Role of magnesium sulfate in neuroprotection in acute ischemic stroke.

AIMS: To study the effect of intravenous magnesium sulfate infusion on clinical outcome of patients of acute stroke. MATERIALS AND METHODS: Sixty consecutive cases of acute ischemic stroke hospitalised within 24 h of an episode of stroke were taken as subjects. All subjects underwent a computed tomography head, and those found to have evidence of bleed/space-occupying lesions were excluded from the study. The subjects taken up for the study were divided into two groups of 30 subjects each. Both the groups received the standard protocol management for acute ischemic stroke. Subjects of Group 1 additionally received intravenous magnesium sulfate as initial 4 g bolus dose over 15 min followed by 16 g as slow infusion over the next 24 h. In all the subjects of the two study groups, serum magnesium levels were estimated at the time of admission (Day 0), Day 1 and Day 2 of hospitalization using an atomic absorption spectrometer. STATISTICAL ANALYSIS USED: Scandinavian stroke scores were calculated on Day 3, day of discharge and Day 28. Paired t-test was employed for comparison of stroke scores on Day 3, day of discharge and Day 28 within the same group and the unpaired t-test was used for the intergroup comparison, i.e. comparison of stroke scores of control group with corresponding stroke scores of magnesium group. RESULTS: Comparison of stroke scores on Day 3 and day of discharge, on the day of discharge and Day 28 and on Day 3 and Day 28 in the magnesium group produced a t-value of 5.000 and P <0.001, which was highly significant. However, the comparison of the mean stroke scores between the magnesium and the control groups on Day 3, day of discharge and Day 28 yielded a P-value of >0.05, which was not significant. CONCLUSIONS: The study failed to document a statistical significant stroke recovery in spite of achieving a significant rise in serum magnesium level, more than that necessary for neuroprotection, with an intravenous magnesium sulfate regime.

Ciprofloxacin-induced QTc prolongation.

Ciprofloxacin has been widely used for treating infections and has been found to have very low cardiovascular side effects. QTc prolongation with the use of ciprofloxacin is yet to be reported in literature. A case report highlighting QTc prolongation by use of ciprofloxacin is being presented.

Life and past one year stressful events in coronary artery disease.

UNLABELLED: Personality type and role of stressful life events in the etiology of various disease has been a fertile field for research for past few decades. OBJECT STUDY: Very limited studies have been conducted especially for the estimation of stressful life events in Indian population with coronary artery disease (CAD), so a study was conducted to evaluate the same. METHODOLOGY: Ninety patients of CAD (positive for TMT or angiographic proved coronary obstruction) formed the study material. These were evaluated by Jenkin's activity survey (JAS) for personality type and on Presumptive Stressful Life Events (PSLE) scale for life events. SUMMARY OF RESULTS: The mean age of subjects was 57 +/- 8.03 years and male: female ratio was 14:1 Fifty one subjects (57%) had Type A personality while thirty nine subjects (43%) had Type B personality. Mean life time stressful life events were 3.4 +/- 1.92 which were higher (p < 0.001) when compared to respective average score of normal Indian population i.e. 10.34 +/- 5.4 and 1.90 +/- 2.62 respectively. CONCLUSION: Based on the present study it may be concluded that Type A personality is more frequently seen in CAD and also that these subjects had a statistically higher incidence of lifetime and past one year stressful events which could have made these subjects more vulnerable to CAD.

A non-calcemic sulfone version of the vitamin D(3) analogue seocalcitol (EB 1089): chemical synthesis, biological evaluation and potency enhancement of the anticancer drug adriamycin.

