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Biomedical subjects

A Carr

Publications and source records attributed to A Carr.

At least 127 records · Page 7Linked to original sources
PubMed1997

Role of desensitisation for drug hypersensitivity in patients with HIV infection.

Drug hypersensitivity is common in patients with HIV infection and manifests as a delayed onset maculopapular rash, often with fever, mucositis and occasionally visceral involvement. In the 50% of patients who require treatment modification, many can be treated with an equally effective alternative that does not cause hypersensitivity. For the remainder, options include 'treating through' the reaction, adjunctive corticosteroids and/or antihistamines, rechallenge and desensitisation. Formal comparisons are lacking but preliminary data suggest that desensitisation is more successful than rechallenge. The most common reason for performing desensitisation is sulphonamide hypersensitivity for treatment or prophylaxis of pneumocystosis, where success rates of 68 to 100% have been reported. Success seems more likely when regimens lasting 7 or more days are used and in patients with lower CD4+ lymphocyte counts. However, the best tolerated, effective and simple desensitisation regimen has not been determined.

Anti-HIV Agents↗
PubMed1997

A trial of relapse prevention with severely dependent male problem drinkers.

Over the last two decades, relapse prevention has emerged as a major focus of the treatment of drug problems. Few studies have demonstrated any impact on generally high relapse rates. In this paper the outcome of a controlled trial of a relapse prevention programme with male problem drinkers (n = 60) attending an Alcohol Treatment Unit is reported. Subjects who met the inclusion criteria were allocated to a relapse prevention (n = 20) procedure or a discussion (n = 20) or no-additional treatment (n = 20) control procedure. Subjects were followed-up at 6 and 12 months by the first author. The relapse prevention programme was associated with significantly greater increases in pre- and post-treatment self-efficacy compared to the discussion control group and significantly greater probability of total abstinence than all controls over the first 6-month follow up. In addition, the relapse prevention programme was associated with significantly longer survival time to an initial lapse and relapse than the controls. At 12-month follow-up, treatment effects had been eroded. It was concluded that the relapse prevention programme was an effective treatment in the short term and that longer-term impact may require greater focus on maintenance factors, such as the individual's environment.

Adult↗
PubMed1996

CD8+ lymphocyte responses to antiretroviral therapy of HIV infection.

CD8+ T lymphocytes may mediate important host responses to human immunodeficiency virus (HIV) infection by human leukocyte antigen (HLA)-restricted cytotoxicity and production of soluble HIV suppressor factors. CD8+ lymphocytes are also important for the suppression of many latent pathogens responsible for opportunistic disease in HIV-infected patients. There has been no systematic analysis of the responses of CD8+ lymphocyte counts to antiretroviral therapy. We compared CD8+ lymphocyte responses in seven trials of nucleoside or non-nucleoside analog reverse transcriptase inhibitors and in two trials of ritonavir, a HIV protease inhibitor. Nucleoside analog and non-nucleoside analog reverse transcriptase inhibitor monotherapy resulted in no substantial changes in CD8+ counts relative to baseline or placebo. Combination nucleoside analog therapy resulted in variable peak responses (-145 to +240 cells/mm3), which remained significantly above baseline for 0 to 12 weeks. In contrast, ritonavir monotherapy caused a peak increase of 892 CD8+ cells/mm3, which remained significantly above baseline for 32 weeks. There was a significant correlation (Rs 0.61, p = 0.01) between the peak CD4+ cell and CD8+ responses to each therapy, but no significant correlation between the peak viral load responses and peak CD8+ cell responses. These findings suggest that the greater CD8+ response seen with ritonavir may be due to its specific inhibition of HIV protease and also that the CD8+ response is dependent on new CD4+ cell production. The CD8+ lymphocyte proliferation observed with protease inhibitor therapy could result in improved suppression of HIV replication by the immune system and should be confirmed in a prospective trial comparing protease inhibitors with both nucleoside and non-nucleoside analog therapies.

Acetamides↗
PubMed1996

Gangliosides expressed in human breast cancer.

