Recombination does not occur in newly identified diverged oceanic picornaviruses.
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Base Sequence↗
Biomedical subjects
M Bower
Publications and source records attributed to M Bower.
Imaging features of multicentric Castleman's disease in HIV infection.
AIM: To describe the computed tomography (CT) features of human immunodeficiency virus (HIV)-associated Castleman's disease. MATERIALS AND METHODS: Nine HIV-positive patients with biopsy-proven Castleman's disease were studied. Clinical and demographic data, CD4 count, histological diagnosis and human herpes type 8 (HHV8) serology or immunostaining results were recorded. CT images were reviewed independently by two radiologists. RESULTS: CT findings included splenomegaly (n=7) and peripheral lymph node enlargement (axillary n=8, inguinal n=4). All nodes displayed mild to avid enhancement after intravenous administration of contrast material. Hepatomegaly was evident in seven patients. Other features included abdominal (n=6) and mediastinal (n=5) lymph node enlargement and pulmonary abnormalities (n=4). Patterns of parenchymal abnormality included bronchovascular nodularity (n=2) consolidation (n=1) and pleural effusion (n=2). On histological examination eight patients (spleen n=3, lymph node n=9, lung n=1, bone marrow n=1) had the plasma cell variant and one had mixed hyaline-vascular/plasma cell variant. The majority had either positive immunostaining for HHV8 or positive serology (n=8). CONCLUSION: Common imaging features of multicentric Castleman's disease in HIV infection are hepatosplenomegaly and peripheral lymph node enlargement. Although these imaging features may suggest the diagnosis in the appropriate clinical context, they lack specificity and so biopsy is needed for diagnosis. In distinction from multicentric Castleman's disease in other populations the plasma cell variant is most commonly encountered, splenomegaly is a universal feature and there is a strong association with Kaposi's sarcoma.
Adult↗
The common heat shock protein receptor CD91 is up-regulated on monocytes of advanced melanoma slow progressors.
Despite advances in our understanding of tumour immunology there is no therapy of proven survival benefit for advanced melanoma. Nevertheless, disease progression is slow in a small proportion of patients with metastatic melanoma, suggesting a contribution to outcome from host factors. Recent data have indicated the importance of the heat shock protein receptor CD91 in immune responses to, and progression of, infectious disease. Here we investigate the relationship between CD91 expression and outcome in malignancy. Rare melanoma patients were recruited with advanced disease that was progressing unusually slowly. CD91 expression on their monocytes was compared with control patients with more typical rapidly advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and adaptive immune subsets, were also measured in the two groups. A significant increase in median CD91 expression levels was observed in slow progressors (P = 0.006). There were no differences in other immune subset markers or inflammatory cytokines. The ability of CD91 to internalize and cross-present tumour antigens through the major histocompatibility complex class I pathway may maintain CD8-positive cytotoxic T cell responses and contribute to slow progression of advanced melanoma.
Adult↗
A questionnaire survey of stress and bullying in doctors undertaking research.
BACKGROUND: Research is an increasingly important aspect of higher medical training for many doctors. Studies investigating sources of stress, isolation, and workplace bullying have not previously sought information in this setting. METHODS: An internet based questionnaire survey of doctors undertaking research (n = 259) was conducted to examine stressors and levels of job satisfaction in this potentially vulnerable group. In order to assess overall levels of satisfaction, we asked whether doctors would recommend their research post to a colleague. RESULTS: There was a statistically significant association between those who would not recommend their post to a colleague and those who had difficulties in arranging funding and in writing up (p<0.001). Further significant correlations were found between dissatisfaction with the post and lack of help, support, and advice from supervisors and colleagues, wanting to change supervisors, experience of the major categories of workplace bullying, and having an inadequate clinical commitment (p<0.001). When the significant variables were entered into a multivariate analysis, the results showed that dissatisfaction was associated with wanting to change supervisors and with a threat to professional status. CONCLUSIONS: Stress and bullying are common in doctors undertaking research. These findings have important implications for medical training and for doctors choosing research projects. Setting up systems of support may have important benefits.
Attitude of Health Personnel↗
Head and neck cancer in patients with human immunodeficiency virus-1 infection: incidence, outcome and association with Epstein-Barr virus.
Head and neck cancers have been described in patients with human immunodeficiency virus-1 (HIV-1) infection. However the incidence, aetiology and clinical features of the disease remain unclear. Patients with head and neck cancer and HIV were identified from a large HIV centre. The incidence and clinical features were recorded, and the tumours were stained for Epstein-Barr virus (EBV). Head and neck cancer occurred more frequently than in an age-matched control group (1.66 vs 0.55/10,000 patient years respectively p < 0.05). Highly active anti-retroviral therapy has not significantly altered the incidence of the disease. All of the tumours tested were positive for EBV. Patients were moderately immunosuppressed at diagnosis and had aggressive tumours. All but one of the patients died of cancer with a median survival of 28 months. Head and neck cancer occurs more frequently in HIV. It is an aggressive disease and EBV may play a role in its pathogenesis.
