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Biomedical subjects

I V Weller

Publications and source records attributed to I V Weller.

At least 37 records · Page 2Linked to original sources
PubMed1994

Zidovudine pharmacokinetics in zidovudine-induced bone marrow toxicity.

1. The major adverse effect of zidovudine (ZDV) is haematological toxicity which results in anaemia and granulocytopenia. The aim of the present study was to investigate if HIV-positive patients developing erythroid aplasia/hypoplasia are exposed to higher plasma concentrations of ZDV owing to impaired hepatic metabolism to the major metabolite, 3'-azido-3'-deoxy-5'-beta-D-glucopyranuronosylthymidine (GZDV). 2. Twelve HIV-positive male patients were studied, six having developed bone marrow aplasia/hypoplasia within the first 6 months of ZDV therapy. Each of the patients exhibiting toxicity were matched for age, weight, risk factors for HIV infection and disease stage with patients who had no evidence of early bone marrow toxicity. 3. ZDV was administered orally in doses of 3-10 mg kg-1 and blood samples taken at intervals to 6 h. Urine was collected over the whole 6 h period. ZDV and GZDV were assayed by h.p.l.c. 4. There were no significant differences in the pharmacokinetic parameters between the two groups of patients. For patients with early bone marrow toxicity the elimination half-life of ZDV was 1.10 +/- 0.16 h with an oral clearance of 2752 +/- 1031 ml min-1 compared with values of 1.06 +/- 0.18 h and 2843 +/- 730 ml min-1 seen in the control group. Similarly there was no significant difference in the pharmacokinetics of GZDV or the urinary ratio of GZDV to ZDV. 5. Therefore, despite the fact that ZDV toxicity to haematopoietic progenitor cells has been previously shown to be dose related, there was no indication from this study that it is directly related to plasma concentrations of ZDV.

Administration, Oral↗
PubMed1994

Serial MRI of the brain in asymptomatic patients infected with HIV: results from the UCMSM/Medical Research Council neurology cohort.

Seventy-six homosexual or bisexual men underwent two cranial MRI studies at a mean interval of 13 months; 23 were HIV seronegative, 41 seropositive but asymptomatic (Center for Disease Control (CDC) groups II/III), and 12 had AIDS related complex (ARC)/AIDS (CDC group IV). Agreement between two neuroradiologists was rated as very good for assessment of enlargement of ventricles and good for widening of cerebral sulci and the presence of focal lesions. For assessment of serial studies, the agreement was moderate. The prevalence of cerebral atrophy and focal white matter lesions was no higher in the asymptomatic patients (CDC group II/III) than in appropriate seronegative controls. Some patients with ARC/AIDS showed evidence of developing cerebral atrophy during the study period when serial scans were compared. The imaging evidence supports the other data obtained from this cohort, which suggest that no significant CNS involvement occurs in HIV infection before the development of ARC/AIDS.

Adult↗
PubMed1993

Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV-infected individuals treated with zidovudine.

Eleven patients with AIDS or AIDS-related complex who developed muscle-related symptoms whilst taking zidovudine were investigated. The clinical details of a further ten patients who did not undergo muscle biopsy are also outlined. The clinical features, quantitative muscle strength testing, electromyographic findings, serial creatine kinase levels, muscle biopsy appearance on light microscopy and the effects of zidovudine withdrawal and rechallenge are described. The spectrum of muscle disease encountered included four cases of frank myopathy diagnosed using clinical, electrophysiological and histological criteria, four patients with mild weakness and myalgia in whom muscle biopsies were normal, three patients with myalgia only and a mild increase in the interstitial cell infiltrate shown by biopsy. The patients presenting with myopathy showed no improvement on withdrawal of zidovudine but responded to immunosuppressive therapy with steroids and, in one case, thalidomide prescribed incidentally. At present, it is not yet possible to clinically define a specific zidovudine-induced myopathy that is distinct from the other effects of HIV infection on muscle structure and function. Our experience suggests that zidovudine may be implicated as a myotoxin in some patients, particularly those with myalgia and mild weakness. In those patients with severe weakness, and with biopsy findings of necrosis and inflammation, the drug effects may be difficult to separate from the primary effects of HIV.