Breast tumors that were histopathologically diagnosed as invasive ductal carcinoma were examined in relation to their abnormal expression of gangliosides. Total ganglioside levels that were expressed as lipid-bound sialic acids were significantly higher in breast tumor tissues than in normal mammary tissues. Two kinds of unusual gangliosides were found to be expressed in many cases of breast tumors. One was a group of O-acetylated gangliosides, such as O-acetyl-GD3 and O-acetyl-GT3. They are known as fetal gangliosides, which appear in fetal brains. The other was an N-glycolylneuraminic acid-containing ganglioside, N-glycolyl-GM3, which had not been previously found in normal human tissues. The finding that unusual gangliosides are expressed in breast tumors may provide the basis for their immunological diagnosis and vaccine therapy.

Breast Neoplasms↗
PubMed1996

Managing HIV. Part 2: Phases of disease. 2.1 Primary HIV infection.

The most important principle in managing primary HIV infection is not to miss the diagnosis. It presents an early opportunity for counselling and education aimed at maximising quality of life and minimising the risk of transmitting HIV (particularly high during the viraemia of primary infection).

Adult↗
PubMed1996

Current clinical experience with nevirapine for HIV infection.

Nevirapine is a potent antiretroviral agent whose use, especially as monotherapy, may be limited by rapid onset of resistance as well as by hypersensitivity reactions. However, virologic features of nevirapine suggest that it may be useful in combination therapy with zidovudine or other antiretrovirals, including for patients infected with zidovudine-resistant strains HIV.

Antiviral Agents↗
PubMed1996

Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir.

Effects of a human immunodeficiency virus (HIV) type 1 protease inhibitor, ritonavir, were evaluated in 21 patients enrolled in a phase I/II study. The magnitude and rates of CD4 and CD8 lymphocyte increase, changes in subsets of CD4 and CD8 lymphocytes, and proliferative responses to mitogen and antigens were analyzed. Significant increases were noted in CD4 and CD8 lymphocyte counts; numbers of CD4CD45RO lymphocytes increased significantly by week 1 of therapy. Increases in the CD4CD45RA subset were observed at week 4. Reductions in the percentage of CD4 and CD8 lymphocytes expressing CD38 were noted. Increases in proliferative responses to phytohemagglutinin were noted in 6 of 7 patients and correlated with duration of virus load suppression. Increased responses to recall antigens and to HIV-specific proteins were observed. Treatment with ritonavir produced alterations in the immune system that included changes in T cell subset distribution and increases in CD4 and CD8 lymphocyte numbers and of lymphocyte function.

ADP-ribosyl Cyclase↗
PubMed1996

Primary infection with zidovudine-resistant human immunodeficiency virus type 1 does not adversely affect outcome at 1 year. Sydney Primary HIV Infection Study Group.

Human immunodeficiency virus type 1 (HIV-1) variants with reduced in vitro sensitivity to zidovudine, conferred by specific mutations in the viral reverse transcriptase, emerge during prolonged therapy. Late-stage disease and declining CD4 cell count are associated with more rapid emergence of these resistant variants. Isolates of HIV-1 from seroconverters were screened for the zidovudine-resistance marker mutation at codon 215. HIV-1 with the altered genotype was detected in 5 (8.2%) of 61 patients soon after onset of symptomatic primary illness and from the sex partner of 1 patient. These transmitted resistant viruses were either replaced by strains susceptible to zidovudine within a few months of infection or persisted for up to 1 year in the absence of prolonged zidovudine therapy. The resistant genotype persisted in 3 of 5 seroconverters but in 2 patients had reverted to wild type at 48 and 52 weeks. Primary infection with zidovudine-resistant variants of HIV-1 was not associated with a more severe symptomatic primary illness or more rapid CD4 cell decline at 1 year after infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A controlled trial of nevirapine plus zidovudine versus zidovudine alone in p24 antigenaemic HIV-infected patients. The Dutch-Italian-Australian Nevirapine Study Group.

