Treatment of Raynaud's phenomenon by intravenous infusion of prostacyclin (PGI2).
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Biomedical subjects
Publications and source records attributed to M F Martin.
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The hemodynamic effects (n = 8) of hemodialysis (HD) and hemofiltration (HF) were compared in the same group of dialyzed patients. The two procedures induced the same decrease in body weight, total blood volume, and blood pressure; however, hemodynamic alterations were different. Cardiac index and stroke index decreased markedly with HD and did not change significantly with HF, and peripheral resistance remained stable after HD and decreased significantly after HF. These results suggest that the maintenance of a high cardiac output may account for the lack of acute hypotensive episodes reported during HF. The reduction of blood pressure after HF is related to the decrease in total peripheral resistance. Thus, the arterial vasodilator effect induced by HF might explain the improvement of severe hypertension on long-term treatment with HF, as reported previously.
A nephelometric assay of concanavalin-A binding of serum acute phase proteins (con-A binding) has been used in cross-sectional and sequential studies of disease activity in rheumatoid arthritis (RA). Con-A binding correlated well with blood viscosity, C-reactive protein, and other individual acute phase reactants in patients with active RA. Twenty-four patients were treated for 6 months with D-penicillamine and assessed clinically and seriologically. Clinical improvement was accompanied by significant falls in both C-reactive protein and con-A binding, although the serological changes did not always occur in parallel in individual patients. The advantages of this simple, cheap assay of acute phase proteins are discussed.
We describe a patient who, 6 months after the onset of Reiter's disease associated with a destructive peripheral arthritis and keratodermia blenorrhagica, developed fulminating colitis. The possible relationship between Reiter's disease and ulcerative colitis is discussed, and the need for further family studies to assess its validity is stressed.
A woman with exacerbation of severe rheumatoid arthritis developed lesions compatible with retinal vasculitis. Laboratory studies confirmed the diagnosis, and the rapid clinical improvement that accompanied a fall in circulating immune complexes suggested that the vasculitis was a direct consequence of the rheumatoid disease. From these observations retinal vasculitis should probably be sought in any patient with rheumatoid disease and the vasculitis added to the list of ocular complications of rheumatoid arthritis.
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Twelve patients with systemic sclerosis (SS) and severe Raynaud's phenomenon received infusions of prostaglandin E1 (PGE1) at a dose of 6-10 ng/kg/min, with either saline or 5% dextrose, for 72 hours in a single-blind cross-over study. The infusions were administered intravenously by centrally positioned catheters. Infusions were well tolerated with only mild side effects. Following the PGE1 infusion cold tolerance improved and attacks of Raynaud's phenomenon were less frequent, less severe, and shorter in duration. This subjective improvement was maintained for several weeks in most patients, and 2 noted healing of ischaemic ulcers. There was no significant change in objective measurements of hand function after either infusion. However, pain measured on a 10 cm visual analogue scale improved 2.19 cm with PGE1 and only 0.91 cm with normal saline (P less than 0.05). Temperature of the fingers and hands recorded by thermography did not change significantly with saline infusions, but did rise during PGE1 infusions (mean rise 2.0 degrees C at 48 hours, p less than 0.001), and was maintained when measured again 2 weeks later (mean rise 1.56 degrees C, p less 0.001). PGE1 may therefore be suitable treatment for Raynaud's phenomenon and the vascular insufficiency of systemic sclerosis and other connective tissue diseases.
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Prostaglandin E1, a vasodilator and potent inhibitor of platelet aggregation, was administered to 26 patients with severe vasospastic disease of the hands. Patients tolerated infusions well and reported appreciable symptomatic improvement. Five of eight ischaemic ulcers healed in six weeks. Non-invasive studies of blood flow were used to observe haemodynamic changes during and after infusions. The Doppler-derived radial artery pulsatility index fell from 8.8 +/- 0.6 to 4.6 +/0 0.5 (mean +/- SEM), indicating hand vasodilatation. This fall was maintained 24 hours after infusion (5.9 +/- 0.9), but the index had returned to normal values at two weeks. The amplitude of finger pulse volume recordings increased (5.6 +/- 0.7 mm to 23.8 +/- 3.4 mm) and was raised two and six weeks after infusion (13.5 +/- 2.1 mm). Hand temperature measured by infrared radiometry also increased (27.4 +/- 0.7 degrees C to 31.2 +/- 1.2 degrees C). Intensity of digital vasospasm induced by cold water challenge was not objectively affected by prostaglandin E1 despite an increased finger temperature after infusion. Nevertheless, patients reported less frequent and severe attacks. Prostaglandin E1 given by central venous infusion is a safe new vasoactive agent that can produce appreciable symptomatic improvement by increasing digital perfusion, which may last for several weeks after treatment. Further study will define its mode of action and its place in the management of peripheral vascular disease.
