Biomedical subjects
Publications and source records attributed to N R Rowell.
Fifty patients with psoriasis undergoing a standard Ingram regime were entered into a double-blind comparison of oral indomethacin and placebo. No significant differences were observed between the two groups in respect of disease activity or dithranol tolerance after 6 weeks.
The acute effects of smoking a single cigarette on peripheral blood flow were investigated by laser-Doppler flowmetry in nine patients with Raynaud's phenomenon and 12 normal controls. In regular smokers, a marked fall in finger blood flow was demonstrated, but this was not present in non- or irregular smokers. In addition, no effect on capillary blood flow was found. There was no difference between subjects with and without Raynaud's phenomenon. In five normal, non-smoking volunteers, 2.4 g of aspirin for 3 days resulted in a similar fall in blood flow due to a single cigarette. These results suggest that regular smoking sensitizes the peripheral vasculature to the vasoconstricting effects of the next cigarette, and that at least part of this sensitization is mediated by the inhibition of endothelial prostacyclin synthesis. Patients with Raynaud's phenomenon, either primary or secondary, are no more sensitive than normal subjects, but should nevertheless avoid cigarette smoking.
The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in systemic lupus erythematosus (SLE). Elevation of C3a anaphylatoxins was found in two out of 24 patients and elevation of C4a anaphylatoxins was found in 20 out of 24 patients, confirming that complement activation, predominantly by the classical pathway, is a common occurrence in the disease. Significantly higher levels of C4a anaphylatoxin were found in 16 patients, with more aggressive disease requiring supplementary treatment with azathioprine, while the remaining eight patients, with less severe disease, required purely steroid therapy. Very strong associations between elevated C4a anaphylatoxins and raised DNA antibody titres, C1q binding activity and low complement C4 levels were also observed, suggesting that anaphylatoxin measurement may be a sensitive additional method for monitoring disease activity in SLE.
The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in patients with systemic sclerosis. Elevations of C3a and C4a anaphylatoxins were found in 2 and 24 out of 30 patients respectively, indicating that complement activation, predominantly by the classical pathway, is a common occurrence in the disease, even though complement C3 and C4 levels were within the reference range.
Sera from 29 patients with systemic sclerosis and 30 normal controls were examined for their effect on prostacyclin release by human umbilical vein endothelial cells during periods of response of 15 min and 72 h and for their effect on endothelial growth and 3H-thymidine uptake during a 72-h culture period. In contrast to previous reports, no significant differences were detected between patient and control sera in their effect on endothelial cell prostacyclin release, growth or 3H-thymidine uptake.
The therapeutic efficacy of conventional superficial radiotherapy and topical psoralen photochemotherapy (topical PUVA) administered over a 6 week period was compared in a double-blind study of 21 patients with chronic bilateral constitutional hand eczema. One hand was treated with conventional superficial radiotherapy and the other with topical 8-methoxy-psoralen and long-wave ultraviolet light (topical PUVA). Significantly better clinical improvement was seen in superficial radiotherapy treated hands over topical PUVA treated hands after 6 weeks of treatment, but this difference was not maintained at 9 or 18 weeks. There was no significant difference in symptom severity between the two treatments after 6 weeks, but superficial radiotherapy produced significantly more symptomatic improvement at 9 and 18 weeks. Superficial radiotherapy is a less time consuming procedure than topical PUVA and leads to more rapid improvement.
We report on the use of a new orally active fungicidal agent, terbinafine (SF 86-327, Lamisil) in the treatment of patients with dermatophyte onychomycosis. Twenty patients with toe-nail, and 10 with finger-nail infection received 250 mg of terbinafine daily: finger-nail infections were treated for 6 months and toe-nail infections for 12 months. All 24 patients who completed the course of therapy achieved mycological cure, as did two subjects who dropped out of the trial. All but two patients had clinically normal nails at the end of the study period. The mean time for mycological cure was 12.5 weeks for finger-nail infection, and 24 weeks for toe-nail infections. The time for a clinical cure with normal nails was 20.5 weeks for finger-nail infection, and 44 weeks for toe-nail infection. An exacerbation of pre-existing dyspepsia occurred in three of the six patients who did not complete the trial but there were no other significant adverse reactions.
Vascular problems are very common in systemic sclerosis with 95% of patients suffering with Raynaud's phenomenon at some stage in their illness. Acute ischaemic lesions are much less common, but when they occur are a serious complication, and are often difficult to treat. Many drugs have been used in this situation, including both oral and intravenous vaso-dilators and low molecular weight dextran, each with varying degrees of success. The phospho-diesterase inhibitor, pentoxifylline, is reported to be useful in peripheral vascular disease, and in Raynaud's phenomenon, and the intravenous form is indicated for acute peripheral ischaemia, though its use in the context of connective tissue disease has not so far been reported. We now report the use of intravenous pentoxifylline in two patients with acute peripheral gangrene due to systemic sclerosis.
