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Biomedical subjects

L Joseph

Publications and source records attributed to L Joseph.

At least 127 records · Page 7Linked to original sources
PubMed1996

Routine immunologic tests in systemic lupus erythematosus: is there a need for more studies?

OBJECTIVE: To evaluate the sensitivity, specificity, and likelihood ratios of anti-dsDNA, C3, C4, and Clq binding tests for predicting flares in systemic lupus erythematosus (SLE) and to evaluate the conflicting results reported in the recent literature. METHODS: Test results from 9 to 3 months preceding 83 flares among 53 patients from a cohort study of 202 patients with SLE were assessed for their ability to predict renal and nonrenal flares and all flares combined. A flare was defined as a 6 point rise in a modified SLE Disease Activity Index. RESULTS: For all 4 tests, sensitivity approximated 50% and specificity was less than 75%. For anti-dsDNA, Clq binding, and C4, both positive and negative likelihood ratios were close to 1.0, suggesting little clinical value for routine testing. For C3, likelihood ratios for a positive test approximated 2.0, meeting the minimal level for clinical significance. Review of previous studies suggested that sample size, the use of a standardized disease activity measure to define a flare, the severity of the flare, and the study duration could not explain the discrepant results among studies. The 2 studies with testing every 4 to 6 weeks found that a rising anti-dsDNA predicted flares, while those with less frequent testing did not. CONCLUSION: While our study provided no major support for routine testing with anti-dsDNA, C3, C4, or Clq binding, additional longitudinal studies are needed to assess monthly testing of anti-dsDNA as a predictor of flare in SLE.

Adult↗
PubMed1995

Molecular support for vicariance as a source of diversity in rainforest.

The origin of high diversity in tropical rainforests is attributed to divergence amongst relatively mesic, late Pleistocene refuges. To test this hypothesis we analysed sequence variation within the mitochondrial DNA of populations of six rainforest-dwelling vertebrate species (one lizard and five birds) in the Wet Tropical rainforests of northeastern Australia. Vicariance among historical refuges was indicated by geographically congruent variation across a historical climatic barrier previously predicted by modelling. Sequence divergence across the barrier varied widely, being highest in species with lowest vagility and greatest restriction to rainforest. A high altitude, rainforest-restricted species was exceptional in lacking mtDNA variation. These data support the suggested role of vicariance in promoting evolutionary diversity in rainforests but also indicate variation in the timing of vicariance events, with most speciation or divergence events occurring well before the late Pleistocene. The relation between the amount of molecular divergence and current ecology suggests a sequence of isolation events, perhaps of increasing severity, occurring between the late Tertiary and the late Pleistocene.

Animals↗
PubMed1995

Do doctors accurately assess coronary risk in their patients? Preliminary results of the coronary health assessment study.

OBJECTIVE: To evaluate the ability of doctors in primary care to assess risk patients' risk of coronary heart disease. DESIGN: Questionnaire survey. SETTING: Continuing medical education meetings, Ontario and Quebec, Canada. SUBJECTS: Community based doctors who agreed to enroll in the coronary health assessment study. MAIN OUTCOME MEASURE: Ratings of coronary risk factors and estimates by doctors of relative and absolute coronary risk of two hypothetical patients and the "average" 40 year old Canadian man and 70 year old Canadian woman. RESULTS: 253 doctors answered the questionnaire. For 30 year olds the doctors rated cigarette smoking as the most important risk factor and raised serum triglyceride concentrations as the least important; for 70 year old patients they rated diabetes as the most important risk factor and raised serum triglyceride concentrations as the least important. They rated each individual risk factor as significantly less important for 70 year olds than for 30 year olds (all risk factors, P < 0.001). They showed a strong understanding of the relative importance of specific risk factors, and most were confident in their ability to estimate coronary risk. While doctors accurately estimated the relative risk of a specific patient (compared with the average adult) they systematically overestimated the absolute baseline risk of developing coronary disease and the risk reductions associated with specific interventions. CONCLUSIONS: Despite guidelines on targeting patients at high risk of coronary disease accurate assessment of coronary risk remains difficult for many doctors. Additional strategies must be developed to help doctors to assess better their patients' coronary risk.

Clinical Competence↗
PubMed1995

Placing trials in context using Bayesian analysis. GUSTO revisited by Reverend Bayes.

Standard statistical analyses of randomized clinical trials fail to provide a direct assessment of which treatment is superior or the probability of a clinically meaningful difference. A Bayesian analysis permits the calculation of the probability that a treatment is superior based on the observed data and prior beliefs. The subjectivity of prior beliefs in the Bayesian approach is not a liability, but rather explicitly allows different opinions to be formally expressed and evaluated. The usefulness of this approach is demonstrated using the results of the recent GUSTO study of various thrombolytic strategies in acute myocardial infarction. This analysis suggests that the clinical superiority of tissue-type plasminogen activator over streptokinase remains uncertain.

