PubMed Health⌕ Search

Biomedical subjects

S Janmohamed

Publications and source records attributed to S Janmohamed.

6 recordsLinked to original sources
PubMed2002

Suprasellar germ cell tumours: specific problems and the evolution of optimal management with a combined chemoradiotherapy regimen.

OBJECTIVE: Suprasellar germ cell tumours are rare, and there are few series of patients outlining the problems in diagnosis and management, and providing clear guidelines for optimal therapy. We have therefore reviewed our own series of 11 such patients who were managed in a joint endocrinology/clinical oncology setting. PATIENTS AND DESIGN: A retrospective case review assessment of all patients seen within a given time. Clinical, biochemical and radiological findings were reviewed, the types of therapy administered noted, and the responses to treatment analysed. RESULTS: In the years 1977-2001, 11 patients with suprasellar (SS) germ cell tumours (GCT) were seen (germinomatous : nongerminomatous = 8 : 3). SSGCT had an approximately equal sex incidence (M : F, 6 : 5), in contrast to pineal tumours, the commonest site of origin of intracranial GCT and which occur predominantly in men. The median age at presentation was 20 years (range 6-49 years) with a median duration of symptoms before diagnosis of 17 months (range 1-35 months). Polyuria was the commonest presenting symptom (10 patients). Diabetes insipidus occurred in all patients, as did partial or complete anterior pituitary failure. Visual failure was present in 55% of cases. Anorexia, weight loss and disturbed thirst sensation were also common. Positron emission tomography scanning was occasionally useful in the evaluation of suprasellar tumours/pituitary stalk lesions deemed too risky to biopsy. A "central nervous system-friendly" chemoradiotherapy regimen comprising vincristine, etoposide and carboplatin and differential daily dose irradiation, usually administered using a partial transmission block technique, produced a 5-year survival of 100% with low morbidity. Treatment did not correct previously abnormal endocrine function although it did improve vision in three of six patients. CONCLUSIONS: We therefore emphasize the use of techniques other than biopsy in the diagnosis of these patients, note the problems in the management of their fluid control, and highlight the favourable response to a combined chemotherapy-radiotherapy protocol.

Adolescent↗
PubMed1999

Gonadotrophin-releasing hormone and oxytocin secretion from the hypothalamus in vitro during pro-oestrus: the effects of time of day and melatonin.

An accurately timed surge of luteinizing hormone (LH), during the second half of the day of pro-oestrus in rats, is a crucial part of the endocrine signal that leads to expulsion of an ovum from an ovarian follicle. LH release is partly controlled by a number of peptides, including gonadotrophin-releasing hormone (GnRH) and oxytocin, which travel from the hypothalamus to the pituitary. The profile of secretion of these peptides is poorly understood. Therefore, the amounts of GnRH and oxytocin that were secreted from hypothalamic explants were determined at several time points during the day of pro-oestrus. Basal secretion of oxytocin from hypothalami taken later in pro-oestrus was greater than from hypothalami taken earlier in the day (p < 0.02). On the other hand, basal secretion of GnRH decreased during the day of pro-oestrus (p < 0.03). The different trends of GnRH and oxytocin secretion reveal that their secretion is regulated by distinct mechanisms. GnRH secretion was higher at midpro-oestrus than late in the day (o < 0.05) consistent with a peak of GnRH having been observed by others in portal blood in the second half of the day of pro-oestrus. Responsiveness of oxytocin to stimulation by K+ of the hypothalami declined from the early light hours to the evening dark hours (p < 0.02). Thus, oxytocin modulation might be achieved partly by modification of intracellular processes. Melatonin, secreted during hours of darkness, is frequently involved in modulating time-dependent events in mammals, but its contribution to peptide regulation during the ovulatory cycle is unclear. Melatonin was observed to inhibit basal oxytocin secretion from hypothalami collected during light hours (p < 0.05). The investigation has, therefore, revealed the potential for melatonin to modulate peptide secretion from the hypothalamus during the day of pro-oestrus. We also observed that secretion from the hypothalamus of the two LH-regulating peptides, GnRH and oxytocin, are differently regulated during the day of pro-oestrus.

Animals↗
PubMed1999

An uncoupling protein 2 gene variant is associated with a raised body mass index but not Type II diabetes.

