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Biomedical subjects

M Bower

Publications and source records attributed to M Bower.

At least 55 records · Page 3Linked to original sources
PubMed2001

Current issues in the biology of AIDS-related lymphoma.

Three important issues have been the focus of much recent attention in the biology of AIDS-related lymphomas. The altered epidemiology in the era of highly active antiretroviral therapy, the role of herpesviruses including human herpesvirus 8 and the molecular genetics of HIV-associated T-cell lymphomas. These topics are covered in this article and their potential application to the clinical management of AIDS-related lymphomas are discussed.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Clostridium difficile infection, hospital geography and time-space clustering.

To analyse spatial and temporal relationships of Clostridium difficile-associated disease in an inner-city hospital, we retrospectively evaluated 283 episodes of confirmed C. difficile diarrhoea in the Chelsea and Westminster Hospital between 1995 and 1998, against a background of relatively stable case mix, antibiotic usage and admission numbers, using Knox analysis to determine the presence of disease clustering in time and space. We found five time-space clusters on four medical wards and between two adjacent units. The clusters were not related to the overall case number on single wards, and were separated in time. Knox time-space analysis provides a simple screening tool to identify disease clusters, assess the efficacy of infection control measures and the influence of hospital geography and traffic. The results support the importance of infection control measures in the prevention of C. difficile-related disease.

Adult↗
PubMed2001

Anal intraepithelial neoplasia in HIV positive people.

OBJECTIVE: To review the current literature on HIV associated anal intraepithelial neoplasia (AIN). METHODS: A comprehensive Medline/Pubmed search was performed for the years 1980-2001 (January) for articles pertaining to HIV associated anal intraepithelial neoplasia. From the MeSH terms "anal intraepithelial neoplasia" and "anal cancer" the following subheadings were used: HIV, homosexual men, HPV, Epidemiology, Etiology, Mortality, Diagnosis, Screening, Drug Therapy, Surgical Therapy, Radio Therapy, Risk factors, ASIL. The search was limited to "human" for all searches. In the absence of enough "randomised controlled trials" the search was extended to clinical trials, reviews, and case reports. One analysis on cost effectiveness and two abstracts presented at 12th World AIDS Conference and 6th Conference on Retrovirus and Opportunistic Infections were included. The 44 publications referred to originate from the United Kingdom (9), the United States (26), and Denmark (5), with one each from Switzerland, Germany, Australia, and France. The Cochrane Database of systematic reviews yielded 11 complete reviews for "anal cancer" and none for "anal intraepithelial neoplasia." The textbook of AIDS-related cancers and their treatment was consulted. We also included our personal experience from the treatment of patients at the Chelsea and Westminster Hospital, one of the largest centres for the management of HIV disease in Europe. CONCLUSION: Routine anal cytological screening followed by appropriate management of AIN is an important issue for HIV infected patients. The natural history of AIN has not been fully established and this prevents clinicians from defining clear management protocols. There is early evidence that the benefits of highly active antiretroviral therapy (HAART) in terms of restoring immune function and reducing opportunistic infections and some neoplasms may not extend to regression of AIN. Under these circumstances it might be predicted that AIN and subsequent progression to invasive anal cancer would rise as HAART prolongs the lives of seropositive people. However, routine anal cytological screening will surely have to await an effective proved intervention for AIN and this would seem to be a pressing clinical goal.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Phase III vehicle-controlled, multi-centered study of topical alitretinoin gel 0.1% in cutaneous AIDS-related Kaposi's sarcoma.

OBJECTIVE: This randomized, double-blind and vehicle-controlled phase III study was conducted to evaluate the efficacy and safety of alitretinoin gel 0.1% for the topical treatment of the cutaneous lesions of AIDS-related Kaposi's sarcoma (KS). METHODS: Patients received treatment with alitretinoin gel (n = 62) or vehicle gel (n = 72) twice daily for 12 weeks. The primary efficacy endpoint was the cutaneous KS tumor response rate according to AIDS Clinical Trials Group (ACTG) objective criteria applied to topical therapy, with the patient as the unit of analysis. RESULTS: Treatment of patients with alitretinoin gel resulted in a significant antitumor effect. The overall patient response rate (complete plus partial response) was 37% (23 of 62) for the alitretinoin-treated patients and 7% (5 of 72) for the vehicle-treated patients (p = 0.00003). The difference in response rates for the 2 treatment groups remained significant even after taking into consideration numerous variables, including age (p = 0.00001), Eastern Cooperative Oncology Group (ECOG) status (p = 0.00002), CD4+ cell count (p = 0.00002), history of opportunistic infection (p = 0.00002), aggregate area of indicator lesions (p = 0.00005), number of raised indicator lesions (p = 0.00002), prior therapy for KS (p = 0.00003), and number of drugs (p = 0.00002) used in concomitant antiretroviral therapy. Generally, treatment with alitretinoin gel was well tolerated. The overall incidence of adverse events was similar for the 2 treatment groups. Adverse events related to treatment with alitretinoin gel tended to be mild to moderate in severity and limited to the site of application. The most frequent adverse event occurring at the application site following alitretinoin gel treatment was irritation coded as rash (32%). CONCLUSIONS: The results of this study provide convincing evidence of the superiority of alitretinoin gel over vehicle gel for the treatment of the cutaneous lesions of AIDS-related KS.

