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Biomedical subjects

C Bombardier

Publications and source records attributed to C Bombardier.

At least 145 records · Page 8Linked to original sources
PubMed1988

Pathogenesis of hypotension in septic shock: correlation of circulating phospholipase A2 levels with circulatory collapse.

Circulating phospholipase A2 (PLA2) has been recognized as a mediator of circulatory collapse in experimental endotoxic shock. To assess the role of serum PLA2 in septic shock in man, we determined serum PLA2 profiles in a prospective study in 12 patients with septic shock. During the hypotensive phase of sepsis, serum PLA2 levels were consistently elevated as high as 33,428 U/ml (normal range 115 +/- 12 [SE]; n = 101). In all 12 patients, PLA2 levels correlated directly with the magnitude and duration of circulatory collapse (p less than .001), with a progressive fall of serum PLA2 levels during convalescence. In contrast, serum PLA2 levels in patients with cardiogenic shock secondary to myocardial infarction remained low. In pancreatitis, PLA2 levels paralleled fluctuations of serum amylase and lipase, whereas in septic shock without pancreatic involvement, PLA2 changes were discordant with changes in pancreatic enzymes. As well, septic shock serum PLA2 failed to crossreact by radioimmunoassay with antiserum against human pancreatic PLA2. These data are consistent with an extrapancreatic source of intravascular PLA2 release during sepsis. Since endogenous serum PLA2 levels correlate directly with the magnitude of hypotension in both experimental endotoxic shock and clinical septic shock, and since parenteral administration of purified exogenous PLA2 reproduces hypotension in experimental models, we conclude that high levels of intravascular PLA2 may contribute similarly to the circulatory collapse in septic shock in man.

Adult↗
PubMed1988

Concordance of endogenous cortisol and phospholipase A2 levels in gram-negative septic shock: a prospective study.

Lipocortins, a group of corticosteroid-induced phospholipase-inhibitory proteins, are thought to play a prominent role in the mediation of the anti-inflammatory effects of steroids. The synthesis and release of these proteins may represent a major endogenous mechanism of regulation of extracellular phospholipase A2 (PLA2) activity. Because soluble PLA2 activity has been associated with circulatory collapse in hyperphospholipasemic conditions, such as septic shock and pancreatitis, we examined the relationship between circulating PLA2 activity and adrenocortical function. In a prospective study of 10 episodes of septic shock, serum PLA2 and cortisol levels correlated significantly in all survivors (p less than 0.0001), whereas such a correlation was absent in all nonsurvivors (p less than 0.07). No significant correlation of cortisol and adrenocorticotropic hormone (ACTH), or PLA2 and ACTH, was found in any patient, suggesting that the stimulus for cortisol release arises from outside the hypothalamic-pituitary axis. These data suggest that, in human beings, the regulation of soluble PLA2 activity may be mediated by adrenocortical hormones, perhaps through the intermediary action of lipocortins.

Adrenocorticotropic Hormone↗
PubMed1988

Serum phospholipase A2 correlates with disease activity in rheumatoid arthritis.

We previously demonstrated a marked elevation of the proinflammatory enzyme phospholipase A2 (PLA2) in all synovial fluids and some sera of patients with rheumatoid arthritis (RA). Since PLA2 was found to induce inflammatory changes in the skin and joints of experimental animals, we tested whether the serum level of PLA2 correlates with the clinical activity of RA. In the group of 51 patients with classical or definite RA, 13 (25%) had high serum levels of PLA2 (over 2 standard deviations above the normal mean). Comparison of clinical disease activity in patients with high levels of PLA2 with those with normal PLA2 levels showed that patients with high PLA2 levels had a significantly higher joint count, more swollen joints, much higher Landsbury index, lower functional class, lower hemoglobin, lymphopenia and higher erythrocyte sedimentation rate (ESR). To more accurately assess the relationship between the PLA2 level and disease activity in RA, we formulated 2 indices. Clinical index consisted of the Landsbury index, number of swollen joints and duration of morning stiffness. Laboratory index consisted of hemoglobin, absolute number of peripheral blood lymphocytes, platelet count and ESR. Our results showed that both indices correlated strongly with PLA2 activity (p less than 0.0001). The results support the hypothesis that PLA2 plays a pathogenetic role in RA and suggest that serum PLA2 levels may serve as an additional measure of disease activity.

