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Biomedical subjects

M Nelson

Publications and source records attributed to M Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2005

The durability of virological success of tenofovir and didanosine dosed at either 400 or 250 mg once daily.

Tenofovir (TDF) co-administered with didanosine (ddI) 400 mg increases ddI plasma concentrations by up to 60%, raising concerns over toxicity. To limit this interaction, the dosage of ddI may be reduced to 250 mg once daily when co-prescribed with TDF. In this clinical cohort, highly active antiretroviral therapy regimens containing TDF and ddI 250 mg were significantly better tolerated than combinations with TDF and ddI at a dose of 400 mg. Low-dose ddI 250 mg once daily plus TDF as part of antiretroviral therapy was effective.

Adenine↗
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

HIV and hepatitis C co-infection.

HIV/HCV co-infection is emerging as a major cause of morbidity and mortality in the 21st century. This editorial reviews the prevalence of co-infection, the factors involved in acquisition of HCV, and the influence of co-infection on disease progression. We examine the results of the major co-infection trials including APRICOT, ACTG 5071 and RIBAVIC. These trials, in association with emerging evidence for future therapies currently undergoing investigation, have led to increased hope of treatment success in co-infected individuals.

Anti-HIV Agents↗
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

Anticoagulation therapy in patients with chronic atrial fibrillation: a retrospective claims data analysis.

OBJECTIVES: This study assessed the risk of thrombo embolic events and bleeding complications among atrial fibrillation patients. METHODS: A cohort of patients with chronic non-valvular atrial fibrillation were identified from medical claims (diagnosis codes 427.31 and 427.32). Subjects were identified from 1 January 1998-31 December 2000 and were continuously enrolled for 6 months prior to the first occurring atrial fibrillation medical claim. Cox proportional hazards analysis with time varying covariates was used for the event analysis. RESULTS: Of 6764 subjects retained for analysis, 3541 (52.4%) were exposed to warfarin. Adjusting for baseline characteristics, warfarin exposure was associated with lower likelihood of an arterial thromboembolic event compared to no exposure (HR: 0.710, CI: 0.540-0.934). No benefit was found in the use of warfarin in the prevention of intracranial events (HR: 1.119, CI: 0.929-1.349). Use of warfarin increased the risk of minor bleeding events (HR: 3.600, CI: 2.537-5.109), and all bleeding events (HR: 1.502, CI: 1.289-1.749). CONCLUSIONS: The risk of arterial thromboembolic events was associated with warfarin exposure as expected. An increase in the risk of minor and total bleeding events among patients treated with warfarin was observed. The results of this study suggest that there may be a gap between the clinical trial and coagulation clinic performance of warfarin in reducing the risk of thromboembolic events versus what is achievable in general practice.

Atrial Fibrillation↗
PubMed2005

Vomiting post tonsillectomy at the University Hospital of the West Indies.

A three-year observational study of patients undergoing tonsillectomy at the University Hospital of the West Indies was conducted to determine the incidence of postoperative vomiting. Data were collected to assess possible risk factors for vomiting as well as possible alleviating agents. Two hundred and fifty-two patients were included in the study and a thirteen per cent incidence of postoperative vomiting was found. This is significantly less than that quoted in other studies (40-73%). Results also showed that steroids significantly reduced the incidence of postoperative vomiting in the study population. Muscle relaxants reversal agents and antibiotics particularly co-trimoxazole and ceftriaxone significantly increased its incidence. Usual antiemetic agents including dimenhydrinate (gravol) and promethazine (phenergan), as well as drugs known to possess antiemetic properties such as midazolam and propofol, lacked any significant protective effect against emesis. Opioid analgesia, inhalational induction and blood loss of greater than 10% of estimated blood volume appeared to increase emesis but failed to achieve statistical significance.

Adolescent↗
PubMed2005

Anaesthesia for operative deliveries at the University Hospital of the West Indies: a change of practice.

There has been an increasing trend worldwide to use regional anaesthesia for operative deliveries. The Confidential Enquiry into Maternal Deaths in the United Kingdom has demonstrated a steady decline in the anaesthesia-related deaths since the introduction of regional anaesthesia. There are lower morbidity profiles in mothers delivering under regional anaesthesia as well as better infant Apgar scores. In 1997, a decision was taken to have at least 60% of all elective Caesarean sections done at the University Hospital of the West Indies (UHWI) performed under spinal anaesthesia. This is a review of the anaesthetic technique for Caesarean sections at the UHWI since 1996. The Deliveries and Anaesthetic Books on the labour ward were reviewed and the type of anaesthesia for elective and emergency Caesarean sections recorded for the period January 1996 to December 2001. At the beginning of the period under study, more than 90% of the Caesarean sections were being done under general anaesthesia. By the middle of 1998, spinal anaesthesia was more commonly employed than general anaesthesia for Caesarean sections and by December 2001, more than eight out of every ten Caesarean sections were being done under spinal anaesthesia. The main reasons for the successful change of practice were that it was consultant-led, there was good communication between relevant departments, the junior staff were properly trained, there was a consistent supply of appropriate drugs and there was a high level of patient satisfaction.

