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J Sibley

Publications and source records attributed to J Sibley.

At least 19 recordsLinked to original sources

Apophysial joint degeneration, disc degeneration, and sagittal curve of the cervical spine. Can they be measured reliably on radiographs?

STUDY DESIGN: Interexaminer reliability study. OBJECTIVES: To determine the reliability of grading apophysial joint and disc degenerative changes and the reliability of measuring sagittal curves on lateral cervical spine radiographs. SUMMARY OF BACKGROUND DATA: Several authors have proposed that the presented of degenerative changes and the absence of lordosis in the cervical spine are indicators of poor recovery from neck injuries caused by motor vehicle collisions. The validity of those conclusions is questionable because the reliability of the methods used in their studies to measure the presence of degenerative changes and the absence of lordosis has not been determined. METHODS: Kellgren's classification system for apophysial joint and disc degeneration, as well as the pattern and magnitude of the sagittal curve on 30 lateral cervical spine radiographs were assessed independently by three examiners. RESULTS: Moderate reliability was demonstrated for classifying apophysial joint degeneration with an intraclass correlation coefficient of 0.45 (95% confidence interval, 0.09-0.71). Classifying degenerative disc disease had substantial reliability, with an intraclass correlation coefficient of 0.71 (95% confidence interval, 0.23-0.88). Measuring the magnitude of the sagittal curve from C2 to C7 had excellent interexaminer agreement, with an intraclass correlation coefficient of 0.96 (95% confidence interval, 0.88-0.98) and an interexaminer error of 8.3 degrees. CONCLUSIONS: The classification system for degenerative disc disease proposed by Kellgren et al and the method of measurement of sagittal curves from C2 to C7 demonstrated an acceptable level of reliability and can be used in outcomes research.

Analysis of Variance

An evidence-based approach to prescribing NSAIDs in musculoskeletal disease: a Canadian consensus. Canadian NSAID Consensus Participants.

OBJECTIVE: To make recommendations for the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) in primary care practice, particularly for patients at high risk for NSAID-induced complications. OPTIONS: The use of misoprostol to prevent gastrointestinal ulceration and other unwanted NSAIDs effects was considered. The role of cyclooxygenase-2 (COX-2) versus COX-1 inhibiting agents was also examined. OUTCOMES: Reduction of complications associated with long-term use of NSAIDs. EVIDENCE: Evidence was gathered in late 1995 from published research studies and reviews. Position papers were prepared by faculty and advisory board members and discussed at the Canadian NSAID Consensus Symposium in Cambridge, Ont., Jan. 26 and 27, 1996. VALUES: Recommendations were based on randomized, placebo-controlled clinical trials (level I evidence) and case-control studies (level II evidence) involving NSAID use when such evidence was available. When the scientific literature was incomplete or inconsistent in a particular area, recommendations reflect the consensus of the participants at the symposium (level III evidence). Physicians were recruited from across Canada for their expertise in rheumatology, gastroenterology, epidemiology, gerontology, family practice, and clinical and basic scientific research. BENEFITS, HARMS AND COSTS: Although a reduction in complications due to inappropriate NSAID use should reduce costs of additional investigations, admissions to hospital and time lost from work, definitive cost analysis studies are not yet available. RECOMMENDATIONS: Currently, no NSAID is available that lacks potential for serious toxicity; therefore, long-term use of NSAIDs should be avoided whenever possible, particularly in high-risk patients (e.g., those who are elderly, suffer from hypertension, congestive heart failure, renal or hepatic impairment or volume depletion, take certain concomitant medications or have a history of peptic ulcer disease) (level I evidence). If NSAIDs are to be used in patients with gastric or nephrotoxic risk factors, the lowest effective dose of NSAID should be used (level III evidence); NSAIDs that are weak COX-1 inhibitors may be preferred (level II evidence). In addition, concomitant administration of misoprostol is recommended in patients at increased risk for upper gastrointestinal complications (level I evidence). However, the clinical judgement of the practising clinician must always be part of any therapeutic decision. VALIDATION: These recommendations are based on the consensus of Canadian experts in rheumatology, gastroenterology and epidemiology, and have been subjected to external peer review.