Adult↗
PubMed1988

Research challenges: overview of epidemiological study designs.

This paper provides an overview of the epidemiological techniques used in pharmacoepidemiology. Definitions, advantages and disadvantages of the various types of study design are presented and potential sources of bias are discussed. An important challenge and the source of major controversies is the evaluation of cause and effect relationships when exposure to a drug is associated with the occurrence of an adverse event; we present an established set criteria suggesting inferences about causation.

Cohort Studies↗
PubMed1988

An experiment in reducing interobserver variability of the examination for joint tenderness.

This experiment was designed to test the feasibility of reducing interobserver variability of the joint examination by agreement on a standard examination. Six rheumatologists independently examined 6 patients with rheumatoid arthritis (RA) in predetermined order, before and after a standardization of examination techniques. Results of an analysis of variance showed a reduction of the percent of variability due to observers from 13.8%, before standardization, to 3.2% after standardization, and an improvement in the percent variability related to patient differences from 70.7%, before standardization, to 86.3% after standardization. Such a reduction in observer variability has a potential for allowing a reduction in sample sizes required for RA clinical trials.

Analysis of Variance↗
PubMed1987

Sickle cell crisis following intraarticular steroid therapy for rheumatoid arthritis.

We describe 2 patients who had coexistent rheumatoid arthritis and sickle cell disease. Both patients developed sickle cell crises following intraarticular injection of corticosteroids to control their arthritis. The mechanism of this phenomenon is not clear, but it is suggested that intraarticular steroids be used with caution in patients with sickle cell disease.

Acute Disease↗
PubMed1987

Pathologic features of diabetic thick skin.

Skin thickening simulating scleroderma, or progressive systemic sclerosis, has previously been reported in children and adults with insulin-dependent diabetes mellitus. We have studied eighty-nine patients with insulin-dependent diabetes mellitus and twenty-five normal control subjects. Clinical evidence of skin thickening (diabetic thick skin) was found in 22% of patients with insulin-dependent diabetes mellitus and in 4% of control subjects (p less than 0.05). Full-thickness skin biopsy specimens were taken from the forearm of nine patients with insulin-dependent diabetes mellitus and diabetic thick skin, four patients with insulin-dependent diabetes mellitus and clinically normal skin, four patients with progressive systemic sclerosis, and four normal control subjects. The sections stained with hematoxylin and eosin showed increased thickness of the dermis of the forearm skin in all diabetic patients. In diabetic thick skin the collagen bundles were large, disorganized, and separated by clear spaces. Small amounts of acid mucopolysaccharides were present in the upper reticular dermis of five patients with diabetic thick skin. Electron microscopy of the dermis showed capillary basement membrane thickening in Groups 1, 2, and 3. All patients with diabetic thick skin showed active fibroblasts and extensive collagen polymerization in the rough endoplasmic reticulum. Occasional collagen flowers were noted in all patients with diabetic thick skin. Measurements of 100 collagen fibers in the upper and lower reticular dermis of each biopsy specimen showed predominance of large fibers (greater than 60 nm) in Groups 1 and 2. Unlike scleroderma, diabetic thick skin resulted in small fiber sizes (less than 60 nm) only rarely, and bimodality of fiber sizes was not seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Low dose cyclosporine in rheumatoid arthritis: a pilot study.

A 6 month open trial of cyclosporine (CyA) was conducted in 20 patients with active rheumatoid arthritis unresponsive to second line therapy. The dosage was monitored to achieve a serum blood level of 75-150 ng/ml. A 25% reduction in ARA joint count (baseline mean 38.2; 6 month or time of CyA withdrawal mean 28.7; p less than 0.001) was observed for all patients. Fifteen completed the 6 month CyA regimen and 5 developed toxicity requiring CyA to be permanently withdrawn. For the 15 patients completing 6 months of CyA, improvement was 36% (baseline 34.7; 6 month mean 22.2; p less than 0.001). Corresponding improvements were also observed on the other main study outcomes of pain and functional ability. Improvement occurred between 12-20 weeks, somewhat later than in other studies. Toxicity included mild hypertension (4 patients) and gastrointestinal intolerance (2). Three patients were withdrawn from CyA due to nephrotoxicity. There was a clinically significant reduction in calculated creatinine clearance but this returned to baseline within 6 months after CyA was withdrawn for all except 2 patients who took 12 months to return to baseline.