Adult↗
Management of HIV-related lymphoma in HIV treatment centres in North Thames Region.
We describe an audit of lymphoma care in HIV-positive patients. In the smaller units (< 500 patients) areas of potentially sub-optimal care were identified.
Acquired Immunodeficiency Syndrome↗
Does HIV adversely influence the outcome in advanced non-small-cell lung cancer in the era of HAART?
The objectives of the study are to assess the impact of HIV status on the outcome of patients with non-small-cell lung cancer (NSCLC) in the era of highly active antiretroviral therapy (HAART). Patients diagnosed with HIV-related NSCLC in the HAART era (since January 1996) were identified from a prospective single-centre lung cancer database. The clinicopathological characteristics and outcome of each HIV-positive patient were compared to three age- and stage-matched HIV-negative controls with NSCLC who were diagnosed over the same time period and treated in an identical manner. The results showed that the two groups had similar disease characteristics and received a similar amount of chemotherapy. The median overall survival of the two groups was the same (4 months, log rank P=0.55). None of the HIV-positive patients developed an AIDS defining illness or died of HIV during treatment or follow-up. In conclusion, in this cohort, HIV status does not influence the prognosis of advanced NSCLC. This suggests that the survival of patients with HIV-related NSCLC may have improved since the introduction of HAART, and this may be due to a decrease in HIV-related deaths.
Adult↗
Multicenter study of human immunodeficiency virus-related germ cell tumors.
PURPOSE: Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors. PATIENTS AND METHODS: Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases. RESULTS: Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy. CONCLUSION: Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.
Adolescent↗
An open-label study of tenofovir in HIV-1 and Hepatitis B virus co-infected individuals.
BACKGROUND: Tenofovir is a novel nucleotide analogue recommended for use in HIV-1 infected treatment-experienced patients. Recent data suggest an effect on Hepatitis B virus (HBV) replication. We therefore investigated the use of tenofovir in HIV-1 and HBV co-infected individuals. METHODS: Twenty HIV-1/HBV co-infected patients with a median of 108 weeks lamivudine experience (range, 0-270 weeks) received tenofovir 245 mg daily in addition to or as part of their combination antiretroviral therapy. Their immunologic parameters and HIV-1 RNA and HBV DNA viral loads were followed over a period of 52 weeks. In addition, their HBV DNA polymerase was sequenced at baseline to measure the frequency of YMDD mutations that are associated with lamivudine resistance. FINDINGS: A significant decrease in HBV DNA viral load (4 x log ) and alanine aminotransferase levels was observed. There were no significant overall differences between the lamivudine-experienced (n = 15) and -naive (n = 5) individuals and tenofovir was well tolerated. Five patients (25%) underwent HBe antigen seroconversion during the study period. Out of the 15 lamivudine-experienced individuals, 10 had YMDD mutations and one had YIDD mutations in HBV DNA. INTERPRETATION: These results indicate that 52 weeks of tenofovir in addition to antiretroviral therapy is active against HBV, and it appears to overcome lamivudine resistance.
Adenine↗
The changing role of radiotherapy in AIDS-related malignancies.
OBJECTIVE: To review the current literature on the role of radiotherapy in AIDS-related malignancies published since 1997. METHODS: A comprehensive literature review was undertaken to review the recent advances in the role of radiotherapy in the management of AIDS-related malignancies. This was combined with the clinical experience from our two London treatment centres for AIDS-related malignancies. A Medline/Pubmed search was performed for articles published since 1997, the year of the previous review, which also coincides with the widespread usage of highly active antiretroviral treatment (HAART). The MESH search terms used were 'HIV or AIDS' and 'radiotherapy'. This search yielded a total of 86 references. CONCLUSIONS: HAART has had a major impact on the role of radiotherapy in AIDS-related malignancy. The use of HAART has led to a decline in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma and has been associated with an improved prognosis in systemic non-Hodgkin's lymphoma in people with HIV. In addition HAART alone has been successfully used as therapy for early KS lesions. Chemoradiotherapy remains the mainstay of management for anal cancer, has a central role in cervical cancer and non-AIDS defining malignancies in this population.
Antiretroviral Therapy, Highly Active↗
Immune reconstitution inflammatory syndrome mimicking relapse of AIDS related lymphoma in patients with HIV 1 infection.
People with HIV infection who commence highly active antiretroviral therapy (HAART) occasionally develop reactivation of subclinical infection. This clinical entity is termed immune reconstitution inflammatory syndrome (IRIS) and is defined as a paradoxical deterioration in clinical status as a result of recovery of the immune system during HAART. We present three cases of IRIS following a diagnosis of AIDS related non-Hodgkin's lymphoma that resembled lymphoma relapse.
Adult↗
Paclitaxel for anthracycline-resistant AIDS-related Kaposi's sarcoma: clinical and angiogenic correlations.
