"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.     

Antitumor polycyclic acridines. Part 12. Physical and biological properties of 8,13-diethyl-6-methylquino[4,3,2-kl]acridinium iodide: a lead compound in anticancer drug design

The biophysical and biological characterization of 8,13-diethyl-6-methylquino[4,3,2-k]lacridinium iodide (6) is reported. The compound binds to DNA, as measured by UV, fluorescence, and circular dichroism studies, and stabilizes the double helix and higher order DNA structures (DNA triplexes and quadruplexes) against thermal denaturation. Unlike many DNA ligands, (6) shows no specificity for binding to specific base pair combinations and does not inhibit topoisomerase I (topo I) or topo II activity. Furthermore, the biological fingerprint elicited by (6) in in vitro evaluations does not compare with clinical agents of the topo II inhibition class. The compound provokes cell cycle arrest in response to DNA damage and the biological sequelae are dependent on the p53 status of the cell line. DNA damage by (6) upregulates p53 and p21(CIP/WAF1) proteins. The unusual structure of (6) and its ease of synthesis in a "one-pot" reaction are features that are being exploited in the design and development of a new series of G-quadruplex stabilizing telomerase inhibitors. However, although the second-generation compounds that resulted from (6) present strong telomerase inhibition, (6) in itself presents yet a different mode of action, with a strong preference for triplex DNA, sequences often found in a number of genes.     

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.