A 20 year old Caucasian woman with Crohn's disease is described in whom axillary artery occlusion due to arteritis dominated the clinical picture. This case demonstrates that isolated large vessel arteritis can be an unusual feature of Crohn's disease. Crohn's disease should be considered in any patient presenting with a large vessel arteritis.
The clinical and serological findings in 13 patients with myocardial infarction and antiphospholipid antibodies (the 'lupus anticoagulant', antibodies to cardiolipin, antibodies to phosphatidylethanolamine (one patient] seen by our unit and other units from 1984 to 1989, are presented (eight males and five females, ages ranging from 20 to 52 years). Five suffered myocardial infarction before the age of 30; four of these five were in their early 20s. Other risk factors such as excessive smoking (greater than 20 cigarettes a day) (two patients), long-term treatment with steroid (one) and use of oral contraceptives (one) were present. One patient had demonstrated a plasminogen activator deficiency and one a deficiency of protein C. Two patients developed myocardial infarction six to eight weeks after warfarin was discontinued for recurrent deep vein thrombosis. Six patients had SLE as defined by the revised 1982 criteria, three suffered from 'lupus-like' disease, while four patients conformed to a 'primary' antiphospholipid syndrome.
The lupus anticoagulant was found in six of 41 unselected patients with systemic lupus erythematosus (14%). Three of these six patients had episodes of thrombosis. Thrombosis occurred in only one patient in the remainder of the series without the lupus anticoagulant. The lupus anticoagulant should be considered as one of the criteria for the diagnosis of systemic lupus erythematosus, and it may be a useful marker for those patients at risk from thromboembolism. It should be looked for in young adults with thrombotic episodes.
Ten sera from 48 patients with systemic sclerosis were found to be capable of producing cytotoxicity of human umbilical venous and arterial endothelium when co-cultured with peripheral blood mononuclear cells. Fractionation of sera on Ultrogel and the preparation of monomeric IgG by ion exchange and affinity chromatography suggested that the cytotoxicity was mediated by anti-endothelial antibodies capable of pre-sensitizing target cells in a mechanism that resembled antibody-dependent cellular cytotoxicity. These anti-endothelial antibodies together with C1q-binding immune complexes and anti-cardiolipin antibodies were found in 18 of 28 patients so investigated, suggesting that multiple immunological mechanisms may be involved in the pathogenesis of the vascular lesion of systemic sclerosis.
Plasma levels of the factor VIII complex (von Willebrand factor antigen, factor VIII coagulant and ristocetin co-factor) were measured in 28 patients with systemic sclerosis. Elevated von Willebrand factor antigen was found in 12 patients overall and in 10 of 16 patients characterized by severe extensive visceral disease, with a resulting positive correlation between the extent of visceral involvement and the plasma level of von Willebrand factor antigen (r = 0.60, p less than 0.001). Factor VIII coagulant and ristocetin co-factor levels, however, frequently failed to parallel the increases of von Willebrand factor antigen, supporting the view that these increases were due to in vivo endothelial damage. The findings suggest that vascular damage is an important aspect of the visceral lesions of systemic sclerosis.
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Finger blood flow was measured by laser Doppler flowmetry in 15 patients with Raynaud's phenomenon (RP) due to systemic sclerosis (SS), and 15 normal controls. Measurements were performed in a temperature controlled room at 28 degrees C. The blood flow in the patients was significantly lower than in the controls (P less than 0.001). After hand warming in water at 35 degrees C for 10 min, blood flow in the patients and controls did not differ significantly. Following this, the response to a standardized cold stress produced similar falls in both groups to levels that were not significantly different and these occurred over a similar time course. After cold stress ended, there was recovery of blood flow in both groups, and blood flow after 20 min was not significantly different between the two groups. The induced vasodilatation persisted, in those patients in whom it was remeasured, for at least 2 h. Repeating the experiments at a room temperature of 24 degrees C produced similar results. This indicates that considerable vasodilatation is possible in these patients, and can be produced by simple means. It also indicates that local and central thermoregulatory reflexes are intact. Cold induced symptoms in patients with SS are related to low resting blood flow, not to cold sensitivity, and simple warming may provide a useful treatment.
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Twelve patients with Raynaud's phenomenon (RP) due to systemic sclerosis (SS) warmed their hands for 5 min in hand hot water every 4 h throughout the day during alternate weeks of a 6-week study. There was a statistically significant decrease in the number and duration of Raynaud's attacks in the weeks in which warming was performed compared with the intervening weeks. An increase in blood flow as measured by laser-Doppler flowmetry accompanied clinical improvement. Simple hand warming appears to be effective in the management of RP in patients with SS.
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