Biomedical subjects
R Marwaha
Publications and source records attributed to R Marwaha.
Magnetic resonance imaging of the brain in idiopathic hypogonadotropic hypogonadism.
Magnetic resonance imaging (MRI) of the pituitary, hypothalamus and olfactory sulci was performed in 40 patients with idiopathic hypogonadotropic hypogonadism (IHH). Twelve of these patients had an impaired sense of smell (Kallmann's syndrome). Sagittal and coronal imaging revealed no morphological abnormalities in the hypothalamic-pituitary region. On axial imaging rudimentary, hypoplastic or aplastic olfactory sulci were found in eight cases. All patients with olfactory sulcal abnormalities had associated hyposmia (one case) or anosmia (seven cases). Structural defects identifiable on MRI were present only in 20 per cent of patients with IHH.
Hydrocephalus presenting as precocious puberty.
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Hypothalamo-pituitary axis by magnetic resonance imaging in isolated growth hormone deficiency patients born by normal delivery.
Magnetic resonance imaging was performed using a 1.5 Tesla magnet in 22 children (14 boys and 8 girls) between 5-20 yr of age with isolated GH deficiency (IGHD), born by normal vaginal delivery without any birth asphyxia or trauma. A total of 22 children (10 boys and 12 girls) without short stature and endocrine disease were evaluated as controls. The IGHD group had a height velocity less than 4 cm/yr and delayed bone age. The peak GH levels were less than 10 micrograms/L (mean, 2.4 micrograms/L). The height of the pituitary gland ranged from 3-7.5 mm in controls. An intact stalk was observed in 21 children with IGHD, with nonvisualization in 1. An apparently thin stalk was seen in 6. The posterior lobe identified by the hyperintensity signal, had a mean diameter of 1.84 mm and was located in a normal position in 21 children. An ectopic posterior pituitary hyperintensity was present in 1 patient. The anterior pituitary was hypoplastic in 17 children, with partial empty sella in 13. A total of 5 children had associated brain anomalies, such as Arnold Chiari malformation, craniovertebral malformation with basilar impression, degenerative plaques around posterior horn of lateral ventricle and parietal area, and infarcts in caudate nucleus and putamen. These findings suggest that IGHD was not related to transection or compression of the stalk.
The comparative effects of verapamil and a new dihydropyridine calcium channel blocker on digoxin pharmacokinetics.
Conflicting conclusions have been reported about interaction of calcium channel blockers with digoxin. The effects of verapamil (240 mg/day) and a new dihydropyridine calcium channel blocker, isradipine (15 mg/day), on the pharmacokinetics of 1 mg intravenous digoxin were compared. All 24 volunteer subjects were healthy, male, nonobese, and aged 18 to 38 years. Groups of 12 subjects received each oral agent over 15 days, with collections of blood and urine for 72 hours after intravenous digoxin. Significant (P less than 0.05) reduction in nonrenal (7.01 +/- 1.97 to 4.00 +/- 1.86 L/hr) and total clearance (14.1 +/- 2.6 to 11.5 +/- 2.5 L/hr) were induced by verapamil, without change in renal clearance. A near-significant (P less than 0.1) increase in peripheral volume of distribution contributed to prolonged elimination half-life (23.1 +/- 4.4 to 34.3 +/- 9.7 hours). By contrast, isradipine caused only a 9% reduction in volume of distribution. Verapamil causes digoxin accumulation by reducing nonrenal elimination. No evidence of clinically relevant interaction of isradipine with digoxin was seen.
The influence of pindolol and hydrochlorothiazide on blood pressure, and plasma renin and plasma lipid levels.
After three weeks' administration of placebo, three groups of eight patients with moderate hypertension were randomly assigned to single daily dose, double-blind treatment with either pindolol 15 mg, hydrochlorothiazide 50 mg, or a combination of both for eight weeks. All determinations were made 24 hours after ingestion of a dose. Reductions in supine, sitting, and standing systolic and diastolic blood pressure were greater in patients receiving hydrochlorothiazide than in those administered pindolol; however, the greatest reductions were registered in individuals receiving combination therapy. Mean basal plasma renin activity rose significantly from 0.45 +/- 0.44 to 1.42 +/- 1.31 ng/mL/hr and from 0.67 +/- 0.46 to 1.27 +/- 0.83 ng/mL/hr in patients receiving hydrochlorothiazide and combination therapy, respectively, but there was no change in those administered pindolol. Hydrochlorothiazide and combination therapy increased mean total cholesterol levels from 247 +/- 25 to 263 +/- 37 mg/dL and 198 +/- 36 to 211 +/- 33 mg/dL, respectively, at eight weeks, and both increased mean triglyceride concentrations at two weeks. Pindolol did not show any tendency to alter lipid levels. Pindolol should be given twice daily. At 15 mg daily, it has little or no effect on basal plasma renin activity or plasma lipid levels.
Variability of steady-state digoxin kinetics during administration of tablets or capsules.