Administration, Topical↗
PubMed2000

Changes in acquired immunodeficiency syndrome-related lymphoma since the introduction of highly active antiretroviral therapy.

Clinical data on 7840 HIV-positive patients, representing 43 745 patient-years of follow-up, has been collected. All patients with ARL since 1986 (n = 150) were assessed at presentation for prognostic factors and outcomes recorded. Comparisons are made between cases in the pre-HAART era (1988-1995), and the HAART era (1996-1999). Statistical models are used to calculate the incidence of ARL and factors predicting its development. The incidence of ARL has not changed over time (3 to 7 of 1000 patients per year, P = .933), but contributes to a greater percentage of first AIDS-defining illnesses (ADI) in the HAART era (P < or = .0001). Older age, nadir CD4 count, and no prior HAART use, predict the development of ARL. There has been no change in stage at presentation, presence of B symptoms, performance status, or marrow involvement between the 2 time cohorts or between patients with or without prior HAART exposure. Similarly, there is no difference in survival duration between the pre-HAART and HAART era (log rank P = .15) or specifically in patients treated with HAART before ARL diagnosis (log rank P = .12). The use of HAART has not yet been shown to influence the incidence or survival of ARL. However, because nadir CD4 count and use of HAART are independent predictors of ARL development, this may translate into a future fall in new cases. (Blood. 2000;96:2730-2734)

Adult↗
PubMed2000

Absence of association between individual thymidine analogues or nonnucleoside analogues and lipid abnormalities in HIV-1-infected persons on initial therapy.

Changes in levels of triglycerides and cholesterol during antiretroviral therapy raise concerns regarding an increased future risk of atherogenic disease and may precede the appearance of fat redistribution. Hypotheses regarding the impact of nucleoside analogues on adipocytes provide a possible explanation for metabolic and clinical fat disturbances. It is unclear whether the choice of nucleoside analogue combination or coadministration of nonnucleoside agents influences change in lipids. We performed a cross-sectional analysis of 135 persons receiving their first nucleoside analogue plus nonnucleoside-based combination antiretroviral regimen for at least 1 month and for whom cholesterol and triglyceride values were available on therapy. Univariate and multivariate regression models were used to explore the relation between cholesterol and triglycerides, as continuous variables with other variables. Both significant and nonsignificant variables from univariate analyses were evaluated in multivariate models to limit possible confounders. No association with drug choice was observed, either when comparing thymidine analogues (stavudine or zidovudine), all nucleoside analogue combinations or choice of either efavirenz or nevirapine as nonnucleoside. Age and triglyceride levels were found in a multivariate analysis to be associated with higher cholesterol. Only higher cholesterol was associated with higher triglyceride levels. In conclusion, no differences were observed between choice of drug or combination on cholesterol or triglyceride values during therapy. Older individuals may be more likely to have elevated cholesterol values.

Adult↗
PubMed2000

Treatment of HIV-associated invasive anal cancer with combined chemoradiation.

