Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

Background  

A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations). In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells.     

Craniofacial resection for lesions involving anterior base of skull

Craniofacial resection represents a major advance in the surgical treatment of tumours of the paranasal sinuses. It allows wide exposure of the complex anatomical structures at the base of skull permitting monobloc tumour resection. The development of computerised tomography has improved patient selection for surgery. The present study analyses results of craniofacial resection in 30 patients, 19 of whom had malignant tumours. Fourteen of these cases are disease-free after periods of 6 to 36 months. Eleven other patients had extensive benign lesions. A satisfactory reduction of proptosis and relief from other symptoms was obtained in all cases in the benign group. Craniofacial resection was thus found to give excellent results with low morbidity in malignant lesions and can also be adapted for benign tumours of anterior skull base.     

Chromaffin cell catecholamine secretion: bisindolylmaleimide compounds exhibit novel and potent antagonist effects at the nicotinic cholinergic receptor in pheochromocytoma cells

Activation of protein kinase C (PKC) stimulates nicotine-induced catecholamine secretion. PKC down-regulation by prolonged pretreatment with phorbol 12-myristate 13-acetate diminished nicotine-induced catecholamine secretion only slightly (approximately 16%), suggesting substantial PKC independence of nicotinic receptor activation. However, we found that bisindolylmaleimide compounds (which are also putative PKC chemical inhibitors) dramatically inhibited nicotine-induced catecholamine secretion (IC(50) values of approximately 24-37 nM). This inhibition was specific for the nicotinic cholinergic receptor. Catecholamine secretion induced by other nicotinic agonists (such as epibatidine, anatoxin, or cytisine) was also powerfully antagonized by bisindolylmaleimide II (IC(50) values of approximately 60-90 nM). Even high-dose nicotinic agonists failed to overcome the inhibition by bisindolylmaleimide II, suggesting noncompetitive nicotinic antagonism by this class of compounds. Nicotinic inhibition by bisindolylmaleimide seemed not to be readily reversible. Structure-activity studies of bisindolylmaleimide compounds revealed that bisindolylmaleimides I through III are the most potent nicotinic antagonists at the nicotinic cholinergic receptor in PC-12 cells (IC(50) < or =37 nM), whereas bisindolylmaleimide IV and V have far less nicotinic antagonist activity (IC(50) >1 microM); the active compounds I through III have cationic tails at an indole nitrogen, whereas the least potent compounds IV and V do not. By contrast, a free NH within the maleimide ring is crucial for PKC inhibition by this class of compounds. We conclude that bisindolylmaleimides I through III are some of the most potent noncompetitive neuronal nicotinic antagonists, indeed the most potent such antagonists we have observed in PC-12 cells. Nicotinic antagonism of these compounds seems to be independent of PKC inhibition.     

Choroid plexus papilloma of the posterior third ventricle during infancy & childhood: report of two cases with management morbidities

We report two cases of posterior third ventricular choroid plexus papilloma, one in an 8-month-old infant and another in a two-year-old child. These cases presented with features of obstructive hydrocephalus. Both these patients underwent a ventriculo-peritoneal (VP) shunt surgery prior to the tumor excision. Following the VP shunt surgery both patients developed ascitis requiring exteriorization of the abdominal end of the shunt. There was a clear proof of CSF overproduction: 1400-1500 ml/day in the eight-month-old infant and 900-1200 ml/day in the two-year-old child. In the former it was transient and could be treated with revision of the VP shunt whereas in the second case a ventriculo-arterial shunt had to be done. In the second case a staged reduction cranioplasty was also performed for an enormously enlarged head (head circumference--74 cm). Interesting clinical and radiological findings and useful management strategies are described.     

Chronic subdural haematoma and the enigmatic eosinophil

Summary.  The membranes from 50 cases of chronic subdural haematomas were examined histologically and correlated with the duration of the lesion. Cases were divided into three groups based on duration from time of trauma and/or onset of clinical symptoms to date of surgery – Group I: 1 to 30 days, Group II: 31 to 90 days and Group III: >90 days. Infiltration with eosinophils was observed in the vascularised and hyalinised granulation tissue of the subdural membrane in 30 of the 50 cases (60%). There was a trend to correlation both of the frequency and the extent of eosinophilic infiltration with duration of haematoma. Thus, eosinophils were encountered in about half the cases with duration up to 3 months which increased to 80% in cases with duration more than 3 months. The extent of eosinophilic infiltration (mild, moderate or severe) also appeared to correlate with duration of haematoma in that mild infiltration was more common in Group I cases while moderate to severe infiltration were more frequently observed in Group II and III cases. No correlation was observed of the eosinophilic infiltrate with age and sex of the patients or with presence of other cellular inflammatory components of the membrane. Interestingly, a finding hitherto unreported in English literature was the demonstration of mast cells in 7 of 16 membranes (44%) which had been stained using toluidine blue. It is possible that the eosinophils appear at this unusual site due to chemotactic stimulus abetted by these mast cells as well as lymphocytes and haemosiderin pigment. The eosinophils may have an important role in the repair and healing process of these membranes. Published online October 10, 2002 Acknowledgments  Authors wish to thank Mr. Rajeshwar Khadia, Mrs. Kiran Rani, Mr. Anil Bisht and Mr. Gajender Singh for their technical help and Mr. Kamal for secretarial assistance. Correspondence: Prof. Chitra Sarkar, Department of Pathology, All India Institute of Medical Sciences, New Delhi.-110029, India.     

Gluteal neuralgia - unusual presentation in an adult with intrasacral meningocele: a case report and review of literature

A nineteen year old man with intrasacral meningocele is reported, who presented with long standing episodic gluteal pain and progressive muscle wasting. Magnetic resonance imaging established the diagnosis. Surgical excision relieved the pain but muscle wasting persisted. Pertinent literature is reviewed.