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Biomedical subjects

J A Baldwin

Publications and source records attributed to J A Baldwin.

At least 19 recordsLinked to original sources
PubMed1992

A qualitative assessment of developmental toxicity within a series of structurally related dopamine mimetics.

A qualitative assessment of developmental toxicity within a series of 12 structurally related compounds, 11 of which were active dopamine mimetics and one was inactive, was conducted in rats treated orally by gavage during the major period of organogenesis. Doses were chosen where possible to be equipotent in terms of pharmacological activity. The series was typified by the compound BRL 16644 (2-[[3,4-dihydro-2,2-dimethyl-4-[3-(trifluoromethyl)phenyl]- 2H-1-benzopyran-7-yl]oxy]-N,N-dimethyl-ethanamine: Chemical Abstracts No. 59257-24-8). Five of these compounds were clearly teratogenic producing specific abnormalities typified by anasarca, brachygnathia and cleft palate. Similar levels of maternal toxicity, particularly stereotypic behaviour, and foetotoxicity were seen in both teratogenic and non-teratogenic compounds suggesting that neither maternal nor foetotoxicity plays a role in the aetiology of the abnormalities. Four of the teratogenic compounds contained a trifluoromethyl group in the 4-phenyl ring and, within this series of compounds, substitution with this group appears to confer teratogenicity. Although equipotent doses were used this only pertained to the adult and as only limited pharmacokinetic data were available, including the extent of placental transfer, the influence of this group is not clear. Investigations have been undertaken to relate the teratogenic potential of these compounds to a number of their chemical descriptors, including electronic, steric, quantum chemical and hydrophobicity parameters, to try and clarify the influence of the trifluoromethyl group.

Abnormalities, Drug-Induced↗
PubMed1992

Multivariate quantitative structure-toxicity relationships in a series of dopamine mimetics.

The techniques of principal components analysis and non-linear mapping are routinely used by computer chemists at SmithKline Beecham Pharmaceuticals in the process of drug development by relating the structure of a compound to its chemical activity. To our knowledge these techniques had not previously been applied to the association between the structure of a compound and its toxicological properties. Using a series of 12 structurally related compounds (11 were active dopamine mimetics and one was inactive), of which five were known to be teratogenic and seven were non-teratogenic, it was possible to demonstrate that molecular modelling techniques could be applied to differentiate toxicological data. The structure/property relationships of these compounds were investigated using calculated physicochemical properties, molecular modelling and multivariate statistical techniques. A data set of 56 molecular descriptors was used to represent this series of compounds. Analysis of the data set using principal components analysis and non-linear mapping suggested that teratogenicity was associated with four molecular properties. Moreover, the electronic nature of the 4-phenyl group appeared to be an important determinant of the teratogenesis.

Abnormalities, Drug-Induced↗
PubMed1979

Cancers of the large bowel: associated disorders in individuals.

The individual medical histories in the files of the Oxford Record Linkage Study for the years 1963 to 1967 were analyzed to ascertain any previously unsuspected associations between cancers of the large bowel and other diseases in individuals, and to quantify the relative risks of disorders already known to be associated. In males significant associations were shown between cancers of the large bowel and cancer of the prostate. In females, cancer of the colon was associated with breast cancer, and cancer of the rectum with a mixed group of genital cancers. The relative risk of colorectal cancer associated with previous benign neoplasms of the large bowel was 20, and with ulcerative colitis, 25. There was no significant association with appendicitis or long-standing diverticular disease.

Abscess↗
PubMed1976

Study of disease associations from linked records.

Comparisons are made between the principal diagnosis on discharge from hospital in successive periods of inpatient care for persons in the Oxford Record Linkage Study area admitted over a period of years. The observed numbers of pairs of diagnoses are compared with expected numbers computed to take account of the discharge rates in the population by age and sex and the number of man years of exposure. Three topics have been selected to display some of the types of analysis possible with the very extensive material: mental disorder and diseases of the central nervous system, hospital discharges preceding those for neoplasm, and discharges following those for tuberculosis. The details of the method of calculation of the observed and expected numbers and the assumptions and approximations involved are given in an Appendix.

Breast Neoplasms↗
PubMed1976

Consultation patterns in a general practice.

A study from the Oxford Community Health Project is reported on the effects on consultation rates in general practice of patients' age, sex, date of registration, address, and usual doctor. The impact on consultation rates of accessibility of surgeries and availability of doctors is examined when the variables are controlled, and the importance of these factors is discussed in relation to planning primary medical care.

Adolescent↗
PubMed1975

Epidemiology and family characteristics of severely-abused children.

Severe child abuse in north-east Wiltshire was studied retrospectively during the period 1965-71, and prospectively for 18 months from January 1972, after a period of consultative activity with those actively involved to increase awareness of the phenomenon. Severe abuse was strictly defined. A rate of 1 per thousand children under four years old was obtained, together with a death rate of 0-1 per thousand. The families of the retrospective series of abused children were studied in detail and identifying characteristics of large family size, youthfulness, low social-class, instability, and gross psychiatric, medical, and social pathology described. The implications of the ascertainment and death rates are discussed in relation to data from some other studies, and the need emphasized for detailed studies of the apparent clustering of disorder in the families, using linked record systems.

Child Abuse↗