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Biomedical subjects

W G Barr

Publications and source records attributed to W G Barr.

At least 19 recordsLinked to original sources
PubMed2003

Hematopoietic stem cell transplantation for systemic sclerosis with rapid improvement in skin scores: is neoangiogenesis occurring?

Systemic sclerosis (SSc) is presumed to be an immune-mediated vasculopathy of unknown etiology. SSc is unresponsive to most immune-modulating therapies except for intravenous cyclophosphamide, which is reported to demonstrate some benefit. We, therefore, dose-escalated cyclophosphamide to 200 mg/kg and added rabbit ATG 7.5 mg/kg along with infusion of unselected hematopoietic stem cells to minimize the cytopenic interval. Engraftment occurred rapidly (day 8) with minimal unexpected toxicity, no infections, and unexpectedly rapid improvement in the modified Rodnan Skin Score.

Antilymphocyte Serum↗
PubMed2001

Open trial of leflunomide for refractory psoriasis and psoriatic arthritis.

Leflunomide was recently approved for the treatment of rheumatoid arthritis. Its role in the treatment of psoriasis and psoriatic arthritis is unclear. Twelve consecutive psoriatic arthritis patients who had not responded to at least one disease modifying anti-rheumatic drug (DMARD) were started on leflunomide alone or in addition to another DMARD. Global assessment of improvement in psoriasis and psoriatic arthritis by the treating rheumatologist was scored on a 0-3 scale. After 2-3 months of treatment, 8 patients had moderate to marked improvement in both psoriasis and psoriatic arthritis. The improvement in modified tender joint counts, patient's global assessments, and grip strengths was statistically significant. However, physicians' global assessments and the modified swollen joint counts did not reach a significant difference. Three patients whose toxicity necessitated the temporary discontinuation of the drug were able to resume the drug at lower dosage with clinical benefit. Leflunomide may prove to be a useful agent for the treatment of recalcitrant cases of psoriasis and psoriatic arthritis.

Journal Article↗
PubMed1998

Managing diabetes during glucocorticoid therapy. How to avoid metabolic emergencies.

Although glucocorticoid therapy carries a risk of promoting or exacerbating hyperglycemia, there are currently no established medical guidelines for detecting or managing diabetes in patients starting such therapy. The authors use three case reports to illustrate a relatively simple strategy that can be used to manage preexisting and new-onset diabetes in the primary care setting.

Aged↗
PubMed1993

In situ expression of cytokines and cellular adhesion molecules in the skin of patients with systemic sclerosis. Their role in early and late disease.

Cytokines and cellular adhesion molecules (CAMs) may play a role in the inflammatory and fibrotic processes underlying systemic sclerosis (SSc). We compared the immunohistological distribution of cytokines and CAMs in skin biopsies from 12 SSc patients and 14 normal (NL) individuals. Among CAMs, vascular cell adhesion molecule-1 (VCAM-1), which mediates leukocyte-endothelial adhesion, showed increased expression on SSc versus NL endothelium and stratum granulosum. P-selectin was up-regulated in SSc versus NL stratum granulosum. The CD44 lymphocyte homing receptor showed the most striking differences between SSc and NL: its expression was increased in SSc stratum granulosum, stratum spinosum, on lymphocytes, and macrophages. Regarding cytokines, interleukin-6 (IL-6) expression was increased on SSc versus NL endothelium and fibroblasts. Tumor necrosis factor-alpha (TNF-alpha) reactivity was more prevalent in SSc than NL stratum granulosum, whereas IL-8 expression was higher on SSc compared to NL endothelium. Some CAMs, such as VCAM-1 and P-selectin, and cytokines, namely TNF-alpha and IL-8, were more commonly found in skin biopsies taken from early (< or = 1 year's duration) SSc, while others, such as IL-6, showed up-regulation in the late stage of the disease. The results suggest that certain CAMs and cytokines may play a differential role in both the early, inflammatory, and the late, fibrotic stage of SSc.

Adult↗
PubMed1993

Acute gouty arthritis. Modern approaches to an ancient disease.

The principles governing the pathogenesis and treatment of gout have been established with greater clarity than those for almost any other rheumatic disease. The benefits of treatment include the virtual cure of a disabling and deforming disease. Adherence to proper management guidelines provides predictable relief of symptoms for patients and great satisfaction for the treating physician.

Acute Disease↗
PubMed1992

Heterotopic ossification presenting as acute arthritis.

We describe a patient with acute myeloblastic leukemia in remission who developed painful, swollen knees 6 weeks after being ventilated for acute respiratory distress syndrome. Synovial fluid analysis was nondiagnostic and initial radiographs of his knees were normal. Repeat radiographs 5 weeks later showed periarticular calcification and the diagnosis of heterotopic ossification was made. Heterotopic ossification should be part of the differential diagnosis of acute arthritis in critically ill patients.