Bayes Theorem↗
PubMed1995

Bayesian estimation of disease prevalence and the parameters of diagnostic tests in the absence of a gold standard.

It is common in population screening surveys or in the investigation of new diagnostic tests to have results from one or more tests investigating the same condition or disease, none of which can be considered a gold standard. For example, two methods often used in population-based surveys for estimating the prevalence of a parasitic or other infection are stool examinations and serologic testing. However, it is known that results from stool examinations generally underestimate the prevalence, while serology generally results in overestimation. Using a Bayesian approach, simultaneous inferences about the population prevalence and the sensitivity, specificity, and positive and negative predictive values of each diagnostic test are possible. The methods presented here can be applied to each test separately or to two or more tests combined. Marginal posterior densities of all parameters are estimated using the Gibbs sampler. The techniques are applied to the estimation of the prevalence of Strongyloides infection and to the investigation of the diagnostic test properties of stool examinations and serologic testing, using data from a survey of all Cambodian refugees who arrived in Montreal, Canada, during an 8-month period.

Bayes Theorem↗
PubMed1995

Socioeconomic status and indicators of asthma in children.

Differential access and utilization of medical care by the poor and rich may contribute to differences in asthma prevalence. We therefore studied the relationship of socioeconomic status (SES) to various indicators of asthma in the Canadian context of universal access to medical care. Information on respiratory symptoms, demographics, and home exposures of 1,111 primary school children was collected by questionnaire. Parental occupation was used to establish SES. Exercise-induced bronchospasm (EIB) after a 6-min free-running test was our measure of airways responsiveness and was available for 989 children. As compared with children from the most advantaged homes, children from the least advantaged homes were more likely to present EIB (OR: 2.26, 95% CI: 1.12 to 4.58) and to report night cough (OR: 2.30, 95% CI: 1.04 to 5.06) and cough with mucus (OR: 3.15, 95% CI: 1.06 to 9.33), while there was no significant excess of the report of wheeze or diagnosed asthma. Among factors potentially linked to SES, the presence of a cat at home (OR: 1.63, 95% CI: 1.02 to 2.61) and lower respiratory infection before 2 yr of age were associated with an excess of EIB (OR: 1.71, 95% CI: 1.16 to 2.52). Our results suggest that unidentified environmental factors contribute to the excess asthma morbidity in poor children.

Adolescent↗
PubMed1995

Absence of an association of rheumatoid arthritis and diffuse idiopathic skeletal hyperostosis: a case-control study.

OBJECTIVE: To compare the frequency of diffuse idiopathic skeletal hyperostosis (DISH), based on an evaluation of chest radiographs, in 2 populations of patients: those with and without rheumatoid arthritis (RA). METHODS: Cases of RA were obtained from the Wichita Arthritis Center databank and controls from a private cardiology practice. Patients with RA and controls had to be older than 50 years and have a chest radiograph available. All radiographs were read, in haphazard order, by a single reader who classified them as definitely DISH, probably DISH (these 2 categories were considered as having DISH), uncertain, probably not DISH, and definitely not DISH (these 3 groups defined the absence of DISH). Logistic regression was used to investigate the probability of DISH while controlling for age and sex. Analyses were conducted to take into account the sensitivity and specificity of chest radiographs for the diagnosis of DISH. RESULTS: Among 748 radiographs (357 RA and 391 controls), 29 were diagnosed as DISH (21 controls and 8 RA). The mean age for the RA group was 66.2 yrs (SD = 11.9 and 108 (30.2%) were men. Control subjects had a mean age of 69.6 yrs (SD = 11.4 and 139 (35.4%) were men. The DISH patients, compared with those without DISH, were more likely to be male (p = 0.004) and older (p < 0.001). After accounting for age and sex, the relative risk of DISH in RA versus the controls was 0.40 (95% confidence interval: 0.20 to 1.01). After taking into account the sensitivity and specificity in this population, the adjusted prevalence of DISH for the RA group was 1% (95% confidence interval: 0.1 to 3.7) and 3.1% (95% confidence interval: 0.2 to 7.9) for the control group. CONCLUSION: We confirmed the increase in frequency of DISH with increasing age and male sex, but failed to support an increased association of DISH with RA.

Age Factors↗
PubMed1994

Life expectancy following dietary modification or smoking cessation. Estimating the benefits of a prudent lifestyle.