An encapsulated solution of digoxin has been repeatedly shown to have greater bioavailability than tablet forms of the drug. It is predicted that such a preparation would show reduced within- and between-patient variability in absorption, as most studies in normal subjects have shown reduced intersubject variation with the capsule. We tested inter- and intrapatient variability during 4-week periods of dosing with digoxin capsules and tablets in 28 subjects with cardiac disease. In the overall group there were no significant differences between the formulations at steady state in between-patient variability in trough serum digoxin concentrations or 24-hour urinary digoxin excretion. Within-patient variability in urinary digoxin excretion was somewhat lower for the capsules. In a subgroup of six patients who excreted significant amounts of cardioinactive bacterial metabolites (digoxin reduction products [DRP]), the mean (+/- SD) percent urinary DRP excretion was less (p less than 0.05) during capsule (20.5% +/- 15.1%) than tablet (34.4% +/- 10.9%) dosing. Within-patient variability in urinary DRP excretion was much greater after tablets than capsules. Certain subgroups of patients should benefit from the enhanced bioavailability of digoxin capsule preparations.
Hemodynamic and metabolic effects of the calcium channel blocking agent nitrendipine.
In an open crossover comparison of propranolol and nitrendipine, 19 patients with hypertension received 40 to 160 mg propranolol and 5 to 20 mg nitrendipine twice a day. Mean (+/- SD) predose supine blood pressure fell from 145/98 +/- 11/7 to 132/88 +/- 12/8 mm Hg with propranolol and to 135/92 +/- 11/9 mm Hg with nitrendipine. Resting heart rate was reduced by propranolol but was unchanged 12 hours after nitrendipine dosing. Neither propranolol nor nitrendipine altered plasma glucose or insulin after oral glucose. Propranolol significantly increased fasting triglyceride levels and reduced high-density lipoprotein cholesterol levels, but nitrendipine induced no change. Propranolol reduced and nitrendipine increased plasma renin activity after exercise. Peak plasma nitrendipine levels were dose proportional and occurred at 1 to 2 hours after dosing, whereas peak blood pressure reductions occurred 4 hours after the last dose of nitrendipine and were associated with mean increases in heart rate. Nitrendipine is almost equivalent in hypotensive effect to propranolol, but nitrendipine increases plasma renin activity after exertion and may produce transient tachycardia. However, nitrendipine does not cause unwanted metabolic effects.
The effects of thiazide diuretics upon plasma lipoproteins.
In a double-blind, placebo-controlled, crossover study in 16 hypertensives, 4 weeks of 50 mg hydrochlorothiazide twice daily, caused significant elevations in total plasma cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, very low density lipoprotein (VLDL)-cholesterol and triglycerides. Significant elevations in fasting plasma glucose and in plasma insulin were observed, but no correlation between individual lipid elevations and either glucose or insulin elevations was apparent. The metabolic effects developed within 2 weeks, and dissipated within 4 weeks. Changes induced within 4 weeks of treatment with hydrochlorothiazide were unaltered at 6 months. Hydrochlorothiazide induces elevation of all lipoprotein cholesterol fractions and VLDL-triglyceride. However, as the important ratio between LDL- and HDL-cholesterol is unchanged, coronary risk may be unchanged.
Comparative effects of propranolol and prazosin upon serum lipids in thiazide- treated hypertensive patients.
Earlier reported thiazide-induced changes in serum lipid concentrations were confirmed with increased triglyceride and total cholesterol levels. However, lipoprotein cholesterol ratios were unchanged. Propranolol caused further increases in triglyceride and very low-density lipoprotein cholesterol, and lowered high-density lipoprotein cholesterol and the high-density lipoprotein:total cholesterol ratio. With the addition of prazosin to the polythiazide regimen, there was a significant increase in serum high-density lipoprotein cholesterol when compared with the placebo.
Effect of metoclopramide on digoxin absorption from tablets and capsules.
The effect of metoclopramide, a drug that increases gut motility, on the consistency of digoxin absorption was examined in 16 healthy men. Each received the following four single-dose digoxin treatments in complete crossover fashion: two 0.25-mg digoxin tablets, alone, and two 0.2-mg digoxin capsules with metoclopramide. Mean serum AUCs over 24 hr (AUC-24) and cumulative urinary digoxin excretion over 48 hr (CUE-48) were of the same order for the tablets and capsules alone treatments. Metoclopramide reduced the mean AUC-24 for tablets from 12.26 +/- 2.70 to 9.38 +/- 3.78 ng X hr/ml (P less than 0.001) and the CUE-48 from 119.0 +/- 22.4 to 97.6 +/- 22.2 micrograms (P less than 0.01). There were no significant differences in mean AUC-24 (12.94 +/- 3.16 and 13.45 +/- 2.33 ng X hr/ml) and mean CUE-48 (117.8 +/- 23.4 and 109.7 +/- 25.0 micrograms) when capsules alone were compared to capsules with metoclopramide. Metoclopramide reduced the time to reach peak concentration for both digoxin dosage forms. The effect of metoclopramide on digoxin absorption is minimized by administration of digoxin in capsules.
Sinus histiocytosis with massive lymphadenopathy.
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Comparative clinical evaluation of two salts of quinidine using 24-hour Holter monitor recordings.
In 13 patients admitted to a coronary care unit, antiarrhythmic efficacy and safety of quinidine gluconate in a nonmatrix formulation were compared to placebo and quinidine sulfate. Both quinidine preparations were effective in reducing the number and severity of ventricular and supraventricular extrasystoles when compared to placebo. Except for a few cases in which quinidine gluconate was significantly more effective, both quinidine preparations appear to have similar clinical antiarrhythmic efficacy and duration of action. A 24-hour Holter ECG monitoring device and electrocardioscanner were utilized in this research. No major unexpected adverse effects were observed.
Lung function in Indian smokers.
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