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Biomedical subjects

J G Morel

Publications and source records attributed to J G Morel.

8 recordsLinked to original sources

Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: meta-analysis of 8 controlled trials.

BACKGROUND: Soluble fibers, including those from psyllium husk, have been shown to augment the cholesterol-lowering effects of a low-fat diet in persons with hypercholesterolemia. As evidence of this, the US Food and Drug Administration recently authorized the use of health claims on food products containing soluble fiber from psyllium that state that they are associated with a decreased risk of coronary heart disease. OBJECTIVE: This meta-analysis was conducted to more precisely define the hypolipidemic effects and safety of psyllium when used adjunctive to a low-fat diet in men and women with hypercholesterolemia. DESIGN: The 8 studies in the meta-analysis included a total of 384 and 272 subjects receiving psyllium or cellulose placebo, respectively. All studies evaluated the hypocholesterolemic effects of 10.2 g psyllium/d adjunctive to a low-fat diet for >/=8 wk in individuals with mild-to-moderate hypercholesterolemia after a low-fat diet lead-in phase lasting >/=8 wk. The safety and adverse events associated with psyllium consumption were summarized from pooled data of 19 clinical studies ranging from 6 wk to 6 mo in duration. RESULTS: Consumption of 10.2 g psyllium/d lowered serum total cholesterol by 4% (P < 0.0001), LDL cholesterol by 7% (P < 0.0001), and the ratio of apolipoprotein (apo) B to apo A-I by 6% (P < 0.05) relative to placebo in subjects already consuming a low-fat diet, with no effect on serum HDL or triacylglycerol concentrations. CONCLUSIONS: Psyllium supplementation significantly lowered serum total and LDL-cholesterol concentrations in subjects consuming a low-fat diet. Psyllium is well tolerated and safe when used adjunctive to a low-fat diet in individuals with mild-to-moderate hypercholesterolemia.

Adult↗

Psyllium is superior to docusate sodium for treatment of chronic constipation.

BACKGROUND: Stool softening is a physician's first step in the management of chronic constipation. AIM: To compare stool softening (stool water content) and laxative efficacy of psyllium hydrophilic mucilloid vs. docusate sodium. METHODS: The multi-site, randomized, double-blind, parallel-design study of 170 subjects with chronic idiopathic constipation involved a 2-week baseline (placebo) phase followed by 2 weeks of treatment. The treatment phase compared psyllium (5.1 g b.d.) plus docusate placebo to docusate sodium (100 mg b.d.) plus psyllium placebo. Stools were collected and assessed. RESULTS: Compared to baseline, psyllium increased stool water content vs. docusate (psyllium 2.33% vs. docusate 0.01%, P = 0.007). Psyllium also increased stool water weight (psyllium 84.0 g/BM; docusate 71.4 g/BM; P = 0.04), total stool output (psyllium 359.9 g/week: docusate 271.9 g/week; P = 0.005), and O'Brien rank-type score combining objective measures of constipation (psyllium 475.1; docusate 403.9; P = 0.002). Bowel movement (BM) frequency was significantly greater for psyllium (3.5 BM/week) vs. docusate (2.9 BM/week) in treatment week 2 (P = 0.02), with no significant difference (P > 0.05) between treatment groups in treatment week 1 (3.3 vs. 3.1 BM/week). CONCLUSION: Psyllium is superior to docusate sodium for softening stools by increasing stool water content, and has greater overall laxative efficacy in subjects with chronic idiopathic constipation.

Adult↗

Clustered binary logistic regression in teratology data using a finite mixture distribution.

