Time course of the antipsychotic effect and the underlying behavioral mechanisms.

Antipsychotic drugs work for patients only when given repeatedly. The overall temporal pattern of symptom improvement is not clear. Some recent data question the traditional 'delayed-onset' hypothesis and suggest that the onset of antipsychotic response may be relatively early, and the improvement may grow with repeated treatment. The present study systematically examined the time course of the antipsychotic effect and the underlying behavioral mechanisms using a conditioned avoidance response (CAR) model. Rats repeatedly treated with either typical (haloperidol) or atypical (olanzapine, risperidone) antipsychotics, but not anxiolytics (chlordiazepoxide), show an early-onset, progressive across-session decline in avoidance responding, which re-emerges when the treatment is stopped. This effect is dose-dependent, transferable between antipsychotics, and cannot be attributed to simple sedation or motor side effects. Furthermore, we found that the pattern of this drug-induced decline depends on the number of exposures to the conditioned stimulus in the presence of the drug, and is best understood as the result of drug-induced attenuation of the reinforcing effectiveness of the conditioned stimulus. We also found that repeated drug exposure can create a drug interoceptive state that allows the attenuated reinforcing property of the stimulus to be maintained over time. Together, these data provide preclinical support for the newly postulated 'early-onset' hypothesis, and suggest that the repeated antipsychotic CAR model may be useful for understanding the neurochemical and behavioral mechanisms underlying the clinical effects of antipsychotics in patients with schizophrenia.     

Evolution of membranous nephropathy from a proliferative and exudative glomerulonephritis--a report of three cases studied by serial biopsies

Three adolescents with clinical nephrotic-nephritic picture were noted to have diffuse proliferative and exudative glomerulonephritis. Although focal membranous changes were noted in two of the initial biopsies, evolution into classical membranous glomerulopathy was seen in subsequent biopsies. This study suggests a relationship between these two different patterns of immune complex-associated glomerular injury, and confirms extrapolations made from experimental models of chronic serum sickness.     

"Nasal gliomas" and related brain heterotopias: a pathologist's perspective

Brain heterotopias are rare congenital malformations embryologically related to encephaloceles. They present as a mass in or about the nose (nasal glioma) or in the nasopharynx. We present the clinical and pathological features of 5 cases of heterotopic brain tissue. Four nasal gliomas consisted of mature neuroglial tissue, including neurons in 2 cases, embedded in a fibrovascular stroma. A nasopharyngeal brain heterotopia showed histologic features of mature neuroglial tissue including neurons and ependymal-lined cystic structures. The finding of mature neuroglial tissue in a mass from the head and neck region raises three differential diagnostic possibilities: teratoma, encephalocele, or heterotopic tissue. A teratoma can be ruled out by examination of the entire specimen. Encephaloceles and brain heterotopias can be distinguished only after correlation with the patient's clinical and radiologic findings.     

Determinants of consultation rate in patients with anxiety and depressive disorders in primary care

BACKGROUND: Although it is recognized that anxiety and depression are associated with frequent attendance in primary care, not all patients with these disorders attend frequently. The factors associated with general practice consultation in the important group of patients with anxiety and depressive disorders are not clear. OBJECTIVES: Our aim was to determine prospectively the factors which predict consultation rate in a cohort of patients with anxiety and depressive disorders in primary care. METHODS: A total of 148 adult patients with a depressive, anxiety or panic disorder (DSM-III criteria) were studied prospectively for 6 months to determine the factors which predicted consultation rate during this time. Measures at baseline included: the Psychiatric Assessment Schedule, Hamilton Depression Rating Scale, Life Events and Difficulties Schedule, Clinical Anxiety Scale, details of substance misuse and demographic data. The principal outcome measure was the number of consultations recorded in the GP records over the following 6 months. The variables associated with consultation rate were assessed by multiple regression analysis, with number of consultations as the dependent variable. RESULTS: The median consultation rate during the 6 months of the study was five (range: 1-22). Thirty per cent of the sample consulted seven or more times during the 6 months and 10% consulted 12 or more times. The regression analysis demonstrated that the following variables contributed to the best model: prior consultation rate, past psychiatric history, ongoing social difficulties, current level of alcohol consumption, total psychiatric symptom score and total anxiety score. These variables together accounted for 41% of the variance in consultation rate. CONCLUSION: The detection and rigorous treatment of psychiatric disorder, the provision of social support and interventions for alcohol dependence may help to reduce the frequency of consultation of anxious and depressed patients in primary care. Future research to identify additional variables which explain the major part of the variance in consultation rate may pave the way for novel treatment approaches to the phenomenon of frequent attendance.     

Contemporary Approaches Toward Understanding the Pathogenesis of Hirschsprung Disease

Hirschsprung disease (HD), or congenital aganglionosis coli, is a birth defect with heterogeneous causes. In an effort to understand the molecular and cellular bases for this disorder, researchers have investigated enteric neurodevelopment in normal animals and compared these findings with observations of inbred animal strains that develop aganglionosis coli due to mutations at specific genetic loci. Recent technological advances, including use of retroviral and fluorescent lineage makers, immunohistochemical probes, and transgenic mice, have provided insights into the origins, behavior, and properties of enteric neuroblasts. Experiments with mutant murine embryos indicate that aganglionosis coli results from primary failure of neural crest-derived neuroblasts to colonize the distal colon. In at least one model, impaired colonization by neuroblasts may be secondary to environmental defects restricted to colonic mesenchyme. The discovery that human piebald trait, a hereditary disorder with a high incidence of HD, is caused by mutations in a growth factor receptor highlights the importance of regulatory intercellular interactions between nonneuroblastic mesenchyme and neuroblasts during normal development of the enteric nervous system. These observations, coupled with advances in molecular genetics, set the stage for dramatic progress in this field of research in the near future.     

Epidermoid carcinoma of the anorectum: Review of 31 cases

Summary Thirty-one cases of epidermoid carcinoma found in 106 cases of carcinoma of the rectum and anal canal are reviewed. Clinical presentation and management are presented. Probable factors in the greater than usual incidence of epidermoid carcinomas of the anorectum are discussed. Indications for radiation therapy, local excision, and abdominoperineal and inguinal block dissection are presented.