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Biomedical subjects

J Stebbing

Publications and source records attributed to J Stebbing.

At least 19 recordsLinked to original sources
PubMed2006

The significance of the time interval between antecedent pregnancy and diagnosis of high-risk gestational trophoblastic tumours.

It is thought that the time interval between the antecedent pregnancy and diagnosis of gestational trophoblastic tumours (GTTs) may influence the outcome of these patients. In this study, we investigate the significance of this time interval. Multivariate analysis was used to investigate if the time interval was of prognostic significance from our cohort of 241 high-risk patients with GTT. Subsequent cutpoint analysis was used to determine an optimal cutpoint for the interval covariate. The outcome of these patients was plotted according to the Kaplan-Meier method. The time interval was of prognostic significance on multivariate analysis. A period of greater than 2.8 years after pregnancy was found to be of most significance. The 5-year overall survival was 62.0% (95% CI: 47-76%) for greater than 2.8 years vs 94% (95% CI: 91-97%) for less than 2.8 years (P<0.001). Multivariate analysis showed the presence of liver metastasis and the number of metastasis was also of prognostic importance. The interval between antecedent pregnancy and diagnosis in high-risk GTT is of prognostic significance. This gives some insight into the pathogenesis of the disease.

Adolescent↗
PubMed2006

Highly active anti-retroviral therapy (HAART)-induced maintenance of adaptive but not innate immune parameters is associated with protection from HIV-induced mortality.

Immunosuppression induced by the human immunodeficiency virus (HIV-1) increases the risk of death. We measured the influence of immunological and virological factors and the type of highly active anti-retroviral therapy (HAART) on this risk. Adaptive (lymphocyte) and innate (natural killer) immune correlates and maximum HIV viral loads were assessed for association with mortality using univariate and multivariate analyses. The protective effect of HAART regimens, containing protease inhibitors (PI) and/or non-nucleoside reverse transcriptase inhibitors (NNRTI) on mortality were also examined in a prospectively recorded cohort of 9621 HIV-infected individuals. From this entire cohort, 5873 HIV infected individuals (61%) have been followed-up in the HAART era and of these 499 (8.5%) have died. In multivariate analyses, CD4 counts below the 50th centile and CD8 and CD19 counts below the 25th centile were significantly associated with mortality, as was increased age (P < 0.001). Innate immune subset levels had no effect on mortality. A maximum HIV viral load greater than the 75th centile was also associated independently with mortality (P < 0.035). Exposure to either a PI or an NNRTI-containing HAART regimen, or both together, was protective against death compared with no anti-retrovirals (P < 0.001). Effective HAART-induced maintenance of the adaptive immune system (CD4, CD8 and CD19 counts) protects from HIV-related mortality.

Adult↗
PubMed2006

Spontaneous splenic haematoma in a multiple myeloma patient receiving pegfilgrastim support.

Growth factors are a significant advance in the supportive care of patients with cancer with a wide range of indications. Frequent side effects of G-CSF include bone pain, headache, fatigue and nausea. We report a case of subcapsular splenic haematoma following pegfilgrastim administration in a 65-year old patient with multiple myeloma. Proposed mechanisms accounting for splenic enlargement include extramedullary haemopoiesis, intrasplenic infiltration by mature and immature myeloid cells and intrasplenic stem cell homing and proliferation. The risk of spontaneous splenic rupture is difficult to quantify. Physicians should be aware of this life-threatening condition and early diagnosis can be difficult since anemia and splenomegaly are common findings in haematologic patients.

Aged↗
PubMed2006

A single centre cohort experience with a new once daily antiretroviral drug.

BACKGROUND: Atazanavir, an azadipeptide protease inhibitor (PI) with once daily dosing, a lack of insulin resistance, lipid increase, and gastrointestinal toxicities, is approved in combination with other antiretrovirals for the treatment of patients infected with HIV. Unboosted atazanavir is also used in highly active antiretroviral therapy (HAART) naive patients. METHODS: The study prospectively followed up an established cohort of patients who received atazanavir, and for whom one year of follow up data were available. RESULTS: It was found that use of atazanavir in intent to treat and on treatment analyses, maintained and led to virological suppression and increases in CD4 count in both PI naive and experienced patients. Virological failure occurred in 7% of patients and the main toxicity was hyperbilirubinaemia, which led to treatment withdrawal in 2%. Its efficacy and safety profile was similar to that seen in previous randomised studies investigating its use. CONCLUSIONS: These data should provide reassurance for clinicians wishing to introduce a new antiretroviral into an established cohort.

