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Biomedical subjects

C Sherlock

Publications and source records attributed to C Sherlock.

12 recordsLinked to original sources
PubMed2001

Transcription-mediated amplification is more sensitive than conventional PCR-based assays for detecting residual serum HCV RNA at end of treatment.

OBJECTIVE: In patients chronically infected with hepatitis C virus (HCV) undergoing antiviral therapy, sustained virologic response is suggested by viral clearance by end of treatment (EOT). Viral clearance is defined by nondetection of serum HCV RNA, usually by qualitative PCR-based assays with limits of detection ranging from 100 to 1000 copies/ml. However, some individuals relapse after achieving apparent viral clearance by EOT. These individuals may have low levels of viremia not detected by current PCR methods. The aim of this retrospective study was to determine whether the Bayer HCV RNA Qualitative Assay, which employs Transcription Mediated Amplification (TMA) and detects 50 HCV RNA copies/ml, could detect residual serum HCV RNA in patients who achieved apparent viral clearance by EOT and subsequently relapsed. METHODS: Samples were obtained at EOT (wk 24 or 48) and follow-up (wk 24-26 posttreatment) from 97 patients treated for HCV (78 relapsing patients, 19 sustained responders). All samples in which HCV RNA was not detected by PCR were tested in a blinded manner for HCV RNA by the TMA-based assay. RESULTS: HCV RNA was detected by the TMA-based assay in 27 (34.6%) EOT and 76 (97.4%) follow-up samples from relapsing patients, but not in any of the EOT or follow-up samples from sustained responders. CONCLUSION: Residual serum HCV RNA was detected by the TMA-based assay in EOT samples from 34.6% of patients that had achieved apparent viral clearance by PCR. The detection of HCV RNA by the TMA-based assay could help redefine EOT response and assist in the antiviral management of HCV infection.

Antiviral Agents↗
PubMed1998

Diagnosis of cytomegalovirus infection in HIV-infected patients with respiratory disease.

BACKGROUND: The role of the cytomegalovirus (CMV) in the respiratory morbidity and mortality of HIV-infected patients remains unclear. This is due in part to difficulties in making an accurate and rapid diagnosis. There has been a limited number of studies, often with few or no AIDS patients, on the use of DNA-DNA in situ hybridization (ISH) and polymerase chain reaction to diagnose CMV respiratory infection directly on bronchoalveolar fluid samples. OBJECTIVES: To compare the centrifugation culture (CC), ISH, and nested-primer polymerase chain reaction (npPCR) techniques (npPCR) techniques on bronchoalveolar fluid for the diagnosis of respiratory CMV infection. STUDY DESIGN: Samples were obtained prospectively from a group of 35 HIV-infected homosexual men evaluated for pneumonia at a university hospital. Sensitivity, specificity, and predictive values of the three techniques were measured and compared, using the conventional roller tube cell culture (CRTC) as the gold standard. RESULTS: Sensitivity, specificity, positive and negative predictive values were as follows: 86%, 86%, 90%, and 80% for the CC; 5%, 100%, 100%, and 41% for ISH; and 86%, 57%, 75%, and 73% for npPCR. Of the six false positive samples by npPCR, two were positive by CC (none by ISH). If the latter were considered true positives, the specificity and positive predictive values of npPCR would increase to 67% and 83%, respectively. CONCLUSIONS: CC appeared to be the best of the three techniques compared in this study for diagnosis of respiratory CMV infection in HIV-infected patients. The sensitivity and predictive values of DNA-DNA ISH were very poor. Results with npPCR were acceptable, and this technique may be considered in situations when rapid diagnosis of CMV infection is necessary.

AIDS-Related Opportunistic Infections↗
PubMed1998

The antiviral effect of ritonavir and saquinavir in combination amongst HIV-infected adults: results from a community-based study.

