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Biomedical subjects

D A Henry

Publications and source records attributed to D A Henry.

At least 109 records · Page 6Linked to original sources

Omeprazole: effects on oxidative drug metabolism in the rat.

Omeprazole, a substituted benzimidazole and a potent gastric antisecretory drug has been tested for inhibition of microsomal drug oxidative function in the rat. A single dose of 40 mg/kg prolonged pentobarbitone sleeping times from 118 (range 73-168) min to 195 (159-222) min (P less than 0.01), pentobarbitone half-lives from 89 (63-114) to 112 (54-146) min (P less than 0.05) and aminopyrine breath 14CO2 half-lives from 43 (37-51) to 56 (49-79) min (P less than 0.05). Omeprazole in doses of 20 mg/kg or less had no significant effect. In prolonging pentobarbitone sleeping times omeprazole 40 mg/kg and an equimolar (30 mg/kg) dose of cimetidine were approximately equipotent. These results contrast with studies in man in which much smaller doses of omeprazole have been shown to produce clinically significant inhibition of drug metabolism.

Aminopyrine↗

Multiple imaging evaluation of sarcoidosis.

This extensive study of thoracic sarcoidosis calls attention to a number of unusual manifestations of the disease including airway compression, venous obstruction and direct pericardial and myocardial involvement.

Bronchography↗

Prevalence of type-specific group B streptococcal antibody in human sera: a study of 405 pregnant women.

Presence of immunoglobulin G antibody against the five standard serotypes of group B streptococcus was measured by means of indirect immunofluorescence in the sera of 405 women at the time of delivery in the obstetric hospital in Vancouver. Antibody to all five serotypes was present in 22% of women whereas only 9.6% had no detectable antibody to any serotype. Among 47 women with group B streptococcus vaginal colonization, IgG antibody was detected against the homologous colonizing serotype in 100%, 75%, 78%, 89%, and 100% of sera for serotypes Ia, Ib, Ic, II, and III, respectively. This contrasted with the women who had heterologous group B streptococcal vaginal colonization or no colonization in whom 71% had serum IgG antibody to serotype Ia, 36% to Ib, 51% to Ic, 66% to II, and 60% to III. Overall the serum antibody titers were low, and few women had titers greater than 1:20 for any of the five standard serotypes.

Antibodies, Bacterial↗

Somatostatin in treatment of haematemesis and melaena.

630 patients with haematemesis and melaena were randomly allocated to treatment by a constant intravenous infusion of either somatostatin or an apparently identical placebo in a double-blind controlled trial. Rebleeding was less common in treated patients (70 episodes in 315 individuals compared with 89 episodes in 315 controls) but the difference was not significant. Operation rates were virtually identical (35 treated patients and 34 controls), while there were slightly more deaths in the treated group than in the controls (31 and 25, respectively). These results are in clear disagreement with those of other smaller series. Though it is not possible to be completely sure that treatment is not useful in some individuals, earlier claims of marked benefit seem unlikely to be justified.

Clinical Trials as Topic↗

[14C]Aminopyrine breath analysis and conventional biochemical tests as predictors of survival in cirrhosis.

Twenty-eight patients with histologically confirmed cirrhosis were followed for up to 3.8 years after [14C]aminopyrine breath analysis. Survival rates were calculated by life-table method and outcome analyzed by log rank test. A normal breath test score was associated with a higher probability of survival than a low score, although the difference was not statistically significant. A normal serum albumin was a better predictor of outcome. Survival curves constructed according to the results of breath analysis and serum albumin differed in that the former appeared to predict early survival and the latter late survival. For this reason, data were reanalyzed by subjects' results for both tests. A normal breath test score and a normal serum albumin was associated with a significantly higher probability of survival than an abnormal result for either test.

Adult↗

Needle embolus: a unique complication of intravenous drug abuse.

We report a unique complication of intravenous drug abuse, central embolization of a needle from a peripheral site. A heroin addict dislodged a needle into the soft tissues of the forearm during self injection. Immediate surgical attempts to visualize and remove the needle were unsuccessful. On a subsequent admission, chest radiograph showed the needle in the right mid-lung field. No attempt at removal was made.

