Hormonal aspects of gouty patients.
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Biomedical subjects
Publications and source records attributed to R Marcolongo.
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The results of an open exploratory trial with different regimens of indoprofen in patients with acute gouty arthritis are described. Two main daily regimens were assessed: (a) indoprofen 200 mg as an intravenous bolus, followed by slow infusion of 100 mg/hour for about 4 hours (24 attacks treated in twenty-three patients); and (b) indoprofen 400 mg as an intravenous bolus (13 attacks treated in twelve patients). In both regimens intravenous indoprofen was supplemented with 400-600 mg daily of indoprofen by mouth. The patient's response, as judged by pain, tenderness, local heat, redness, range of motion and joint circumference, was dramatic in both series, with no significant difference between them at any time of observation. Substantial improvement was apparent for subjective variables already within 2 hours after the beginning of treatment, and a complete resolution was obtained in 35 of 37 attacks within 48 hours. A mild adverse reaction was recorded in one patient for each group (dizziness and gastric pain, respectively). Intravenous indoprofen appears to afford an extremely rapid relief of acute gout; of the two regimens assessed, the second should be preferred in that it seems to be at least equally effective but less troublesome for the patients.
The Authors have analyzed the complex problems of the possible binding between uric acid and plasma proteins using two methods consisting of serum ultrafiltration at 22 degrees C or electrophoresis on different supports with successive specific coloration of the free and bound uric acid. The percentage of free and bound uric acid was established in serum from normal subjects, patients with primary gout, patients with renal insufficiency treated by dialysis and subjects with type IV dyslipidemia. The Authors discuss the results obtained as regards the possible role played by urate-plasma proteins binding in the interpretation of a genetic defect present in gouty patients involving a diminished uric acid binding capacity of plasma proteins.
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Administration of 500 mg/day chenodeoxycholic acid for 60 days in a series of 44 patients with type IV dyslipidaemia led to gradual normalisation of triglycerides by the end of the treatment. Falls were greater in subjects with initially higher values, but were independent of age, sex, weight and type of diet. Further falls were obtained by repeating the treatment in some cases when prebetalipoproteins rose again. Decreases were already evident by the 5th day (about 24%) and could be obtained with only 4 mg/Kg/day. The rapid effect of the acid and its specific action on prebetalipoproteins were demonstrated by examination of lipid curves after a glyco-lipid load with and without pretreatment with chenic acid. Encouragement of the shunt of triacylglycerols towards the phosphoglycerides during hepatic synthesis of triglycerides is put forward as the most likely mechanism of action in endogenous hyper-triglyceridaemia. The chemical composition of bile is interfered with, which may explain why cholesterol lithiasis is significantly more common in type IV dyslipidaemia than in other forms and in controls, as shown by statistical analysis.
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The effect of chenodeoxycholic acid on the fasting serum triglycerides was studied in 30 patients with type IV hyperlipemia and in 20 patients with primary gout and associated endogenous hypertriglyceridemia, the triglycerides being determined before treatment and at monthly intervals for three months. Chenodeoxycholic acid treatment resulted in a significant lowering of the serum triglycerides in both groups of patients. The drug was well tolerated and there were no undesirable side-effects. Although the mechanism of action is still not known, the drug is thought to reduce triglyceride synthesis in the liver. Chenodeoxycholic acid appears to be electively indicated in type IV hyperlipemia treatment.
Administration of chenodeoxycholic acid (CDCA) to patients with primary hypertriglyceridemia caused the diminution of serum triglyceride concentrations of 54.31% and 46.04% at dosages of 500 mg/day and of 250 mg/day, respectively. Results after 1 month of treatment with 250 mg/day are not statistically different from those obtained with 500 mg/day. Administration of CDCA did not change the serum cholesterol, SGOT, SGPT, total bilirubin, gammaGT or alkaline phosphatase levels.
Administration of chenodeoxycholic acid (CDCA), 200 mg/day, for 5 days to patients with primary hypertriglyceridemia reduced by 34% the serum triglycerides concentration. Reduction after CDCA is statistically significant vs. the placebo. Even after a short time of CDCA administration, the pharmacological effect is clearly evident.
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A double-blind, crossover clinical trial has been carried out in subjects with knee joint osteoarthritis to assess the activity of two nonsteroidal antiinflammatory drugs. Eighteen outpatients with a severe systemic form were given orally indoprofen (800 mg/day), indomethacin (80 mg/day), and placebo for one week without interval between treatment periods. Significant improvement was seen in subjective and objective signs and symptoms after both drugs, which gave similar results. No significant differences between drugs were noted as to patients' opinions and preferences, which were in agreement with clinical indexes. No improvement in most cases and deterioration in a few subjects followed placebo administration, probably because the majority of the sample was made up of placebo non-reactors. Consequently, the activity data of the trial might be interpreted as expression of the pure pharmacologic activity of the tested drugs. Safety was very satisfactory: patients complained only rarely of trivial and clinically unimportant side effects; no variations in laboratory tests were noted.
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