychiatric examination. The psychological assessment was focused on the differentiation between dementing and affective disorders. The test performance showed a highly significant difference between the two groups as diagnosed, and when patients were allocated to groups on the basis of tests alone these allocations showed a high rate of agreement with initial psychiatric diagnosis. There was a similar high rate of agreement between test allocation and hospital diagnosis in the U.K., but this was not so in the U.S. No significant differences were found between the test performance of U.K. and U.S. patients, except on the WAIS Vocabulary and the Angles Error measurement of the Bender-Gestalt test. When the effects of age and Vocabulary score were eliminated these differences disappeared. The hypothesis that the diagnosis of affective disorder would be confirmed by a relatively greater improvement in test performance over time in this group of patients was not upheld by the non-parametric analysis of change scores. However, an analysis of covariance utilizing age and initial score did indicate the expected differential improvement.

Affective Symptoms↗

PubMed2002

Kinetic studies on the hydrogen peroxide elimination by cultured PC12 cells: rate limitation by glucose-6-phosphate dehydrogenase.

Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders and brain ischemia, and hydrogen peroxide (H(2)O(2)) plays a central role in the stress. In this study, we have examined the kinetics of H(2)O(2) elimination by PC12 cells as a neuronal model in connection with the enzyme activities supporting the reaction. Similarly to other cell lines previously studied, H(2)O(2) removal kinetics could be divided into two reactions: one apparently following the Michaelis-Menten kinetics (GSH-dependent reaction) and the other following the first-order kinetics (mainly catalyzed by catalase). Based on the enzyme activities in the cell homogenate, it was inferred that glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the GSH- and NADPH-dependent H(2)O(2) elimination by PC12 cells. This is in contrast with fibroblasts and endothelial cells previously examined, in which glutathione reductase (GR) is rate-limiting in the reaction sequence. Treatment of PC12 cells with nerve growth factor increased G6PD activity in the cell homogenate and H(2)O(2) removal activity of the whole cells, with a concomitant increase in the resistance against H(2)O(2) toxicity. These results suggest the importance of G6PD in the antioxidant function of brain and pathogenesis of the oxidative stress-related diseases.

Animals↗

PubMed1987

Stress and intestinal microflora.

In this overview the actual international knowledge regarding phenomenons and their proven or speculated mechanisms of adaptative microecological, hormonal and immunological responses to neuroemotional stress conditions including space-flights is represented. In most cases a decreased stability of the intestinal microflora provokes further reactions of the body. The necessity to predict the various possible disorders and to find optimal measures for their prophylaxis and elimination is emphasized.

Humans↗

PubMed1987

Factors influencing the caffeine test for cytochrome P 448-dependent liver function.

Liver functions in patients with liver disease can be estimated by caffeine clearance. Our data, however, demonstrate the additional influence of factors other than liver disease on the caffeine test. Smoking enhances caffeine clearance in both healthy volunteers and patients with severe hepatic disorders, whereas co-medication with mexiletine strongly inhibits caffeine elimination.

Caffeine↗

PubMed2001

Probing the cons and pros of lectin-induced immunomodulation: case studies for the mistletoe lectin and galectin-1.

When imagining to monitor animal cells through a microscope with resolution at the molecular level, a salient attribute of their surfaces will be the abundance of glycan chains. They present galactosides at their termini widely extending like tentacles into the extracellular space. Their spatial accessibility and their potential for structural variability endow especially these glycan parts with capacity to act as docking points for molecular sensors (sugar receptors such as lectins). Binding and ligand clustering account for transmission of post-binding signals into the cell interior. The range of triggered activities has turned plant lectins into popular tools in cell biology and immunology. Potential for clinical application has been investigated rigorously only in recent years. As documented in vitro and in vivo for the galactoside-specific mistletoe lectin, its apparent immunomodulatory capacity reflected in upregulation of production of proinflammatory cytokines will not necessarily be clinically favorable but a double-edged sword. In fact, lectin application has been shown to stimulate tumor growth in cell lines, histocultures of human tumors and in two animal models using chemical carcinogenesis or tumor transplantation. When testing immunological effects of the endogenous lectin galectin-1, protection against disorders mediated by activated T cells came up for consideration. Elimination of these cells via CD7-dependent induction of apoptosis, and a shift to the Th2 response by the galectin, are factors to ameliorate disease states. This result encourages further efforts with other galectins. Functional redundancy, synergism, diversity or antagonism among galectins are being explored to understand the actual role of this class of endogenous lectins in inflammation. Regardless of the results of further preclinical testing for galectin-1, these two case studies break new ground in our understanding how glycans as ligands for lectins convey reactivity to immune cells, with impact on the course of a tumor or autoimmune disease.