BACKGROUND: Murine data indicate that angiogenesis is central to the aetiopathogenesis of Kaposi's sarcoma (KS). Therefore, we measured angiogenic cytokines and growth factors in patients with AIDS-related KS during treatment with both antiretrovirals and second-line paclitaxel chemotherapy. Cytokines measured included tumour necrosis factor-alpha (TNF-alpha), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and the interleukins IL-2, -6 and -12. PATIENTS AND METHODS: Enzyme-linked immunosorbent assays (ELISAs) were carried out to measure plasma cytokine levels in 17 patients with AIDS-related KS who had progressed within 6 months of receiving liposomal anthracyclines and were treated with paclitaxel 100 mg/m(2) every 2 weeks. Measurements were carried out before progression, at commencement and at the completion of paclitaxel. RESULTS: The objective response rate to paclitaxel was 71% (95% confidence interval 60% to 81%). In 17 patients with AIDS-related KS, we observed eight partial responses and four complete responses. Patients with AIDS Clinical Trial Group stage T1 disease had higher plasma VEGF (P = 0.05) and lower plasma TNF-alpha levels (P = 0.05) than patients with earlier stage T0 KS. There were no correlations between plasma cytokines (bFGF, VEGF, TNF-alpha, and IL-2,-6 and -12) and the CD4 and CD8 cell counts or HIV-1 RNA viral load. Response to paclitaxel was associated with a fall in plasma IL-6 levels (P = 0.04) but no change in other cytokines. There were no significant changes in CD4, CD8, CD16/56, CD19 cell counts and HIV-1 viral loads during chemotherapy. CONCLUSIONS: Angiogenic cytokines may correlate with KS disease extent but not with cellular immune function or HIV viraemia. Response to paclitaxel therapy correlates with a fall in plasma IL-6 levels and recent data indicate this may be a surrogate marker of KS-associated herpesvirus viral load. Overall, clinical response in KS correlates poorly with known angiogenic cytokines.
Acquired Immunodeficiency Syndrome↗
Prospective cohort study showing changes in the monthly incidence of Pneumocystis carinii pneumonia.
Pneumocystis carinii pneumonia (PCP) remains a serious opportunistic infection in HIV infected individuals. Seasonal changes in climate are associated with changes within individual susceptibility to infection. The possibility of monthly variability in the incidence of PCP was therefore examined by means of a cohort study of a database of 8640 HIV infected individuals attending the Chelsea and Westminster Hospital. There were 792 cases of PCP diagnosed since 1985. A marked decline was observed in the incidence of PCP in mid-1992 coincident with the introduction of PCP prophylaxis. There was a further decline in 1996 after the introduction of highly active antiretroviral therapy. Despite no significant monthly variation in the mean attendance to clinic and CD4 count, both new and all cases of PCP were higher in January than in other months (15.9% and 14.5% of all cases, respectively). A correlation with low rainfall in January and new cases of PCP was observed. These data are consistent with an influence of climatic conditions on the presentation of PCP. The diagnosis of PCP is more common in winter months suggesting that this is a transmissible infection.
AIDS-Related Opportunistic Infections↗
HIV-related lung cancer -- a growing concern?
There is an increasing awareness of the importance of non-AIDS-defining malignancies occurring in HIV-seropositive people since the introduction of highly active antiretroviral therapy (HAART). Amongst these tumours, lung cancer occurs at an increased frequency compared to age- and gender-matched populations and this increase is not accounted for by smoking alone. Moreover, the incidence of lung cancer in people with HIV is rising as overall survival improves due to HAART. The development of lung cancer is not associated with a low CD4 cell count, suggesting that immune function has a less central role in these tumours than in Kaposi's sarcoma and primary cerebral lymphomas. Most patients present with advanced stage lung cancer and the outcome is very poor. In contrast to the AIDS-defining malignancies, the prognosis in HIV-associated lung cancer does not appear to be improving in the era of HAART. Thus lung cancer and possibly other non-AIDS-defining malignancies may become an increasingly frequent problem whose prognosis has not improved in the era of HAART.
Antiretroviral Therapy, Highly Active↗
Pneumonia due to antibiotic resistant Streptococcus pneumoniae and Pseudomonas aeruginosa in the HAART era.
Antibiotic resistance profiles are useful in directing therapeutic strategies during bacterial infections. Patterns of antimicrobial resistance in Streptococcus pneumoniae and Pseudomonas aeruginosa associated pneumonia were investigated in an HIV-1 infected cohort during the era of highly active antiretroviral therapy. The median CD4 count at presentation was significantly lower for cases of P aeruginosa than for S pneumoniae. However, the number of antibiotic resistant cases of P aeruginosa decreased throughout the study period, while the incidence of S pneumoniae remained unchanged. In contrast to pneumococcal pneumonia, we show that antiretrovirals have protected from pneumonia due to antibiotic resistant P aeruginosa. These findings have implications for the treatment of individuals presenting with serious infections in which antibiotic therapy needs to be instituted before identification and sensitivities are known.
AIDS-Related Opportunistic Infections↗
Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.
PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.
Adult↗
Acquired immunodeficiency syndrome-related systemic non-Hodgkin's lymphoma.
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Antineoplastic Combined Chemotherapy Protocols↗