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Biomedical subjects

G H Elta

Publications and source records attributed to G H Elta.

At least 37 records · Page 2Linked to original sources
PubMed1993

Stereoselective, competitive, and nonlinear plasma protein binding of ibuprofen enantiomers as determined in vivo in healthy subjects.

The plasma protein binding and competitive inhibition parameters of R(-)- and S(+)-ibuprofen were determined in vivo in 12 healthy subjects. Subjects participated in a 4 x 4 Latin square design in which oral solutions of drug were administered as 300 mg R(-)-ibuprofen, 300 mg S(+)-ibuprofen, 300 mg R(-)- + 300 mg S(+)-ibuprofen, and 300 mg R(-)- + 600 mg S(+)-ibuprofen. Unlabeled ibuprofen enantiomers were quantitated using a stereospecific reversed-phase HPLC assay, and plasma protein binding experiments were performed using radiolabeled 14C-enantiomers and an ultrafiltration method at 37C. At therapeutic drug concentrations, the protein binding of each enantiomer was greater than 99%. Furthermore, the binding of ibuprofen enantiomers was stereoselective and mutually competitive, as well as nonlinear. The bound-free data were fitted to a model in which the non-linearity of plasma protein binding and competition between enantiomers for binding sites could be accommodated. There were substantial differences in the affinity of ibuprofen enantiomers for protein binding sites (RP2 = 0.358 +/- 0.185 vs. SP2 = 0.979 +/- 0.501 micrograms/ml; mean +/- SD) but no differences in their binding capacity (RP1 = 160 +/- 86 vs. SP1 = 161 +/- 63 micrograms/ml). Although statistically significant, the differences in competitive inhibition parameters were more modest (SKI = 0.661 +/- 0.363 vs. RKI = 0.436 +/- 0.210 micrograms/ml). As a result, the intrinsic binding (i.e., P1/P2) of R(-)-ibuprofen was greater than S(+)-ibuprofen, and the unbound fraction was significantly greater for S-enantiomer vs. R-enantiomer after a given dose of R-ibuprofen or racemate.

Adult↗
PubMed1992

Absorption of flurbiprofen in the fed and fasted states.

The oral absorption of flurbiprofen, an antiinflammatory nonsteroidal compound, was compared in the fasted vs the fed state. When ingested as an aqueous solution of the sodium salt, absorption kinetics followed a monoexponential pattern in half of the subjects and a bimodal pattern with a lag time before the onset of the second phase of absorption in the other half of the subjects. When ingested in the free acid form as a tablet either with water (fasted state) or with water 15 min after 330 ml of apple juice (fed state), flurbiprofen absorption was always bimodal, and the lag time before the onset of the second phase was shown to be dependent on the gastric emptying time (r = 0.623, P less than 0.01). The gastric emptying times were significantly longer when the drug was administered in the fed state (average GET = 57 min in the fasted state and 102 min in the fed state; P less than 0.01). These results suggest that gastric emptying effects are one important way in which absorption of drugs can be affected by meal intake.

Administration, Oral↗
PubMed1991

Injection sclerotherapy-induced esophageal strictures. Risk factors and prognosis.

Injection sclerotherapy (IS) has become an effective modality for the treatment of bleeding esophageal varices. Despite improvements in equipment, sclerosant solutions and operator technique, injection sclerotherapy-induced esophageal strictures (ISES) remain a significant cause of patient morbidity. To analyze the risk factors and prognosis of ISES, the records of 117 patients who underwent IS over a 6-year period at a single teaching institute were reviewed. The predictive value of multiple risk factors including the patient's age, Child's risk classification, previous bleeding episodes, etiology of varices, cumulative amount of sclerosant used, and the number of IS treatments were determined using ANOVA. A P value of less than 0.05 was considered significant. In all cases, a free-hand injection technique, flexible endoscopes and sodium morrhuate were used. During a mean follow-up period of 228 days (1-1,469 days), 41 patients (35%) died and 24 patients (20.5%) developed symptomatic strictures. The cumulative amount of sclerosant used (81.4 +/- 9.5 ml) and the number of IS treatments (6.5 +/- 0.7) required in the stricture group was significantly greater than in the nonstricture group (49.1 +/- 2.7 and 4.0 +/- 0.3, respectively). The risk of stricture formation did not correlate with the volume of sclerosant injected per treatment, cause of varices, number of previous bleeds, or Child's hepatic risk class. A mean of 3.6 +/- 4.5 dilations was required for treatment of established strictures and 18 patients (75%) required r 4 dilations. One esophageal perforation occurred following dilation. Mortality correlated with hepatic risk class as 30/41 (73%) of deaths occurred in Child's C patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal Stenosis↗
PubMed1990

Gastroduodenal mucosal damage with salsalate versus aspirin: results of experimental models and endoscopic studies in humans.