AIDS-Related Complex↗
PubMed1993

The natural history of cryptosporidial diarrhoea in HIV-infected patients.

OBJECTIVE: To determine the natural history of cryptosporidial infection in HIV-infected individuals. DESIGN: Retrospective study. SETTING: University teaching hospital HIV inpatient and outpatient unit. PATIENTS: Thirty-eight HIV-infected patients presenting with cryptosporidial diarrhoea between April 1986 and July 1991 were identified retrospectively from laboratory records. RESULTS: Eleven of the 38 patients had a clinical remission of their diarrhoea. Median lymphocyte count of the remission group was significantly higher than that of the non-remission group (1100 and 550 x 10(6)/l, respectively; P = 0.003). Median survival times were 66 and 11.5 weeks for the remission and non-remission groups, respectively (P = 0.001). Liver function tests performed at the initial diagnosis of cryptosporidial diarrhoea were available for 28 patients. Aspartate transaminase was raised in 16 and alkaline phosphatase in 10 of these 28 patients. Ten patients showed evidence of AIDS-associated sclerosing cholangitis, one patient had an episode of acute pancreatitis and another presented with acute cholecystitis. CONCLUSIONS: This study suggests that HIV-associated cryptosporidial diarrhoea does not have a uniformly poor prognosis. Eleven out of 38 patients had a spontaneous clinical remission, which appears to be predicted by the absolute lymphocyte count. Abnormal liver function tests and hepatobiliary disease were common.

AIDS-Related Opportunistic Infections↗
PubMed1993

Proton spectroscopy of the brain in HIV infection: correlation with clinical, immunologic, and MR imaging findings.

Abnormalities at cerebral proton spectroscopy occur in patients with the acquired immunodeficiency syndrome (AIDS). N-acetyl aspartate (NAA) is believed to be a neuronal marker, and neuronal loss is thought to underlie the human immunodeficiency virus (HIV)-associated cognitive/motor complex. The proton spectra in 103 HIV-seropositive patients and 23 control subjects were compared and correlated with clinical, immunologic, and radiologic measures of HIV infection. Significant (P < .05) reductions in the mean NAA/choline (Cho) and NAA/creatine (Cr) ratios were seen in patients with immune suppression and neurologic signs. Significant increases in the Cho/Cr ratios were seen in patients with low CD4 lymphocyte counts and abnormal magnetic resonance (MR) images. Reduced NAA ratios correlated with diffuse but not focal MR imaging abnormalities. Combined MR imaging and spectroscopy provides closer relationships to clinical and immunologic measures of disease than either modality alone. Spectroscopy is an adjunct to MR imaging and augments the value of an MR imaging study.

Adult↗
PubMed1991

Failure to deliver hepatitis B vaccine: confessions from a genitourinary medicine clinic.

OBJECTIVE: To audit hepatitis B immunisation of homosexual or bisexual men in a genitourinary medicine clinic. DESIGN: Retrospective case note review of all homosexual and bisexual men presenting to a genitourinary clinic as new patients during 12 months in 1988 and follow up review of notes to May 1990. SETTING: One department of genitourinary medicine, Middlesex Hospital. PATIENTS: 758 homosexual or bisexual men, of whom 207 started a course of hepatitis B vaccine in 1988. Case notes were unavailable for one patient. MAIN OUTCOME MEASURES: The proportion of patients screened for hepatitis B virus markers, the proportion of susceptible patients immunised, the proportion completing the vaccine course, and the proportion rendered immune. RESULTS: 25 men had been previously tested for hepatitis markers; of the 732 not previously tested, 440 (60.1%) were screened for hepatitis B markers. 207 (69%) of the 300 patients without hepatitis B serological markers started the vaccine course, and 141 (68%) completed it, with 75 (84%) of the 89 tested after immunisation being immune. An estimated 24% of susceptible new patients were rendered immune as a result of the immunisation policy. Patients who presented with a further episode of a sexually transmitted disease were more likely to have been screened (25% v 12%, p less than 0.0001) and immunised (31% v 18% p = 0.02); those known or found to be positive for HIV antibody were more likely to have been screened (23% v 14%, p = 0.047) but less likely to have been immunised (6% v 17%, p = 0.004). CONCLUSIONS: The major failure was that in not screening; failure to immunise patients found to be susceptible and failure of compliance with the vaccine course contributed. Non-response to the vaccine was of minor importance. Improvements in vaccine delivery are required. IMPLICATIONS: Other providers should be encouraged to review their performance.

