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Biomedical subjects

B Gazzard

Publications and source records attributed to B Gazzard.

At least 91 records · Page 5Linked to original sources
PubMed1997

A double-blind placebo-controlled phase II trial of thalidomide in asymptomatic HIV-positive patients: clinical tolerance and effect on activation markers and cytokines.

A randomized double-blind, placebo-controlled study was performed to determine the safety, efficacy, and effect of thalidomide on a variety of immunological and biochemical parameters in asymptomatic human immunodeficiency virus (HIV)-positive patients. Nineteen male patients with elevated markers of immune activation and CD4 cell counts above 400/mm3 were randomized to either placebo or thalidomide at 100 mg/day for 24 weeks. However, only 3 (of 10) patients receiving thalidomide completed all 24 weeks compared to 6 (of 9) patients receiving placebo. This was mainly due to fatigue (somnolence is a recognized side effect), although this was also seen to a lesser extent in the placebo group and so may not be drug attributable. No significant changes in CD4/CD8 count, activation markers, TNF-alpha, or TNFR1 were observed. However, a nonsignificant trend toward inhibition of mitogen-induced TNF-alpha production was observed in the thalidomide arm. The lack of systemic effect and the lower tolerance of thalidomide (at this dose) in asymptomatic patients highlights the need for pharmacokinetic analysis to address possible absorption problems and the need for more potent and less toxic TNF-alpha inhibitors to be developed for use in this type of study.

Adult↗
PubMed1997

CD4 cell counts of 200 x 10(6)/1 or below in natural history studies and surveillance: is one enough or are two better?

A retrospective cohort study was performed to examine the extent and clinical significance of misclassification associated with using the current United States AIDS case defining category of an initial CD4 count < or = 200 cells x 10(6)/l (< or = 200) compared with a definition requiring two consecutive counts below this level. The main outcomes examined were the probability of subsequent CD4 counts > 200 x 10(6)/l (> 200) and progression times to AIDS and death. Of the 2025 predominantly male homosexual HIV-positive patients attending two hospital based HIV clinics with initial CD4 cell counts < or = 200, 1524 (75%) subsequently had consecutive counts < or = 200, but only half did so at the next CD4 count. Ten per cent had either no further or only non-consecutive counts < or = 200, and 15% had only one CD4 count available for analysis. The cumulative proportion of patients with a CD4 count > 200 at one year after a first count of < or = 200 was about twice (39%) that observed among the subgroup with at least two consecutive counts < or = 200 (19%). The times from the initial counts of < or = 200 to AIDS and death were also shorter by six months and two months, respectively, in the subgroup with two or more consecutive counts < or = 200. A significant proportion of patients will be prematurely classified as having a CD4 cell count < or = 200 if a single CD4 count below this level is accepted. A definition of two consecutive counts < or = 200 should be adopted in preference to a single count < or = 200 for natural history studies and clinical trials, in which precise estimates of the time to or from a defined CD4 threshold are important. In surveillance programmes, however, such an approach may be impractical because of missing or infrequent serial CD4 counts, although adjustments can be made based on these estimates of premature misclassification.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Survival after diagnosis of AIDS: a prospective observational study of 2625 patients. Royal Free/Chelsea and Westminster Hospitals Collaborative Group.

OBJECTIVE: To estimate median survival and changes in survival in patients diagnosed as having AIDS. DESIGN: Prospective observational study. SETTING: Clinics in two large London hospitals. SUBJECTS: 2625 patients with AIDS seen between 1982 and July 1995. MAIN OUTCOME MEASURES: Survival, estimated using lifetable analyses, and factors associated with survival, identified from Cox proportional hazards models. RESULTS: Median survival (20 months) was longer than previous estimates. The CD4 lymphocyte count at or before initial AIDS defining illness decreased significantly over time from 90 x 10(6)/1 during 1987 or earlier to 40 x 10(6)/1 during 1994 and 1995 (P < 0.0001). In the first three months after diagnosis, patients in whom AIDS was diagnosed after 1987 had a much lower risk of death (relative risk 0.44, 95% confidence interval 0.22 to 0.86; P = 0.017) than patients diagnosed before 1987. When the diagnosis was based on oesophageal candidiasis or Kaposi's sarcoma, patients had a lower risk of death than when the diagnosis was based on Pneumocystis carinii pneumonia (0.21 (0.07 to 0.59). P = 0.0030 and 0.37 (0.16 to 0.83), P = 0.016). Three months after AIDS diagnosis, the risk of death was similar in patients whose diagnosis was made after and before 1987 (1.02 (0.79 to 1.31), P = 0.91). There were no differences in survival between patients diagnosed during 1988-90, 1991-3, or 1994-5. CONCLUSIONS: In later years, patients were much more likely to survive their initial illness, but long term survival has remained poor. The decrease in CD4 lymphocyte count at AIDS diagnosis indicates that patients are being diagnosed as having AIDS at ever more advanced stages of immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Thalidomide: a novel therapy for microsporidiosis.

