Gertrude Belle Elion (1918-1999).
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Biomedical subjects
Publications and source records attributed to M Colvin.
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BACKGROUND: The passage of hard stools is significantly more common in formula fed infants than breast fed infants and this might be the result of differences in fat absorption between breast and formula fed infants. Experimental studies indicate that long chain polyunsaturated fatty acids (LCPUFAs) might influence fat hydrolysis and absorption. AIM: To investigate the relation of LCPUFA supplementation to stool frequency and consistency during the first 4 months of life. DESIGN: Double blind, randomised, controlled study of 88 healthy infants. RESULTS: 1905 stools (858 from LCPUFA supplemented infants, 1047 non-supplemented infants) were examined. The mean (SEM) number of stools passed for each three day study period was significantly less in the LCPUFA group (5.5 (0.3) v 6.2 (0.2); p < 0.05). In both groups, there was a significant reduction in the number of stools passed with age (p < 0.001). During the first 3 months, the mean (SEM) percentage of hard stools passed by infants in the LCPUFA supplemented group was 7.7 (2.1) compared with 19.2 (2.8) for unsupplemented infants (p = 0.001). CONCLUSION: The prevalence of hard stools is significantly reduced in infants fed a formula that is supplemented with LCPUFAs.
Sexually transmitted infections (STIs) are of major public health concern in developing countries, not least because they facilitate transmission of human immunodeficiency virus (HIV). The present article presents estimates of the prevalence, on any given day, of STIs among women in rural South Africa and the proportion who are asymptomatic, symptomatic but not seeking care, and symptomatic and seeking care. The following data sources from Hlabisa district were used: clinical surveillance for STI syndromes treated in health facilities, microbiological studies among women attending antenatal and family planning clinics, and a community survey. Population census provided denominator data. Adequacy of drug treatment was determined through quality of care surveys. Of 55,974 women aged 15-49 years, a total of 13,943 (24.9%) were infected on any given day with at least one of Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, or Treponema pallidum. Of the women investigated, 6697 (48%) were asymptomatic, 6994 (50%) were symptomatic but not seeking care, 238 (1.7%) were symptomatic and would seek care, and 14 (0.3%) were seeking care on that day. Only 9 of the 14 women (65%) were adequately treated. STIs remained untreated because either women were asymptomatic or the symptoms were not recognized and acted upon. Improved case management alone is therefore unlikely to have a major public health impact. Improving partner treatment and women's awareness of symptoms is essential, while the potential of mass STI treatment needs to be explored.
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BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and brain development. Although present in human milk, LCPUFA have until recently been absent from artificial formulas, and infants may have limited ability to synthesise LCPUFA. To determine the clinical significance of this relative deficiency of LCPUFA, we undertook a randomised trial of the relation between LCPUFA supplementation and infant cognitive behaviour. METHODS: 44 term infants had been randomised to a formula supplemented with LCPUFA (21) or not supplemented with LCPUFA (23), which they had taken from birth to age 4 months. Infant cognitive behaviour was assessed at 10 months of age by a means-end problem-solving test--the intentional execution of a sequence of steps to achieve a goal. The problem required three intermediate steps to achieve the final goal, uncovering and retrieving a hidden toy. FINDINGS: Infants who received LCPUFA-supplemented formula had significantly more intentional solutions than infants who received the no-LCPUFA formula (median 2.0 vs 0, p=0.021). Intention scores (median 14.0 vs 11.5 [maximum 18]) were also increased in this group (p=0.035). INTERPRETATION: These findings suggest that term infants may benefit from LCPUFA supplementation, and that the effects persist beyond the period of supplementation. Since higher problem-solving scores in infancy are related to higher childhood IQ scores, supplementation with LCPUFA may be important for the development of childhood intelligence.
Long-chain polyunsaturated fatty acids (LCPUFA) are important for normal visual and cortical development. In a previous study of the effects of LCPUFA on cognitive function of term infants at the age of 3 mon, we indicated that infants with evidence of reduced growth parameters at birth and impaired attention control as manifested by a late peak fixation during infant habituation assessment may benefit from LCPUFA supplementation. The aim of this prospective study was to determine whether LCPUFA supplementation and late peak fixation are related to means-end problem-solving ability in these same infants at the age of 9 mon. Term infants (58) were randomized to one of two formulas containing either LCPUFA or no LCPUFA and completed 4 mon of feeding with their formula. Cognitive function was assessed at 3 mon of age by measures of infant habituation. Infants (20 LCPUFA and 20 no-LCPUFA) completed the problem-solving assessment at 9 mon. The no-LCPUFA group had lower scores on both measures of intention and number of solutions, but neither of these differences was significant. Analysis of covariance for the effects of group and peak fixation, covaried with gestation and birth weight, showed that the number of solutions was significantly reduced in the late peak-fixation infants receiving no LCPUFA (P<0.02). Intention scores tended to be reduced in this group (P<0.06). The late peak-fixation infants who received LCPUFA had solution and intention scores similar to early peak-fixation infants receiving LCPUFA or no LCPUFA. These findings suggest that in term infants who have reduced growth parameters at birth and who show evidence of impaired attention control, information processing and problem-solving ability in infancy may be enhanced by LCPUFA supplementation.
