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Biomedical subjects

K B Klein

Publications and source records attributed to K B Klein.

9 recordsLinked to original sources
PubMed1999

Design of treatment trials for functional gastrointestinal disorders.

Until recently many clinical trials of functional gastrointestinal disorders (FGIDs) suffered from important weaknesses in trial design, study execution, and data analysis. This makes it difficult to determine whether truly efficacious therapies exist for these disorders. One of the important methodologic problems is the absence of validated outcome measures and lack of consensus among stakeholders on how to measure outcome. Currently much of the effort is being put into the development of validated outcome measures for several of the FGIDs. The randomized, controlled trial with parallel groups is the design of choice. In this report, guidelines are given for the basic architecture of intervention studies of FGIDs. Further studies on design issues are required to ensure the recommendations will become evidence based in the future.

Cross-Over Studies↗
PubMed1996

311C90, a new central and peripherally acting 5-HT1D receptor agonist in the acute oral treatment of migraine: a double-blind, placebo-controlled, dose-range finding study.

311C90 is a novel, centrally and peripherally, acting 5-hydroxytryptamine1D receptor agonist. We investigated the efficacy and safety of 1, 5, and 25 mg of oral 311C90 in the acute treatment of migraine in a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 84 patients. The proportion of patients in whom the headache improved within 2 hours from moderate or severe to mild or no pain (primary efficacy measure) was 15% for placebo-treated patients and 27% (1 mg), 62% (5 mg), and 81% (25 mg) for patients treated with 311C90. Treatment differences compared with placebo were 12% (95% CI - 12, 37; p = 0.460) for 1 mg 311C90, 47% (CI 21, 73; p < 0.005) for 5 mg 311C90, and 66% (CI 43,89; p < 0.001) for 25 mg 311C90. Photophobia and nausea also showed improvement after 311C90. Adverse events were generally mild and transient in all treatment groups. There were no clinically significant changes in ECG recordings, blood pressure, or laboratory tests. Oral 311C90 (5 and 25 mg) is highly effective and well tolerated in the acute treatment of migraine. The response rates and treatment differences compared with placebo in this study suggest possible superiority over existing antimigraine therapies. This needs to be confirmed in formal comparative trials.

Administration, Oral↗
PubMed1989

Pharmacokinetics of acrivastine after oral and colonic administration.

Six healthy male volunteers participated in this randomized, crossover open-label pharmacokinetic study consisting of two dosing segments separated by a washout period of at least 5 days. During each dosing segment, each volunteer received 12 mg of acrivastine, an investigational histamine H1-receptor antagonist, in a syrup form either orally or by colonic administration in random order. After oral and colonic administration, respectively, the following mean +/- SD pharmacokinetic parameters were obtained: Cmax 179 +/- 11 and 13.8 +/- 5.2 ng/ml; tmax, 0.85 +/- 0.13 and 3.60 +/- 0.56 hr; AUC0-12 hr, 576 +/- 57 and 104 +/- 46 hr.ng/ml. Differences between the oral and colonic administration for all three parameters were statistically significant (P less than 0.001). The mean +/- SD relative bioavailability of acrivastine from colonic compared to oral dosing was 0.18 +/- 0.09. It may be concluded, therefore, that appreciable absorption of acrivastine from the colon does not take place. These results suggest that comparison of pharmacokinetic profiles of some drugs after oral and colonic administration may be a useful technique for predicting bioavailability from a sustained release oral formulation.

Administration, Oral↗
PubMed1989

Modulation of gastric acid secretion by hypnosis.

The ability of hypnosis to both stimulate and inhibit gastric acid secretion in highly hypnotizable healthy volunteers was examined in two studies. In the first, after basal acid secretion was measured, subjects were hypnotized and instructed to imagine all aspects of eating a series of delicious meals. Acid output rose from a basal mean of 3.60 +/- 0.48 to a mean of 6.80 +/- 0.02 mmol H+/h with hypnosis, an increase of 89% (p = 0.0007). In a second study, subjects underwent two sessions of gastric analysis in random order, once with no hypnosis and once under a hypnotic instruction to experience deep relaxation and remove their thoughts from hunger. When compared to the no-hypnosis session, with hypnosis there was a 39% reduction in basal acid output (4.29 +/- 0.93 vs. 2.60 +/- 0.44 mmol H+/h, p less than 0.05) and an 11% reduction in pentagastrin-stimulated peak acid output (28.69 +/- 2.34 vs. 25.43 +/- 2.98 mmol H+/h, p less than 0.05). We have shown that different cognitive states induced by hypnosis can promote or inhibit gastric acid production, processes clearly controlled by the central nervous system. Hypnosis offers promise as a safe and simple method for studying the mechanisms of such central control.

Adult↗
PubMed1988

Controlled treatment trials in the irritable bowel syndrome: a critique.

The irritable bowel syndrome (IBS) is a common and poorly understood chronic condition that is treated with a great variety of drugs and other therapies without notable enduring success. As there are no objective markers of improvement, and because there may be a very large placebo response, potential treatments for IBS are difficult to assess. Probably the only method that can reliably evaluate IBS therapies is the randomized, double-blind, placebo-controlled treatment trial. The purpose of this review is to critically examine issues central to establishing the efficacy of treatments for IBS in such trials. These include the definition of IBS, measures of efficacy, the placebo response, trial length, maintaining blindedness, the crossover design, ability to generalize, and statistical considerations. With this background, all published IBS treatment trials are examined. It is concluded that not a single study offers convincing evidence that any therapy is effective in treating the IBS symptom complex. Well-designed and executed IBS treatment trials are urgently needed; suggestions are given for essential features of such trials.

Clinical Trials as Topic↗
PubMed1987

Metabolic bone disease in asymptomatic men after partial gastrectomy with Billroth II anastomosis.

We sought to determine whether gastric surgery might be associated with metabolic bone disease in a well-characterized population, and if so to explore its etiology. Sixteen asymptomatic middle-aged men who had had partial gastrectomy with Billroth II anastomosis but no other risk factors for metabolic bone disease were compared with unoperated healthy controls. Studies included a dietary survey, biochemical tests of bone and mineral metabolism, radiographs of the spine, determinations of bone mineral content, and bone histomorphometry. The gastric surgery subjects exhibited frequent vertebral fractures and an unusual constellation of bone abnormalities characterized by decreased bone mineral content and hyperosteoidosis without evidence of osteomalacia. Although serum immunoreactive parathyroid hormone and 25-hydroxyvitamin D levels were not different, 1,25-dihydroxyvitamin D levels were significantly higher (p = 0.037), and 24,25-dihydroxyvitamin D levels were significantly lower (p less than 0.0001) in subjects than in controls. Partial gastrectomy with Billroth II anastomosis may be associated with asymptomatic but clinically important metabolic bone disease. The pathophysiology is uncertain, but appears to involve alterations in vitamin D metabolism.

Bone Diseases, Metabolic↗