Adult↗
PubMed1991

Hepatitis C virus: evidence for sexual transmission.

OBJECTIVE: To determined the prevalence of hepatitis C virus infection and associated risk factors in patients attending a genitourinary medicine clinic, as evidence for sexual transmission. DESIGN: Seroprevalence estimated by reactivity in an enzyme immunoassay for antibodies to C100 protein with supplementary testing with a recombinant immunoblot assay and an assay for hepatitis C virus RNA. SETTING: Outpatient genitourinary medicine clinic in central London. PATIENTS: The panel of 1046 serum samples was from 1074 consecutive patients attending the clinic during November and December 1987 and having blood taken for routine testing for syphilis. Before samples were anonymised demographic and risk factor information was extracted from the clinic notes. Samples had already been tested for antibody to HIV-I and antibody to hepatitis B core antigen. MAIN RESULTS: Significantly more homosexual subjects than heterosexual subjects were positive for hepatitis C antibody determined by enzyme immunoassay alone (19/275 (6.9%) v 8/771 (1.0%), odds ratio 7.14, p less than 0.0001) and also when reactive serum samples were also tested by recombinant immunoblot assay (6/270) (2.2%) v 3/770 (0.4%), odds ratio 5.88, p less than 0.02). There were also significant associations in patients positive for hepatitis C antibody with positivity for antibodies to HIV and to hepatitis B core antigen, lifetime number of sexually transmitted diseases (homosexual men only), and age (all groups combined). Most patients whose serum samples contained specific antibodies to hepatitis C virus were viraemic. CONCLUSIONS: The study provides strong evidence for the sexual transmission of hepatitis C virus. Assays derived from other gene products are desirable to investigate the specificity and sensitivity of the enzyme immunoassay for C100 antibody as a marker of hepatitis C virus infection.

Adolescent↗
PubMed1991

No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection.

Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity.

Adult↗
PubMed1991

Recognition of poliovirus/HIV chimaeras by antisera from individuals with HIV infection.

The neutralization of five poliovirus/HIV chimaeras by serum from HIV-infected individuals was examined to evaluate the presentation of HIV envelope sequences, to assess the immune response of individuals to specific epitopes, and to relate it to the stage of disease. The sera were unable to differentiate between four of the chimaeras and the Sabin vaccine strain. With a fifth construct containing an immunodominant gp41 sequence, significant differential recognition was observed in approximately 67% of individuals with asymptomatic HIV infection [groups II and III of the Centers for Disease Control (CDC) classification of HIV infection] and 37% of patients with symptomatic disease (CDC group IV). Furthermore, among patients with CDC stage IV disease antibody levels against this construct and the titre achieved decreased with progression to further disease from approximately 40% in AIDS-related complex (ARC) patients (CDC group IVA and IVC-2 to 14% in those with AIDS (other group IV diseases). Loss of antibody to this construct did not result from a reduction in the anti-polio or anti-envelope response, but from a decline in antibody levels to the HIV sequence inserted in antigenic site 1.

Amino Acid Sequence↗
PubMed1991

Early therapeutic intervention in HIV infection--stepping stones to success.

The improvement in survival observed in symptomatic HIV disease in the last three years may be accounted for by factors over and above the introduction of zidovudine therapy. Such factors include earlier diagnosis and advances in the treatment and prophylaxis of life threatening opportunistic infections. These advances in the management of symptomatic HIV disease considerably influenced the move towards early intervention in asymptomatic infected individuals. Currently two developments are changing clinical practice, namely the primary prophylaxis of pneumocystis carinii pneumonia and antiretroviral treatment with zidovudine. This review concerns itself with the scientific data supporting such changes in practice and the uncertainties and unanswered questions that remain, particularly with respect to the timing of intervention with and appropriate dose of zidovudine.

