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Biomedical subjects

J H Renwick

Publications and source records attributed to J H Renwick.

At least 19 recordsLinked to original sources

Fetal detriment used as an index of effects of diethylene glycol on Syrian hamster fetuses.

The effect of diethylene glycol (digol, diEG; specific gravity = 1.12) on the embryo was studied in the pregnant Syrian hamster at dosages from 2 1/4 to 4 ml/kg (2.52-4.48 g/kg). The hamsters were dosed by (single) intraperitoneal injection because previous experiments had indicated that oral dosing in the drinking water (and therefore possibly gavage dosing also) causes the hamsters to drink less. The digol was diluted with distilled water and injected on d 8 of pregnancy. Distilled water was used for the controls. At all dosages, fetuses from treated animals examined at autopsy on d 15 were found to be lighter than those from control animals. Abnormalities were seen at all dosages, mainly neural-tube defects (exencephaly, cranial bleb, and myelomeningocele). No neural-tube defects were observed in control animals. A dosage-related deficit in the number of live, externally nonmalformed fetuses was observed and was matched by a dosage-related increase in the number of live externally abnormal fetuses. Few dead full-term fetuses were found, but there was a dosage-related increase in the "late" resorption rate. A new summarizing measure, the fetal detriment (FD), the deficit from control expectations of live, nonmalformed litter mass per live litter, was found to be proportional to the square of the dose-rate D, the regression through the origin in this study being FD = (0.934 +/- 0.329)D2. The 50% attrition dosage, the AD50, was 2.90 ml/kg (3.25 g/kg) in the hamster, with 95% confidence interval 2.21-5.41 ml/kg (2.48-6.06 g/kg). Diethylene glycol in high dosage produces damage to the fetuses of pregnant Syrian hamsters. It is not known whether this is an indirect result of the maternal toxicity, which was observed even at the lowest dosage used, or is the effect of digol or of its metabolites on the conceptus.

Abnormalities, Drug-Induced

On avoiding statistical bias in linkage-based counselling.

Using the Succession Rule of Laplace (1795) and related reasoning, this paper shows how to give unbiased counselling to patients when predictions are to be based on small samples. The recombination fraction can be regarded as a probability parameter, theta, which itself has a probability distribution between the limits of 0 and 1/2. The probability of a recombinant, P(Rec), is not numerically equal to the maximum likelihood estimate of theta, nor is it numerically equal to the maximum posterior probability estimate in Bayesian inference. Rather it is equal to the infinite sum of all possible theta values, each weighted according to its probability density p(theta) which denotes the relative probability that that theta value is the true one. The various published proposals for obtaining an unbiased estimate of theta are shown to be equivalent one to another, except for the simplifying approximations used.

Bias

Search for association between MCV and miscarriage, reflecting ethanol consumption or otherwise.

In 38 miscarrying women and 38 pair-matched controls, all studied retrospectively, the mean pair-difference in MCV is + 1.2 fl, P less than 0.05 (one-tailed). As ethanol elevates MCV, this might weakly support the suggested role of ethanol in some miscarriages, although folate/B12 deficiencies cannot be excluded. The paper demonstrates only the feasibility of a first step in defining the possible role of ethanol in some miscarriages. It identifies a difficulty encountered from earlier attendance in the miscarrying group so that a later study could circumvent it and perhaps lead to a case for funding of a prospective enquiry into the dose-response relations of any association that might exist.

Abortion, Spontaneous

Caffeine cubes.

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Abnormalities, Drug-Induced

A locus for a human hereditary cataract is closely linked to the gamma-crystallin gene family.

Within the human gamma-crystallin gene cluster polymorphic Taq I sites are present. These give rise to three sets of allelic fragments from the gamma-crystallin genes. Together these restriction fragment length polymorphisms define eight possible haplotypes, three of which (Q, R, and S) were found in the Dutch and English population. A fourth haplotype (P) was detected within a family in which a hereditary Coppock-like cataract of the embryonic lens nucleus occurs in heterozygotes. Haplotype P was found only in family members who suffered from cataract, and all family members who suffered from cataract had haplotype P. The absolute correlation between the presence of haplotype P and cataract within this family shows that the gamma-crystallin gene cluster and the locus for the Coppock-like cataract are closely linked [logarithm of odds (lod) score of 7.58 at its maximum at phi = 0]. This linkage provides genetic evidence that the primary cause of a cataract in humans could possibly be a lesion in a crystallin gene.

Cataract

Fetal growth and moderate drinking in early pregnancy.

Heavy maternal drinking during pregnancy has consistently been linked to decreased intrauterine growth, but the effect of smaller amounts of alcohol is less clear. In this study, the relationship between fetal growth and "moderate" drinking by low-risk, nonsmoking prenatal patients is explored. The sample consists of 144 women seen for the first time at the prenatal clinic of University College Obstetrics Hospital, London, England, between July 1979 and May 1980 and meeting the following criteria: white, aged 19-35 years, 8-16 weeks gestation at first prenatal visit, nonsmoker, nonalcoholic, lower middle class or higher, and in general good health. Average daily consumption of 10 g of ethanol (about one drink) in the week prior to recognition of pregnancy is related to a decrease in infant birth weight of 225 g, after adjustment for gestational age, sex of child, and maternal age, weight, height, pregnancy weight gain, social class, gravidity, and parity. In addition, consumption of this amount in the week before first prenatal visit is related to a comparable decrease in birth weight for male but not for female infants. These findings suggest that risk of decreased intrauterine growth begins very early in pregnancy, and that fetal response to later alcohol use may vary with sex of the child.

Alcohol Drinking

Hereditary cataract. Perspective for prenatal screening.

The possibility that defects in lenticular proteins are one cause of hereditary cataract is discussed. Possible mutant loci for such proteins can be detected by linkage to restriction fragment length polymorphisms within or around these loci. In a family in which a Coppock cataract occurs, close linkage between the locus for this cataract and the gamma-crystallin gene cluster was found. The restriction fragment length polymorphism within the gamma-crystallin gene family is sufficiently informative to allow prenatal diagnosis of this disease within this family.

Aquaporins

The pattern of loci on Drosophila chromosomes.

In this study, we have attempted to detect and describe patterns in the arrangement of gene loci within chromosomes of a metazoon. Known loci (842 of them) on the first three chromosomes of Drosophila melanogaster have been characterised according to a list of 45 properties and the distributions of these properties have been examined systematically. For all these properties, there is little, if any, evidence of clustering between known loci that are not close enough to belong to the same 10-locus group. Our analysis has, however, revealed evidence confirming that some properties show a tendency to cluster within a 10-locus group. Even this tendency is not strong, except for some of the morphological properties. However, it is apparently at variance with the findings of Elston and Glassman (1967), based on fewer data.

Animals

Predisposition to spina bifida: Search for a relation to maternal gastric acid secretion.

The peak acid output of the stomach in a group of 71 mothers of spina bifida children and in 71 matched controls was estimated indirectly by the serum level of group I pepsinogens. The mean levels did not differ significantly, suggesting that the conjectured teratogen is not specially acid-labile. The variance was significantly higher in index subjects than in controls, but the interpretation of this finding is not clear.

Female

If not, why not?

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Research