AIMS/HYPOTHESIS: Linkage between markers close to the uncoupling protein 2 and 3 genes (11q13) and resting metabolic rate and a pre-diabetic phenotype have been found. The syntenic region in mouse has been found to be linked to quantitative traits associated with obesity and diabetes. UCP2 and UCP3 could therefore have an important role in body weight regulation and susceptibility to diabetes. We investigated a recently identified variant of the UCP2 gene in exon 8 as a marker for glucose and weight homeostasis. METHODS: Length variation of the UCP2 exon 8 variant was studied by the polymerase chain reaction and agarose gel electrophoresis. Sequence variants of the UCP3 gene were sought by semi-automated DNA sequencing. RESULTS: In 453 South Indian subjects, we found an association in women between the UCP2 exon variant and body mass index (p = 0.018). These findings were replicated in a separate group of South Indian subjects (n = 143, p < 0.001) irrespective of sex. Although no association was found between the UCP2 exon 8 variant and overt obesity in British subjects, the UCP2 genotype of obese women (n = 83) correlated with fasting serum leptin concentration (p = 0.006) in the presence of extreme obesity. These observations could not be explained by tight linkage disequilibrium with a coding region variant in the region of the UCP3 gene of biological significance. Lastly, no association was found between UCP2 and Type II (non-insulin-dependent) diabetes using either a family based design (85 families) or case control study (normal glucose tolerance n = 335, impaired glucose tolerance n = 42, Type II diabetes n = 76). CONCLUSION/INTERPRETATION: We have described a UCP2 gene exon 8 variant that may affect susceptibility to weight gain by influencing regulation of leptin.

Adult↗
PubMed1999

In vitro basal and GnRH-stimulated secretion of gonadotrophins reflects long-lasting modulatory effects, and peripheral levels are not predicted by pituitary responsiveness to GnRH.

OBJECTIVE: Production of the appropriate pattern of gonadotrophin levels is crucial to proper functioning of the female reproductive system. We aimed to establish whether the pituitary has invariant secretory characteristics when isolated from in vivo controls. We aimed to obtain information during both the rising and declining phases of the gonadotrophin surge. DESIGN: This study investigated factors that are directed at the pituitary by isolating it from the acute influences of the in vivo environment and studying gonadotrophin secretion in vitro. METHODS: Pituitaries of adult female rats were collected at selected times during the day of pro-oestrus and incubated in vitro, and at the same time blood was collected. Peripheral levels of LH and FSH were measured over the whole day of pro-oestrus, basal in vitro secretions of LH and FSH from pituitaries were measured, GnRH-stimulated LH and FSH secretion were assessed, and the responsiveness of LH and FSH secretion to GnRH were calculated. RESULTS: Peripheral levels of LH peaked at 1800 h (P<0.02) followed by a subsequent decline. In contrast, although FSH had a peak at 1800 h (P<0.01), serum levels were also high at the end pro-oestrus. The profile of basal LH and FSH secretion from the pituitary in vitro, in the absence of added secretagogue, resembled that of the peripheral blood levels of each gonadotrophin. Pituitaries collected at 1800 h secreted most LH (P<0. 02). FSH secretion was low early on the day of pro-oestrus and then increased to and was maintained at high levels in the last quarter of the day (P<0.01). When the pituitaries were stimulated with GnRH the patterns of LH release and FSH release approximated those observed for basal release. Responsiveness of the pituitaries to GnRH was calculated by determining the ratio of GnRH-stimulated release to basal release. However, low levels of gonadotrophin were secreted even from pituitaries which were highly responsive as determined from consideration of percentage increase in secretion induced by GnRH. CONCLUSIONS: The secretory activity was dependent on the time of day the pituitaries were collected. Since the secretion occurred after the tissue had been removed from the direct influence of the in vivo environment, the variations in secretion must reflect long-lasting components of the mechanism that regulate gonadotrophin concentrations. There were changes in both LH and FSH responsiveness to GnRH stimulation over the day of pro-oestrus. Delineation of the time courses and changing predominance of multiple processes is needed to assist understanding the mechanisms underlying the female reproductive cycle.

Animals↗
PubMed1997

Carcinoid tumours.

The use of long-acting and potent somatostatin analogues is a major advance in the management of carcinoid tumours. In addition to providing effective symptom relief in malignant carcinoid syndrome, octreotide can also be used for diagnostic purposes. Despite its expense, octreotide is the current agent of choice for the treatment of this condition while analogues with different receptor specificities and pharmacokinetics hold promise for the future. Gastric carcinoids have aroused interest because of their experimental association with chronic hypergastrinaemia, a condition now commonplace because of the widespread use of H2-blockers and proton-pump inhibitors. This subject is reviewed. The slow evolution of many tumours demands prolonged follow-up and the active use of a variety of palliative interventions. These include measures such as hepatic and cardiac surgery, which might be deemed inappropriate for patients with other types of metastatic malignancy. Interferons may have a role when first-line treatments have failed. Chemotherapy is, generally, of limited value.

Animals↗