OBJECTIVE: To characterize the antiviral effect and predictors of response to ritonavir and saquinavir-based antiretroviral combination therapy. DESIGN: Intent-to-treat analysis with suppression of plasma viral load to levels below 2.7 log10 copies/ml as the main outcome measure. PATIENTS: All adult HIV-positive individuals in the province of British Columbia who started taking ritonavir and saquinavir (each at 600 mg twice daily) in combination from 1 September 1996 to 28 February 1997, with a minimum of two plasma viral load measurements, one at baseline and one after the initiation of therapy. RESULTS: A total of 58 participants were prescribed ritonavir and saquinavir. The median plasma viral load at entry was 4.80 log10 copies/ml (interquartile range, 4.51-5.15 log10 copies/ml). A total of 29 (50%) subjects demonstrated a decrease in plasma viral load to levels below 2.7 log10 copies/ml. This level of suppression was associated with higher baseline CD4 cell counts (P=0.022) and no prior exposure to protease inhibitors (P=0.001). After controlling for baseline CD4 cell count and plasma viral load, participants naive to protease inhibitors were almost seven times (odds ratio, 6.99; 95% confidence interval, 1.85-26.39; P=0.004) more likely to suppress their plasma viral load to below 2.7 log10 copies/ml than those who had previously used protease inhibitors. CONCLUSION: Our analysis demonstrates that a ritonavir and saquinavir-based combination can produce a substantial decrease in plasma viral load with half of the participants decreasing their plasma viral load to below the limit of quantification of the assay. This response, however, is seriously compromised by prior exposure to protease inhibitors.

Adult↗
PubMed1998

Antiviral effect of double and triple drug combinations amongst HIV-infected adults: lessons from the implementation of viral load-driven antiretroviral therapy.

OBJECTIVE: To study the antiviral effect and predictors of response to two- and three-drug regimens amongst antiretroviral-naive individuals using an intent-to-treat analysis. MAIN OUTCOME MEASURE: Suppression of plasma viral load to < 500 copies/ml. PATIENTS: A total of 420 (264 double drug, 156 triple drug) individuals in a province-wide treatment programme were studied. RESULTS: A decrease in plasma viral load to < 500 copies/ml was documented in 197 (47%) subjects. This was independently associated with a lower baseline plasma viral load (odds ratio, 3.67; 95% confidence interval, 2.13-6.30) and initiation onto a three-drug regimen (odds ratio, 3.86; 95% confidence interval, 2.24-6.66). Median plasma viral load failed to reach < 500 copies/ml and in fact rebounded in the two-drug group. In contrast, 91 (58%) subjects receiving three drugs reached < 500 copies/ml during the study period. CONCLUSION: These results support the use of powerful triple drug regimens as initial therapy in HIV-infected individuals.

Adult↗
PubMed1998

Do dual nucleoside regimens have a role in an era of plasma viral load-driven antiretroviral therapy?

This study was undertaken to characterize predictors of response to double nucleoside combinations among 245 human immunodeficiency virus-infected persons initiating antiretroviral therapy. The median time for receiving antiretroviral therapy in this group was 6 months, and the plasma virus load was 58,000 copies/mL. The most commonly prescribed regimens were zidovudine/lamivudine (154 subjects, 63%) and stavudine/lamivudine (46 subjects, 19%). A total of 96 (39%) subjects had their virus load decrease to < 500 copies/mL after the initiation of therapy. Of the 245 study subjects, 102 (41.6%) had > or = 5 months of follow-up and two or more consecutive virus load determinations performed after the start of antiretroviral therapy. Multivariate analysis demonstrated that baseline virus load was the only significant factor associated with obtaining two or more plasma virus loads of < 500 copies/mL. Overall, these data demonstrate that dual nucleoside therapy (using currently licensed agents) cannot reliably achieve a high level of suppression of plasma virus load.

Adult↗
PubMed1998

Comparison of costs of strategies for measuring levels of human immunodeficiency virus type 1 RNA in plasma by using Amplicor and Ultra Direct assays.

The costs of four algorithms for monitoring plasma human immunodeficiency virus type 1 RNA were compared. For patients with strong virologic responses, the use of Ultra Direct exclusively was the cheapest strategy. For patients with weak virologic responses, small savings could be obtained by using Amplicor and retesting only samples with values below 500 copies/ml with Ultra Direct.

Algorithms↗
PubMed1996

Variation in plasma RNA levels, CD4 cell counts, and p24 antigen levels in clinically stable men with human immunodeficiency virus infection.

Short-term variability in CD4 cell counts, plasma RNA levels, and p24 antigenemia was measured in clinically stable men with human immunodeficiency virus infection. Blood samples were obtained three times in each of 2 weeks 4 weeks apart. Differences between duplicate assays were considered to be due to technical factors; variation among visits was attributed to physiologic factors. Median enrollment values of CD4 cell counts, plasma RNA levels, and immune complex-dissociated (ICD) p24 antigenemia were 400 cells/mm3, 3.4 log10 copies/mL, and 38 pg/mL, respectively. Median absolute differences between duplicate CD4 cell counts, plasma RNA levels, and ICD p24 antigen were 16 cells/mm3, 0.21 log10 copies/mL, and 9.3 pg/mL. Median intraindividual ranges were 119 cells/mm3, 0.83 log10 copies/mL, and 18 pg/mL. Above 500 copies/mL, plasma RNA levels have a variability of 0.5 log10; the test is unreliable below this level.

