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Biomedical subjects

L Joseph

Publications and source records attributed to L Joseph.

At least 109 records · Page 6Linked to original sources

Remarks on the phylogeny and structure of fatty acid binding proteins from parasitic platyhelminths.

Four fatty acid binding proteins (FABPs) have been described in 4 parasitic platyhelminths: Schistosoma mansoni, Schistosoma japonicum, Fasciola hepatica and Echinococcus granulosus. FABPs form a multigenic family of cytosolic proteins widely distributed in metazoan tissues, the function of which is still poorly understood. These helminth proteins have recently received attention, since there are reports to indicate that S. mansoni and F. hepatica FABPs may be protective antigens. In addition, these proteins could play a major role in the parasites' life-cycles because platyhelminths are unable to synthesize de novo most of their lipids. We have undertaken phylogenetic and structural analyses of platyhelminth FABPs in an attempt to characterize features of biological relevance. Phylogenetically, these FABPs appear to be more closely related to those of vertebrate heart, mammary gland, muscle, retina, skin, brain and myelin, although no clear functional relationships were established between them. We describe several conserved motifs characteristic of specific groups of FABPs. Hydrophilicity, flexibility and accessibility analyses revealed several major putative epitopes for the E. granulosus FABP, EgDf1, that appear to be centred in loops of the EgDf1 3-dimensional structure modelled by molecular replacement.

Amino Acid Sequence↗

Role of CD44 in nonpalpable T1a and T1b breast cancer.

Primary infiltrating ductal carcinomas (IDCs) of the breast which measure less than 0.5 cm (T1a lesions) and between 0.5 and 1.0 cm (T1b lesions) are associated with a small risk of nodal metastasis. The role of axillary dissection in T1a and T1b breast cancer is controversial. In the absence of axillary dissection, comparable prognostic information might be obtained by examination of the primary cancer. The adhesion molecule CD44 represents a family of transmembrane proteins that mediate cell-cell and cell-matrix interactions. Previous investigators have correlated expression of CD44 and its isoforms with prognosis in breast cancer. We investigated the value of CD44 isoform expression as a predictor of nodal metastases in nonpalpable T1a and T1b IDC. Monoclonal antibody against the standard form of CD44 (CD44s) and polyclonal antibody directed against the variant isoform (CD44v6) was tested on 34 cases of nonpalpable node-negative infiltrating ductal carcinoma (IDC) less than 1.0 cm and 9 cases of nonpalpable node-positive IDC less than 1.0 cm. The expression of CD44s was significantly decreased in node-positive T1a and T1b IDC versus node-negative T1a and T1b IDC (11% vs 65%). In contrast, 97% of the node-negative IDC and 100% of the node-positive IDC expressed the CD44v6 isoform. We conclude that CD44s expression is significantly altered in T1a and T1b IDC with nodal metastases but that the CD44v6 isoform does not correlate with nodal metastases in nonpalpable stage T1a and T1b IDC.

Antigens, Neoplasm↗

Extension of receiver operating characteristic analysis to data concerning multiple signal detection tasks.

RATIONALE AND OBJECTIVES: When receiver operating characteristic (ROC) studies involve multiple detection tasks in the same patient, the correlations among the within-patient interpretations and the shortage of patients raise several analytic challenges. The authors propose methods for both parametric and nonparametric analysis of this type of data. METHODS: First, they computed one accuracy statistic for each task. Then one jackknife "pseudovalue" was calculated for each task and each patient. Then, they formed a summary index from the accuracy statistics and calculated the standard error of this summary index on the basis of the observed correlations among the jackknife pseudovalues. The method was extended to comparisons of two diagnostic systems and illustrated by using data from a clinical study. RESULTS AND CONCLUSION: This approach can be used with rating or quantitative data and with any index of accuracy, whether calculated parametrically or nonparametrically.

Angiography↗

Costs and effectiveness of extracorporeal gallbladder stone shock wave lithotripsy versus laparoscopic cholecystectomy. A randomized clinical trial. McGill Gallstone Treatment Group.

