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Biomedical subjects

S B Squire

Publications and source records attributed to S B Squire.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fully intermittent dosing with drugs for tuberculosis.

BACKGROUND: The number of people infected with tuberculosis continues to rise world-wide. Rifampicin-containing treatment regimens can achieve high cure rates. Intermittent drug treatment delivered in the community has the potential to improve adherence to treatment. OBJECTIVES: The objective of this review was to compare the effectiveness of rifampicin-containing short-course chemotherapy regimens, given two or three times a week, with similar regimens given daily in patients with pulmonary tuberculosis. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, and reference lists of articles. We contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of any multi-drug regimen containing rifampicin in patients with confirmed pulmonary tuberculosis. Treatment had to be given up to three times a week for up to nine months, with any initial daily dosing period not more than one month, and was compared to daily dosing throughout for the same period. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality. MAIN RESULTS: One trial involving 399 patients was included. The trial compared treatment three times per week with daily treatment for six months. There was no difference in cure rate (198 out of 199 people in the intermittent group compared to all 200 in the daily group), but 5 patients relapsed in the group receiving intermittent therapy compared to one in the group receiving the daily regimen. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the equivalence of effect between fully intermittent, rifampicin-containing short-course chemotherapy and similar daily therapy in patients with pulmonary tuberculosis. Larger randomised studies are required to establish the effectiveness of fully intermittent, short-course chemotherapy.

Antitubercular Agents↗
PubMed2000

Trial-of-antibiotic algorithm for the diagnosis of tuberculosis in a district hospital in a developing country with high HIV prevalence.

OBJECTIVE: To evaluate a diagnostic algorithm for pulmonary tuberculosis based on smear microscopy and objective response to trial of antibiotics. SETTING: Adult medical wards, Hlabisa Hospital, South Africa, 1996-1997. METHODS: Adults with chronic chest symptoms and abnormal chest X-ray had sputum examined for Ziehl-Neelsen stained acid-fast bacilli by light microscopy. Those with negative smears were treated with amoxycillin for 5 days and assessed. Those who had not improved were treated with erythromycin for 5 days and reassessed. Response was compared with mycobacterial culture. RESULTS: Of 280 suspects who completed the diagnostic pathway, 160 (57%) had a positive smear, 46 (17%) responded to amoxycillin, 34 (12%) responded to erythromycin and 40 (14%) were treated as smear-negative tuberculosis. The sensitivity (89%) and specificity (84%) of the full algorithm for culture-positive tuberculosis were high. However, 11 patients (positive predictive value [PPV] 95%) were incorrectly diagnosed with tuberculosis, and 24 cases of tuberculosis (negative predictive value [NPV] 70%) were not identified. NPV improved to 75% when anaemia was included as a predictor. Algorithm performance was independent of human immunodeficiency virus status. CONCLUSION: Sputum smear microscopy plus trial of antibiotic algorithm among a selected group of tuberculosis suspects may increase diagnostic accuracy in district hospitals in developing countries.

AIDS-Related Opportunistic Infections↗
PubMed1998

Effect of preventive treatment for tuberculosis in adults infected with HIV: systematic review of randomised placebo controlled trials.

OBJECTIVE: To determine whether preventive treatment for tuberculosis in adults infected with HIV reduces the frequency of tuberculosis and overall mortality. DESIGN: Systematic review and data synthesis of randomised placebo controlled trials. MAIN OUTCOME MEASURES: Active tuberculosis, mortality, and adverse drug reaction requiring cessation of the study regimen. Outcomes stratified by status of purified protein derivative skin test. RESULTS: Four trials comprising 4055 adults from Haiti, Kenya, the United States, and Uganda were included. All compared isoniazid (6-12 months) with placebo, and one trial also compared multidrug treatment for 3 months with placebo. Mean follow up was 15-33 months. Overall, frequency of tuberculosis (relative risk 0.57, 95% confidence interval 0.41 to 0.79) was reduced in those receiving preventive treatment compared with placebo: mortality was not significantly reduced (0.93, 0.83 to 1.05). In subjects positive for purified protein derivative receiving preventive treatment, the risk of tuberculosis was reduced substantially (0.32, 0.19 to 0.51) and the risk of death was reduced moderately (0.73, 0.57 to 0.95) compared with those taking placebo. In adults negative for purified protein derivative receiving preventive treatment, the risk of tuberculosis (0.82, 0.50 to 1.36) and the risk of death (1.02, 0.89 to 1.17) were not reduced significantly. Adverse drug reactions were more frequent, but not significantly so, in patients receiving drug compared with placebo (1.45, 0.98 to 2.14). CONCLUSIONS: Preventive treatment given for 3-12 months protects against tuberculosis in adults infected with HIV, at least in the short to medium term. Protection is greatest in subjects positive for purified protein derivative, in whom death is also less frequent. Long term benefits remain to be shown.