Anti-Inflammatory Agents, Non-Steroidal

Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug-based treatment strategies.

OBJECTIVE: Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional "pyramid" approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs (DMARDs), in the hope of improving long-term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long-term functional outcomes. METHODS: We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with > or = 1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D-penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ). RESULTS: Increased DMARD use was strongly associated with better long-term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)-positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0-3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0-4, 5-9, 10-14, 15-19, and 20+ years). "Control" correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal anti-inflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R2 of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDS more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30 percent reduction in long term disability with consistent DMARD use, are most likely conservative. CONCLUSION: An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data.

Antirheumatic Agents

Laboratory tests.

Despite impressive advances in our understanding of the natural history of the rheumatic diseases and their treatments, there remains much to be learned. The management of most of these diseases is far from satisfactory for either the clinician or patient. There is little distinction between clinical practice and clinical research. How much and what type of data one should collect clearly depends on the setting and on the clinical/research questions being asked. One must ensure that the literature is relevant to his or her practice. The corollary is that research must be derived from a variety of settings, including both the traditional researcher and the traditional clinician.

Biochemistry

Outcome in patients with rheumatoid arthritis receiving prednisone compared to matched controls.

OBJECTIVE: To determine the longterm outcome including disease activity, mortality, and adverse events in patients with rheumatoid arthritis (RA) treated with prednisone. METHODS: A case-control study was performed, based on our cohort of 893 mostly Caucasian patients with adult onset RA, followed since 1966. Data collection was based on protocols and included single physician global assessment. Prednisone was started in 122 patients (85 women, 37 men) after 1966. All were matched for age, sex, disease duration, and global assessment to 122 controls from the same cohort who have never received prednisone. RESULTS: Mean disease duration before prednisone was 14.1 years. Mean duration of use was 6.9 years with a mean dose of 8.0 mg/day. Prednisone was eventually stopped in 34% of patients. Life expectancy and causes of death were similar in both groups. No differences in hemoglobin, erythrocyte sedimentation rate, global assessment, Lansbury index, functional class or Health Assessment Questionnaire (HAQ) disability index were seen between the 2 groups before or 5 years after starting prednisone. Ten years after starting prednisone, HAQ scores were similar but Lansbury and global assessment were worse in the prednisone treated group. As expected, adverse events, notably cataracts and fractures, were observed more often in the prednisone group. CONCLUSION: Case-control matching can only reduce, not eliminate, potential selection bias. Nonetheless, the lack of demonstrable longterm benefit with prednisone use in this and other studies is disconcerting. Caution and further studies are required before the more aggressive use of longterm prednisone therapy in RA is embraced.

Adolescent

Radiological progression in rheumatoid arthritis: how many patients are required in a treatment trial to test disease modification?

OBJECTIVE: To determine whether the number of patients required in a therapeutic trial that uses progression of radiological abnormalities as the outcome measure would be similar for multiple centres. METHODS: The progression of radiological damage to the fingers and wrists of patients with rheumatoid arthritis in five centres, three in North America and two in Europe, was examined. The reproducibility of repeated readings by the same and multiple observers was examined. The number of patients required in a two group trial was calculated for several combinations of power and significance. RESULTS: Scoring progression of radiological abnormalities in sequential films taken between 0.5 and 2.1 years was found to be highly reproducible. When the scores of a single reader were used the rate of change of radiological scores was similar in all centres. Based on the mean progression rate for all centres it was estimated that 153 patients in each group would be required to assure 90% power for detecting a 50% slowing of radiological progression at a significance of 0.05. Review of the experience in three trials showed a large variability in the radiological progression rates. CONCLUSION: The progression of scores for radiological damage in rheumatoid arthritis is relatively uniform in North America and Europe and thus the number of patients required in a trial would be similar. Experience in three trials showed that patient selection is of paramount importance in setting up a successful study.