Acute Disease↗
PubMed1992

Treatment of systemic sclerosis with extracorporeal photochemotherapy. Results of a multicenter trial.

BACKGROUND AND DESIGN: In a pilot study of extracorporeal photochemotherapy, two patients with systemic sclerosis who received this therapy experienced significant clinical improvement. These results prompted the development of a multicenter trial to examine the benefit of extracorporeal photochemotherapy in the treatment of systemic sclerosis. Seventy-nine patients with systemic sclerosis of recent onset (mean symptom duration, 1.83 years) and progressive skin involvement during the preceding 6 months entered a randomized, parallel-group, single-blinded clinical trial comparing extracorporeal photochemotherapy treatments given on 2 consecutive days monthly with treatment with D-penicillamine at a maximum dose of 750 mg/d. Blinded clinical examiners evaluated skin severity score (thickness), percent surface area involvement, oral aperture, and hand closure. Serial skin biopsies and pulmonary function studies were also performed. RESULTS: Following 6 months of treatment, significant improvement in skin severity score occurred in 21 (68%) of 31 patients receiving photochemotherapy and in eight (32%) of 25 receiving D-penicillamine treatment, while significant worsening occurred in three (10%) of 31 receiving photochemotherapy and in eight (32%) of 25 receiving penicillamine treatment, thus indicating a significantly higher response rate for individuals who received photochemotherapy (P = .02). At both the 6- and 10-month evaluation points, the mean skin severity score, mean percent skin involvement, and mean oral aperture measurements were significantly improved from baseline among those who received photochemotherapy. Mean right and left hand closure measurements had also improved significantly by 10 months of therapy. By comparison, among the patients treated with D-penicillamine, none of the parameters of cutaneous disease had improved significantly after 6 months of therapy, although for those individuals in whom treatment was continued, the mean skin severity score and mean percent skin involvement had improved by 10 months. Skin biopsy studies revealed a correlation between clinical improvement and decreased thickness of the dermal layer. Adverse effects of extracorporeal photochemotherapy were minimal and did not require discontinuation of treatment in any of the patients receiving this therapy; six patients permanently discontinued the use of D-penicillamine treatment due to adverse effects. CONCLUSIONS: For patients with systemic sclerosis of recent onset, extracorporeal photochemotherapy is a well-tolerated treatment that may partially reverse the process that results in cutaneous sclerosis.

Adult↗
PubMed1992

Systemic lupus erythematosus with central nervous system involvement.

Real or suspected brain involvement occurs in the majority of patients with systemic lupus erythematosus. The clinical manifestations are myriad and are accounted for by diverse pathogenic mechanisms. Purely psychological disturbances and psychiatric syndromes with organic components account for the majority of cases. Metabolic disturbances, drug effects, and infections may masquerade for immune-related brain dysfunction. In the absence of reliable and specific indicators of lupus brain activity, successful management requires the combined skills and clinical judgment of the rheumatologist, neurologist, and psychiatrist.

Brain Diseases↗
PubMed1991

Current topics in the diagnosis and treatment of scleroderma.

Scleroderma has been viewed as one of the most discouraging diffuse connective tissue diseases to manage. In the last 10 years, we have seen major advances in our understanding of its pathogenesis. New techniques for earlier diagnosis widen the window of opportunity for therapeutic intervention. A multitude of possible disease-modifying therapies are under study. Advances in molecular biology, including increased understanding of the cellular messages controlling the process of fibrosis, provide additional hope for better treatment. Clinical research in this disease is inhibited by limited numbers of patients and the difficulties encountered in evaluating progression and response to treatment. All patients with suspected or newly diagnosed scleroderma should be evaluated at a medical center actively engaged in the research of this disease. Such research is likely to accelerate the gains made during the last decade.

Adult↗
PubMed1988

Carpal tunnel syndrome as the initial manifestation of scleroderma.

Two cases of scleroderma (systemic sclerosis) in which carpal tunnel syndrome was the initial manifestation are described. The development of persistent bilateral swelling of the hand after division of the transverse carpal ligament was a clue to the underlying disorder.

Aged↗
PubMed1988

Reduction of pulmonary capillary blood volume following cold exposure in patients with Raynaud's phenomenon.