BACKGROUND & AIMS: Microsporidiosis is a common cause of chronic diarrhea in human immunodeficiency virus (HIV)-seropositive individuals and often does not respond to treatment. Fecal tumor necrosis factor alpha (TNF-alpha) is elevated in microsporidiosis; therefore, thalidomide, an anti-TNF-alpha agent, was used as therapy. METHODS: Eighteen subjects with chronic diarrhea caused by Enterocytozoon bieneusi that had not responded symptomatically to albendazole and 1 untreated subject with Encephalitozoon intestinalis received 1 month of thalidomide, 100 mg nocte. Clinical response was assessed by stool frequency and body weight, histological response by light microscopy with villus height/crypt depth ratios and electron microscopy, and immunologic response by fecal TNF-alpha level. RESULTS: Seven subjects with chronic diarrhea due to E. bieneusi had a complete clinical response, and 3 had a partial response to thalidomide. There was a significant decrease in stool frequency from 5.3 to 3.1 per day (P = 0.001), and weight increased significantly by 1.2 kg (P < 0.02). Thalidomide significantly increased the villus height/crypt depth ratio (1.95 to 2.07; P = 0.045) and number of abnormal forms of microsporidia (P < 0.01). Fecal TNF-alpha level nonsignificantly decreased from 17.9 to 8.9 U/mL. There was apparent disruption of all stages of the life cycle of E. intestinalis. CONCLUSIONS: Thalidomide may be an effective therapy for diarrhea and weight loss from E. bieneusi.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Reasons given by patients for "non-progression' in HIV infection.

Identification of the reasons for long-term survival in HIV infection is an area of current intense research. The objective of this study was to determine the perceptions among patients with different rates of disease progression as to the reasons for a good outcome with HIV. In a case-control study of 134 long-term (> or = 8 years) HIV-infected participants, 62 were defined as non-progressors; current CD4 cell count > or = 500 x 10(6)/L and asymptomatic or only mildly symptomatic. Two groups of control patients were identified: intermediate progressors who also had been HIV-infected for > or = 8 years, but whose current CD4 cell count was < 500 x 10(6)/L (n = 61), and a group of rapid progressors who had developed AIDS within 5 years of HIV infection (n = 11). Non-progressors were asked 'what do you feel are the reasons for your good outcome with HIV-infection?' and intermediate and rapid progressors were asked 'what do you feel are the reasons for a good outcome with HIV infection?'. Mental attitude, and in particular a positive outlook was the reason most frequently given for a good outcome among both non-progressors (NP) 42%, and progressors (P) 40%, followed by lifestyle measures and personal action (NP 31%, P 35%). Medical treatments such as anti-retroviral drugs were rarely suggested (< 3%). No significant differences were observed in the frequency of the different reasons given by non-progressors and progressors. The belief among our long-term HIV-infected individuals, that a positive outlook, lifestyle and personal action are important determinants of a good prognosis, is in sharp contrast to the biomedical model of disease progression that prevails among the medical and scientific research community.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Aquagenic urticaria and human immunodeficiency virus infection: treatment with stanozolol.

We report the first case of aquagenic urticaria in a patient with human immunodeficiency virus (HIV) infection. This is a rare physical urticaria not previously described in this context. The disorder proved unamenable to conventional treatment with antihistamines, but did respond dramatically to stanozolol, suggesting a novel indication for this anabolic steroid.

Adult↗
PubMed1997

Biochemical assessment of pancreatic disease in human immunodeficiency virus infected men.

AIM: To determine the usefulness of measuring amylase activity as an indicator of pancreatic disease in human immunodeficiency virus (HIV) positive patients. METHODS: A prospective study of 129 ambulant HIV positive males. Total amylase, pancreatic amylase, and lipase activities were assayed using commercial test kits on an automated analyser. Samples with raised amylase were examined for the presence of macroamylasaemia using cellulose acetate electrophoresis. RESULTS: Thirty six (28%) of the subjects had raised total amylase activities compared with healthy, age matched blood donors. However, almost half of these were because of an increase of the salivary fraction. Four subjects were found to have macroamylasaemia. Pancreatic amylase and lipase assays, more specific indicators of pancreatic disease, produced significantly fewer abnormal results. There was no association between abdominal symptoms and elevated enzyme levels. CONCLUSIONS: Total amylase is a poor indicator of pancreatic disease in HIV infected outpatients. Specific assays for pancreatic amylase offer advantages over the traditional total amylase assay. The lipase assay produced the least number of abnormal results and its use could improve the biochemical identification of patients with possible pancreatic disease and allow a more selective investigation of these cases.