Anti-HIV Agents↗
PubMed2006

A review of the ethnic differences in breast cancer.

Women of African descent have a lower incidence of breast cancer than their white counterparts; however, the overall age-adjusted breast cancer mortality rates are higher. They also present at a younger age, and have more advanced disease that exhibits poor prognostic features including significantly larger tumors of higher grade, higher rates of estrogen receptor and progesterone receptor negativity and a higher rate of p53 mutations and HRAS1 proto-oncogene expression, all of which confer a poor prognosis. While there are many possible contributory factors to the discrepancies in outcome in women of African descent, there is no satisfactory explanation as to why women of African origin tend to present at a younger age with hormone receptor-negative tumors and more adverse prognostic features.

Black or African American↗
PubMed2005

The presentation and survival of patients with non-cutaneous AIDS-associated Kaposi's sarcoma.

BACKGROUND: Acquired immune deficiency syndrome related Kaposi's sarcoma (AIDS-KS) remains a significant cause of morbidity and mortality. We describe for the first time a proportion of patients with AIDS-KS who presented with no evidence of cutaneous disease. PATIENTS AND METHODS: From our cohort of 5932 individuals infected with the human immunodeficiency virus (HIV-1) treated in the HAART era, 319 were identified with KS. Of these, 11 patients (5.4%) were diagnosed with KS without the presence of any cutaneous disease. We compared their survival, clinical, immunological and virological characteristics to other individuals with KS. RESULTS: There were no statistically significant differences in survival, CD4 count or HIV viral load at KS presentation. We observed that tumour-associated oedema (P = 0.046) and non-oral gastrointestinal KS (P = 0.042) were significantly more common in patients with non-cutaneous KS. Only one case of non-cutaneous KS was observed prior to the era of highly active anti-retroviral therapy (HAART). CONCLUSIONS: Non-cutaneous KS is a recognisable condition; patients should be treated with the standard of care as their prognosis is not inferior. This is likely to reflect a strong immune response, in the era of HAART.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma.

PURPOSE: A proportion of patients with HIV infection who subsequently receive highly active antiretroviral therapy (HAART) exhibit a deterioration in their clinical status, despite control of virologic and immunologic parameters. This clinical response, known as the immune reconstitution inflammatory syndrome (IRIS), occurs secondary to an immune response against previously diagnosed pathogens. PATIENTS AND METHODS: From our cohort of 5,832 patients treated in the HAART era, we identified 150 therapy-naive patients with a first presentation of Kaposi's sarcoma (KS). Their clinicopathologic features and progress were recorded prospectively. RESULTS: After commencing HAART, ten patients (6.6%) developed progressive KS, which we identify as IRIS-associated KS. In a comparison of these individuals with those whose KS did not progress, we found that IRIS-KS occurred in patients with higher CD4 counts (P = .03), KS-associated edema (P = .01), and therapy with both protease inhibitors and non-nucleosides together (P = .03). Time to treatment failure was similar for both groups, although the CD4 count declined more rapidly at first, in those patients with IRIS-associated KS. Despite this initial decline, in our clinical experience HAART could be successfully continued in those with IRIS-associated KS. CONCLUSION: We have identified IRIS-KS in a cohort of HIV patients with KS who start HAART.

Adult↗
PubMed2005

Impact of antiretroviral choice on hypercholesterolaemia events: the role of the nucleoside reverse transcriptase inhibitor backbone.

