Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung

Lung carcinoids occur sporadically and rarely in association with multiple endocrine neoplasia type 1 (MEN1). There are no well defined genetic abnormalities known to occur in these tumors. We studied 11 sporadic lung carcinoids for loss of heterozygosity (LOH) at the locus of the MEN1 gene on chromosome 11q13, and for mutations of the MEN1 gene using dideoxy fingerprinting. Additionally, a lung carcinoid from a MEN1 patient was studied. In four of 11 (36%) sporadic tumors, both copies of the MEN1 gene were inactivated. All four tumors showed the presence of a MEN1 gene mutation and loss of the other allele. Observed mutations included a 1 bp insertion, a 1 bp deletion, a 13 bp deletion and a single nucleotide substitution affecting a donor splice site. Each mutation predicts truncation or potentially complete loss of menin. The remaining seven tumors showed neither the presence of a MEN1 gene mutation nor 11q13 LOH. The tumor from the MEN1 patient showed LOH at chromosome 11q13 and a complex germline MEN1 gene mutation. The data implicate the MEN1 gene in the pathogenesis of sporadic lung carcinoids, representing the first defined genetic alteration in these tumors.      

Evaluation of inhibitory effect of diphenhydramine on benzodiazepine dependence in rats

Effect of diphenhydramine was investigated on withdrawal signs in lorazepam dependent rats. Physical dependence was produced by giving lorazepam admixed with the food in the following dose schedule: 10 x 4, 20 x 4, 40 x 4, 80 x 4 and 120 x 7 (mg/kg, daily x days). The parameters observed during the periods of administration of lorazepam and after its withdrawal were spontaneous locomotor activity (SLA), body temperature, reaction time to pain, foot shock aggression (FSA) and audiogenic seizures. Diphenhydramine was administered orally in the dose schedules of once daily (10, 20 and 40 mg/kg) and twice daily (5, 10 and 20 mg/kg) in separate groups during the withdrawal period. The withdrawal signs observed in control group (without diphenhydramine) were hyperkinesia, hyperthermia, hyperaggression and audiogenic seizures. Hyperkinesia and hyperthermia were blocked in all the groups of diphenhydramine-treated rats. FSA was inhibited only by diphenhydramine (10 and 20 mg/kg) given twice daily. Audiogenic seizures were completely blocked by once daily (20 and 40 mg/kg) as well as twice daily (20 mg/kg) doses of diphenhydramine. It may be concluded that diphenhydramine exerts a protective effects on benzodiazepine withdrawal syndrome.     

EFFICACY OF SUCRALFATE IN PREVENTING GASTROINTESTINAL SIDE EFFECTS OF NSAIDs

To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs     

THE ROLE OF RAPID SLIDE CULTURE IN THE DIAGNOSIS AND MANAGEMENT OF PULMONARY TUBERCULOSIS

Rapid slide culture method using human blood medium was utilized for the primary culture of Mycobacterium tuberculosis and the results obtained were compared with results of smear examination of sputum specimens from fresh cases of pulmonary tuberculosis. Smear and rapid slide culture results of a total of 320 patients were analyzed. Slide culture was positive in 104 cases whereas smears were positive in 90 cases. Early culture confirmation in 7 days coupled with positivity better than smear examination, makes rapid slide culture a better method for diagnosis.KEY WORDS: Mycobacterium tuberculosis, Rapid slide culture, Bacteriological techniques, Colony count microbial     

ASSESSMENT OF VAGOTOMY BY POST-PRANDIAL ALKALINE TIDE

The effect of vagotomy on the post-prandial alkaline tide was assessed by measuring the fasting and postprandial urinary pH before and after vagotomy in 50 cases of chronic duodenal ulcer treated by posterior truncal vagotomy or gastrojejunostomy or pyloroplasty. Results showed that post-prandial urinary pH fell after vagotomy confirming the completeness of vagotomy. This test is safe, reliable, noninvasive and a simpler bedside procedure as compared to the conventional Hollander''s insulin test.KEY WORDS: Vagotomy, Alkaline tide     

Effect of partial water deprivation and restricted feeding on age-related changes in two enzymes of energy metabolism in the brain of male garden lizards

