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Biomedical subjects

A Wilkins

Publications and source records attributed to A Wilkins.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pericardial, retroperitoneal, and pleural fibrosis induced by pergolide.

Three patients with Parkinson's disease are described who developed pericardial, retroperitoneal, and pleural fibrosis associated with pergolide treatment. Surgical intervention was required in all three cases, either to reach a tissue diagnosis or for potentially life threatening complications. Symptoms emerged on average 2 years after the institution of treatment, and were sufficiently non-specific to cause significant delays in diagnosis in all cases. The erythrocyte sedimentation rate (ESR) was raised in the two patients in whom it was measured. Serosal fibrosis is a rarely reported adverse effect of pergolide treatment, although it is well described with other dopamine agonists. We suggest that patients with Parkinson's disease who receive pergolide treatment should be regularly monitored for the development of such complications.

Aged↗
PubMed1999

The virtual workplace.

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Computer Communication Networks↗
PubMed1998

Effects of electroconvulsive therapy and desipramine on neuroendocrine responses to the clonidine challenge test.

OBJECTIVE: To investigate responses to the clonidine challenge test in depression, and after electroconvulsive therapy (ECT) or desipramine treatment for depression, in order to determine the usefulness of noradrenergic responses to clonidine as a state or trait marker in depression. PATIENTS: Twenty-six patients with depression and 15 control subjects. SETTING: The psychiatric ward of St. Joseph's Hospital in Hamilton. INTERVENTIONS: In the patients with depression: clonidine challenge pre- and post-treatment with ECT or desipramine. In the controls: 2 clonidine challenge tests 4 to 8 weeks apart. OUTCOME MEASURES: The primary measure was the growth hormone response to the clonidine challenge. Plasma norepinephrine, 3-methoxy-4-hydroxyphenylglycol (MHPG), cortisol, blood pressure, pulse and sedation levels were examined in subgroups of participants as secondary measures. RESULTS: The pre-treatment growth hormone response to clonidine was significantly more blunted in patients than in controls (p = 0.02). This response improved in both treatment groups after therapy and, although it remained decreased, there was no longer a significant difference in response between the patients and the controls. In the patients, a decreased growth hormone response to clonidine at baseline was correlated with response to treatment. Of the secondary measures, patient baseline norepinephrine levels were significantly elevated pre- and post-treatment, although there were no significant group-by-time challenge effects. MHPG levels were not significantly different pre- and post-treatment between patients and controls. Baseline blood pressure and pulse were elevated in the patients pre- and post-treatment. These differences were not statistically significant and did not change after treatment. Sedation levels were not significantly different among the groups at baseline. Clonidine-induced sedation occurred significantly earlier in the patients pretreatment and improved to the range of the controls after treatment. Pretreatment cortisol response was significantly more blunted in the patients who received ECT than in the controls; however, the group-by-time effect post-treatment was no longer significant. DISCUSSION: Treatment with either desipramine or ECT modified noradrenergic functioning in patients with depression, as assessed by growth hormone response to the clonidine challenge. In the patients, a decreased growth hormone response at baseline was correlated with clinical response. Changes between pre- and post-treatment measures suggest that this challenge test may not be sensitive enough to serve as a trait marker but may correlate with the state of depression in a subpopulation of these patients.

Adrenergic alpha-Agonists↗
PubMed1997

Rate of decline of percentage CD4+ cells is faster in HIV-1 than in HIV-2 infection.

Increasing evidence suggests that the pathogenesis of HIV-1 is different from that of HIV-2. Thus, we have measured, longitudinally at various times over a median follow-up of 2.1 years, the percentage CD4+ cells of 94 patients infected with HIV-1 and 164 patients infected with HIV-2. The pattern of decline of CD4% over time was linear for patients with either infection. Multilevel statistical modeling techniques showed that after stratifying for HIV status, the rate of decline of CD4% was faster among patients who died than among those who survived (difference in rate of decline = 2.34% CD4+ cells/year; p = 0.0002). After stratifying for survival status, the rate of decline was faster and less variable among patients infected with HIV-1 than among patients infected with HIV-2 (difference in rate of decline = 1.12% CD4+ cells/year; p = 0.05). The proportion of patients who showed no fall in CD4+ cells was higher in HIV-2 than in HIV-1 infection (p = 0.026). These data suggest fundamental differences between the two infections, with HIV-1 being more pathogenic resulting in a faster and more homogeneous rate of decline than HIV-2. In HIV-2 infection, disease in many patients progresses slowly, but in some the advance is just as fast as that in HIV-1 infection. The reasons for this marked heterogeneity need elucidation to understand the disease and to target therapeutic interventions against HIV-2 in those most at risk.