There is an increased frequency of invasive anal cancer in HIV-seropositive men. Early treatment strategies in this patient group employed reduced dosages of chemotherapy or radiotherapy alone to reduce toxicity. Since 1989 we have used combined modality treatment consisting of chemotherapy 5-fluorouracil (5-FU) and mitomycin C, and concomitant radical radiotherapy to the pelvis (38-51 Gy in 20-30 fractions), with most patients receiving a perineal boost (10-18 Gy). 12 homosexual HIV-positive men have been treated. The median CD4 count at diagnosis of anal cancer was 209 cells/microl (range: 29-380 cells/microl), 5 had prior AIDS defining diagnoses. No patients had metastatic disease. Complete remissions were obtained in 9/11 evaluable patients and in 1 further patient following surgery. 2 patients relapsed both within 6 months of diagnosis. At a median follow-up of 4.8 years (range: 0.4-10 years), 4 patients have died (2 from anal cancer, 1 from treatment-related consequences and 1 from opportunistic infection in remission). Actuarial 2-year survival is 60% (95% confidence interval (CI): 29-91%). Grade 3 haematological toxicity was recorded in 3 patients, grade 4 and 5 gastrointestinal toxicity in 1 patient each and grade 3 skin toxicity in 1 patient. Radical chemoradiation may be given safely at conventional doses in HIV-positive patients, with a high complete response rate.

Adult↗
PubMed2000

Surveillance for stage I testicular germ cell tumours: results and cost benefit analysis of management options.

Between 1979 and 1996 303 men with stage I testicular germ cell tumours (120 seminoma and 183 non-seminomatous germ cell tumours (NSGCT)) were enrolled onto a programme of surveillance. In our institutions the frequency of computed tomography (CT) scans is reduced compared with other centres. For all 303 men, the median follow-up is 5.1 years (range: 0.1-21.7 years) and there have only been 3 deaths (1 from disease, 1 from neutropenic sepsis and 1 from secondary leukaemia). 52/183 (28%) patients with NSGCT and 18/120 (15%) patients with seminoma have relapsed. The relapse-free survival at 5 years is 82% for seminoma and 69% for NSGCT (Logrank P=0.004). All men who relapsed, except 1 man with NSGCT, were in the International Germ Cell Cancer Collaborative Group good or intermediate prognosis group at relapse. Half of the seminoma relapses presented with symptoms and 31% of the NSGCT relapses. The remaining relapses were detected serologically or radiologically by the surveillance programme. 5 men (2%) on surveillance, 3 with initial diagnosis of seminoma and 2 with NSGCT, have developed second contralateral testis tumours (all stage I seminomas). In a well motivated centre a policy of surveillance for stage I testicular germ cell tumours (both NSGCT and seminoma) is associated with a low mortality rate (3/303, 1%) and may have the advantage of sparing overtreatment with potentially toxic therapies in this group of young men.

Adolescent↗
PubMed2000

Weekly alternating combination chemotherapy for good prognosis AIDS-related lymphoma.

Early studies reported that the major adverse prognostic factors in AIDS-related non-Hodgkin's lymphoma (ARL) are low CD4 cell count, prior AIDS defining diagnosis and poor performance status. Since 1989 we have adopted a prognosis-stratified approach for ARL. In this study, we identified a group of good prognosis patients. These patients with one or no adverse prognostic factors were treated with alternating weekly chemotherapy using the bleomycin, etoposide, vincristine, methotrexate, prednisolone/cyclophosphamide, doxorubicin (BEMOP/CA) schedule (Bower M, Block C, Gulliford T, et al. Cancer Chemother Pharmacol 1995, 38, 106-109). Modifications to the regimen with the aim of reducing toxicity were a briefer duration (12 weeks) and the addition of prophylaxis against pneumocystis and mycobacteria. Intrathecal methotrexate was administrated fortnightly to patients with Burkitt's histology, meningeal involvement or base of skull disease. 30 patients were treated, including 5 with prior AIDS, 3 with ECOG status 3 and 1 with CD4 <100/microl. The mean age was 40 (range 22-60 years), the median CD4 cell count at ARL diagnosis was 262/microl (range 44-588/microl). The International non-Hodgkin's lymphoma (NHL) prognostic factors project classifications were low risk 8 (maximum 5.4 years) (27%), low-intermediate risk 6 (20%), high-intermediate risk 11 (37%) and high risk 5 (17%). The median follow-up was 2.1 years. 3 patients withdrew from treatment within 2 weeks due to toxicity, 2 patients died within 2 weeks of starting chemotherapy. The major toxicity was myelosuppression with 14 patients developing grade 4 neutropenia. The 2-year overall survival rate is 46% (95% confidence interval (CI)=27-65%), and lymphoma-specific survival at 2 years is 59% (95% CI: 40-78%). For selected patients with good prognosis ARL 12 weeks BEMOP/CA therapy produces good overall survival at 2 years.

Adult↗
PubMed2000

Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival.

