Search PubMed⌕ Search

Biomedical subjects

P Graham

Publications and source records attributed to P Graham.

At least 91 records · Page 5Linked to original sources
PubMed1995

Ethical issues in biological psychiatric research with children and adolescents.

OBJECTIVE: This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents. METHOD: Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors. RESULTS: Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, "piggybacking" onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; "coercive" inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity. CONCLUSIONS: The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects.

Adolescent↗
PubMed1994

Human immunodeficiency virus type 1 protease inhibitors: evaluation of resistance engendered by amino acid substitutions in the enzyme's substrate binding site.

The human immunodeficiency virus type 1 (HIV-1) protease is a homodimeric aspartyl endopeptidase that is required for virus replication. A number of specific, active-site inhibitors for this enzyme have been described. Many of the inhibitors exhibit significant differences in activity against the HIV-1 and HIV type 2 (HIV-2) enzymes. An initial study was conducted to ascertain the HIV-1 protease's potential to lose sensitivity to several test inhibitors while retaining full enzymatic activity. The substrate binding sites of the HIV-1 and HIV-2 enzymes are almost fully conserved, except for four amino acid residues at positions 32, 47, 76, and 82. Accordingly, recombinant mutant type 1 proteases were constructed that contained the cognate type 2 residue at each of these four positions. The substitution at position 32 resulted in a significant adverse effect on inhibitor potency. However, this substitution also mediated a noted increase in the Km of the substrate. Individual substitutions at the remaining three positions, as well as a combination of all four substitutions, had very little effect on enzyme activity or inhibitor susceptibility. Hence, the four studied active site residues are insufficient to be responsible for differences in inhibitor sensitivity between the HIV-1 and HIV-2 proteases and are unlikely to contribute to the generation of inhibitor-resistant mutant HIV-1 protease.

Amino Acids↗
PubMed1994

Multiple organ dysfunction: pathophysiology and therapeutic modalities.

This article focuses on the physiologic systemic inflammatory immune response system that occurs normally to any event resulting in cellular injury. A review of the mediators of the inflammatory immune response system is presented along with the pathophysiologic description of the development of multiple organ dysfunction syndrome and the complex interrelationships between inflammatory mediators and the host cell. Endotoxin is reviewed as a suspicious precursor in the development of the multiorgan cascade and the response of key mediators in the complement system, tumor necrosis factor, interleukin 1, and oxygen radicals. A review of the literature is presented in an effort to describe new therapeutic modalities specifically developed in an effort to alter mediator-induced inflammatory immune responses at the cellular level.

Complement Activation↗
PubMed1994

Lipid peroxidation as a measure of oxygen free radical damage in the very low birthweight infant.

(ABSTRACTOxygen free radical mediated tissue injury is implicated as a major factor in the pathogenesis of the long term complications seen in the premature infant, and direct evidence of their role in the development of these long term problems is lacking. A prospective observational study of 78% of very low birthweight infants admitted to a level III neonatal intensive care unit in 1992 was undertaken to determine the relationship between lipid peroxidation products, antioxidant activity, and outcome. Lipid peroxidation (malondialdehyde-thiobarbituric acid, MDA-TBA) and antioxidant activity (vitamin E and glutathione peroxidase activity) were measured in 22 very low birthweight infants in the cord blood and the infant's blood at 24 hours, 48 hours, and 1 week of age and correlated with outcome measures. The normal range for these measures was established in the cord blood samples of 48 consecutive healthy full term infants. The concentration of MDA-TBA at 1 week correlated with the number of days of oxygen treatment and number of days of positive pressure ventilatory support. Controlling for gestational age and antenatal complications simultaneously the MDA-TBA concentration remained significantly associated with the number of days of oxygen treatment and the number of days of positive pressure ventilatory support. Glutathione peroxidase was low in the premature and full term infants consistent with the low concentrations of selenium known to be present in southern New Zealand. There was evidence of a quadratic relationship between vitamin E at 1 week and the total number of days of supplementary oxygen requirement, with both high and low values associated with increased oxygen requirement. This association, however, did not remain after controlling for gestational age and antenatal complications. These results support the role of oxygen free radicals in mediating tissue damage associated with the development of chronic lung disease in the premature infant.

Chronic Disease↗
PubMed1994

Adolescent girls. I. Self-reported mood disturbance in a community population.