Thirty-five patients were randomized to extracorporeal shock-wave lithotripsy (ESWL) and 25 to laparoscopic cholecystectomy (LC). Stone disappearance occurred in only 12 of 32 ESWL patients [38% (95% CI: 21-56%)] during a 15-month follow-up. Greater incremental gains in quality of life after 6 months were observed among LC patients (p < .01). Total duration of disability was 6.8 +/- 8.5 days for ESWL, and 22.7 +/- 16.6 days for LC (p < .01). Nine (28%) patients crossed over electively to the LC group, but only 44% of these underwent LC within the next 3 years. ESWL cost Can $58.9/ day of disability saved. ESWL is limited by its selective applicability and modest stone disappearance rate. Its cost-effectiveness is largely dependent on patient acceptance of recurrent episodes of biliary colic due to the persistence of stone fragments.

Adolescent↗

Evaluation of aperture efficiency of a radiofrequency electric field strength meter antenna.

With present-day rapid increases in the applications of radiofrequency microwave radiation in research, medicine, defense, communications, and industry, it has become necessary to have simple inexpensive portable radiofrequency microwave field strength meters for health and safety surveys around operating equipment. This paper presents the results of a study conducted at Trombay calibrating grid to evaluate the receiving aperture efficiency of the 1-m long antenna of a simple narrow band electric field strength meter, with frequency response centered around 27.12 MHz. An aperture efficiency of 0.47 with a coefficient of variation of +/-3.46% is considered adequate for field use.

Health Physics↗

A controlled study of diffuse idiopathic skeletal hyperostosis. Clinical features and functional status.

Diffuse idiopathic skeletal hyperostosis (DISH) is a common but little-studied disorder in the elderly that is infrequently recognized by physicians. Its prevalence in adults over 40 years of age is estimated at 3.8% for men and 2.6% for women. The present case-control study evaluated the history of pain and stiffness, radicular pain and enthesitis, physical findings on the musculoskeletal examination, and level of physical and psychologic disability in 130 persons: 56 patients with DISH, 43 control patients with spondylosis of the lumbar spine, and 31 healthy control patients. DISH patients were more likely to report a past history of upper extremity pain, medial epicondylitis of the elbow, enthesitis of the patella or heel, or dysphagia than spondylosis patients. They had more extremity and spinal stiffness and pain than healthy controls. DISH patients weighed more at a young age and their body mass index was greater at the time of the clinical evaluation than either spondylosis or healthy control patients. On musculoskeletal examination, DISH patients had a greater reduction in neck rotation and thoracic movements than either spondylosis patients or healthy controls, and had a greater reduction in lumbar movement than healthy controls. DISH patients had similar levels of spinal disability and physical disability overall, as measured by standardized indices, as spondylosis patients. No differences were found among the 3 groups of patients for the laboratory tests evaluated. DISH is clearly a distinct disorder with signs and symptoms that distinguish it from other causes of spinal complaint and from healthy individuals. It has the potential to cause major disability. Future studies need to address the natural history of DISH, pursue pathogenic mechanisms, and evaluate treatment modalities.

Activities of Daily Living↗

Spatial relationships in early signaling events of flow-mediated endothelial mechanotransduction.

Blood flow interactions with the vascular endothelium represent a specialized example of mechanical regulation of cell function that has important physiological and pathological cardiovascular consequences. The endothelial monolayer in vivo acts as a signal transduction interface for forces associated with flowing blood (hemodynamic forces) in the acute regulation of artery tone and chronic structural remodeling of arteries, including the pathology of atherosclerosis. Mechanisms related to spatial relationships at the cell surfaces and throughout the cell that influence flow-mediated endothelial mechanotransduction are discussed. In particular, flow-mediated ion channel activation and cytoskeletal dynamics are considered in relation to topographic analyses of the luminal and abluminal surfaces of living endothelial cells.

Animals↗

Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus. Why some tests fail.