Adjuvants, Immunologic↗

PubMed2000

Usefulness of screening program for celiac disease in autoimmune thyroiditis.

We determined the prevalence of celiac disease in subjects with autoimmune thyroiditis compared with sick and healthy subjects. The screening was performed with IgA-class endomysium antibody, by indirect immunofluorescence using human umbilical cord as the antigenic substrate. Six of the 172 patients with autoimmune thyroiditis were found to be anti-endomysium positive (3.4%) and five of these underwent intestinal biopsy, which showed total villous atrophy. By contrast, 3 (0.75%) of 396 patients with nongastroenterologic malignancies and 10 (0.25%) of 4000 blood donors were found to have celiac disease. The prevalence of autoimmune diseases was significantly higher in patients with both celiac disease and autoimmune thyroiditis than in patients with autoimmune thyroiditis alone (P = 0.01). This study confirms that celiac disease is increased among patients with autoimmune thyroiditis. We suggest that these patients may benefit from screening for celiac disease so as to eliminate symptoms and limit the risk of developing other autoimmune disorders.

Adolescent↗

PubMed2006

The place of sirolimus in kidney transplantation: can we reduce calcineurin inhibitor renal toxicity?

Sirolimus, a macrocylic lactone, blocks T-cell activation by a mechanism of action distinct from calcineurin inhibitors (CNIs). Therefore, it may be expected that sirolimus would display a safety profile without the vasomotor form of nephrotoxicity characteristic of CNIs. Initial studies in rodent models and in psoriasis patients showed that sirolimus alone did not impair renal function. Subsequently, two pivotal, randomized double dummy, phase III trials in human renal transplantation demonstrated that sirolimus exacerbated the nephrotoxicity of full doses of CNIs. Both pharmacokinetic and pharmacodynamic mechanisms have been implicated in the pathogenesis of this disorder. Subsequent experience has shown that cyclosporin A dose reduction, elimination, or avoidance mitigates these effects, particularly in patients distant from the transplant procedure. However, there is concern about recovery from ischemia-reperfusion injury. Animal models suggesting that sirolimus may delay recovery in this setting have been supported by non-randomized experiences at single centers, which have observed an increased incidence of delayed graft function among sirolimus-treated recipients. In contrast, large single- and multi-center studies have not confirmed this finding; impaired renal recovery has been observed in only occasional instances. Thus, present data indicate that sirolimus does not impair the function of an uninjured kidney, but whether the drug acts alone or potentiates conditions that delay recovery after ischemic injury remains to be established by large randomized trials specifically targeted to recipients at high risk for this complication.

Animals↗

PubMed1997

Drug distribution in the vitreous humor of the human eye: the effects of aphakia and changes in retinal permeability and vitreous diffusivity.

The majority of eyes that receive drug therapy exhibit some form of pathophysiological degradation. Two common pathophysiological states are retinal inflammation, which results in breakdown of the blood-retinal barrier, and aphakia. The purpose of this study was to examine the effects of aphakia and changes in retinal permeability and vitreous diffusivity on drug distribution in the vitreous humor of the human eye. The study was performed using a finite element model that accurately accounts for the vitreous geometry and boundary conditions. Intravitreal injection is the most common method for treating posterior segment disorders; therefore, this administration method was simulated using the models. Elimination from aphakic and phakic eyes was compared for four extreme injection locations and for two retinal permeabilities. When the retinal permeability was fixed at 5.0 x 10(-5) cm/s, increasing the drug diffusivity through the vitreous from 5.4 to 10(-7) to 2.4 x 10(-5) cm2/s decreased the half-life of drug from 64 hours to 2.7 hours. When the drug diffusivity was fixed at 5.6 x 10(-6) cm2/s, increasing the retinal permeability of the drug from 1.0 x 10(-7) to 1.0 x 10(-4) cm/s decreased the half-life of drug from 44 to 7 hours. Therefore, drug diffusivity and retinal permeability are key factors that influence elimination from the vitreous, and must be considered, particularly if the blood retinal barrier has been compromised. Faster drug elimination was observed in aphakic eyes than in phakic eyes, especially for drugs with a low retinal permeability and injected close to the lens capsule. Injection position is also important if the drug is injected in close proximity to a primary elimination barrier.

Aphakia↗

PubMed2002

Exertional dizziness and autonomic dysregulation.