Acquired Immunodeficiency Syndrome↗
PubMed1997

HIV type 2 pathogenicity is not related to subtype in rural Guinea Bissau.

Data from an MRC case-control study in rural Guinea Bissau suggest older HIV-2 carriers (aged 55 to 80 years) appear, over a period of 2 years, to have a mortality similar to that of uninfected controls, whereas in HIV-2 carriers under the age of 55 there is a significantly higher mortality, compared with uninfected controls. Genotyping of viruses from both groups revealed only subtype a to be circulating. Thus, although putative nonpathogenic HIV-2 subtypes have been described in patients from West Africa, these do not appear to be contributing significantly to the nonpathogenic clinical phenotype in this population.

Aged↗
PubMed1997

Epigenetics.

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Animals↗
PubMed1997

Prolonged use of coloured overlays for classroom reading.

Ninety-three children in a primary school and 59 children in two first-year classes of a secondary school were asked individually to observe a paragraph of random letters arranged to resemble text, and to compare the perceptual effects on its clarity of coloured plastic sheets overlaid on the text. A total of 29 colours were compared using 10 coloured plastic sheets and 19 pairwise combinations of sheets, one superimposed on another. The resulting colours sampled CIE 1976 hue angle (huv) and saturation (suv) systematically and efficiently. All the children who reported beneficial perceptual effects (53 per cent) were given their preferred overlay or combination of overlays to use as and when they wished. When the children were examined three months later the children tended to choose a colour similar to one they had chosen previously. Ten months later, 22 per cent of those offered the overlaps were still using them of their own volition. These children, but not those who had ceased to use their overlay(s), read randomly ordered simple words more quickly with their overlay than without. In a second independent group of children referred to the Norfolk Sensory Support Service, who used overlays routinely, the reading speed was similar with a grey or clear overlay; and slower than with the chosen coloured overlay, suggesting that reduction of contrast was not the critical factor. In a third independent group of children in a primary school in Kent, the increase in reading speed with the chosen overlay predicted the children who continued to use their overlay during the ensuing eight weeks.

Attention↗
PubMed1997

Intermittent fluoxetine dosing in the treatment of women with premenstrual dysphoria.

Some women experience premenstrual mood symptoms that severely disrupt their lives and relationships. These women often require pharmacologic treatment. Selective serotonin reuptake inhibitors, particularly daily fluoxetine, have been proven superior to placebo in several randomized controlled trials. Twenty-four women with confirmed premenstrual dysphoric disorder (PMDD) and with a history of affective disorders or alcoholism were treated with fluoxetine 20 mg/day (continuous), and 24 women with PMDD and no psychiatric history were treated with fluoxetine 20 mg/day for 14 days premenstrually only (intermittent). Both groups received treatment for three menstrual cycles. Sixteen women (66.7%) in the continuous dosing group and 18 women (75.0%) in the intermittent group were classified as treatment responders. Intermittent dosing of fluoxetine seems to be effective and mostly free of side effects in women with PMDD and, therefore, may offer an attractive treatment option for a disorder that is itself intermittent.

Adult↗
PubMed1997

Immune stimulation by syphilis and malaria in HIV-2-infected and uninfected villagers in West Africa.