OBJECTIVES: Nevirapine is a non-nucleoside reverse transcriptase inhibitor of HIV-1 which exhibits synergy in vitro with zidovudine (ZDV) and also is active against ZDV-resistant HIV. We evaluated the activity and safety of nevirapine in combination with ZDV in patients receiving long-term ZDV therapy. METHODS: We conducted a randomized, open-label, controlled 28-week study of nevirapine (200 mg daily for 2 weeks followed by 200 mg twice daily for 26 weeks) and continued ZDV (500-600 mg daily) versus continued ZDV alone in 49 HIV-1 p24 antigenaemic patients with CD4+ lymphocyte counts < 500 x 10(6)/l and who had been treated with ZDV for at least 6 months. RESULTS: Addition of nevirapine to ZDV resulted in a significant and rapid reduction in circulating RNA load (mean, 0.65), a mean CD4+ lymphocyte rise of 34 x 10(6)/l, a reduction in serum beta 2-microglobulin and a median fall in immune complex dissociated p24 antigen levels of 69%. These changes remained statistically significant for 4, 4, 12 and at least 28 weeks, respectively. The principal adverse event due to nevirapine was a hypersensitivity reaction comprising rash with or without fever and mucositis in eight (32%) patients, which was dose-limiting in seven patients. CONCLUSION: Nevirapine exhibits significant although transient anti-HIV activity in ZDV-pretreated patients but its use is frequently associated with a hypersensitivity reaction.

Adult↗
PubMed1996

Genetic characterization of human immunodeficiency virus type 1 in blood and genital secretions: evidence for viral compartmentalization and selection during sexual transmission.

To explore the mechanism of sexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared HIV-1 gp120 sequences in longitudinal samples from five acute seroconvertors with those from their corresponding sexual partners (transmitters). We used a quantitative homoduplex tracking assay to compare the overall genetic composition of HIV-1 quasispecies in each transmission pair and to track the transmitted viruses during the acute and asymptomatic stages of HIV-1 infection. In the chronically infected transmitters, HIV-1 variants in genital secretions differed from those in blood and variants in cells differed from those in cell-free plasma, indicating remarkable sequence heterogeneity in these subjects as well as compartmentalization of the virus in different bodily sites. Conversely, two of five seroconvertors had only a few related variants and three of five harbored only one viral population, indicating that in these subjects the transmitted viruses were typically homogeneous. Transmitted viruses were evident in the donor's seminal plasma (one of five cases) and even more so in their seminal cells (three of five cases), suggesting that both cell-associated and cell-free viruses can be transmitted. In every pair studied, the transmitted variant(s) represents only a minor population in the semen of the corresponding transmitter, thereby providing evidence that HIV-1 selection indeed occurs during sexual transmission.

Amino Acid Sequence↗
PubMed1996

Comparison of measures to assess outcomes in total hip replacement surgery.

OBJECTIVES: To compare the performance of a disease specific and a general health questionnaire in assessing changes resulting from total hip replacement. DESIGN: Two stage prospective study of patients undergoing total hip replacement surgery involving an assessment at a clinic before and six months after surgery. 60(32%) patients were followed up by post. SETTING: Outpatient departments at a specialist orthopaedic hospital and peripheral clinics within Oxfordshire. PATIENTS: 188 patients admitted for unilateral total hip replacement between February and mid-August 1994. MAIN MEASURES: Patients' self assessed scores with the 12 item Oxford hip score and SF-36 general health questionnaire together with surgeons' assessment with Charnley hip score obtained before and again at six months after surgery. RESULTS: 186 patients were followed up six months after total hip replacement; a subsample (n=60) by post. Of the 60 postal patients, 59(98.3%) fully completed the Oxford hip score compared with 44(73.3%) who fully completed the SF-36. For the followup sample as a whole, post operative changes in scores produced a large effect size of 2.75 on the Oxford hip score, compared with -1.89 physical function (SF-36), -2.13 pain (SF-36). With the exception of physical function and role (physical), postoperative SF-36 scores were shown to be similar to or better than those found by two population surveys on patients of comparable age. The responsiveness of a disease specific questionnaire, the Oxford hip score, and relevant sections of a general questionnaire, SF-36, were found to be similar as assessed by three different criteria. CONCLUSIONS: A disease specific questionnaire, the Oxford hip score, and a general state of health questionnaire, SF-36, performed similarly in assessing outcomes of total hip replacement except that the disease specific questionnaire resulted in a higher completion rate and greater responsiveness in some sections. On the other hand the general health questionnaire drew attention to broader problems of physical function not considered by the Oxford hip score. The health questionnaires examined here offer a valid and practical means of monitoring outcomes of hip replacement surgery.