Novel side-chain diene sulfones 5, analogues of the natural hormone 1alpha,25-dihydroxyvitamin D(3) (calcitriol, 1), were designed to incorporate some of the therapeutically most favorable structural features of the Leo Pharmaceutical Company's drug candidate diene EB 1089 (seocalcitol, 4) and of the Hopkins' non-calcemic side-chain sulfone analogues 2 and 3. Synthesis of diene sulfones 5 features selective Swern oxidation of a primary silyl ether in the presence of a secondary silyl ether (9-->10) and Horner-Wadsworth-Emmons aldehyde addition by a 1-phosphonyl-3-sulfonyl stabilized carbanion regiospecifically at the 1-position to form E,E-diene sulfone 11. Sulfone diene analogue 5a with natural 1alpha,3beta-diol functionality, but not its diastereomer 5b with unnatural A-ring stereochemistry, is antiproliferative in vitro toward murine keratinocytes and malignant melanoma cells, as well as toward MCF-7 human breast cancer cells. Combining diene sulfone 5a with the currently used anticancer drug adriamycin (ADR) caused a noteworthy 3-fold enhancement of ADR antiproliferative potency in MCF-7 cells. Sulfone diene analogue 5a is weakly active transcriptionally in MCF-7 and ROS 17/2.8 cells, binds poorly but measurably to the vitamin D receptor (VDR), and desirably is non-calcemic in vivo at a daily dose (7 days) of 10 microg/kg of rat body weight.

Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats.

Diindolylmethane (DIM) is formed by acid catalyzed dimerization of the phytochemical indole-3-carbinol, and both compounds inhibit formation and/or growth of mammary tumors in rodents. In this study, we have investigated the aryl hydrocarbon receptor (AhR) agonist activity and inhibitory AhR-estrogen receptor crosstalk induced by the following methyl-substituted DIMs: 1,1'-dimethyl-, 2,2'-dimethyl-, 5,5'-dimethyl-, 6,6'-dimethyl-, and 7,7'-dimethylDIM and 1,1',2,2'-tetramethylDIM. The six compounds bound to the rat cytosolic AhR in a transformation assay but, at concentrations < or = 10 microM, exhibited minimal to non-detectable AhR agonist or antagonist activities associated with CYP1A1 induction. In contrast, the methyl-substituted DIMs inhibited estrogen-induced T47D human breast cancer cell growth and the four most active compounds (1,1'-, 2,2'-, 5,5'-dimethylDIM and 1,1',2,2'-tetramethylDIM) inhibited one or more estrogen-induced responses in the 21-day-old female B6C3F1 mice at a dose of 100 mg/kg/day (X3). Induction of hepatic CYP1A1-dependent activity was not observed at this high dose. The antitumorigenic activity of these compounds was examined in 7,12-dimethylbenz[a]anthracene-induced rat mammary tumor model in which the DIM analogs were orally administered (by gavage in corn oil) at a dose of 1 mg/kg/day (X10). 1,1'-DimethylDIM, 5,5'-dimethylDIM and 1,1',2,2'-tetramethylDIM significantly inhibited mammary tumor growth, and this was not accompanied by changes in organ/body weights or histopathology. These studies demonstrate that methyl-substituted DIMs are selective AhR modulators (SAhRMs) with potential for clinical treatment of breast cancer.

Analysis of benzo[a]pyrene partitioning and cellular homeostasis in a rat liver cell line.

The uptake and subcellular partitioning of benzo[a]pyrene (BaP) were examined in a rat-liver cell line (Clone 9) using confocal and multiphoton microscopy. Following a 16-h treatment, intracellular accumulation of BaP increased with increasing concentration, and cytoplasmic BaP fluorescence reached saturation at 10 microM. Analysis of the kinetics of BaP uptake at this concentration indicated that BaP is rapidly partitioned into all cytoplasmic membranes within several min, although saturation was not reached until 4 h. Based upon the rapid uptake of BaP into membranes, the chronology of changes in gap junction-mediated intercellular communication (GJIC), plasma membrane potential (PMP), and steady state levels of intracellular Ca2+ in relation to the time-course for induction of microsomal ethoxyresorufin-0-deethylase (EROD) activity were examined. EROD activity in Clone 9 cells treated for 16 h increased with increasing concentrations of BaP and reached the highest levels at 40 microM BaP. In addition, kinetic analysis of EROD activity in Clone 9 cells treated with 10 microM BaP indicated that significant induction of EROD activity was not detected before 3 h, and it reached maximal levels by 16 h of treatment at this concentration. Both GJIC and PMP were directly affected by the partitioning of BaP into cellular membranes. The most sensitive index of BaP-induced changes in membrane function was GJIC which revealed a 25% suppression in cells exposed to 0.4 microM BaP for 16 h. Kinetic analysis revealed that suppression of GJIC occurred within 15 min of exposure of cells to 10 microM BaP, whereas significant suppression of PMP was not detected prior to 30-min exposure at this concentration. Elevation of basal Ca2+ level was also detected simultaneously with PMP at this dose. These data suggest that early changes in cellular membrane functions occur prior to detectable induction of EROD activity, although basal metabolic activation of BaP may contribute to these changes.