Drug Administration Schedule↗
PubMed1990

Response of serum p24 antigen and antibody to p24 antigen in patients with AIDS and AIDS-related complex treated with zidovudine.

In an open study of the treatment of patients with AIDS-related complex (ARC) and AIDS with zidovudine, we evaluated the response of serum p24 antigen (p24Ag) and antibody to p24Ag (anti-p24) levels. Before treatment, serum from 49 out of 73 (67%) patients was p24Ag-positive, and of these patients 42 received zidovudine 800-1200 mg daily for greater than 4 weeks and had a baseline mean serum level of p24Ag of 119 pg/ml (s.e. 15.7). On zidovudine there was a reduction of p24Ag to 21.12% (s.e. 4.76) of pretreatment values at 3 months; however, there was a subsequent trend for levels after 6 months to increase to greater than 50% of pretreatment levels at 12 months. Serum levels of anti-p24 were measured in 26 patients. Of 16 patients whose serum contained p24Ag and 10 whose serum did not, four and nine, respectively, had detectable levels of anti-p24. There was no significant change in the serum anti-p24 with zidovudine therapy.

AIDS-Related Complex↗
PubMed1990

The natural history of human immunodeficiency virus infection: a five year study in a London cohort of homosexual men.

Progression rates from asymptomatic to symptomatic Human Immunodeficiency Virus (HIV) infection according to the CDC classification were prospectively studied in a cohort of 172 seropositive homosexual and bisexual men. The median follow-up time was 4 years. The progression from data of entry to the study to any group IV disease was 56% (SE 7%) at 5 years. However, the progression from an estimated date of seroconversion to any group IV disease was 36% (SE 4%) at 5 years. This was more than double the progression rate to AIDS-14% (SE 3%) at 5 years calculated in the same way. There were no differences in progression to AIDS from group IV A (systemic symptoms such as unexplained fever, weight loss or persistent diarrhoea) and group IV C-2 (oral candida or oral hairy leukoplakia). Progression rates to AIDS were significantly lower (p = 0.02) in patients who were under 25 years of age at entry than in those over 25. A review of progression rates to AIDS among homosexual cohorts shows that they tend to be higher than in cohorts of haemophiliac patients, in the early stage of infection. However, when Pneumocystis carinii pneumonia is the outcome measure, progression rates in all studies are remarkably similar.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Cytomegalovirus in the lungs of patients with AIDS. Respiratory pathogen or passenger?

A total of 166 consecutive clinical episodes of pneumonitis in patients with acquired immune deficiency syndrome (AIDS) or antibody positive for human immune deficiency virus (HIV) were investigated for evidence of cytomegalovirus (CMV) infection in their lungs and at peripheral sites to determine the pathogenicity of this virus in the lung and its relationship to peripheral CMV shedding. Evidence of CMV infection was sought in bronchoalveolar lavage (BAL) fluid, blood, saliva, and urine using a specific monoclonal antibody to antigens produced by CMV-infected cells within 24 h. Although CMV was detected in 31 (19%) of BAL fluid specimens, in only six episodes was this the sole pathologic finding. In the remaining episodes either another infectious agent, Kaposi's sarcoma, or lymphoid interstitial pneumonitis was found or no pathogen was detected. None of the patients were given specific anti-CMV treatment, and all but two recovered, including those patients in whom CMV was the sole finding at BAL. The presence of peripheral shedding of CMV did not have any significance in mortality or morbidity. Our findings are in direct contrast to those in recipients of allogeneic bone marrow transplants, in whom CMV pneumonitis is associated with a high mortality. We postulate that this difference is because AIDS patients cannot mount the destructive immune response to CMV in the lung, which we believe to be the basis of the pathology seen in the former group. We conclude that CMV is not a pathogen in the lungs of patients with HIV infection, and we suggest that its presence at this site does not warrant specific therapy in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