In a previous study we induced digital vasospasm with cold pressor stimulus, and an acute decrease in the lung diffusing capacity for carbon monoxide (Dsb) resulted. We hypothesized its cause to be spasm occurring simultaneously in the pulmonary vasculature and the digital arteries. We measured in this study the Dsb, the diffusing capacity of the pulmonary membrane (Dm), and the volume of blood in the pulmonary capillaries (Vc) after cold-induced digital vasospasm in patients with Raynaud's phenomenon. Control subjects showed no significant decrease in Dsb, Dm, or Vc after cold exposure. Eight of 12 subjects with Raynaud's phenomenon had a significant decrease in Dsb 60 min after testing (25.3 +/- 6.6 vs 19.8 +/- 6.1 ml/min/mm Hg, p less than 0.01). The acute decrease in Dsb was due to a significant decrease in Vc (54 +/- 20 vs 39 +/- 10 ml, p less than 0.05), while Dm was unchanged (52 +/- 17 vs 51 +/- 20 ml/min). Four subjects who had a decrease in Dsb after cold challenge had repeated studies later after pretreatment with sublingual nifedipine. The magnitude of change in Dsb was similar to that observed in the untreated state (23.6 +/- 10.6 vs 20.9 +/- 9.6 ml/min/mm Hg). We conclude that digital vasospasm is accompanied by an acute reduction in Vc in both primary and secondary Raynaud's phenomenon and indicates concurrent vasoconstriction within the pulmonary vaculature.

Adult↗
PubMed1988

Systemic sclerosis and digital gangrene without scleroderma.

We report a case of a 67-year-old man with digital gangrene and no other cutaneous evidence of scleroderma. The presence of anticentromere antibody, scleroderma pattern capillary abnormalities, and the histology of the digital artery all supported a diagnosis of systemic sclerosis. Newer diagnostic tools may identify patients who do not fit easily into the current classification of that disease.

Aged↗
PubMed1985

The accessory cell function of murine Peyer's patches.

The cellular composition and certain functional characteristics of murine Peyer's patches (PP) were examined and compared with other lymphoid tissues. The composition of PP resembled most closely that of the spleen with the exception of a significant decrease in the number of adherent and phagocytic cells. Very few cells with dendritic morphology could be identified in Peyer's patches. Whole PP (and the nonadherent population) were capable of presenting antigen ovalbumin, human gammaglobulin, and purified protein derivative in a T proliferative assay to sensitized lymph node cells and to an antigen-specific T-cell clone. The antigen-presenting cell in both the spleen and PP was concentrated in the low-density population which floated on 1.080 bovine plasma albumin. However, equal numbers of whole and PP floaters were deficient in their capacity to present antigen compared with similar populations from spleen. Moreover, in PP the antigen-presenting cell appeared in the nonadherent rather than the adherent population as found with other lymphoid tissues. Similar results were obtained with (B6A)F1, CBA, A.TFR-1 and B10.S (12R) mice, suggesting that the inability of adherent cells from PP to present antigen effectively was not genetically determined. Whole and nonadherent PP contained cells capable of stimulating an allogeneic MLR, although again they were generally inferior to those of the spleen when comparable numbers of cells were employed. The adherent population of PP did not elicit an MLR. However, whole PP contained accessory cells needed for mitogen-induced proliferation since passage over nylon-wool columns resulted in a nonadherent fraction which did not respond to concanavalin A or phytohemagglutinin and the addition of adherent peritoneal exudate cells restored the lectin response. The differences noted in the accessory cell function in PP and other lymphoid tissues suggest the possibility that quantitative or qualitative differences in the function of these cells may explain some of the previously observed characteristics of PP, such as the inability to detect a primary antibody response in this tissue. The possibility that the development of gut-associated suppressor cells and their migration to peripheral tissues may be involved in the systemic tolerance that follows oral immunization and that these may be related to numerical and/or functional differences in macrophages or accessory cells is discussed.

Animals↗
PubMed1983

Oral tolerance and accessory-cell function of Peyer's patches.

Whole and nonadherent Peyer's patch cells were shown to present antigen to cloned antigen specific T-cells, albeit less efficiently than spleen cells. Unlike spleen cells, adherent PP cells did not present antigen, and PP lacked cells with classical dendritic morphology. The antigen presenting and MLR-stimulating cell in both spleen and PP were concentrated in the low density (BPA floaters) population. Soluble antigens (OVA, HGG, HSA, and KLH) are poorly presented by PP and do not elicit a T-cell proliferative response in PP when fed orally. These antigens induce oral tolerance and Ts cells in PP, MLN, and spleen. As with systemic tolerance, however, Ts (as measured by adoptive transfer) are not necessary for the induction of tolerance and can be eliminated by colchicine and Cytoxan without a significant effect on the initiation of tolerance. Evidence from studies in various inbred strains of mice suggests that oral tolerance is dependent on genetic factors, but the susceptibility of the strain is different from that induced by the systemic injection of the same antigen. Data are also presented that suggest that in studies of oral tolerance to various antigens, care must be exercised in excluding the effect of diet.

Animals↗