Radical retropubic prostatectomy is considered by many centres to be the treatment of choice for men aged less than 70 years with localized prostate cancer. A rise in serum prostate-specific antigen after radical prostatectomy occurs in 10-40% of cases. This study evaluates the usefulness of novel ultrasensitive PSA assays in the early detection of biochemical relapse. 200 patients of mean age 61. 2 years underwent radical retropubic prostatectomy. Levels < or = 0.01 ng ml-1 were considered undetectable. Mean pre-operative prostate-specific antigen was 13.3 ng ml-1. Biochemical relapse was defined as 3 consecutive rises. The 2-year biochemical disease-free survival for the 134 patients with evaluable prostate-specific antigen nadir data was 61.1% (95% CI: 51.6-70.6%). Only 2 patients with an undetectable prostate-specific antigen after radical retropubic prostatectomy biochemically relapsed (3%), compared to 47 relapses out of 61 patients (75%) who did not reach this level. Cox multivariate analysis confirms prostate-specific antigen nadir < or = 0.01 ng ml-1 to be a superb independent variable predicting a favourable biochemical disease-free survival (P < 0.0001). Early diagnosis of biochemical relapse is feasible with sensitive prostate-specific antigen assays. These assays more accurately measure the prostate-specific antigen nadir, which is an excellent predictor of biochemical disease-free survival. Thus, sensitive prostate-specific antigen assays offer accurate prognostic information and expedite decision-making regarding the use of salvage prostate-bed radiotherapy or hormone therapy.

Adult↗
PubMed2000

AIDS related systemic non-Hodgkin's lymphoma.

OBJECTIVE: To review the current literature on HIV associated non-Hodgkin's lymphoma. METHODS: A comprehensive Medline/Pubmed search of articles pertaining to HIV associated non-Hodgkin's lymphoma as well as personal experience from the treatment of over 200 patients at the Chelsea and Westminster Hospital, one of the largest centres for the management of HIV disease in Europe. CONCLUSION: High grade B cell non-Hogdkin's lymphoma is the second commonest tumour affecting people with HIV. The incidence of this tumour is not declining following the introduction of highly active antiretroviral therapy. Chemotherapy has been employed with modest success in this group of patients; however, the prognosis remains worse than for immunocompetent patients. Advances in molecular genetics and virology have led to a greater understanding of the biology of these tumours. However, these advances have yet to be translated into improvements in the clinical management of patients with AIDS associated non-Hodgkin's lymphoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

HIV-associated Hodgkin's disease.

Hodgkin's disease (HD) appears to occur more frequently in people with HIV and within this population HD demonstrates a number of differences. In people with HIV, Epstein-Barr virus (EBV) is found more frequently in Reed-Sternberg cells and mixed cellularity and lymphocyte depleted histological subtypes predominate. Patients with HIV present with more advanced stage HD often with extranodal disease. The prognostic variables for HD in patients with HIV relate to the HIV rather than the HD. In people with HIV the response rates are lower, the relapse rates higher, the infectious complications more frequent and the overall survival worse than for HD in the general population.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The molecular genetics of human herpesvirus 8.

Epidemiological evidence from the early 1990s suggested that a sexually transmitted infectious agent other than the HIV virus was associated with the development of Kaposi's sarcoma in patients with HIV. A novel gamma herpesvirus was identified in Kaposi's sarcoma lesions. The molecular genetics of this virus are reviewed in this article.

AIDS-Related Opportunistic Infections↗
PubMed1999

Highly active anti-retroviral therapy (HAART) prolongs time to treatment failure in Kaposi's sarcoma.

OBJECTIVE: To evaluate the impact of highly active antiretroviral therapy (HAART) on Kaposi's sarcoma. DESIGN: Retrospective study of patients who had received systemic or local treatment for AIDS-related Kaposi's sarcoma who subsequently commenced HAART. METHODS: Case note review to determine time to treatment failure for Kaposi's sarcoma before and after starting HAART. Time to treatment failure was calculated from the end of last therapy to the start of the next new treatment for Kaposi's sarcoma. RESULTS: The cohort contained 78 patients. Only 38% had good risk Kaposi's sarcoma (stage T0I0) at presentation. The median time to treatment failure before starting HAART was 0.5 years. Initial HAART therapy was three or more drugs including a protease inhibitor for 38 (49%), three or more drugs without a protease inhibitor for 27 (35%) and a two-drug protease combination for 13 (16%). The median follow-up after starting HAART was 12 months (range, 0.5-52 months) and anti-Kaposi's sarcoma treatment has been required for 24 (31%) patients. The median time to treatment failure for Kaposi's sarcoma from the start of HAART is 1.7 years. This is statistically longer than the time to treatment failure for the same cohort of patients before they started HAART (log rank chi2 = 16.5, P < 0.0001). The serum HIV RNA viral load (VL) at the time of Kaposi's sarcoma progression revealed virological failure of HAART (defined as VL > 5000 copies/ml) in 14 of 24 (58%) and good control (VL < 200 copies/ml) in five of 24 (21%). CONCLUSION: HAART is associated with prolonged time to treatment failure in Kaposi's sarcoma. Progression of Kaposi's sarcoma while on HAART is not necessarily associated with virological failure as determined by rising viral RNA titre.