Adult↗

L-643.441: an H2-receptor antagonist with potent and long-lasting effects in man.

Submaximal dose pentagastrin tests conducted in normal male volunteers with L-643.441, a novel histamine H2-receptor antagonist, indicate that it is a potent and long-acting inhibitor of gastric acid secretion. The effect appears dose-dependent and single doses of 50 mg are sufficient to reduce secretory potential by at least 50% when examined 24 h after drug administration. No adverse effects attributable to treatment were observed.

Adult↗

Dose requirements and hemodynamic effects of transdermal nitroglycerin compared with placebo in patients with congestive heart failure.

The dose requirements and duration of effect of transdermal nitroglycerin in patients with heart failure are not clearly established. In a first series of eight patients with chronic heart failure we gave transdermal nitroglycerin in incremental doses until pulmonary capillary wedge pressure fell at least 30% within 4 hr in three consecutive patients. Thus we found that a single dose of 60 mg/24 hr (120 cm2) was the minimal effective dose. Transdermal nitroglycerin or placebo was then given as a single application of 60 mg/24 hr in random double-blind fashion to 15 additional patients with heart failure (eight received transdermal nitroglycerin and seven received placebo), and hemodynamics were monitored for up to 24 hr. After administration of transdermal nitroglycerin, the control pulmonary capillary wedge pressure of 22 +/- 7 mm Hg fell by 6 +/- 6 mm Hg at 2 hr (p less than .05) and reached maximal reduction of 8 +/- 6 mm Hg (p less than .01) at 4 hr. The reduction in wedge pressure remained significant through 12 hr but was no longer statistically significant by 18 hr after administration of the drug. Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures as well as pulmonary vascular resistance from 4 through 12 hr but did not affect systemic hemodynamics. No significant hemodynamic changes occurred after administration of placebo. Thus transdermal nitroglycerin is an effective vasodilator in patients with heart failure, but a dose of at least 60 mg/24 hr is needed. Even with this dose, hemodynamic effects do not last beyond 18 hr, suggesting altered absorption or development of tolerance.

Administration, Topical↗

Parenteral aluminum administration in the dog: I. Plasma kinetics, tissue levels, calcium metabolism, and parathyroid hormone.

Aluminum (Al) may cause both osteomalacia and encephalopathy in dialysis patients. Little is known about the biology of Al. This study examined the initial distribution kinetics of Al and its biological effects after injections of 1 mg/kg/day into dogs for 3 to 5 weeks. Following one intravenous dose, the plasma half-life (x +/- SE) was 276 +/- 51.8 min, with an apparent volume of distribution of 1.30 +/- 0.17 liters or 5.90 +/- 0.30% body wt; 10 to 21% of administered Al was excreted in the urine over 150 min, and the renal contribution to plasma clearance of Al correlated with GFR (r = 0.77, P less than 0.05). The total plasma clearance of Al (4.43 +/- 2.83 ml/min) exceeded the renal contribution to plasma clearance (1.94 +/- 0.36 ml/min) in each dog, and in only two instances did the renal contribution reach 50% of total plasma clearance. Serum calcium rose from 9.4 +/- 0.2 to 11.1 +/- 0.3 mg/dl and immunoreactive parathyroid hormone (iPTH) fell by 27 +/- 4% following one Al injection. With repeated Al injections, serum calcium increased from baseline levels of 10.2 +/- 0.07 mg/dl to 11.1 +/- 0.22 and 11.3 +/- 0.46 mg/dl after 1 and 2 weeks, respectively. Renal function declined in all dogs, and serum creatinine exceeded 3.5 mg/dl in four; over the 5 weeks of study, serum calcium correlated with serum creatinine (r = 0.91, P less than 0.001). Liver, kidney, and spleen showed the highest tissue content of Al, and there was substantial uptake by bone; the parathyroid content of Al was modest.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

Parenteral aluminum administration in the dog: II. Induction of osteomalacia and effect on vitamin D metabolism.