Adult

Polymyositis with plasma cell infiltrate in essential mixed cryoglobulinaemia.

A patient with essential cryoglobulinaemia who presented with polymyositis is described. Muscle biopsy showed intense plasma cell infiltration of muscle. Plasmapheresis produced a rapid resolution of the cutaneous manifestations of the disease, but little improvement in muscle strength. Oral steroids resulted in moderate improvement in muscle strength. There have been no previously reported cases of polymyositis in association with essential cryoglobulinaemia.

Administration, Oral

Cardiac abnormalities in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the prevalence of cardiac abnormalities in patients with systemic lupus erythematosus. DESIGN: Prospective survey. SETTING: Rheumatic diseases unit of a university hospital. PATIENTS: Volunteer sample comprising 83% of patients with systemic lupus erythematosus followed annually in the rheumatic disease unit (93 patients; mean age 46 +/- 13 years; female 79, male 14). These patients were age-matched with 16 female control volunteers (mean age 43 +/- 5 years) recruited from hospital staff. INTERVENTIONS: Electrocardiograms, two-dimensional echocardiograms and radionuclide angiograms were performed in patients and controls. Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay in the systemic lupus erythematosus patients. MAIN RESULTS: At least one cardiac abnormality was detected in 44 of 93 systemic lupus erythematosus patients (47%). These abnormalities included: aortic valve thickening 12%; mitral valve thickening, prolapse, vegetations or stenosis 23%; left ventricular segmental dysfunction 4%; left ventricular global hypokinesis 4%; right ventricular hypokinesis 4%; left ventricular hypertrophy 14%; left ventricular diastolic dysfunction 16%; and pericardial effusion 2%. Three of the 16 controls (19%) had cardiac abnormalities consisting of mitral valve prolapse (one), right ventricular hypokinesis (one) and pericardial effusion (one). Cardiac abnormalities were more common in the systemic lupus erythematosus group compared with controls (47% versus 19%, P less than 0.05). Raised anticardiolipin antibodies were specific (88%) but not sensitive (33%) for the presence of cardiac abnormalities in systemic lupus erythematosus patients. Renal disease and prednisone therapy were more common in systemic lupus erythematosus patients with cardiac involvement than in such patients without evidence of cardiac disease (40% versus 16%, P = 0.03; and 81% versus 59%, P = 0.04, respectively). CONCLUSIONS: Cardiac abnormalities can be identified noninvasively in 47% of patients with systemic lupus erythematosus.

Adult

Ultrastructural analysis of the endothelial-pericyte relationship in diabetic cutaneous vessels.

The microvessels in the buttock skin of 15 patients with long-standing juvenile diabetes were studied both by electron microscopy and three-dimensional (3D) computer reconstruction of a prototypical diabetic postcapillary venule. Endothelial cell gaps were found in postcapillary venules and capillaries, but only in association with an increased deposition of basement membrane-like material in the vascular wall. In parallel with the increased amounts of deposited basement membrane-like material, the space between pericytes and endothelial cells was wider and the cytoplasmic processes that formed the contact points between them were longer and thinner than normal. Pericytes, devoid of any cytoplasmic contacts with the underlying endothelial cells, were observed as isolated cells within the outer third of the vascular wall in markedly thickened vessels. These observations offer an explanation for the known increased vascular permeability of diabetic vessels, and suggest a possible explanation for the development of diabetic retinopathy with aneurysm formation.

Adolescent

Ultrastructural and three-dimensional analysis of the contractile cells of the cutaneous microvasculature.