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The objective was to determine the prevalence of HIV and other sexually transmitted infections (STIs) in a rural community. A population-based survey of adults in 110 homesteads was conducted in 1995. A questionnaire on demographics, sexual practices and history of STDs was administered. Neisseria gonorrhoeae and Chlamydia trachomatis infections were detected using ligase chain reaction (LCR) assay of urine. The seroprevalence of syphilis rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) and HIV infection (ELISA) was determined. Among 259 subjects the prevalence of HIV was 10.5%, N. gonorrhoeae 4.5%, C. trachomatis 6.1% and active syphilis 8.8%. All infections were asymptomatic. Forty per cent of sexually active men had more than one concurrent sexual partner. Only 14% of subjects had ever used condoms. The STI epidemic is being promoted by high levels of asymptomatic infections, high partner concurrency and low condom use.
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The cooked meat mutagen 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) is metabolized in vivo to electrophilic intermediates that covalently bind to DNA guanines. Here we address the mechanism of PhIP's non-covalent interaction with DNA by using spectroscopic and computational methodologies. NMR methodologies indicated that upon addition of DNA, PhIP aromatic protons underwent a small, 0.11-0.12 p.p.m. upfield shift. DNA phosphorus resonances of non-covalent PhIP-DNA complexes broadened and slightly shifted upfield, while DNA base imino proton resonances shifted slightly downfield relative to DNA alone. UV and fluorescence spectra of PhIP titrated with DNA showed no detectable shifting and hypochromism of absorbance or fluorescence bands. In the presence of DNA, PhIP fluorescence was efficiently quenched by acrylamide, but not by silver ion. Further, the NMR spectra suggest that PhIP is in fast exchange with the DNA, and is slightly specific for adenine-thymine (A-T) sequences. Finally, structural arguments based on quantum chemistry calculations suggested that PhIP and its metabolites are unlikely to intercalate into DNA. These data collectively indicate that PhIP non-covalently binds in a groove of DNA.
There has been some recent concern in Britain and North America that the increasing institutionalization of hospice care may compromise the movement's founding ideals. The threats posed by the encroachment of mainstream medicine and the medical technological imperative to treat, are also a source of concern to hospice administrators and staff. This study uses Australian data based on interviews with nurses and participant observation in an in-patient hospice unit and a community based hospice service to investigate whether the Good Death ideal, as central to the hospice philosophy, is compatible with the institutionalization of hospice care. The issues that arise, although interrelated are conceptualized as the following five challenges to hospice care: (1) encroachment of mainstream medicine and the medical technical imperative; (2) competing motivations; (3) delimitation of intellectual structures; (4) organizational maintenance; and (5) routinization of the Good Death. This conceptual framework is based on the way in which nurses and other health care professionals have used shared logic and strategies to negotiate the daily demands of their work and illustrates the tension that arises between the maintenance of the ideal and the maintenance of the organization.
Neurobehavioral impairments in 84 workers with long-term exposure to organic solvents in a paint manufacturing plant were examined cross sectionally. The World Health Organization (WHO) Neurobehavioral Core Test Battery, the NES-2 computerized battery, and four additional South African tests were used. Exposure to solvents was determined by using company industrial hygiene data as well as from an industrial hygiene survey of current total solvent levels in air. Indexes for cumulative exposure and average lifetime intensity of exposure were calculated for groups of homogeneously exposed workers in each department. Exposure levels were below the AGGIH threshold limit values. Multiple linear regression revealed that education level, age, and alcohol consumption were strong predictors for several neurobehavioral test scores. After adjusting for potential confounding from this source, average lifetime intensity of solvent exposure was the most significant predictor of the NES-2 Continuous performance test (measuring sustained visual attention) score of the WHO Digit span backward test score (measuring attention span and double tracking). Pursuit aiming (measuring fine visuomotor tracking speed) was significantly associated with the cumulative exposure index, possibly indicating early neurotoxic effects.
The neurobehavioral effects of organic solvent exposure were assessed in 68 South African workers in a paint manufacturing plant in which the maximum current combined solvent level in workplace air was 0.72 of the Threshold Limit Value. A 17-test battery was assembled from the WHO-NCTB, NES 2, and the University of South Africa Neuropsychological Assessment Procedure. Extensive modifications were made to some tests in the battery, using a guided learning rationale derived from the cross-cultural literature. In light of test correlations with demographic variables (age, education, and alcohol consumption), the construct and likely predictive validity of the tests in the battery are reviewed, and promising procedures identified. Finally, it is noted that in developing countries, the results of neuropsychological tests that have been well standardized in the West may be misleading unless the underlying validity issues that arise when a test developed in one culture is applied to another have been addressed.
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Many cancer cells are resistant to chemotherapeutic treatment with mechlorethamine and other alkylating agents. These drug-resistant cells often show an increase in the intracellular concentration of glutathione and an increase in the activity of glutathione-S-transferase when compared to the sensitive cells. Both of these components are thought to be involved with inactivation of the drug either through conjugation with glutathione or by hydrolysis. NMR spectroscopy was used to monitor the nonenzymatic conjugation of mechlorethamine with glutathione. Several intermediates along the pathway to the doubly glutathione substituted mustard, including both mustard-aziridinium adducts, can be observed. The assignment of the 1H NMR spectrum of these adducts are presented. At 30 degrees C, pH 7.0, no hydrolyzed mustard was detectable. With the use of 13C-labeled mustard, the conjugation reaction can be shown to proceed through an aziridinium intermediate rather than by direct nucleophilic substitution.