England↗
PubMed1996

The problem of 'noise' in monitoring patient-based outcomes: generic, disease-specific and site-specific instruments for total hip replacement.

OBJECTIVES: To compare the performance of three types of patient-based health status instrument--generic, disease-specific and site-specific--in assessing changes resulting from total hip replacement (THR). METHODS: A two-stage prospective study of patients undergoing surgery for THR involving an assessment at a pre-surgical clinic and a follow-up clinic at 6 months. 173 patients with a diagnosis of arthritis and being admitted for unilateral THR were recruited in the outpatient departments of a specialist orthopaedic hospital and peripheral clinics within Oxfordshire. Patients' health status was assessed using the 12-item Oxford Hip Score, the Arthritis Impact Measurement Scales (AIMS) and SF-36 general health questionnaire together with their surgeons' assessment using Charnley hip score obtained before and 6 months after surgery. RESULTS: Effect sizes, used to compare change scores, revealed that pain and function domains changed most following THR on both the AIMS and the SF-36. 71 patients (41%) were assessed as having symptoms or problems currently affecting lower limb joints other than the hip recently replaced. Change scores were compared between these patients and all other patients who reported no current problems with other joints. The Oxford Hip Score found no significant difference between change scores for these two groups of patients while both AIMS and SF-36 physical and pain dimensions recorded significant differences of similar magnitude (physical P < 0.01, pain P < 0.05). Likely reasons for this were apparent on closer inspection of the item content of each instrument. CONCLUSIONS: Assessment of outcomes in THR is necessarily long-term. Within studies of this kind, a hip-specific instrument (Oxford Hip Score) is likely to be more able to distinguish between symptoms and functional impairment produced by the index joint, as compared with other joints and conditions, than either a disease-specific instrument (AIMS) or a generic health status measure (SF-36). This is important given the high probability of existing and subsequent co-morbidity affecting such populations of patients. This consideration is likely to be relevant to any long-term assessment programme following treatment for a condition which threatens bilateral expression over time.

Activities of Daily Living↗
PubMed1996

Amplified ELISA to detect autoantibodies to N-glycolyl-GM3 ganglioside.

Numerous immunochemical methods are now available for the detection of antibodies to gangliosides. An amplified ELISA method for detection of autoantibodies to NGcGM3 ganglioside in the sera of patients with various type of renal diseases was developed. IgM antibodies were found in 39 out of 53 sera of patients using 30 normal healthy blood donor as a negative control. For human IgG conjugate no reactivity to NGcGM3 was seen in the sera. Positive ELISA results were confirmed by TLC-immunostaining using GM3, NGcGM3, NGcGM2 and Standard bovine gangliosides (GM1, GD1a, GD1b and GT1b). All sera were also assayed for reactivity with GM3 in ELISA to determine the line specificity of these antibodies. Based on these results, a protocol for a sensitive and reproducible amplification ELISA system for serum anti-NGcGM3 antibodies in patients with renal or other diseases is presented. The ELISA method described here in appear to be useful adjunt to measure antiNGcGM3 antibodies in sera of patients with various type of renal or other diseases.

Autoantibodies↗
PubMed1996

Questionnaire on the perceptions of patients about total hip replacement.

We developed a 12-item questionnaire for completion by patients having total hip replacement (THR). A prospective study of 220 patients was undertaken before operation and at follow-up six months later. Each completed the new questionnaire as well as the SF36, and some the Arthritis Impact Measurement Scales (AIMS). An orthopaedic surgeon assessed the Charnley hip score. The single score derived from the questionnaire had a high internal consistency. Reproducibility was examined by test-retest reliability and was found to be satisfactory. The validity of the questionnaire was established by obtaining significant correlation in the expected direction with the Charnley scores and relevant scales of the SF36 and the AIMS. Sensitivity to change was assessed by analysing the differences between the preoperative scores and those at the follow-up. The standardised effect size for the new questionnaire compared favourably with that for the SF36 and the AIMS. The new questionnaire provides a measure of outcome for THR which is short, practical, reliable, valid and sensitive to clinically important changes.

Activities of Daily Living↗