Adult↗
PubMed1997

Indirect calorimetry, body composition and small bowel function in asymptomatic HIV-seropositive women.

Extrapolation of data from energy balance studies in HIV-seropositive men to HIV-seropositive women may be inaccurate due to gender differences in body composition, hormones and metabolism. If women have a different metabolic response to the human immunodeficiency virus (HIV), nutritional advice may differ from HIV-seropositive men. Ten asymptomatic HIV-seropositive women were matched with 10 heterosexual female controls from low-risk groups. Subjects and controls had assessment of energy and protein intake, resting energy expenditure (REE) and substrate oxidation, small bowel absorption and permeability and body composition. There were no significant differences in REE, substrate oxidation and body composition. Energy and protein intake and small bowel permeability were increased and sugar absorption decreased in HIV-seropositive women (all P < 0.05). Unlike asymptomatic HIV-seropositive men, asymptomatic HIV-seropositive women do not have significant alterations in metabolism or body composition. Therefore, nutritional advice may need to vary according to the gender of the asymptomatic HIV-seropositive subject.

Adult↗
PubMed1997

To sequence or not to sequence?

There is now incontrovertible evidence that a combination of two nucleoside analogues is superior to AZT monotherapy for the treatment of HIV infection. There is also evidence that a range of antiretroviral combinations can produce profound drops in plasma HIV viral load, often below the detectable limits of the assay. A lower rate of viral replication is associated with delays in the selection of viral mutants resistant to drugs; the principal reason for therapeutic failure. These highly effective combinations are likely to delay clinical events and considerably improve the prognosis in HIV-infected individuals. Using mathematical modelling techniques to assess the half-life of plasma virus infectious cells and proviral DNA, one group has gone so far as to suggest it may be possible to stop therapy after several years, as the virus will have been eliminated. More sanguine investigators, however, believe that this is unlikely, as some infected cellular compartments may have long half-lives and the virus may persist, or even continue to replicate slowly, in sanctuary sites, such as the CNS and genital tract, poorly penetrated by drugs. Thus, some virologists and clinicians believe that it is crucially important to give initial therapy with the strongest possible combination of drugs to achieve an 'undetectable' plasma viral load and that, providing compliance is good, this will lead to a prolonged therapeutic effect. In these circumstances no sequencing issues arise. Others, however, continue to believe that, in due course, the virus is likely to evade drug pressure. In these circumstances, consideration of a sequence of drugs, to avoid initial and subsequent therapy from squandering future therapy options through, principally, cross-resistance, becomes an important issue. None of the issues discussed in this review has been tested by controlled clinical trials but they generate hypotheses requiring urgent evaluation.

Editorial↗
PubMed1996

Gastrointestinal manifestations of HIV infection.

The harrowing picture of emaciated terminally ill AIDS patients is a reminder of our lack of understanding of immunological mechanisms that normally control opportunistic infections. Many gastrointestinal pathogens in patients with AIDS are resistant to treatment and lead inexorably to weight loss and death. Although knowledge of the pathogenesis and clinical significance of weight loss has improved considerably, this has not yet led to a sustained effort to improve nutritional status during early stages of disease.

AIDS-Related Opportunistic Infections↗
PubMed1996

The psychological impact on staff of caring for people with serious diseases: the case of HIV infection and oncology.

Psychological stress and work-related burnout in staff working with AIDS and with cancer patients were compared using a self-report method of assessment. Measures included the General Health Questionnaire (GHQ), Maslach Burnout Inventory (MBI), and the Social Adjustment Scale (SAS-M). More than 80% of those staff who were approached responded to the questionnaire, including 70 doctors and nurses working with people with AIDS and 41 doctors and nurses working in oncology. More than a third of staff had substantial levels of psychological morbidity, and about a fifth had significant levels of work-related stress. Factors associated with the presence of high levels of psychological morbidity and with abnormal levels of emotional exhaustion, depersonalization, and concerns about personal accomplishment were identified. Staff described the work situations with which they had difficulty dealing and some of the coping strategies they used. The findings confirm that staff working with people with cancer or AIDS experience psychological difficulties of the kind likely to respond to interventions aimed at improving their ability to cope with work-related stresses. The mental health services could play an important role in carrying out research in this field and in providing practical help to deal with staff's difficulties.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Women and HIV infection: investigation of its psychosocial consequences.