The lactate dehydrogenase (LDH) activity of garden lizard brain did not change with advancing age. On the other hand the succinate dehydrogenase (SDH) activity showed a decline during maturation (young to middle-aged) remaining stabilized thereafter. Seven days of partial water deprivation did not alter the LDH activity of lizards of all three age groups but caused an increase in SDH activity of old lizards only. Restricted feeding led to a decline in the activities of both the enzymes (LDH and SDH) in young lizards and an increase in LDH activity of only the old, the response in middle-aged being insignificant. The protein content of the brain did not change during maturation, but declined in old lizards. Partial water deprivation caused an increase in protein content of the brain of both middle-aged and old lizards but not in young counterparts. Only the young lizards showed an increase in protein content of the brain in response to food restriction.     

Randomised controlled trial of zinc supplementation in malnourished Bangladeshi children with acute diarrhoea

OBJECTIVE: To evaluate the impact of zinc supplementation on the clinical course, stool weight, duration of diarrhoea, changes in serum zinc, and body weight gain of children with acute diarrhoea. DESIGN: Randomised double blind controlled trial. Children were assigned to receive zinc (20 mg elemental zinc per day) containing multivitamins or control group (zinc-free multivitamins) daily in three divided doses for two weeks. SETTING: A diarrhoeal disease hospital in Dhaka, Bangladesh. PATIENTS: 111 children, 3 to 24 months old, below 76% median weight for age of the National Center for Health Statistics standard with acute diarrhoea. Children with severe infection and/or oedema were excluded. MAIN OUTCOME MEASURES: Total diarrhoeal stool output, duration of diarrhoea, rate of weight gain, and changes in serum zinc levels after supplementation. RESULTS: Stool output was 28% less and duration 14% shorter in the zinc supplemented group than placebo (p = 0.06). There were reductions in median total diarrhoeal stool output among zinc supplemented subjects who were shorter (less than 95% height for age), 239 v 326 g/kg (p < 0.04), and who had a lower initial serum zinc (< 14 mmol/l), 279 v 329 g/kg (p < 0.05); a shortening of mean time to recovery occurred (4.7 v 6.2 days, p < 0.04) in those with lower serum zinc. There was an increase in mean serum zinc in the zinc supplemented group (+2.4 v -0.3 mumol/l, p < 0.001) during two weeks of supplementation, and better mean weight gain (120 v 30 g, p < 0.03) at the time of discharge from hospital. CONCLUSIONS: Zinc supplementation is a simple, acceptable, and affordable strategy which should be considered in the management of acute diarrhoea and in prevention of growth faltering in children specially those who are malnourished.     

Central motor conduction time in malnourished children

The functional status of the descending motor pathways was assessed in malnourished children using transcranial electromagnetic stimulation of the cortex. Twenty children with different severities of malnutrition and 20 control subjects were studied electrophysiologically. The circular coil of a Dentac MAG 2 magnetic stimulator was applied tangentially over the vertex to stimulate the cortex. The muscle evoked potential in the children's arms was recorded from the abductor pollicis brevis muscle and in their legs from the extensor digitorum brevis muscle on both sides of the body using surface electrodes. The muscle evoked potential of the abductor pollicis brevis and extensor digitorum brevis muscles was further obtained using root stimulation by applying the coil at the cervical and lumbar spine, respectively. The indices of cortical threshold, cortical latency, and central motor conduction time (ms) were evaluated in both arm and leg muscles on both sides. The results showed an increased cortical threshold (mean (SD) 1232.5 (134.06) in the study group v 1147.5 (99.31) in the control group) for the abductor pollicis brevis muscle and for the extensor digitorum brevis muscle (1325.00 (115.70) in the study group v 1190.0 (125.24) in the control group). Similarly, significant prolongation of the central motor conduction time (ms) (study group 6.67 (0.91) v control group 5.71 (0.74)) in the abductor pollicis brevis muscle was seen in malnourished children.     

Does a single plasma phenylalanine predict quality of control in phenylketonuria?

A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00 and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 mumol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 mumol/l occurred in 46% of children below 11 years, three having concentrations < 30 mumol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = -0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.