OBJECTIVES: To define the clinical characteristics and treatment of dizziness induced by physical exertion and to investigate autonomic nervous system function in exertional dizziness. STUDY DESIGN: Retrospective case series from a review of 1400 patients evaluated for dizziness at a neurotology referral center, identifying those with predominantly exertional symptoms. METHODS: Records of patients with exertional dizziness were screened to eliminate those with known vestibular deficits, cardiopulmonary illnesses, and psychiatric disorders. The clinical characteristics, evaluation results, and treatment of nine patients with purely exertional dizziness were described. RESULTS: The cohort included 4 male and 5 female patients (age range, 13-53 y) with symptoms for 1 to 8 years. Only one patient had a history of autonomic symptoms: phlebotomy-induced syncope in childhood. No patient was taking medications that caused dizziness or orthostasis. All patients experienced "spacey" or "foggy" head sensations without vertigo during exertion. Provocative activities ranged from standing upright for extended periods to running and swimming. On examination, voluntary hyperventilation provoked moderate symptoms in all patients (without nystagmus or anxiety), although no patient had spontaneously occurring, hyperventilation-related complaints. Seven patients underwent autonomic testing. Tilt table tests (n = 5) produced severe symptoms in one patient and mild symptoms in two patients. Sodium lactate infusions (n = 6) provoked marked symptoms in four patients and moderate symptoms in one patient. All were treated for autonomic dysregulation. Seven patients improved substantially and resumed all of their premorbid activities. Two improved slightly. CONCLUSIONS: In nine patients with exertional dizziness, autonomic challenges were provocative, and medications for autonomic dysregulation were effective. Exertional dizziness may be a clinical manifestation of autonomic nervous system dysregulation.

Adolescent↗

PubMed2004

Evaluation and selection of potential live kidney donors.

PURPOSE: Renal transplantation is an optimal therapy for patients with end stage kidney disease. A thorough evaluation of potential donors is necessary to provide the best functional outcome for recipients and ensure no or minimal morbidity for donors. MATERIALS AND METHODS: Between 1992 and 2001, 1661 ABO compatible potential living donors were evaluated clinically as well as by laboratory and imaging studies. RESULTS: Of 1661 potential donors 814 (49%) were excluded. The reasons for elimination were general medical reasons in 34.4% of cases, nephrological disorders in 25.6%, urological diseases in 11.7% and immunological causes in 16.2%. Exclusion on an ethical basis accounted for 12.2% of cases. CONCLUSIONS: Although kidneys from living donors provide the best functional outcome, 50% of potential candidates must be excluded.

Adult↗

PubMed2005

Crystals cause acute necrotic cell death in renal proximal tubule cells, but not in collecting tubule cells.

BACKGROUND: The interaction between renal tubular cells and crystals generated in the tubular fluid could play an initiating role in the pathophysiology of calcium oxalate nephrolithiasis. Crystals are expected to form in the renal collecting ducts, but not in the proximal tubule. In the present investigation, we studied the damaging effect of calcium oxalate crystals on renal proximal and collecting tubule cells in culture. METHODS: Studies were performed with the renal proximal tubular cell lines, porcine proximal tubular cells (LLC-PK(1)) and Madin-Darby canine kidney II (MDCK-II) and the renal collecting duct cell lines, RCCD(1) and MDCK-I. Confluent monolayers cultured on permeable growth substrates in a two-compartment culture system were apically exposed to calcium oxalate monohydrate crystals, after which several cellular responses were studied, including monolayer morphology (confocal microscopy), transepithelial electrical resistances (TER), prostaglandin E(2) (PGE(2)) secretion, DNA synthesis ([(3)H]-thymidine), total cell numbers, reactive oxygen species [hydrogen peroxide (H(2)O(2))] generation, apoptotic (annexin V and DNA fragmentation), and necrotic (propidium iodide influx) cell death. RESULTS: Crystals were rapidly taken up by proximal tubular cells and induced a biphasic response. Within 24 hours approximately half of the cell-associated crystals were released back into the apical fluid (early response). Over the next 2 weeks half of the remaining internalized crystals were eliminated (late response). The early response was characterized by morphologic disorder, increased synthesis of PGE(2), H(2)O(2), and DNA and the release of crystal-containing cells from the monolayers. These released cells appeared to be necrotic, but not apoptotic cells. Scrape-injured monolayers generated even higher levels of H(2)O(2) than those generated in response to crystals. During the late response, crystals were gradually removed from the monolayers without inflammation-mediated cell death. Crystals did not bind to, were not taken up by, and did not cause marked responses in collecting tubule cells. CONCLUSION: This study shows that calcium oxalate crystals cause acute inflammation-mediated necrotic cell death in renal proximal tubular cells, but not in collecting tubule cells. The crystal-induced generation of reactive oxygen species by renal tubular cells is a general response to tissue damage and the increased levels of DNA synthesis seem to reflect regeneration rather than growth stimulation. As long as the renal collecting ducts are not obstructed with crystals, these results do not support an important role for crystal-induced tissue injury in the pathophysiology of calcium oxalate nephrolithiasis.