3,3'4,4'-Tetrachlorobiphenyl exhibits antiestrogenic and antitumorigenic activity in the rodent uterus and mammary cells and in human breast cancer cells.

3,3',4,4'-Tetrachlorobiphenyl (tetraCB) binds to the aryl hydrocarbon receptor (AhR), and several reports have demonstrated that AhR agonists exhibit antiestrogenic and antitumorigenic activities in human breast cancer cells, the rodent uterus and breast. In contrast, a recent study showed that 3,3',4,4'-tetraCB bound the estrogen receptor (ER) and exhibited ER agonist activities, and we therefore have reinvestigated the estrogenic and antiestrogenic activities of 3,3',4,4'-tetraCB. Our results showed that 3,3',4,4'tetraCB and a structurally related analog, 3,3',4,4',5-pentaCB, did not bind the mouse uterine or human ER, did not induce proliferation of MCF-7 or T47D human breast cancer cells or induce reporter gene activity in cells transfected with E2-responsive constructs derived from the creatine kinase B (pCKB) or cathepsin D (pCD) gene promoters. Moreover, 3,3',4,4'-tetraCB and 3,3',4,4',5-pentaCB did not induce an increase in uterine wet weight, peroxidase activity or progesterone receptor binding in the 21-25-day-old female B6C3F1 mouse uterus. In contrast, both compounds inhibited 17beta-estradiol (E2)-induced cell proliferation and transactivation in MCF-7/T47D cells and uterine responses in B6C3F1 mice; surprisingly inhibition of E2-induced reporter gene activity was not observed in T47D cells transfected with pCKB, and this was observed as a cell-specific response with other AhR agonists. Additionally, 3,3',4,4'-tetraCB significantly inhibited mammary tumor growth in female Sprague-Dawley rats initiated with 7,12-dimethylbenzanthracene. Our results indicate that 3,3',4,4'-tetraCB does not exhibit ER agonist activity but exhibits a broad spectrum of antiestrogenic responses consistent with ligand-mediated AhR-ER crosstalk.

Severe non-ketotic hyperosmolar coma--intensive care management.

We report a case of non-ketotic hyperosmolar coma, which presented with blood sugar levels far exceeding any previously recorded in the literature. The patient developed acute renal failure, probably because of rhabdomyolysis, which was successfully managed with continuous veno-venous haemofiltration. He developed blurring of vision resulting from biochemical changes, which was managed conservatively. We discuss the mechanisms of causation of the renal failure and visual blurring.

Epiphysiodesis using a cannulated tubesaw.

A technique for epiphysiodesis using a cannulated tubesaw has been developed to combine the precision of the original Phemister method with newer percutaneous methods. The approach is unilateral, and requires minimal access. Reinsertion of the removed core of bone reduces haemorrhage from the defect and augments arrest of the growth plate. In 35 patients treated by this method predicted discrepancies of 2 to 4.5 cm were reliably reduced to 0.7 +/- 0.6 cm, with no serious complications. The timing of surgery is critical, and relies upon careful monitoring of the pattern of discrepancy over several years, using clinical and radiographic measurements. Undercorrection of the disparity in three patients was the direct result of late referral.

Cerebellar haemangioblastoma presenting as systemic hypertension.

Neurogenic hypertension is not common and hence is usually overlooked. We are presenting a case of cerebellar haemangioblastoma presenting as systemic hypertension but without any neurological deficit till very late. The patient improved after surgery and is controlled on minimal antihypertensives.