Adult↗
PubMed1987

Methodological considerations in functional assessment.

A large number of functional status assessments are currently available. Choosing among them can be difficult. Instruments vary widely in their content, detail of questions, type of scale and length of administration. In addition, some have undergone more extensive testing for reliability and validity than others. We have developed a checklist to compare and evaluate the usefulness of such instruments.

Disability Evaluation↗
PubMed1986

Measuring disease-specific quality of life in clinical trials.

While measurement of quality of life is a vital part of assessing the effect of treatment in many clinical trials, a measure that is responsive to clinically important change is often unavailable. Investigators are therefore faced with the challenge of constructing an index for a specific condition or even for a single trial. There are several stages in the development and testing of a quality-of-life measure: selecting an initial item pool, choosing the "best" items from that pool, deciding on questionnaire format, pretesting the instrument, and demonstrating the responsiveness and validity of the instrument. At each stage the investigator must choose between a rigorous, time-consuming approach to questionnaire construction that will establish the clinical relevance, responsiveness and validity of the instrument and a more efficient, less costly strategy that leaves reproducibility, responsiveness and validity untested. This article describes these options and outlines a pragmatic approach that yields consistently satisfactory disease-specific measures of quality of life.

Clinical Trials as Topic↗
PubMed1986

Auranofin therapy and quality of life in patients with rheumatoid arthritis. Results of a multicenter trial.

In a six-month, randomized, double-blind study at 14 centers, auranofin (3 mg twice daily) was compared with placebo in the treatment of patients with classic or definite rheumatoid arthritis. All patients had unremitting disease for at least the previous six months and at least three months of therapy with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, oral steroids, and analgesics were allowed throughout the trial. Efficacy was analyzed in 154 patients who received auranofin and 149 who received placebo. To reflect an expanded view of outcome assessment, the measures used included some 20 nontraditional measures of functional performance, pain, global impression, and utility (worth or value) in addition to five standard clinical measures of rheumatoid synovitis (e.g., number of tender joints). The nontraditional measures were mainly in the form of structured questionnaires administered by trained interviewers. To minimize the statistical problem of multiple comparisons, most of the measures were grouped into four composites--clinical (standard measures), functional, global, and pain--and the treatment effect for each composite was tested at the 0.0125 level of significance. Auranofin was superior to placebo in the clinical (p = 0.003), functional (p = 0.001), and global (p = 0.007) composites and trended similarly in the pain composite (p = 0.021). Individual measures within the composites consistently favored auranofin. Other measures, not part of the composites, also favored auranofin, including a patient utility measure designed for this study, the PUMS (p = 0.002). Results confirm the hypothesis that the favorable effect of auranofin on clinical synovitis is accompanied by improvements across a range of outcomes relevant to the patient's quality of life.

Adult↗
PubMed1985

Epidemiology of musculoskeletal disorders (complaints) and related disability in Canada.

Data on musculoskeletal disorders (complaints), collected as part of the Canada Health Survey were analyzed. Sixteen percent of those sampled reported having arthritis, rheumatism or back, limb or joint disorders with a greater prevalence among females and in the older population. In 21% this was associated with limitation of activity with an average of 11 disability days/person/year. Serious back disorders were reported in 4.4% of the population. While the majority of health consultations (53%) were with a physician, a substantial number (34%) were with chiropractors.

Adolescent↗
PubMed1983

The effectiveness of a regulatory strategy in containing hospital costs. The Ontario experience, 1967-1981.

This study documents the increases in real inputs (e.g., labor and equipment) employed in Ontario's hospital sector between 1968 and 1981--a period of universal government-financed hospital insurance and a government regulatory strategy involving global budgeting. Total expenditures in Ontario increased by only 16 per cent in terms of real inputs, as compared with an increase of 101 per cent in the United States. Real inputs per patient-day increased at a mean annual rate of 0.68 per cent in Ontario versus 5.19 per cent in the United States (P less than 0.001). Real inputs per admission decreased at a mean annual rate of 1.12 per cent in Ontario, as compared with an increase of 4.15 per cent in the United States (P less than 0.0001). We conclude that regulation can contain the growth of real inputs employed in the hospital sector even in the face of an incentive structure that does not promote cost consciousness on the part of patients or physicians. Although the effect of this strategy on the quality of care is unknown, so far it appears to have been politically acceptable in Ontario.

Budgets↗