AIDS-Related Opportunistic Infections↗
PubMed1998

Treatment for mycobacterial infections.

Mycobacterium tuberculosis remains the most important global cause of mycobacterial disease in humans. The central roles of consistent delivery, adherence to therapy, and built-in audit of practice have recently received heavy emphasis in the treatment of M. tuberculosis, particularly in new guidelines from the World Health Organization. The management of mycobacterial disease in the context of HIV infection continues to pose problems, particularly in resource-poor settings. The most significant development for the clinical management of HIV-associated M. tuberculosis infection in the past year has been the establishment of the efficacy of isoniazid monotherapy as preventive therapy, after the publication of three new randomized, placebo-controlled trials.

Journal Article↗
PubMed1993

Lymphocyte activation in HIV-1 infection. I. Predominant proliferative defects among CD45R0+ cells of the CD4 and CD8 lineages.

OBJECTIVES AND DESIGN: The proliferative defects of CD4 and CD8 cells taken from 474 HIV-1-seropositive individuals during various stages of disease were quantitated. Phytohaemagglutinin (PHA) and soluble anti-CD3 were used in optimal mitogenic concentrations in the presence of recombinant interleukin-2 (rIL-2) and conditioned medium, and the proliferation of cells from HIV-1-seropositive donors was assessed in co-culture with HIV-1-seronegative cells in order to exclude effects of cytokine deficiency. Defects within the CD45RA+ ('unprimed') and CD45R0+ ('primed') T-cell populations were also investigated. METHODS: Quantitative immunofluorescence and double and triple labelling in flow cytometry were performed for (1) CD25 (IL-2 receptor alpha chain) expression, (2) lymphocyte and T-cell survival, and (3) blast transformation and proliferation--in relation to the original input of cells for each subpopulation. RESULTS: T cells from normal and HIV-1-seropositive donors were CD25+ at day 1. In HIV-1-seropositive patients a variable number of CD4 and CD8 lymphocytes failed to further increase CD25, and died as a sign of activation-associated lymphocyte death (AALD). Forty-two per cent of asymptomatic subjects, including 32% of those with CD4 cell counts > 400 x 10(6)/l, showed a poor blast transformation (< 30% blasts). Cells from HIV-1-seropositive donors showed poor blast responses when co-cultured with HIV-1-seronegative cells; both CD4 and CD8 cells were handicapped. In asymptomatic HIV-1-seropositive people T cells with the CD45R0+ RA- ('primed') phenotype were three to five times more vulnerable to AALD than the CD45RA+ RO- ('unprimed') cells. In patients in Centers for Disease Control and Prevention (CDC) disease stage IV both CD45R0+ and -RA+ populations were severely affected. CONCLUSIONS: This is the first quantitative analysis to demonstrate that in HIV-1 infection mitogen-stimulated CD45R0+ ('primed') T cells preferentially die upon activation. Both the CD4 and CD8 lineages are affected, as seen in animal models of graft versus host disease. AALD may explain defects of immunological memory. The analysis of AALD may be a suitable assay for studying whether antiviral drugs influence the proliferative responses of lymphocytes.

CD3 Complex↗
PubMed1993

Antiretroviral treatment reverses HIV-induced reduction in the expression of surface antigens on alveolar macrophages in AIDS patients.