HIV infection is associated with substantial psychological and social morbidity, although there is a dearth of studies of women with the infection. In recent years, developed countries have reported an increase in the prevalence of HIV infection in women, a fact that makes it all the more important to address the study of their psychological and social status. The study is a controlled investigation of HIV seropositive (n = 49) and seronegative women (n = 43), including study of psychological status and history, social functioning and perceived supports, coping style, life events, and sexual difficulties. The results show that about a third of women were psychiatric cases, regardless of HIV status, although more than half of symptomatic women were psychiatric cases. Seropositive women were less likely to use instrumental social supports and more likely to use mental disengagement as ways of coping. Regarding perceived social supports, positive women had lower scores on social integration and guidance. Positive women were more likely to experience sexual difficulties and not to be in a relationship. Negative women reported more adverse life events in the last 6 months. Psychiatric morbidity was associated with poorer social adjustment and more adverse life events, but not with serostatus. HIV positive women and those at risk of HIV infection have substantial levels of psychological and social morbidity that require recognition by those involved in their care and provision of adequate mental health intervention.

Adaptation, Psychological↗
PubMed1996

Are people with HIV in London able to die where they plan?

Being able to die where you plan is a measure of quality of life near death, in that it implies awareness of diagnosis and prognosis, adequate symptom control and involvement in decision-making in late-stage HIV disease. This study presents trends in place of death for patients attending a large central London HIV centre and examines whether patients dying over a 6-month period in 1994 were able to die where they planned. Early in the epidemic almost all people with HIV died in hospital, but in the late 1980s there was an increase in death at home and in hospices. Of people attending this hospital in 1994, 46% died in hospital, 31% at home, 20% in hospices and 2% abroad. A total of 59% of deaths were where the dying person had planned. Most unplanned deaths were in hospital, two-thirds being due to an unexpected deterioration which precluded planning. The rest were a mixture of people waiting for discharge to die elsewhere, and people who wished to continue active treatment. This pattern of place of death is unlikely to change in the near future. It is therefore essential that hospitals can provide for the needs of patients dying on acute wards.

Choice Behavior↗
PubMed1996

Faecal alpha 1 antitrypsin as a marker of gastrointestinal disease in HIV antibody positive individuals.

Hypoalbuminaemia and diarrhoea are common complications of HIV infection and substantial causes of morbidity, but the specific intestinal pathologies that cause enteric protein loss have not been clearly defined. Two hundred and twenty stool samples from patients with a variety of HIV related conditions were analysed for faecal alpha 1 antitrypsin. Patients with intestinal Kaposi's sarcoma had a significantly raised faecal alpha 1 antitrypsin value and hypoalbuminaemia. A faecal alpha 1 antitrypsin value of greater than 0.3 mg/g wet stool has a sensitivity of 94% and a specificity of 76% for the diagnosis of intestinal Kaposi's sarcoma in HIV positive individuals. Patients with cytomegalovirus and bacterial enteritis had raised faecal alpha 1 antitrypsin values but levels were normal for all other intestinal pathologies compared with pathogen negative stool. The combination of faecal alpha 1 antitrypsin concentration greater than 0.2 mg/g, a negative stool culture for enteric bacteria, and the absence of palatal Kaposi's sarcoma has a sensitivity of 55% and specificity of 88% for the diagnosis of enteric cytomegalovirus infection.

AIDS-Related Opportunistic Infections↗
PubMed1996

Mycobacterium kansasii: its presentation, treatment and outcome in HIV infected patients.

AIM: To report the clinical significance and treatment of Mycobacterium kansasii infection in the context of HIV disease. DESIGN/METHODS: Retrospective case review of all isolates of M kansasii until June 1994. RESULTS: Ten cases of M kansasii were isolated. All but one patient with this infection had clinical symptoms compatible with generalised infection. The majority had chest infections with the organism isolated on induced sputum but not routine sputum. All isolates were sensitive to ethambutol and nine of 10 to rifampicin. All isolates were resistant to isoniazid and pyrazinamide. CONCLUSION: M kansasii is a pathogen in HIV infected patients and should be treated when isolated. Treatment should be with rifampicin and ethambutol but not isoniazid, as has been recommended previously.

AIDS-Related Opportunistic Infections↗