Co-infections such as Mycobacterium tuberculosis (TB) and Pneumocystis pneumonia may affect the progress of HIV infection and speed the onset of death. As malaria and syphilis are both endemic in West Africa we examined their effects on HIV-2 infection, for these may also accelerate the progress of disease. A community-based case-control study was undertaken in a rural village in Guinea-Bissau, West Africa. One hundred and fifty asymptomatic subjects seropositive for HIV-2 and 154 age- and sex-matched controls were enrolled. Venous blood samples taken into EDTA were stained within six hours of collection with CD4 and CD8 monoclonal antibodies and processed by Q-Prep machine in the field. The stained cells were then transported on ice by road and analysed by FACS-can at the base laboratory in The Gambia within a week. The mean CD4% was significantly lower and geometric mean neopterin and beta 2-microglobulin levels were significantly higher in the HIV-2-infected subjects than in the controls (P < 0.01 for all cases versus all controls). The mean CD4% was lower and beta 2-microglobulin level was higher in both HIV-2 and control subjects with active or past syphilis when compared with subjects with no syphilis; however, syphilis did not have a marked effect on plasma neopterin level. Malaria infection raised neopterin levels, but had little effect on CD4%. Overall multiple regression analysis allowing for HIV-2 infection and other variables showed that syphilis lowered CD4% (P = 0.01) and raised beta 2-microglobulin levels (P = 0.05) and malaria raised neopterin levels (P = 0.05). The conclusions are that HIV-2 infection is associated with lower CD4% and higher neopterin and beta 2-microglobulin levels than controls, and co-infection with syphilis is associated with a further lowering of CD4%, suggesting a worse suppression of the immune system. Co-infection with malaria is associated with a modest immune disturbance.

Adult↗
PubMed1996

A community-based study of human immunodeficiency virus type 2 provirus load in rural village in West Africa.

A community-based study of provirus load in human immunodeficiency virus (HIV) type 2-infected subjects was done in a rural village in Guinea-Bissau. HIV-2 provirus load varied considerably, with a geometric mean of 124.3 (95% confidence interval, 86.0-179.6) copies/10(5) CD4 cells, which is a level similar to that found in HIV-1 infection. Neither malaria parasitemia, active syphilis, or human T cell leukemia virus coinfection significantly influenced provirus load, nor did age. Eleven of 104 HIV-2-infected subjects had died after 3 years of follow-up; 9 of those who died had a high provirus load of > or = 100 copies/10(5) CD4 cells and a relatively low CD4 cell percentage of < 29%.

Adult↗
PubMed1996

Age of wife as a major determinant of male-to-female transmission of HIV-2 infection: a community study from rural West Africa.

OBJECTIVE: To examine whether proviral load is important for transmission between spouses, since we have previously found that the proviral load of HIV-2 predicts the severity of infection. DESIGN: Proviral load was examined in 121 HIV-2-infected adults in a rural area of Guinea-Bissau. For the 68 subjects who had a spouse of known HIV status the risk of the spouse being infected was examined. METHODS: Statistical methods for dependent data were used, because several couples were polygamous. RESULTS: Twenty-seven HIV-2-infected men had 52 current wives of whom 17 (33%) were HIV-2-seropositive. Forty-one HIV-2-infected women had 36 current husbands of known HIV serostatus; nine (25%) were HIV-2-positive. In univariate analyses, concordance of female partners of HIV-2-infected men increased with a previous history of prostitution, age of wife, lack of age difference between the spouses, number of previous husbands, number of wives of the man, and the proviral load. The only significant predictor of concordance in multivariate analyses when wives with a history of prostitution were excluded was an age of 45 years or older [odds ratio (OR), 8.68; 95% confidence interval (CI), 2.34-32.22]. This tendency was not explained by the length of current marriage. Although husbands with a high proviral load were more likely to have concordant spouses than those with a low proviral load (< 20 copies/10(5) CD4 cells), this association was not statistically significant (OR, 2.59; 95% CI, 0.90-7.46). Among spouses of HIV-2-infected women, none of the examined factors, including previous prostitution or proviral load in the woman, predicted whether the husband was HIV-2-infected. CONCLUSIONS: Women appear to be more susceptible to HIV-2 infection after 40-45 years of age. The apparent change in susceptibility may be a major reason for the distinctive age pattern of HIV-2 infection observed in West Africa.