OBJECTIVE: To evaluate whether changes in laboratory test values are either simultaneous with or precede disease exacerbations in patients with systemic lupus erythematosus (SLE). METHODS: At 9, 6, and 3 months preceding a flare in disease activity (defined as a rise of > or = 6 points in the modified SLE Disease Activity Index), laboratory tests were performed to measure patients' hematocrit levels, white blood cell, lymphocyte, and platelet counts, erythrocyte sedimentation rate, C1q binding, DNA binding, and levels of C3 and C4. Flares were classified as either present or absent, and were divided into renal, vasculitic, central nervous system, skin, serosal, and musculoskeletal subgroups. The predictive patterns were 1) the simultaneous change in the test value from the mean of 9, 6, and 3 months preceding a flare to the time of the flare; 2) the gradual change, following a linear time trend, in test results for the same time points; and 3) the change from the mean of 9 and 6 months to 3 months preceding a flare, as a measure of predictive ability. These analyses used repeated-measures analysis of variance models. Multiple linear regression was used to study the cross-sectional association of average-over-time differences in test results with patients' flare subgroup. RESULTS: Among 202 patients with SLE (median followup 86.5 months), 83 flares occurred in 53 patients. Of 189 statistical contrasts performed, only 14 were significant (versus 10 expected), and the differences were of minor importance. Nonetheless, evaluation of all test results over each patient's observed disease course revealed significant differences between selected test values in association with specific types of flare. CONCLUSION: Fluctuations in laboratory test values are poor predictors of disease exacerbations in SLE. Cross-sectional evaluation of some test results revealed differences at the time of flare for those patients who were destined to have different types of flares, because these values differed over the entire study period. This pattern explains the frequent cross-sectional association of disease activity with laboratory test results, and the inconsistent association of flares with recent changes in test values.

Adolescent↗

Relationship between dietary intake and coronary heart disease mortality: lipid research clinics prevalence follow-up study.

The diet-heart hypothesis proposes that elevated intakes of total fat, saturated fat, and dietary cholesterol raise serum cholesterol, which in turn increases the risk of developing coronary heart disease (CHD). To examine the relationship between dietary intake and 12-year CHD mortality we used data from the Lipid Research Clinics Prevalence Follow-Up Study. Dietary intake was measured at study entry using the 24-hour recall technique among 4546 North American men and women who were at least 30 years old and initially free of CHD. Proportional hazards analyses controlling for total energy intake indicated that increasing percentages of energy intake as total fat (RR 1.04, 95% CI = 1.01-1.08), saturated fat (RR 1.11, CI = 1.04-1.18), and monounsaturated fat (RR 1.08, CI = 1.01-1.16) were significant risk factors for CHD mortality among 30 to 59 year olds. The increasing percentage of energy intake from carbohydrate had a significant protective effect (RR 0.96, CI = 0.94-0.99). The strength of these associations was not diminished after adjustment for specific serum lipids, suggesting that serum lipids did not mediate the effect of diet on CHD mortality. None of the dietary components were significantly associated with CHD mortality among those aged 60-79 years. We conclude that future research must be directed toward better understanding the pathway between dietary intake and coronary disease as the current diet-lipid-heart hypothesis may be overly simplistic.

Adult↗

Technology assessment in laparoscopic general surgery and gastrointestinal endoscopy: science or convenience?

Gastrointestinal endoscopy and laparoscopic general surgery have been significantly affected by the emergence of new techniques. These two disciplines share many similarities, including the use of sophisticated and expensive technologies. Their proper assessment is essential because they are developed amidst ever-decreasing health care budgets. Gastroenterologists and general surgeons must both participate in such evaluations and feel confident in interpreting pertinent published data. The present review uses a clinician's point of view with relevant examples to discuss the methodologies adopted in technology assessment and to highlight common pitfalls encountered in study design, patient selection, timing and selection of the study, blinding, and outcome measurement. Cost and statistical considerations, as well as ethical issues, are also reviewed in the context of technology assessment.

Costs and Cost Analysis↗

Effects of age on energy expenditure and substrate oxidation during experimental overfeeding in healthy men.

Relatively little is known about the influence of age on energy regulation during energy imbalance. We compared the effects of overfeeding on changes in energy expenditure, substrate oxidation, and energy deposition between young men (age 23.7 +/- 1.1 [SEM] years) and older men (age 70.0 +/- 7.0) of normal body weight who were leading unrestricted lives. Changes in total energy expenditure, resting energy expenditure (REE), the thermic effect of feeding (TEF), respiratory quotient (RQ), and body energy content were determined in response to overeating by 4.09 +/- 0.07 Megajoule (MJ)/day for 21 days in 16 healthy subjects consuming a typical diet. After excluding data from one young subject with unusual results and adjusting for individual differences in excess energy intake, there was a tendency towards a smaller increase in REE in older men compared to the young men (p = .07) which was accounted for by their lower fat-free mass (p = .016). There was also a significantly smaller increase in resting energy expenditure averaged over fasting and fed states (i.e, REE + TEF) with overfeeding in older men than in young men (p < .01). Combined, these smaller increases in energy expenditure with overfeeding in the older subjects averaged an estimated 365 kilojoule (kJ)/day (8.9% of the excess energy intake) (p < .02). There were also significant effects of age on fasting RQ (p < .001) and the change in RQ with overfeeding (p < .001), but no significant increase in energy expenditure for physical activity and thermoregulation with overfeeding in either age-group. These results are consistent with the suggestion that older individuals experience both a reduction in the ability to increase energy expenditure, and an alteration in the pattern of substrate utilization, in response to overfeeding. These changes may promote cumulative increases in body energy during normal cycles of positive energy balance unless compensated for by adaptive variations in energy intake.