MoAbs and immunoperoxidase methods were used to identify antigen-presenting and phagocytic cells and to assess expression of HLA-DR molecules on cells obtained by bronchoalveolar lavage (BAL) from 33 AIDS patients and nine normal volunteers. In 17 patients, not receiving antiretroviral therapy, the expression of HLA-DR molecules (MoAb RFDR1) as well as the percentages of cells expressing RFD1 marker for antigen-presenting cells and RFD7 marker for mature phagocytes were significantly reduced. However, in BAL obtained after commencing treatment with zidovudine (AZT) in 21 patients or with 2',3'-dideoxyinosine (DDI) in five patients, the expression of the markers studied was found to have returned to levels of expression seen in normal lavages. The changes observed were clearly associated with antiretroviral treatment and did not correlate with applications of other drugs, blood CD4 counts or presence of infectious organisms in BAL fluid. As the alterations in the expression of HLA-DR molecules and RFD1 marker on macrophages have been shown to be associated with functional capacities of these cells, the reversal of impaired expression of phenotypic markers on alveolar macrophages in AIDS patients by AZT and DDI signifies an important ability of these drugs to modify immune reactivity and emphasizes the need to monitor such functions in HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection.

OBJECTIVE: To establish the incidence of herpes simplex virus (HSV) ulceration in relation to CD4+ cell counts in HIV-infected patients. DESIGN: Swabs were taken from all ulcerated lesions in HIV-infected patients and cultured for HSV. CD4+ cell counts were performed at regular intervals. SETTING: The HIV unit at a London teaching hospital (the Royal Free Hospital, London, UK). PATIENTS: All HIV-infected patients (n = 500) attending the HIV unit. RESULTS: Two hundred and twenty-three swabs were obtained from 118 patients; 83 (37.2%) swabs from 62 (52.5%) patients were positive for HSV. Of 96 swabs taken from patients with CD4+ cell counts < 50 x 10(6)/l, 56 (58.3%) were positive for HSV, compared with 27 of 127 (21.2%) swabs from patients with higher CD4+ cell counts (P < 0.0001). Of patients with CD4+ cell counts < 50 x 10(6)/l, 37 of 47 (78.7%) had positive cultures compared with 25 of 71 (35.2%) of patients with higher counts (P < 0.0001). This trend was observed with swabs from all body sites; sufficient samples were available from oral and perianal lesions to demonstrate statistical significance (P < 0.0001 and P = 0.007, respectively). CONCLUSIONS: These results show a sharp rise in the incidence of HSV with CD4+ cell counts < 50 x 10(6)/l and thus provide important data for the design of studies of anti-HSV prophylaxis. Furthermore, since nearly 60% of all ulcers in patients with such low CD4+ counts are HSV-positive, we suggest appropriate empirical therapy on presentation.

AIDS-Related Opportunistic Infections↗
PubMed1992

Severe cytomegalovirus pneumonitis in HIV infected patients with higher than average CD4 counts.

BACKGROUND: Cytomegalovirus may replicate within the lungs both of recipients of transplants and of patients infected with the human immunodeficiency virus (HIV). A hypothesis formulated by this group was that a host damaging immune response might be provoked by cytomegalovirus infection and cause a severe pneumonitis in recipients of allogeneic transplants, whereas the progressive impairment of cellular immunity in patients with HIV disease would preclude a damaging immune response in the lungs, and thus protect these patients from severe cytomegalovirus pneumonitis. This study set out to discover whether severe cytomegalovirus pneumonitis arises in HIV infected patients. METHODS: Data were prospectively collected on severity of pneumonitis and infectious agents identified in consecutive respiratory episodes in HIV infected patients undergoing diagnostic bronchoalveolar lavage during 20 months. RESULTS: Eighty five episodes of pneumonitis occurred in 68 patients. Cytomegalovirus was identified as the only infectious agent in nine episodes (nine patients). Seven of the episodes were mild; all these patients had CD4 counts below 0.1 x 10(9)/1. The remaining two episodes were severe and ventilatory support was required. In both cases the CD4 counts were above 0.2 x 10(9)/1 and HIV infection appeared to have been acquired shortly before presentation. CONCLUSION: Although rare, severe cytomegalovirus pneumonitis may occur in HIV infected patients. Both patients with severe pneumonitis in this series had relatively well preserved immune function. These findings support the hypothesis that severe cytomegalovirus pneumonitis is an immunopathological condition.

Adult↗
PubMed1992

Alveolar macrophage populations are distorted in immunocompromised patients with pneumonitis.