Animal models have identified multiple mechanisms of aspirin toxicity. Aspirin inhibits cyclooxygenase in the gastroduodenal mucosa leading to a decrease in endogenous prostaglandins. Prostaglandin mediated mucus and bicarbonate secretion, epithelial hydrophobicity, blood flow, and cellular proliferation are all decreased. Salicylates may cause direct cellular toxicity via inhibition of energy metabolism and membrane transport properties. Salicylate preparations have been designed to decrease gastroduodenal absorption. Endoscopic studies in humans have confirmed that buffering of aspirin does not ameliorate damage, but enteric coating does. Salicylsalicylic acid (salsalate) is an effective antirheumatic drug that bypasses gastric absorption and also avoids cyclooxygenase inhibition. In a randomized, single-blind, endoscopic comparison of salsalate versus enteric-coated aspirin, significantly less gastroduodenal damage was observed in volunteers after salsalate administration compared to enteric-coated aspirin. An endoscopic study in rheumatoid arthritics also confirmed the ability of salsalate to spare gastroduodenal mucosa when compared to naproxen administration. Salsalate may cause less gastroduodenal damage than enteric-coated aspirin based on the results of animal models and endoscopic studies in humans.

Animals↗
PubMed1990

Comparison of coffee intake and coffee-induced symptoms in patients with duodenal ulcer, nonulcer dyspepsia, and normal controls.

Coffee and decaffeinated coffee stimulate acid secretion. In addition, many patients experience dyspepsia after coffee ingestion. Therefore, coffee is often prohibited by physicians in patients with peptic diseases. However, the association between peptic disease and symptoms remains unclear. This study compares coffee intake and the induction of symptoms by coffee in patients with duodenal ulcer disease, nonulcer dyspepsia, and normal controls. We have studied the coffee drinking habits of 58 duodenal ulcer patients, 55 nonulcer dyspepsia patients, and 55 normal controls. The use of coffee on a daily basis was not significantly different between duodenal ulcer patients (64%) and controls (56%), or between nonulcer dyspepsia patients (55%) and controls. There was also no difference between the three groups in the use of decaffeinated coffee, the number of cups per day, the method of preparation, the length of time of coffee use, or any change in coffee intake in the previous year. The intake of tea, caffeinated carbonated beverages, and aspirin or nonsteroidal anti-inflammatory drugs was also similar in the three groups. The duodenal ulcer patients were more likely to be cigarette smokers (45%) than either the controls (16%) or the nonulcer dyspepsia patients (24%). Daily alcohol intake was not significantly different in the three groups. The prevalence of coffee induction of dyspeptic symptoms was similar in duodenal ulcer patients (29%) and controls (22%), but was much more common in nonulcer dyspepsia patients (53%) than in controls (22%), p = 0.0036. In conclusion, there was no difference in coffee intake between patients with duodenal ulcer, nonulcer dyspepsia, or normal controls. However, patients with nonulcer dyspepsia, but not duodenal ulcer, were more likely to experience dyspeptic symptoms after coffee ingestion.

Caffeine↗
PubMed1990

Persistent immune deficiency in patients with alcoholic hepatitis.

T-lymphocyte subset numbers, recall-antigen skin test responses and mitogen-induced lymphocyte proliferation assays were investigated in 12 patients with severe alcoholic hepatitis (AH). Serial studies of these parameters were obtained at intervals of 1 or 2 wk. Patients with AH had lower peripheral blood lymphocyte counts with corresponding decreases in T-cell subset numbers that were persistent in the serial evaluations. T8 cells were disproportionately decreased, with a significant resultant increase in the T4:T8 ratios. Compared with controls, AH patients had significantly smaller cutaneous responses to Candida albicans antigen (p less than 0.05) and mumps antigen (p less than 0.005). Fifty-eight percent of patients were anergic when tested with a battery of four antigens. Patients with AH had increased concanavalin A-, but not phytohemagglutinin-induced lymphocyte proliferative responses. These serial analyses confirm previous observations of cell-mediated immune dysfunction in patients with severe AH. Moreover, there is a persistence of these abnormalities for at least 6 wk after withdrawal from alcohol.

Hepatitis, Alcoholic↗
PubMed1989

Salicylsalicylic acid causes less gastroduodenal mucosal damage than enteric-coated aspirin. An endoscopic comparison.

The gastroduodenal mucosal damage caused by aspirin and nonsteroidal antiinflammatory drugs is a common clinical problem. We compared two medications designed to diminish mucosal damage: enteric-coated aspirin and salicylsalicylic acid (salsalate). Ten healthy volunteers were randomized to receive either 1.5 g salsalate twice a day or 650 mg enteric-coated aspirin four times a day for six days and were then crossed over to the other drug after a one-week medication-free period. Endoscopic inspection of gastroduodenal mucosa was performed at entry and again after six days of drug therapy for each medicine. Mean serum salicylate concentrations taken before the morning drug dose were 11.2 mg/dl for enteric-coated aspirin and 18.1 mg/dl for salsalate. Only one of 10 subjects receiving salsalate developed mild (grade 1) mucosal damage while six of 10 receiving enteric-coated aspirin developed moderate to severe damage (grade 2-3) (P = 0.01). Symptoms were mild in both groups. We conclude that salsalate causes less gastroduodenal mucosal damage than enteric-coated aspirin.

Adolescent↗