BACKGROUND: The use of highly active antiretroviral therapy (HAART) has profoundly altered the life expectancy of individuals infected with HIV. Metabolic abnormalities associated with antiretrovirals and cumulative exposure to combination antiretroviral therapy, including dyslipidaemia and insulin resistance, have been linked to an increased risk of myocardial infarction. METHODS: Longitudinal data from a large prospectively collected clinical database were analysed. All patients who commenced first antiretroviral therapy (ART) [two nucleoside reverse transcriptase inhibitors (NRTIs)+one nonnucleoside reverse transcriptase inhibitor (NNRTI) or one active protease inhibitor (PI)] since 1996 were identified. Patients with elevated cholesterol levels [>5.5 mmol/L (215 mg/dL)] prior to therapy initiation were excluded. Quantitative data were categorized into quartiles and presented stratified by individuals developing abnormal levels of cholesterol during first-line HAART. Event time was defined as time from commencing first-line ART to either development of cholesterol level >6.5 mmol/L (254 mg/dL) or switch of first-line therapy. The Kaplan-Meier product limit survival method was used to estimate time to abnormal cholesterol level, and the chi2 test was used for comparisons between drug classes. Cox's proportional hazards regression analysis was used to identify factors predicting a likelihood of raised cholesterol level. RESULTS: A total of 1664 patients were included in the study: 57.1% on two NRTIs+one NNRTI, 38.4% on two NRTIs+one PI, and 4.4% on two NRTIs+a boosted PI regimen. Regimens containing stavudine or PIs were associated with a significantly higher event risk and earlier time to event. No differences between efavirenz and nevirapine or between didanosine and lamivudine were observed. In 28 patients exposed to the combination of tenofovir+lamivudine+efavirenz, there were no episodes of elevated cholesterol level. CONCLUSION: Dyslipidaemia has emerged as an important issue in HIV-infected individuals receiving antiretroviral therapy. This study demonstrates that age at start of therapy, baseline cholesterol level, stavudine use and PI use are all associated with increased risk of hypercholesterolemia on initial therapy. Both NRTI and NNRTI/PI choice influence risk of hypercholesterolaemia.

Adult↗
PubMed2005

Isolated conjunctival lymphoma metastasis from previous low grade non-Hodgkin's lymphoma.

Ocular involvement of systemic non-Hodgkin's lymphoma is rare. This report describes the unusual occurrence of a biopsy confirmed low grade lymphoma recurring in the conjunctiva, three years after initial diagnosis of systemic disease. The tumour was surgically resected and the patient remains disease free four years later. After the diagnosis of lymphoma, long term follow up is advised as recurrences in unusual sites can occur.

Conjunctival Neoplasms↗
PubMed2005

Assessment of the efficacy of total lymphocyte counts as predictors of AIDS defining infections in HIV-1 infected people.

BACKGROUND: The CD4 count is a dominant prognostic and predictive factor in HIV infection. This study assessed the utility of the total lymphocyte count (TLC) in place of the CD4 count to predict the development of AIDS defining opportunistic infections (ADOI). METHODS: The Chelsea and Westminster cohort was used to identify those people with a first episode of an ADOI. Corresponding CD4 and TLCs were recorded before diagnosis or at the time of first prescribing prophylaxis; patients without an AIDS defining opportunistic infection were defined as being at "risk" and receiver operating characteristic (ROC) curves were used to display the results of sensitivity and the false positive error rate of total lymphocyte and CD4 count groups. RESULTS: A significant linear correlation was seen between the log(10) CD4 count and log(10) TLC (Pearson's correlation coefficient = 0.70, p<0.001). The finer cut off value for TLC where false positive error rate is minimum and sensitivity maximum was 1500-2000 cells/mm(3). Patients with TLC 1000-1500 cells/mm(3) were estimated to be at 40% increased risk of developing an ADOI. The cut off value for CD4 counts measured 200 cells/mm(3) above which the risk developing an ADOI decreased. Patients with a CD4 count of 150-200 cells/mm(3) were at a 34% increased risk of developing an ADOI. The area under the ROC curve for TLC was 10% lower than that for CD4 count. CONCLUSIONS: The TLC is minimally less reliable than the CD4 count as a predictor of ADOIs. In the absence of expensive equipment for CD4 measurement, the TLC is a useful test.

AIDS-Related Opportunistic Infections↗
PubMed2005

The value of anal cytology and human papillomavirus typing in the detection of anal intraepithelial neoplasia: a review of cases from an anoscopy clinic.