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A simple, rapid GLC method for the determination of lidocaine in plasma is described. After addition of mepivacaine as an internal standard, the plasma sample is deproteinated and centrifuged. The supernate is alkalinized, and the lidocaine and internal standard are extracted into a microvolume of carbon disulfide. By using GLC with a flame-ionization detector, linear concentration-response curves were obtained in the 1-6 microgram/ml range. The method can easily determine plasma concentrations at the 250-ng/ml level when a 1-ml plasma sample is analyzed.
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Assessment of a standardized test as one criterion for student admission to a physical therapist assistant program is made. Comparisons are made of ACT scores between the physical therapist assistant and associate degree nurse, and the physical therapist assistant and the practical nurse. A correlation matrix was used to analyze data with differences among the three groups determined by t test computation. This sample supports a positive correlation of ACT test scores with graduation grade point average. The means show no significant difference between the two associate degree programs and a significant difference between the associate degree programs and the practical nurse program.
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The effects on severe arterial ischaemia of infusions of Prostaglandin E1 (PGE1) a vasodilator and inhibitor of platelet aggregation, were studied in 49 patients (aged 17-80). Criteria for patient selection included rest pain and/or digital ulceration and gangrene secondary to predominantly small vessel disease. PGE1 was infused at a low (6 ng/kg/min), intermediate (10 ng/kg/min) or high (14 ng/kg/min) dose rate via a central venous cannula on 52 occasions without serious side effects. Doppler studies, pulse volume recordings and infra red radiometry were used to quantify the clinical effects. Improvements in digital perfusion were demonstrated by increased pulse volume amplitude (7.1 +/- 1.1 to 21.6 +/- 2.7 mm mean +/- SEM) which remained significantly raised at 6 weeks (14.2 +/- 2.9 mm; P = less than 0.001 paired t test). Infra red digital temperatures were also significantly raised 6 weeks post infusion (27.2 +/- 0.6 degrees C to 29.5 +/- 0.6 degrees C; P less than 0.001). The majority of patients reported improvement in pain, and two thirds of 12 superficial ulcers healed in 6 weeks. These results show that PGE1, improves digital perfusion for several weeks in patients with severe arterial ischaemia.
STUDY OBJECTIVE: To characterize a time-dependent disposition of oral tacrolimus and its relationship with plasma endothelin-1 concentrations. DESIGN: Randomized, crossover study. SETTING: Clinical research center of a university-affiliated hospital. PATIENTS: Twelve stable liver transplant recipients. INTERVENTIONS: In the steady state, 23 blood samples were taken from each patient before and after tacrolimus administration over 24 hours. MEASUREMENTS AND MAIN RESULTS: Whole blood samples for tacrolimus and plasma endothelin-1 were analyzed by enzyme immunoassay. The relationship of their concentrations and their pharmacokinetic parameters between morning and evening doses were compared. The area under the curve (AUC) of tacrolimus in the morning dose was significantly larger than that in the evening dose (219 +/- 54 ng.hr/ml and 188 +/- 57 ng.hr/ml, respectively, p = 0.004). The mean time to peak concentration (Tmax) was significantly shorter for the morning dose than for the evening dose (1.6 +/- 0.7 hrs and 3.5 +/- 2.9 hrs, respectively, p = 0.01). The mean peak concentration (Cmax) was significantly higher in the morning dose than in the evening dose (32.2 +/- 9.1 ng/ml and 21.6 +/- 8.3 ng/ml, respectively, p = 0.008). However, the mean through concentration (Cmin) was not significantly different between doses. Endothelin-1 concentrations followed the same pattern as tacrolimus, with AUC and Cmax for the morning significantly higher than those for the evening dose of tacrolimus (AUC 13.8 +/- 3.7 pg.hr/ml, morning, and 11.0 +/- 3.5 pg.hr/ml, evening, p = 0.005; Cmax 2.4 +/- 1.1 pg/ml morning, and 1.5 +/- 0.6 pg/ml evening, p = 0.02). Tacrolimus levels did not correlate with endothelin-1 levels (r2 = 0.06, p = 0.001). CONCLUSIONS: Tacrolimus disposition in liver transplant patients is determined by time of administration. Plasma endothelin-1 concentrations follow the same pattern as blood tacrolimus concentrations.