OBJECTIVE: To evaluate the maximum benefits of dietary modification or smoking cessation to the life expectancy of North American adults. DESIGN: Using a computer model, we estimated the change in life expectancy for men and women following risk factor modification. We then estimated the total number of adults who would be targeted by national guidelines and the total person-years of life that would be saved. PATIENTS: Men and women aged 30 to 74 years who were free of coronary heart disease. INTERVENTIONS: Smoking cessation or serum cholesterol-reducing diets with 8% to 10% saturated fat and 240 to 300 mg of daily cholesterol, respectively. RESULTS: On average, dietary modification would reduce serum cholesterol levels from 0.45 mmol/L (17.4 mg/dL) to 0.75 mmol/L (29.1 mg/dL) in men and 0.12 mmol/L (4.6 mg/dL) to 0.55 mmol/L (21.4 mg/dL) in women, thereby increasing life expectancy by 0.03 to 0.4 year and 0.01 to 0.16 year, respectively. Smoking cessation would increase life expectancy from 2.59 to 4.43 years among men and from 2.6 to 3.68 years among women. Among adult Canadians, dietary modification would save 373,000 to 683,000 person-years of life. The majority of these benefits would occur among men who start dieting at ages 30 to 59 years. Smoking cessation would add more than 4 million person-years of life to the Canadian population. The relative impact of either intervention among American adults would be similar to these Canadian estimates. CONCLUSIONS: Younger men, aged 30 to 59 years, might live slightly longer after dietary change, but among women and older men the average benefits would be negligible. The benefits of smoking cessation are more uniform across age and sex and are substantially greater than those predicted for dietary change.

Adult↗
PubMed1994

Lymphoma models for B cell activation and tolerance. X. Anti-mu-mediated growth arrest and apoptosis of murine B cell lymphomas is prevented by the stabilization of myc.

Treatment of the WEHI-2131 or CH31 B cell lymphomas with anti-mu or transforming growth factor (TGF)-beta leads to growth inhibition and subsequent cell death via apoptosis. Since anti-mu stimulates a transient increase in c-myc and c-fos transcription in these lymphomas, we examined the role of these proteins in growth regulation using antisense oligonucleotides. Herein, we demonstrate that antisense oligonucleotides for c-myc prevent both anti-mu- and TGF-beta-mediated growth inhibition in the CH31 and WEHI-231 B cell lymphomas, whereas antisense c-fos has no effect. Furthermore, antisense c-myc promotes the appearance of phosphorylated retinoblastoma protein in the presence of anti-mu and prevents the progression to apoptosis as measured by propidium iodide staining. Northern and Western analyses show that c-myc message and the levels of multiple myc proteins were maintained in the presence of antisense c-myc, results indicating that myc species are critical for the continuation of proliferation and the prevention of apoptosis. These data implicate c-myc in the negative signaling pathway of both TGF-beta and anti-mu.

Animals↗
PubMed1994

Factors determining conversion to laparotomy in patients undergoing laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) has been performed increasingly in an outpatient setting. Conversion from LC to open cholecystectomy (OC) is sometimes required. To predict conversion to OC, a single institutional study of 1,676 consecutive patients in whom LC was attempted was performed. Factors evaluated were age, sex, history of acute cholecystitis, pancreatitis, or jaundice, previous abdominal surgery, abnormalities of liver function tests, thickened gallbladder wall identified by preoperative ultrasound, obesity or morbid obesity, and cumulative institutional experience in LC. Conversion to OC was required in 90 of 1,676 (5.4%) patients. Significant preoperative predictors of conversion were acute cholecystitis, increasing age, male sex, obesity, and thickened gallbladder wall found by ultrasound. Nonobese women younger than age 65 years with symptoms of biliary colic and normal gallbladder wall thickness found by preoperative ultrasound required conversion only 1.9% of the time. These predictors may be useful in planning a program of ambulatory or short stay surgical units for patients undergoing LC and for comparing data between series.

Age Factors↗
PubMed1994

The diagnostic value of CA 27-29, CA 15-3, mucin-like carcinoma antigen, carcinoembryonic antigen and CA 19-9 in breast and gastrointestinal malignancies.

In the past decade, considerable interest has arisen for defining the role of various tumor markers in the diagnosis of cancer. This cross-sectional study evaluates four breast cancer markers (CA 27-29, CA 15-3, MCA and CEA) and two gastrointestinal (GI) markers (CA 19-9 and CEA) in 213 patients. Receiver operating curves (ROC) revealed a sensitivity for the 90% specificity cutoff for breast cancers compared to breast benign diseases of 70% for CA 27-29, 67.5% for CA 15-3, 52.5% for MCA and 40% for CEA. When GI tumors were compared to benign GI disease, the sensitivity for 90% specificity was 40.3% for CEA and 32.3% for CA 19-9. Comparison of breast cancer and GI malignancies with other malignancies leads to a marked shift of the ROC curve to the right and loss of specificity. Late stage for all breast and GI tumor markers was found to be a predictor of high serum antigen level (p < 0.001). The presence of liver metastases in breast cancer was associated with abnormal levels of CA 27-29 (p = 0.028). Pancreas adenocarcinomas had a higher CA 19-9 antigen level (p < 0.001) than other GI malignancies. CA 27-29 appears to be at least as sensitive and specific as CA 15-3 in patients with breast cancer. None of the above markers retain their specificity when compared with a control group consisting of other malignancies.