Adolescent↗
PubMed1994

HIV type 2 proviral load measured by quantitative polymerase chain reaction correlates with CD4+ lymphopenia in HIV type 2-infected individuals.

The efficiency of detection of 2 sets of primer pairs from putatively conserved regions of the human immunodeficiency virus type 2 (HIV-2) genome were assessed in 86 seropositive individuals from The Gambia by nested polymerase chain reaction (PCR). HIV-2 long terminal repeat (LTR) target sequences were detected in DNA extracted from peripheral blood mononuclear cells (PBMCs) in 84 of 86 (97%) individuals whereas HIV-2 integrase (pol) gene sequences were detected in 39 of 41 (95%) individuals. The use of LTR target sequences and recombinant Pfu DNA polymerase, rather than Taq polymerase, in a modified secondary amplification reaction mediated the incorporation of 35S-labeled nucleotides in a quantitative radiometric assay. This sensitive assay was used to quantify HIV-2 proviral DNA in clinical samples and compared well with estimations by limiting end-point dilution of target molecules. A linear response between counts and the number of copies amplified from serial dilutions of pROD10 plasmid DNA (3-2000 copies) yielded a standard curve to allow extrapolation to clinical data. Increased levels of HIV-2 proviral DNA, expressed as copies per 10(5) CD4-positive lymphocytes, were associated with declining CD4 count in 63 adult patients (Spearman rank correlation, r = -0.71, n = 63, p < 0.001) and with the occurrence of HIV-related clinical disease. Kruskall-Wallis analysis of variance analysis showed the mean proviral copy number (log10) to be significantly different between groups (p < 0.001) where CD4 counts were grouped as < 200/mm3 (3.4 +/- 1.05 copies), 200-500/mm3 (2.84 +/- 0.93 copies), and > 500/mm3 (1.88 +/- 0.43 copies).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The effects of HIV-2 infection in a rural area of Guinea-Bissau.

OBJECTIVE: To investigate the clinical and immunologic effects, and pattern of mortality associated with HIV-2 infection. SETTING: A rural community in Guinea-Bissau. METHODS: Serologic screening of 2774 subjects aged > 14 years followed by studies of the prevalence of clinical and immunologic abnormalities among 133 subjects with HIV-2 infection and 160 seronegative controls, and surveillance of mortality among all subjects who were screened during a mean of 2 years of follow-up. RESULTS: Generalized lymphadenopathy was the only clinical abnormality significantly associated with HIV-2 infection. Infection was associated with lower CD4 counts and higher beta 2-microglobulin and neopterin levels. During follow-up, 5.5% of infected subjects died compared with 1.8% of the seronegatives (rate ratio adjusted for age and sex, 3.5; 95% confidence interval ((CI), 1.8-6.7). Proportional hazard regression analysis showed that the rate ratio varied with age (P = 0.003) and there was some evidence that the excess of mortality in infected subjects was, in absolute terms, least in the oldest subjects (trend test; P = 0.08). CONCLUSIONS: The findings support previous suggestions that HIV-2 is less pathogenic than HIV-1; the data also suggest that mortality associated with infection may be lower in older subjects.

Adolescent↗
PubMed1994

HIV-2-infected patients survive longer than HIV-1-infected patients.

OBJECTIVE: To compare survival of patients infected with HIV-1 and HIV-2. DESIGN: Longitudinal follow-up of 175 HIV-1- and 294 HIV-2-infected patients identified in, or referred to a hospital in The Gambia. METHODS: Survival analysis methods were used and the death rate ratios for HIV-2 relative to HIV-1 patients were estimated using proportional hazard regression models that allowed for age, sex and clinical or immunological features. RESULTS: The overall death rate ratio for HIV-2 relative to HIV-1 was 0.67 [95% confidence interval (CI), 0.49-0.91] when adjusted for age, sex and World Health Organization Bangui clinical classification. When allowing for age, sex and three strata of CD4+ count, the rate ratio was 0.64 (95% CI, 0.43-0.94), and for three strata of beta 2-microglobulin levels 0.60 (95% CI, 0.42-0.84). CONCLUSION: Mortality rate in HIV-2-infected patients is approximately two-thirds of that for HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