The beta-binomial distribution introduced by Skellam has been applied in many teratology problems for modelling the litter effect. Recently, Morel and Nagaraj proposed a new distribution for modelling cluster multinomial data when the clustering is believed to be caused by clumped sampling. It turns out that the distribution is a mixture of two binomial distributions and accommodates the estimation of an additional parameter to account for intra-litter effect. The new distribution arises from a cluster mechanism in which some individuals within a cluster exhibit the same behaviour while the remaining individuals from the cluster react independently of each other. Such a mechanism is a natural model in teratology problems, where typically a genetic trait is passed with a certain probability to the foetuses of the same litter. In this article, we use the new distribution to model binary responses with logistic regression. We analyse data from a teratology experiment to demonstrate that the new model provides a useful addition to current methodology. The experiment investigates the synergistic effect of the anticonvulsant phenytoin and trichloropopene oxide on the prenatal development of inbred mice. In a simulation study we investigate the type I error rate and the power of the maximum likelihood ratio test when the data follow a finite mixture distribution.

Animals↗

Influence of a methanogenic flora on the breath H2 and symptom response to ingestion of sorbitol or oat fiber.

BACKGROUND AND OBJECTIVES: We investigated the possibility that a variant of the normal colonic flora, a high concentration of methanogens, influences the host's response to ingestion of nonabsorbable, fermentable materials. METHODS: To better evaluate symptomatic and breath H2 and methane (CH4) responses, subjects were placed on a basal diet (primarily rice and hamburger) that contained minimal amounts of nonabsorbable, fermentable substrate. A breath CH4/H2 ratio of greater or less than 1 on the second day of the basal diet was used to categorize subjects as high (N = 9) or low (N = 25) CH4 producers. After stabilization of the breath gas excretion (day 3 or 4 on the basal diet), the subjects ingested either sorbitol (8.8 g) or oat fiber (10.2 g). RESULTS: The low CH4 producers had a significantly higher (p < 0.05) breath H2 concentration than the high producers on the basal diet and after ingestion of sorbitol (27.1 +/- 2.7 ppm vs 15.8 +/- 3.6 ppm) or oat fiber (13.1 +/- 0.08 ppm vs 9.6 +/- 1.2 ppm). Low producers of methane reported significantly increased bloating and cramping after sorbitol ingestion and increased bloating after fiber ingestion, whereas high CH4 producers reported no significant increase in these symptoms. CONCLUSION: The presence of a methanogenic flora is associated with a reduced symptomatic response to ingestion of nonabsorbable, fermentable material in healthy subjects. Manipulation of the normal flora could be of therapeutic value in nonmethanogenic patients with irritable bowel syndrome.

Avena↗

Phenytoin embryopathy: effect of epoxide hydrolase inhibitor on phenytoin exposure in utero in C57BL/6J mice.

Previous animal research has suggested that the phenytoin arene oxide metabolite is teratogenic in acute studies and that the fetal effects were increased after injecting an inhibitor of microsomal epoxide hydrolase (mEH) (Martz et al., Pharmacol Exp Ther 203:231-239, 1977, Barcellona et al., Teratog Carcinog Mutagen 7:159-168, 1987). We have studied the effects of chronic oral phenytoin exposure in utero and the mEH inhibitor trichloropropene oxide (TCPO) on the prenatal growth and development of an inbred mouse strain with a low incidence of spontaneous oral clefting (C57BL/6J). Chronic daily gastric gavage of phenytoin produced a plasma level (mean 10.7 micrograms/ml on gestation Day 8) within the range recommended to prevent epilepsy in humans; this did not produce an increase in oral clefting or ventricular septal defects in the exposed C57BL/6J pups. It did produce a significant delay in prenatal growth and development, including phalangeal ossification. However, except for percentage resorptions/implantation, there was no synergism between phenytoin and TCPO in contrast to the finding reported by Martz et al. in Swiss mice. This issue was also assessed in a test of the fetal effect of phenytoin injected with TCPO, as had been done by Martz et al. There were no oral clefts or ventricular septal defects or a difference (P > 0.05) in prenatal growth and development in these C57BL/6J pups compared to the chronic gastric phenytoin plus TCPO group. This suggests either that differences in the genotypes of Swiss and C57BL/6J mice may be a contributing factor or that other teratogenic mechanisms were involved.