BACKGROUND: Previous studies have reached differing conclusions about the utility of anal cytology as a screening tool for anal intraepithelial neoplasia (AIN). There is a need also to establish whether HPV typing offers a useful adjunct to screening. METHODS: We analysed data from 99 consecutive homosexual/bisexual male patients (89 HIV-1 positive) who underwent high resolution anoscopy. Follow up visits for these patients were also included, giving a total of 160 anoscopic procedures. Comparison was made between results of anal cytology using the sampling method of Palefsky, and histological findings of biopsies taken from abnormal areas seen on high resolution anoscopic examination of the anal canal. Swabs taken concurrently with the cytology were analysed for the presence of human papillomavirus (HPV) DNA and compared with the cytological and histological findings. RESULTS: The sensitivity of the cytology was 83%, and the specificity 38% when compared with histology. At screening of 34 asymptomatic men, 83% had anal cytological dysplasia and 78% had AIN. There were no significant differences in the prevalence of hrHPV genotypes between different cytological or histological grades of abnormalities. CONCLUSION: Anal cytology by the Palefsky method is simple to undertake, has a sensitivity and specificity comparable with cervical cytology, and can therefore be used as the basis of a pilot screening project in centres with large cohorts of HIV positive homosexual men who have a high risk of developing anal carcinoma. HPV genotyping is not a useful adjunct to cytological screening.

Analysis of Variance↗
PubMed2004

A comparison of the CD4 response to antiretroviral regimens in patients commencing therapy with low CD4 counts.

OBJECTIVE: To compare the immunological response to highly active antiretroviral therapy (HAART) in treatment-naive patients with a baseline CD4 count of <200 cells/mm(3). DESIGN AND METHODS: We identified treatment-naive human immunodeficiency virus (HIV-1)-infected individuals who had commenced HAART since 1996 and who had a starting CD4 count of <200 cells/mm(3). Immunological success was defined as achieving a CD4 count of >200 cells/mm(3) and treatments were compared using univariate and multivariate Cox's proportional hazards models in order to establish whether protease inhibitor (PI)-based regimens were significantly different to regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs). Both regimens utilize a nucleoside analogue (NA) backbone. RESULTS: A total of 599 patients were identified. When the variables were entered into a multivariate analysis, no significant differences between HAART regimens were found. We showed that compared with efavirenz regimens a two NA plus one PI regimen was not significantly less likely to achieve immunological success (adjusted HR: 0.65, 95% CI 0.41-1.03, P=0.07). Two NA and boosted PI (adjusted HR: 1.33, 95% CI 0.81 to 2.16) or two NA and nevirapine (adjusted HR: 0.93, 95% CI 0.67-1.29) regimens were also not significantly different from efavirenz-based regimens, based on the endpoint of immunological success. CONCLUSION: PI-, boosted PI- and NNRTI-based HAART regimens are not significantly different in achieving increased CD4 counts in individuals who commence therapy with a low CD4 count.

Adult↗
PubMed2004

Outcome of patients with HIV-related germ cell tumours: a case-control study.

Testicular germ cell tumour (GCT) is not an AIDS-defining illness despite an increased incidence in men with HIV infection. We performed a matched case-control study comparing outcomes in HIV-positive men and the general population with GCT, using three age and stage matched controls for each case. There was no difference in the 5-year GCT-free survival between cases and controls. However, overall survival was significantly decreased in the cases (log rank P=0.03). HIV was responsible for 70% of this mortality. The relapse-free survival for stage I patients treated with orchidectomy and surveillance was not affected by HIV status (log rank P=0.68). There was no difference in disease free survival in patients with metastatic disease (log rank P=0.78). The overall survival has not improved since the introduction of highly active antiretroviral therapy (log rank P=0.4). Thus, HIV-related GCT is not more aggressive than GCT in the general population.

Adult↗
PubMed2004

Model-based inference of recombination hotspots in a highly variable oncogene [corrected].

An emergent problem in the study of pathogen evolution is our ability to determine the extent to which their rapidly evolving genomes recombine. Such information is necessary and essential for locating pathogenicity loci using association studies, and it also directs future screening, therapeutic and vaccination strategies. Recombination also complicates the use of phylogenetic approaches to infer evolutionary parameters including selection pressures. Reliable methods that identify the presence of regions of recombination are therefore vital. We illustrate the use of an integrated model-based approach to inferring recombination structure using all available sequences of the highly variable, transforming Kaposi's sarcoma-associated herpesviral gene, ORF-K1. This technique learns the parameters of a statistical model that takes recombination hotspots, population genetic effects, and variable rates of mutation into account. As there are no known mechanisms to explain the high mutation rate in this DNA viral gene, recombination may account for some of the variability observed. We infer recombination hotspots in conserved sites such as the tyrosine kinase signaling motif, referred to here as recombination drift, as well as in nonconserved sites, a process described as recombination shift.

Bayes Theorem↗