Anesthesia, Conduction↗
PubMed2005

Microbial isolates from patients in an intensive care unit, and associated risk factors.

A retrospective one-year analysis of blood, sputum and urine samples taken from all patients admitted for more than 48 hours to the Intensive Care Unit at the University Hospital of the West Indies (UHWI) was undertaken. Positive trapped sputum cultures were found in 50% of patients, positive blood cultures in 32.7% and positive urine cultures in 23.1%. Gram-negative organisms predominated especially Pseudomonas aeruginosa (41.3%) and Acinetobacter spp (33.5%). Coagulase-negative staphylococcus (20%) and streptococcus group D (18.7%) were the most common gram-positive organisms. The Acinetobacter spp showed marked resistance to most antibiotics except for meropenem (82.7% susceptibility) while P. aeruginosa was most susceptible to ceftazidime (84.4%) and amikacin (89.1%). Both the coagulase-negative staphylococcus and streptococcus group D were relatively sensitive to amoxycillin/clavulanate (80.6% and 79.3% respectively). There was a high incidence of yeast found in sputum (27.1%) and urine (16.8%). Mechanical ventilation was a significant risk factor for developing a positive sputum culture (p = 0.01), this effect being particularly prominent in those ventilated for > 5 days. Central venous pressure lines significantly increased the risk of a positive blood culture (p = 0.005). This increase was seen particularly in those with CVP lines for > 7 days. Other risk factors for developing positive cultures included preadmission infection, antibiotic use just prior to ICU admission, increasing APACHE II score and increasing age.

Adolescent↗
PubMed2005

Regulation of trophic factor expression by innervating target regions in intraocular double transplants.

Trophic factors have been found to play a significant role both in long-term survival processes and in more rapid and dynamic processes in the brain and spinal cord. However, little is known regarding the regulation of expression of growth factors, and how these proteins interact on a cell-to-cell basis. We have studied protein levels of one growth factor known to affect the noradrenergic innervation of the hippocampal formation, namely brain-derived neurotrophic factor (BDNF). The purpose of the present study was to determine if appropriate innervation or contact between the LC noradrenergic neurons and their target, the hippocampus, affects expression of this growth factor in either brain region. Fetal brain stem tissue, containing the LC, and hippocampal formation were dissected from embryonic day 17 rat fetuses and transplanted together or alone into the anterior chamber of the eye of adult Fisher 344 rats. The tissue was grown together for 6 weeks, after which the animals were sacrificed and ELISAs for BDNF were undertaken. Transplantation to the anterior chamber of the eye increased the expression of BDNF in the hippocampal but not the brain stem tissue, compared with levels observed in fetal and adult rats in vivo. In addition, double grafting with hippocampal tissue more than tripled BDNF levels in brain stem grafts and doubled BDNF levels in the hippocampal portion of double grafts compared with hippocampal single grafts. Triple grafts containing basal forebrain, hippocampus, and brain stem LC tissue increased brain stem and hippocampal BDNF levels even further. Colchicine treatment of LC-hippocampal double grafts gave rise to a significant decrease in hippocampal BDNF levels to levels seen in single hippocampal grafts, while only a partial reduction of BDNF levels was seen in the brain stem portion of the same double grafts treated with colchicine. The findings suggest that an appropriate hippocampal innervation or contact with its target tissues is essential for regulation of BDNF expression in the brain stem, and that retrograde transport of BDNF can occur between double grafted fetal tissues in oculo.

Animals↗
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↗
PubMed2004

Technical review of the Laboratory Biosphere closed ecological system facility.

Laboratory Biosphere is a 40 m3 closed life system that commenced operation in May 2002. Light is from 12,000 W of high pressure sodium lamps over planting beds with 5.37 m2 of soil. Water is 100% recycled by collecting condensate from the temperature and humidity control system and mixing with leachate collected from under the planting beds. Atmospheric leakage was estimated during the first closure experiment to be 0.5-1% per day in general plus about 1% for each usage of the airlock door. The first trial run of 94 days was with a soybean crop grown from seeds (May 17, 2002) to harvest (August 14, 2002) plus 5 days of post-harvest closure. The focus of this initial trial was system testing to confirm functionality and identify any necessary modifications or improvements. This paper describes the organizational and physical features of the Laboratory Biosphere.

Air Conditioning↗
PubMed2004

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↗