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Biomedical subjects

J Sibley

Publications and source records attributed to J Sibley.

34 records · Page 2Linked to original sources

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↗

Destructive arthritis of the hip in a patient with Crohn's disease.

OBJECTIVE: Isolated destructive peripheral arthropathy is a rare complication of Crohn's disease. We describe the clinical course and radiographic findings of such a case. CLINICAL FEATURES: A 28-yr-old male presented to our chiropractic clinic with chronic left hip pain. The patient was known to have Crohn's disease. Five years earlier the gastrointestinal symptoms resolved with a brief course of prednisone. However, the left hip pain continued. A radiograph of the left hip was read as normal. Repeat radiograph, 2 yr later, revealed destructive changes of the left hip and, in retrospect, early destructive changes could be seen on the initial radiograph. INTERVENTION AND OUTCOME: The diagnosis, in this case, was destructive arthritis of the left hip secondary to Crohn's disease. The treatment selected in this case was observation and nonsteroidal anti-inflammatory drug use. CONCLUSION: This diagnosis, a relatively rare complication of Crohn's disease, should be considered in a young adult patient with Crohn's disease and persistent peripheral joint pain.

Adult↗