There is an association between bone aluminum (Al) accumulation and dialysis-associated osteomalacia (OM). To study whether Al is pathogenic in OM, quantitative bone histomorphometry was done in six dogs before (Bx 1) and after (Bx 2) 3 to 5 weeks of intravenous Al administration (1 mg Al /kg/day). Bone Al was determined by histochemical and chemical methods. The percent osteoid rose from 2.8 +/- 0.8 to 7.0 +/- 4.3% (mean +/- SD), P less than 0.05, and osteoid width increased from 5.7 +/- 0.6 to 8.0 +/- 1.2 mu, P less than 0.01, after Al. Bone Al rose from 1.3 +/- 1.6 to 94.0 +/- 19.0 mg/kg after Al, and the severity of OM, expressed as either percent forming surface or percent osteoid, correlated with bone Al measured histochemically and expressed as either percent surface or percent area of trabecular bone staining for Al (r = 0.85 - 0.90, P less than 0.01). Poor tetracycline uptake (six dogs), which indicates impaired mineralization, and little or no separation of tetracycline labels (four dogs) were noted at Bx 2; thus, bone apposition and formation rates were below the limits of detection. Resorptive surface did not change but trabecular volume, expressed as percent of tissue volume, fell from 22.1 +/- 3.0 to 17.1 +/- 1.4%, P less than 0.05. Serum levels of 1,25(OH)2D fell from 26.8 +/- 9.1 to 4.5 +/- 5.5 pg/ml after 17 days of Al; serum 25(OH)D levels were unchanged. These data indicate that Al can cause OM and that its severity correlates with the bone Al content.2 +

Aluminum↗

Omeprazole: effects on oxidative drug metabolism.

Omeprazole, a substituted benzimidazole, and a potent inhibitor of gastric parietal cell H+/K+ ATPase, was tested for drug interactions at two dose levels (30 mg and 60 mg/day) in man using the model drugs [14C]-aminopyrine and antipyrine. Elimination of both models was assessed before and after 15 days treatment with omeprazole. In addition [14C]-aminopyrine metabolism was assessed on day 2 of treatment to investigate the rapidity of onset of any effect. In 10 healthy male volunteers omeprazole 60 mg/day for 14 days prolonged aminopyrine 14CO2 half life (t1/2), measured on the 15th day, by 21% (P less than 0.05), and reduced percent dose demethylated in 2 h (ABT2) by 19% (P less than 0.005). No effect was seen on day 2 of therapy. After 14 days treatment antipyrine half-life was prolonged by 10% (P less than 0.025) and clearance was reduced by 14% (P = 0.063). In nine healthy male volunteers omeprazole 30 mg/day for 14 days prolonged aminopyrine 14CO2 by 13% and reduced ABT2 by 11%. Both changes just failed to reach statistical significance. At this dose antipyrine metabolism was unaltered. As the dose of omeprazole used in clinical practice may be less than 30 mg/day it is unlikely that metabolic inhibition will occur during routine use, although it will be necessary to test for interactions with therapeutically more important compounds. Interactions should be looked for when large doses of omeprazole are being used to treat hypersecretory states.

Adult↗

Renal osteodystrophy.

As is apparent from the preceding discussion, renal osteodystrophy is a complex entity with multiple causes and many manifestations. Significant problems have included the identification and management of the various forms of bone disease seen in uremia. The prevention and therapy of osteitis fibrosa and secondary hyperparathyroidism have been significantly improved as a result of adequate phosphate restriction and the use of active forms of vitamin D (primarily calcitriol in the U.S., dihydrotachysterol and 1 alpha-hydroxyvitamin D in Europe). Recently, a major problem has been the recognition of bone disease due to aluminum accumulation. The therapy of this bone disease was generally unsuccessful until recent preliminary data suggested that deferoxamine therapy may be useful in these patients. The study of renal osteodystrophy has certainly advanced our knowledge of mineral metabolism, with clarification of the metabolism and action of PTH and vitamin D metabolism and identification of the pathogenic role for aluminum. In the future, most manifestations of renal osteodystrophy may be preventable or adequately treated.

Alkaline Phosphatase↗

Tracheal stenosis in sarcoidosis.

A 58-year-old woman with sarcoidosis had dyspnea found to be caused by a rare manifestation of that disease--tracheal stenosis. Tracheal dilatation has been beneficial.

Female↗