Cardiovascular manifestations in aluminium phosphide poisoning with special reference to echocardiographic changes.

Twenty five patients of aluminium phosphide poisoning along with clinical evidence of peripheral circulatory failure were studied. Chief symptoms noted were vomiting and epigastric pain though subsequently three patients developed respiratory distress. Sensorium was normal in most of the patients. Three patients developed pulmonary edema. Raised JVP, feeble heart sounds and S3 gallop beside tachy and bradycardia were other cardiovascular manifestations observed in these patients. In 80% of the patients, various types of ECG changes were observed. ST-T changes were observed in 40% of the patients. Echo-cardiography on day 1 revealed marked LV systolic dysfunction (mean ejection fraction-43.52 +/- 10.18% and mean fractional shortening 17.35 +/- 4.97%) in them whereas repeat echocardiography on day 5 indicated normalisation of these values (mean ejection fraction 71.64 +/- 8.61% and mean fractional shortening 34.35 +/- 8.23%). This might be because of direct toxic action of phosphine on myocardium and later when phosphine gets excreted either through lungs or kidney leads to improvement in LV systolic function.

Phage-mediated conjugation in staphylococci as a means of transfer of drug-resistance.

Penicillin resistance plasmid was transferred from Staphylococcus aureus B4 (PcrKms, donor) to S. aureus ML351 (PcsKmr, recipient) by co-cultivation of the donor with the recipient in nutrient broth with or without the modifying effects of CaCl2 or sodium dodecyl sulfate. It was found that the transfer of drug-resistance occurred maximally between 6 and 18 hr postinoculation; however, addition of DNase (200 micrograms/ml) could totally prevent such a transfer up to 6 hr and significantly reduce it thereafter. Cell-free filtrate of the donor culture when mixed with the recipient was ineffective in bringing about the transfer of Pcr.

Diltiazem as adjunctive oral therapy in patients with chronic atrial fibrillation.

Digoxin frequently fails to control the heart rate in patients of chronic atrial fibrillation particularly during exertion. We have studied in 20 such patients the effect of adding diltiazem (180 mg/day) on resting and peak exercise heart rates. An attempt was also made to determine its effects on exercise tolerance by using treadmill and 6 minute walk test. Addition of diltiazem resulted in significant attenuation of heart rate both at rest and at peak exercise. The resting and exercise mean heart rates on digoxin alone were 98.9 +/- 21.5 b.p.m. and 160.2 +/- 35.68 b.p.m. respectively. After diltiazem this reduced to 78.7 +/- 12.30 b.p.m. at rest and 132.4 +/- 40.4 b.p.m. at peak exercise (p < 0.01). There was no significant effect on exercise tolerance. In conclusion, the addition of diltiazem substantially reduced the excessive heart rate response to exercise in digitalised patients of chronic atrial fibrillation.

Spectrum of psychiatric symptomatology in children in high and low socio-economic groups in Ludhiana.

A door to door survey was conducted to study the spectrum of psychiatric symptomatology in children aged 1-12 years belonging to high and low socio-economic groups. One hundred families in each group were studied. Symptom prevalence rate was comparable in the two groups, i.e., 479/1000 in the high socio-economic (HSE) group and 487/1000 in the low socio-economic (LSE) group. However, there were significant differences in the spectrum of symptomatology. Symptoms like quarrelsomeness, disobedience, abusive language, stealing, truancy, pica, school refusal, enuresis, mental subnormality and poor scholastic performance were significantly more in the LSE group. In the HSE group, symptoms like nail biting, food refusal, food fads and temper tantrums were significantly more.

Jaccoud's arthritis.

A 16 year old girl with multivalvular heart disease and recurrent episodes of polyarthritis with correctable deformities of hands and feet fitting into that of Jaccoud's arthritis is reported. The condition is rare and often difficult to differentiate from rheumatoid arthritis.

Aluminium phosphide poisoning. Two cases with rare presentation.

We report two cases of aluminium phosphide poisoning who presented with rare manifestations, one with bleeding diathesis, hepatitis and acute tubular necrosis and the other with acute respiratory failure.