BACKGROUND: This study was undertaken to fill gaps in our knowledge of the rate of mood disorder in teenage girls in transition from school to further education, employment or unemployment. METHOD: Girls aged 15-20 years (n = 529) whose names were drawn from general practitioner age/sex registers were interviewed at home and completed the Great Ormond Street Mood Questionnaire. Their mothers completed the 28-item General Health Questionnaire (GHQ). Social background variables were obtained. RESULTS: Of the girls, 20.8% scored over the cut-off point previously established to indicate risk of psychiatric disorder. Scoring over the cut-off point was not associated with age or parental social class. It was associated with parental separation/divorce (P < 0.004), with maternal self-report on the GHQ (P < 0.001), and with parental unemployment (P < 0.04). Lowest self-report scores were obtained by girls who had left school and were in employment (P < 0.01). CONCLUSIONS: About one in five of girls aged 15-20 are at risk of affective disorder. Self-reported mood disturbance is associated with a wide range of social and familial background variables, but not with age or parental socioeconomic status.

Absenteeism↗
PubMed1994

Adolescent girls. II. Background factors in anxiety and depressive states.

BACKGROUND: This study investigated the prevalence and background variables associated with anxiety and depressive disorders occurring in a community population of older teenage girls. METHOD: Girls aged 15-20 years (n = 529) whose names were drawn from general practitioner age/sex registers completed self-report Great Ormond Street Mood Questionnaires. From this sample, 143 girls (69 with high self-report scores and 74 controls) were intensively interviewed. Information was obtained on confiding/supportive relationships, family arguments and rows, quality of marital relationship, and degree of parental control. Psychiatric state was assessed by use of the Clinical Interview Schedule to provide a Total Weighted Score. A modified form of the Bedford Life Events and Difficulties Schedule was applied. RESULTS: The estimated one-year prevalence rate for psychiatric disorder was 18.9%, and 16.9% for depression and anxiety disorders. Using a logit analysis, it was shown that maternal distress (P < 0.02) and the quality of the mother's marriage (P < 0.02) were independently associated with the presence of depression and anxiety disorders. CONCLUSIONS: About 17% of girls in a community sample living at home showed a depression or anxiety disorder. Even in late adolescence, the presence of a mood disorder is closely linked to the quality of family relationships within the home.

Adolescent↗
PubMed1993

Primary versus proxy respondents: comparability of questionnaire data on alcohol consumption.

Questionnaire data on alcohol consumption obtained from primary respondents participating in a community-based case-control study of coronary heart disease were compared with similar data obtained from their next of kin. The primary respondents were men and women aged 25-64 years who were a representative sample of myocardial infarction cases (n = 58) and controls (n = 456) from the case-control study. The study was conducted in Auckland, New Zealand between 1986 and 1988. When alcohol drinking frequency was collapsed into five categories, exact agreement between primary respondents and next of kin was 64% for cases and 62% for controls. Agreement within one category (plus or minus) was 89% for both cases and controls. Tests of marginal homogeneity showed no evidence that next of kin systematically over- or underestimated the primary respondents' self-reported drinking frequency. With respect to the amount of alcohol drunk, mean differences between primary respondents and next of kin were small (mean difference: 2.25 g per day for cases; -0.77 g per day for controls), although there was considerable variability between individual pairs in the level of agreement. The findings suggest that studies which use proxy sources of data to assess alcohol drinking are unlikely to produce biased estimates of alcohol consumption at the aggregate level, particularly with regard to frequency measures.

Adult↗
PubMed1993

Giardiasis in Canterbury: the first nine months reported cases.

AIM: To obtain epidemiological information about giardiasis in Canterbury. METHOD: From October 1990 general practitioners were requested to report laboratory confirmed cases. The first 100 cases were sent a questionnaire and also asked to provide the details of two persons to be controls. RESULTS: In the first nine months 109 cases were reported. Eighty four cases completed questionnaires and 51 were matched with controls. The overall reported attack rate was 4.0 per 10,000 population per year. The rate was highest for preschool children and young adults and in rural areas. There was a significant risk associated with having contact with sewage or travelling overseas and a marginal risk for drinking water outside Christchurch. CONCLUSION: The results indicated that giardiasis was relatively common in Canterbury and confirmed that the major mechanisms of infection were probably the same as those previously identified overseas, namely person to person spread via faecal-oral transmission and the drinking of inadequately filtered water.

Adolescent↗
PubMed1993

The analysis of ordinal agreement data: beyond weighted kappa.

The weighted kappa statistic has been used as an agreement index for ordinal data. Using data on the comparability of primary and proxy respondent reports of alcohol drinking frequency we show that the value of weighted kappa can be sensitive to the choice of weights. The distinction between association and agreement is clarified and it is shown that in some respects weighted kappa behaves more like a measure of association than an index of agreement. In particular, it is demonstrated that the weighted kappa statistic is not always sensitive to differences in the observed proportion in exact agreement and that high values of weighted kappa can be observed even when the level of agreement is low. We illustrate the use of statistical models in the analysis of epidemiologic agreement data and conclude that modelling ordinal agreement data produces insights which cannot be obtained through the use of weighted kappa statistics.

Alcohol Drinking↗