The three-dimensional relationships between smooth muscle cells and endothelial cells and between pericytes and endothelial cells in four segments of the microcirculation were analyzed by computer reconstructions from serial electron micrographs. In elastic-containing arterioles, the smooth muscle cells formed an inner longitudinal layer above and parallel to the elastica and an outer spiral layer. In the terminal arterioles the two layers of smooth muscle cells and elastica were replaced by a single smooth muscle cell that completely encircled the endothelial cell tube. The pericytes in the post-capillary venules completely encircled and gripped the endothelium through multiple contact points from their lateral processes. In the large venules the pericytes only partially encircled the endothelial cell tube and were more randomly placed.

Adult

A study of the veil cells around normal, diabetic, and aged cutaneous microvessels.

The veil cells around normal, diabetic, and aged vessels were reconstructed in 3 dimensions by a computer graphics system from 120-140 serial ultrathin sections. The normal vessel was surrounded by a single layer of veil cells which had a wrinkled and pleated surface. The diabetic vessels were surrounded by 3-6 layers of cellular material produced by increased numbers of veil cells and their associated cytoplasmic sheets. The veil cells around aged vessels appeared to have the same length as young and diabetic veil cells but were underdeveloped in their lateral extensions so that they did not cover the vessel circumferentially as well as did the normal veil cells. Preliminary data suggest that young, diabetic, and aged veil cells have the same metabolic activity per unit area of cytoplasm and are of the same length. The abnormal thickness or thinness of the vascular wall of dermal microvessels appears to be related to the degree of development and numbers of veil cells around the vessels rather than any change in their basic metabolic activity from normal.

Adult

The response of psoriatic epidermis and microvessels to treatment with topical steroids and oral methotrexate.

In a previous paper we showed that the microvessels in a psoriatic plaque as studied by electron microscopy returned to normal before the labeling index of the basal cells did during successful therapy with PUVA or the Goeckerman treatment. In this paper we studied the same parameters in 4 additional psoriatic patients: 2 received oral methotrexate and 2 were treated with a topical steroid under plastic wrap occlusion. The labeling index of the basal cells returned to normal in 3 and near normal in 1. The histologic features of the psoriatic epidermis became normal except for mild to moderate acanthosis, but the capillary loops in the dermal papillae retained their venous capillary ultrastructure and showed no signs of reversion to a normal arterial capillary configuration. The lack of response of the dermal capillaries to the topical steroid and oral methotrexate during the initial clinical improvement raises the possibility that the clinical relapses in psoriasis which may promptly follow discontinuation of topical steroid therapy and oral methotrexate may be related to an inability of these drugs to restore the microvasculature to normal in such situations.

Administration, Oral

Role of the microcirculation in the treatment and pathogenesis of psoriasis.

Controversy exists whether the initiating events in psoriasis are primarily epidermal or dermal (vascular). To study this point, serial biopsies from 6 patients were taken from the periphery of individual plaques before, and at 1 to 3 day intervals during, Goeckerman and PUVA treatments. Part of the biopsy was studied by electron microscopy to determine the fine structure of the capillary loops and part was incubated with tritiated thymidine to determine the labeling index (LI) of the basal cells. Normal appearing buttock skin of the 11 other psoriatic patients not under treatment was studied by identical methods. In 4 of the 6 treated patients, the capillary loops began to return toward normal 3 to 8 days before the LI began to decrease. Two patients did not show a return toward normal of either capillaries or LI during the period of the experiment. The LI was elevated in the normal appearing buttock skin of 6 of 11 untreated psoriatics. In 4 of the 6, the loops were normal arterial capillaries. We did not observe abnormal (venous) capillaries associated with a normal LI in the other 5 untreated patients. These data support the concept that the initiating factors in psoriasis are in the epidermis, but epidermal hyperplasia cannot occur without vascular proliferation. Understanding the factors responsible for shortening the capillary loops during epidermal normalization and for inhibition of capillary growth in the presence of an increased LI could lead to other ways of controlling psoriasis.

Autoradiography