CD4 Lymphocyte Count↗
PubMed1993

Combining pooling and alternative algorithms in seroprevalence studies.

Data from two seroprevalence studies and one comparative study of confirmatory algorithms were used to compare the costs and sensitivities of six algorithms for determining seropositivity to human immunodeficiency virus (HIV). We evaluated confirmatory strategies by using the CBC Recombigen HIV enzyme immunoassay (EIA; Cambridge BioScience, Worcester, Mass.) and immunoblotting followed by radioimmunoprecipitation assay to confirm indeterminate immunoblotting results with and without pooling of samples during screening. The least expensive algorithm was that in which sera were pooled during screening and EIA was used to confirm positive test results. The cost savings associated with this confirmatory test were greater when the prevalence of HIV infection was higher. Savings from pooling of sera for screen testing diminished as HIV prevalence increased. The sensitivity and specificity of EIA with respect to immunoblotting and radioimmunoprecipitation assay were estimated to be 0.9992 and 0.9977, respectively. We found that the implementation of pooling during screening and the use of EIA as the confirmatory test do not affect the statistical reliability of estimates of seropositivity but do result in considerable cost savings.

Algorithms↗
PubMed1990

Clinical study of herpes simplex virus infection in leukemia.

Twenty-nine patients with leukemia were observed for the development of and recovery from oral herpes simplex virus (HSV) lesions. In patients with seropositive test results, lymphocyte and monocyte counts may provide a guide to predict the onset of HSV infections and to indicate when to institute acyclovir prophylaxis. When HSV developed, acyclovir was effective in preventing progression of the lesions, which did not resolve until white cell counts had recovered.

Acyclovir↗
PubMedDate not supplied

A case-control study of the role of cold symptoms and other historical triggering factors in asthma exacerbations.

BACKGROUND: Asthma exacerbations can be provoked by many triggers such as allergens, respiratory irritants and viral infections. The relative importance of these has not been prospectively documented in a case-control study. OBJECTIVE: To assess the relative importance of colds and other nonclimatic historical triggers of asthma exacerbations. METHODS: One hundred and nineteen adults and children with asthma in two Canadian cities participated in a one-year study of the role of exacerbating factors in asthma. Among these, 36 pairs (21 adult, 15 children) completed the case-control study. Patients were considered cases if they developed an acute asthma exacerbation and notified the centre within 24 h to allow the completion of a questionnaire and viral studies (cultures of nasopharyngeal swabs and serology). Control people with asthma were matched for sex, age and area of residence, had no exacerbation during the preceding four weeks and participated within 48 h of the case patients. RESULTS: Case patients versus control patients had a mean age of 22 years versus 20 years, 50% versus 55% were male, and 92% versus 86% had at least one positive aeroallergen skin test. Cases were more likely to have taken regular inhaled steroids (63% versus 33%, P<0.002). Cases were more likely to report the following within the previous week: fever (P<0.001), sore throat (P<0.001), increase in nasal symptoms (P<0.01), increased dust exposure (P<0. 05), exposure to others with a cold (P<0.001) and, over the previous year, increased passive smoke exposure (P<0.05). Viral cultures and paired serology were negative. CONCLUSIONS: Symptomatic colds were the most common trigger of asthma exacerbations in the winter and spring, while a transient increase in dust exposure was also identified as a significant trigger. The association with chronic, passive smoke exposure and the use of inhaled costicosteroid medications likely reflected less stable pre-study asthma in those with exacerbations.

Adult↗
PubMedDate not supplied

The patient handover: a study of its form, function and efficiency.

This study investigates the nature of the ward handover report. It was undertaken following observations that student nurses seemed not to receive enough knowledge to care for patients in an informed way. Data were gathered through participant observation on two busy medical wards over a period of two weeks. The data revealed a complex system of communication was necessary to allow nurses to provide continuity of care for patients in a safe manner. The handover was seen as working effectively but with scope for improvement. It was often long, lasting up to 60 minutes, and its information so comprehensive that it was difficult to assimilate in one session. It was found to be a process of variable quality due to the lack of supporting framework. The findings are discussed and recommendations are made to improve the handover's quality and effectiveness.

Communication↗