Animals↗

Maternal erythropoietin in singleton pregnancies: a randomized trial on the effect of oral hematinic supplementation.

OBJECTIVE: Our purpose was to study the effect of hematinic supplementation on the maternal erythropoietin response during singleton pregnancy. STUDY DESIGN: In a randomized, double-blind trial 97 patients with a first-trimester hemoglobin level > or = 14.0 gm/dl received either iron and folic acid (hematinic group, n = 53) or a placebo (n = 44). Serial hemoglobin, hematocrit, and serum erythropoietin were recorded from maternal blood and from cord blood on delivery. Serum ferritin was measured in the first trimester, at 36 weeks' gestation, and in cord blood. RESULTS: In both groups (1) the mean hemoglobin was lower (p < 0.01) at 40 weeks' gestation than when first examined and (2) the mean serum erythropoietin was higher (p < 0.01). The mean serum ferritin was lower (p < 0.001) in both groups at 36 weeks' gestation than at presentation but higher (p = 0.04) in the hematinic group than in the placebo group. The mean hemoglobin and hematocrit were similar in the two groups until the third trimester but thereafter were higher (p < 0.05) in the hematinic group. The mean maternal serum erythropoietin was higher (p < 0.05) in the placebo group than in the hematinic group after 24 weeks' gestation. The mean cord blood hematologic values were similar in the two groups. CONCLUSION: Maternal serum erythropoietin increased during pregnancy, but this response was reduced in the third trimester in the hematinic-supplemented group.

Double-Blind Method↗

On the use of the generalized t and generalized rank-sum statistics in medical research.

We have used Monte Carlo methods to compare the type I error properties of the conditional and unconditional versions of the generalized t and the generalized rank-sum tests to those of the independent samples t and Wilcoxon rank-sum tests. Results showed inflated type I errors for the conditional generalized tests but not for the unconditional tests. We also compared the power of the unconditional generalized tests to that of the t and Wilcoxon tests under a variety of conditions. Results showed the generalized tests to be much more efficient than their traditional counterparts in some circumstances, but substantially less powerful in others. Based on these and other considerations, we conclude that the application of these newer statistics in medical research needs further consideration.

Data Interpretation, Statistical↗

Statistical analysis of the effect of cadmium and zinc on hamster teratogenesis.

Maternal smoking is correlated with lower average birth weights and an increase in malformations in some studies. Increased maternal cadmium levels and reduction of zinc levels in certain tissues from fetuses of women who smoke suggest a biological association during pregnancy. Zinc has a protective effect on hamster teratogenesis caused by cadmium. To determine whether this protective effect is additive or synergistic (interactive), pregnant golden Syrian hamsters were injected (iv) on Day 8 of gestation with a test solution based on maternal body weight (0.5 ml per 100 g). Five doses were given: 2 mg/kg zinc chloride, 2 mg/kg cadmium chloride, 3 mg/kg cadmium chloride, 2 mg/kg zinc chloride plus 2 mg/kg cadmium chloride, and 2 mg/kg zinc chloride plus 3 mg/kg cadmium chloride. Fifty dams were randomly placed into one of the groups, for a total of 10 pregnant dams in each group. Twenty other dams were randomly placed into untreated or saline control groups. Fetuses were recovered on Day 15 and weighed, crown-rump length was measured, and fetuses were examined for viability and external malformations. Resorptions were noted. Statistical analyses included one- and two-way nested ANOVA, and logistic regression adjusted for litter effect. Zinc's protective effect on acute cadmium embryonic/fetal toxicity and teratogenicity was confirmed. The protective effect was of the same magnitude relative to the dose-dependent effect of the cadmium exposure, indicating that the effect was statistically additive and not synergistic. This suggests that the effect depends on competition of the two elements at some common binding site(s).

Abnormalities, Drug-Induced↗