Adult↗
PubMed1999

An evolutionary approach to constructing prognostic models.

A prognostic model is sought to determine whether or not patients suffering from an uncommon form of cancer will survive. Given a set of case histories, we attempt to find the relative weightings of the different variables that are used to describe the cases. Our first innovation is to use a diffusion genetic algorithm (DGA) to find weightings which will give optimal survival predictions. The DGA enables a number of criteria to be satisfied simultaneously, making it particularly suitable for model building. A further innovation is a method of representing synergies between interacting factors. The evolved model correctly predicts 90% of the survivors and 87% of deaths, an improvement over the current model. More significantly, the method enables a simple model to be evolved, one that produces well-balanced predictions, and one that is relatively easy for clinicians to use. The method was validated by running it on a training set made up of 90% of the original database and then studying the performance of the generated models on a test set consisting of the remaining 10% of the cases.

Adolescent↗
PubMed1999

Treatment outcome in presumed and confirmed AIDS-related primary cerebral lymphoma.

A retrospective analysis identified 38 HIV seropositive patients with a diagnosis of presumed (n = 26) or confirmed (n = 12) primary cerebral lymphoma (PCNSL). All patients had failed to respond to empirical antitoxoplasma therapy and the clinical diagnosis of PCNSL was confirmed by brain biopsy (n = 4), cerebrospinal fluid (CSF) examination for Epstein-Barr virus (EBV) by PCR (n = 7) or postmortem examination (n = 1). There was no difference in the age, performance status, CD4 counts, antiretroviral usage or interval since first HIV serodiagnosis between patients with presumed or confirmed PCNSL. 16 patients received either radiotherapy (n = 14) or chemotherapy (n = 2). Patients with confirmed or presumptive PCNSL were equally likely to receive treatment. The median overall survival, which was measured from the end of unsuccessful antitoxoplasma therapy, was 1.2 months for the whole cohort. There was no difference in overall survival between patients with presumptive (median 0.8 months) and confirmed (median 1.3 months) PCNSL (logrank P = 0.69). This suggests that there may be little value in positively diagnosing PCNSL in the current diagnostic algorithm. Recent improvements in outcome have been reported with systemic chemotherapy in HIV-PCNSL and may influence the need for earlier definitive diagnosis in the future.

Adult↗
PubMed1999

Loss of chromosome 10 is an independent prognostic factor in high-grade gliomas.

Loss of heterozygosity (LOH) for chromosome 10 is the most frequent genetic abnormality observed in high-grade gliomas. We have used fluorescent microsatellite markers to examine a series of 83 patients, 34 with anaplastic astrocytoma (grade 3) and 49 with glioblastoma multiforme (grade 4), for LOH of chromosome 10. Genotype analysis revealed LOH for all informative chromosome 10 markers in 12 (35%) of patients with grade 3 and 29 (59%) grade 4 tumours respectively, while partial LOH was found in a further eight (24%) grade 3 and ten (20%) grade 4 tumours. Partial LOH, was confined to the long arm (10q) in six and the short arm (10p) in three cases, while alleles from both arms were lost in four cases. Five tumours (one grade 3 and four grade 4) showed heterogeneity with respect to loss at different loci. There was a correlation between any chromosome 10 loss and poorer performance status at presentation (chi2 P = 0.005) and with increasing age at diagnosis (Mann-Whitney U-test P = 0.034) but not with tumour grade (chi2 p= 0.051). A Cox multivariate model for survival duration identified age (proportional hazards (PH), P= 0.004), grade (PH, P= 0.012) and any loss of chromosome 10 (PH, P= 0.009) as the only independent prognostic variables. Specifically, LOH for chromosome 10 was able to identify a subgroup of patients with grade 3 tumours who had a significantly shorter survival time. We conclude that LOH for chromosome 10 is an independent, adverse prognostic variable in high-grade glioma.

Brain Neoplasms↗