Alveolar macrophages (AM) were obtained by bronchoalveolar lavage (BAL) from patients presenting with pneumonitis: 30 human immunodeficiency virus (HIV)-infected individuals and 12 transplant recipients. Nine normal volunteers acted as controls. The cells were washed and cytospins prepared. Monoclonal antibodies (MoAbs) and immunoperoxidase methods were used to analyse the expression of HLA-DR molecules as well as phenotypic macrophage markers. P values apply to the differences between medians using the Mann-Whitney test. Median percentages of macrophages, lymphocytes and neutrophils were similar in all three groups. No differences were found in the median percentages of macrophages expressing the monocyte phenotype (MoAb UCHM1, CD14). However, in HIV-infected patients and transplant recipients a median of only 45% of macrophages expressed the pan-macrophage phenotype identified by MoAb EBM11 (CD68) in contrast with 98% in the normal volunteers. The AM population expressing the dendritic cell marker (MoAb RFD1) was also markedly reduced in both groups of immunocompromised patients (2 vs 28% in normal volunteers). Transplant recipients had significantly more phagocytic cells identified by MoAb RFD7 than the HIV-infected patients (25 vs 2%), but the numbers were still low when compared with the volunteers (48%). HLA-DR expression on BAL cells was reduced by 90% in both immunocompromised groups. For the transplant recipients, severity of pneumonitis was correlated with expression of dendritic cell marker RFD1, (Spearman's rank correlation r = 0.538, p less than 0.05) and pan-macrophage marker EBM11 (r = 0.581, p less than 0.05), while no such correlation was found in HIV-infected patients. These results suggest that a defective macrophage population is probably a serious factor contributing to immunosuppression.

Adult↗
PubMed1991

Open access clinic providing HIV-I antibody results on day of testing: the first twelve months.

OBJECTIVES: To determine the sociodemographic profile, risk category, and prevalence of HIV-I infection among people attending a clinic providing counselling, medical advice, and results of HIV-I antibody testing on the day of consultation; to determine the stage of infection and peripheral blood CD4 cell count among attenders with detectable HIV-I antibodies. DESIGN: Analysis of prospectively collected data for the 12 months from March 1989. SETTING: Same day testing clinic run by the HIV/AIDS team at an urban teaching hospital. PATIENTS: 561 consecutive people choosing to attend and proceeding to HIV-I testing. RESULTS: The demand for the service caused it to run to capacity within six months. The median age of those attending was 28 years and 65% (364 patients) were male. The overall prevalence of HIV-I infection was 3.9% (22 patients). The greatest prevalence was in men reporting their primary risk as homosexual contact (11.9%, 13/109). The median CD4 cell count in the 22 patients who had detectable HIV-I antibodies was 0.31 x 10(9) cells/l (normal range 0.5 x 10(9)/l to 1.2 x 10(9)/l). Twenty of these patients were asymptomatic (Centers for Disease Control stages II or III), 14 had CD4 cell counts below 0.5 x 10(9)/l. CONCLUSIONS: There is a recognisable demand for a service providing rapid results of HIV-I antibody testing in this setting. The overall seroprevalence of 3.9% is comparable with the 5.8% reported from freestanding clinics in the United States. Most patients with HIV-I antibodies detected in this way are asymptomatic but could benefit from early medical intervention because of low CD4 cell counts.

Acquired Immunodeficiency Syndrome↗
PubMed1991

New methods in the diagnosis and management of cerebral toxoplasmosis associated with the acquired immune deficiency syndrome.

Cerebral toxoplasmosis is a life-threatening condition associated with the acquired immune deficiency syndrome (AIDS). Current diagnostic and therapeutic methods have serious limitations. The diagnosis of cerebral toxoplasma infection in a patient with AIDS was assisted by the detection of specific IgM in a highly sensitive immunosorbent agglutination assay and by the demonstration of Toxoplasma gondii nucleic acid in a brain biopsy specimen by means of the polymerase chain reaction. Following initial failure of the patient to respond to treatment with sulphadiazine and pyrimethamine, clinical improvement was observed during treatment with clindamycin followed by dapsone. Further assessment of novel methods in the management of cerebral toxoplasmosis is required.

Acquired Immunodeficiency Syndrome↗