Adult↗
PubMed1994

Screening for alcoholism in general hospitals.

In a recently completed study at the North Bay Psychiatric Hospital, a tertiary resource serving a population of about 600,000 in Northern Ontario, systematic screening on admission showed a very high proportion of past or present alcoholism. Fifty-seven percent of the patients were identified as having a life prevalence of (current or past) alcohol-related problems through a combination of a questionnaire and a liver function test. This figure is much higher than what is generally observed in mental hospitals. Does it reflect a widespread prevalence of alcoholism in Northeastern Ontario or is it distorted by the pattern of referral to the North Bay Psychiatric Hospital which typically serves an under-privileged segment of the population? In an attempt to answer this question, this study was carried out in general hospitals (medical and surgical wards). It confirms a higher prevalence of alcohol-related problems (biological, psychological and/or social) in Northern Ontario general hospitals, compared with Southern Ontario general hospitals, using identical methods of screening and assessment in both populations. The regional difference (odds ratio) is more evident in higher social classes. A diagnosis of alcohol abuse or dependence (currently active or in remission) was confirmed in 83.5% of the cases with positive screening who underwent the Diagnostic Interview Schedule (revised). This is a robust confirmation of the value of screening. These findings confirm the importance of systematic screening for alcoholism in general hospitals.

Adult↗
PubMed1994

The benefit of early treatment with immunosuppressive agents in lupus nephritis.

OBJECTIVE: In a cohort of 87 patients with lupus nephritis, delay between the detection of the onset of renal disease and renal biopsy was a significant predictor at the time of a first renal biopsy for subsequent renal insufficiency (relative risk - 4.9; 95% confidence interval = 1.7 to 14.5; p < 0.001) and death due to lupus renal involvement (relative risk = 6.7; 95% confidence interval = 2.1 to 21.2; p < 0.001). We evaluated the role of lead time bias, 2 variants of prognostic selection bias (length biased sampling), and the benefit of early treatment as explanations for this effect. METHODS AND RESULTS: Evaluation using the time of renal onset rather than the time of renal biopsy for the analysis suggested that lead time bias was unlikely to be an explanation for the effect of duration on renal insufficiency or death due to renal involvement. Identical values of age, serum creatinine and 24 hour urinary protein excretion at renal onset for those with a long duration versus short duration prior to biopsy, suggested that differences in prognostic selection were unlikely to explain the observed results. A 2nd type of prognostic selection bias arising from the failure to include patients who did not undergo a renal biopsy was further assessed by statistical simulation. The results of this approach indicated that prognostic selection bias was not solely responsible for the significant associations. Because treatment with high dose prednisone and immunosuppressive drugs was not instituted until a renal biopsy had been performed, delay in instituting these therapies remained a possible explanation for the increased frequency of renal insufficiency and death due to renal involvement observed in those with longer delays before renal biopsy. In addition, there was significant deterioration in serum creatinine (median change 0.6 mg/dl) and 24 hour urinary protein excretion (median change 2.5 gm) over the period from renal onset to renal biopsy, and significantly higher scores for the activity, chronicity and tubulointerstitial indices on renal biopsy in those in whom therapy was delayed. CONCLUSION: Prompt therapy with prednisone and immunosuppressive agents in lupus nephritis has a beneficial effect on longterm prognosis.

Adult↗
PubMed1994

Response to treatment as a predictor of longterm outcome in patients with lupus nephritis.

OBJECTIVE: To evaluate response to therapy over one year as a predictor of several longterm outcomes in lupus nephritis. METHODS: Response to treatment was evaluated by comparing serum creatinine and 24 h urine protein excretion at initial renal biopsy to those obtained after one year of treatment. Response at one year was evaluated as a predictor of renal failure, death due to lupus nephritis, and total lupus mortality, using survival analysis. RESULTS: Eighty-five patients with lupus nephritis diagnosed between 1967 and 1983 and followed through 1990 were studied. Change in proteinuria was a powerful predictor of renal failure (p = 0.001) death due to lupus nephritis (p < 0.001) and overall lupus mortality (p = 0.001). In contrast to a recent study of patients selected for severe lupus nephritis, serum creatinine was not found to be of prognostic significance. CONCLUSION: Response of proteinuria to treatment over one year is a useful predictor of longterm outcomes in lupus nephritis.

Adolescent↗