Animals↗

PubMed1984

L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia.

Treatment with L-carnitine greatly enhanced the formation and excretion of short-chain acylcarnitines in three patients with propionic acidemia and in three normal controls. The use of fast atom bombardment mass spectrometry and linked scanning at constant magnetic (B) to electric (E) field ratio identified the acylcarnitine as propionylcarnitine in patients with propionic acidemia. The normal children excreted mostly acetylcarnitine. Propionic acidemia and other organic acidurias are characterized by the intramitochondrial accumulation of short-chain acyl-Coenzyme A (CoA) compounds. The substrate specificity of the carnitine acetyltransferase enzyme and its steady state nature appears to facilitate elimination of propionyl groups while restoring the acyl-CoA:free CoA ratio in the mitochondrion. We suggest that L-carnitine may be a useful therapeutic approach for elimination of toxic acyl CoA compounds in several of these disorders.

Acyl Coenzyme A↗

PubMed1993

Atrial natriuretic peptide. An overview of clinical pharmacology and pharmacokinetics.

The atrial natriuretic peptide (ANP) is part of a new family of cardiac hormones regulating water and salt homeostasis. Besides acting as a blood pressure-lowering agent, it also exerts potent natriuretic and diuretic effects. ANP can be considered an endogenous antagonist of the reninangiotensin-aldosterone system and the antidiuretic hormone. One of the roles of ANP is to protect the body against fluid overload: it decreases intravascular fluid volume, which in turn diminishes cardiac secretion of ANP. The pharmacokinetic parameters of ANP reported in the literature vary widely. In general, ANP rapidly disappears from plasma with a high total body clearance. This is in agreement with the short-lived effects of the hormone. The actions of ANP have led to efforts to use this peptide hormone in the treatment of various cardiovascular disorders such as hypertension and congestive heart failure. Intravenous ANP administration indeed resulted in beneficial effects in these disorders. However, the peptide nature of ANP and its rapid elimination from the circulation limit its suitability as a drug. More promising is the development of long-acting ANP analogues and inhibitors of ANP degradation. Proper understanding of ANP pharmacokinetics is essential for the clinical use of these pharmacological agents.

Animals↗

PubMed1980

Danazol in the treatment of mammary dysplasia.

While employing danazol in the management of women with endometriosis, a voluntary comment patients frequently offerd was that breast pain, nodularity and premenstrual engorgement were alleviated. Because of this unexpected finding, our attention was directed to the treatment of women with mammary dysplasia, particularly fibrocystic disease of the breast. Since the incidence of mammary cancer increases rapidly with age, we obtained xerommamograms in all suspected cases to exclude such a possibility. Danazol was employed in dosages varying from 100 to 400mg per day for 3 to 6 months, depending on the severity of the disorder. More than 75% of patients experienced marked improvement or elimination of the nodularity and engorgement, and many women were spared unnecessary surgery. When surgical interference was deemed necessary in cases of multiple nodosities, danazol treatment helped to identify for biopsy a dominant nodule that did not respond to therapy. Danazol has much to offer in the treatment of benign breast disease, and represents an important advance over 'traditional' hormonal regimens proposed in the past.

Breast Diseases↗

PubMed1999

Expression and function of Fas during differentiation and activation of B cells.

Fas (Apo-1, CD95) cell surface antigen belongs to the tumor necrosis factor receptor family and mediates apoptosis of a variety of cell types, including lymphocytes, after ligation with Fas ligand (FasL). Recent studies on the role of Fas/FasL interaction in the immune responses strongly suggest the relevance of dysregulation in Fas-mediated apoptosis as a cause of autoimmune disorders. While Fas is not an essential molecule in the elimination or functional inactivation (anergy) of autoreactive B cells, it is indispensable to the maintenance of peripheral tolerance and prevention of autoimmunity. Studies in the past few years have begun to reveal the mechanism by which susceptibility to Fas-mediated apoptosis in B cells is regulated to allow antigen-specific B cells survive and differentiate and to eliminate nonspecifically activated, potentially selfreactive B cells.

Animals↗