Adult↗

Usual dietary salt intake and asthma in children: a case-control study.

BACKGROUND: A decline in host resistance due to an alteration in diet--primarily of salt--was recently put forward as a possible explanation for rising rates of asthma. METHODS: A case-control study was conducted in participants in a prevalence survey which included 187 children with asthma (defined by prior diagnosis and/or a decline in forced expiratory volume in one second (FEV1) of > or = 10% after exercise) and 145 age and sex matched controls. Subjects were selected from 989 children aged 5-13 years attending 18 elementary schools on the island of Montreal. Usual dietary salt intake was estimated from a food frequency questionnaire administered to the mother, and a salt intake score was used to group the children into quartiles from I (lowest) to IV (highest salt intake). Bronchial hyperresponsiveness to methacholine was assessed by Yan's method. Cases and controls were combined in one group to examine the relationship of salt intake to bronchial hyperresponsiveness to methacholine. Methacholine responsiveness was expressed as a dose-response slope and ranks of dose-response slopes were used in the analysis. RESULTS: After accounting for important confounding variables, there was no association between asthma and salt intake, while methacholine dose-response slope ranks increased with increasing salt intake and methacholine responsiveness was greater in the highest quartile than in the lowest quartile of salt intake. The median dose-response slopes in % fall in FEV1 per mumol methacholine for quartiles I, II, III, and IV were 5.4, 5.9, 7.7, and 8.7. CONCLUSIONS: No association was found between asthma or exercise-induced bronchospasm and dietary salt intake. Bronchial hyperresponsiveness to methacholine did, however, appear to increase with greater salt intake, but the relevance of this association to asthma is unclear.

Adolescent↗

[Significance of organ donor characteristics in renal function at 1 month: reflection on the allocation of renal transplant].

In a series of 731 kidneys taken from brain-dead donors for renal transplantation, 652 were grafted, and the renal function at 1 month is known for 490 of them. The results show that some donor-related factors influence the outcome of the transplant. In particular, haemodynamic instability refractory to medical treatment is responsible for a 50 mumol increase of serum creatinine one month after transplantation and the use of UW solution during organ collection is responsible for an improvement of serum creatinine compared to other preservation solutions. Haemodynamic instability is a criterion which must be added to those already demonstrated in donors, such as the cause of death, age and sex. The authors propose that donor-related factors be taken into account in the allocation of organs in the same way as immunological factors which, at the present time, constitute the only criterion for kidney allocation.

Adolescent↗

[The competence of family physicians in caring for dementia patients. A survey of general practitioners in Quebec].

OBJECTIVE: To assess the knowledge and skills of general practitioners in Quebec with respect to persons with dementia. DESIGN: A questionnaire containing 47 multiple-choice questions on aptitude and nine questions on practice profiles and demographics. SETTING: Province of Quebec. PARTICIPANTS: Twelve hundred general practitioners selected randomly. MAIN OUTCOME MEASURES: Performance with respect to the questionnaire's four objectives: to rate background knowledge, to evaluate physicians' knowledge of the assessment and treatment of dementia, to assess follow-up, and to assess interpersonal skills. RESULTS: Average performance on the questionnaire was 64.7%, with a standard deviation of 11.79%. Performance did not differ markedly from one objective to the next. Most respondents were male (61.6%), working in urban settings (61.7%). Most (72.5%) were between 25 and 44 years, and 44.7% had between 6 and 15 years' experience. About half (44.7%) belonged to group practices, 43.8% worked in acute care hospitals, and 20.6% worked in extended care hospitals. CONCLUSIONS: Quebec general practitioners have average ability to care for patients with dementia. Continuing education should focus on increasing physicians' knowledge of dementia, especially for those with the lowest scores; physicians 55 years and older, those practising alone, and those who spend less than 60% of their practice time with elderly patients.

Adult↗