Intercurrent disease in healthy volunteers in pharmacological research.
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Biomedical subjects
Publications and source records attributed to R Levrat.
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All the clinical, laboratory and electrocardiographic adverse events detected during 24 Phase I studies in the same unit over a 5 y period are reported here. 430 healthy male volunteers were involved, corresponding to 5488 days of follow-up. The overall incidence of adverse events was 13.5%, with a significant difference between active drug (15.3%) and placebo (7.4%) treatments. There were 69 distinct types of adverse events. Headache was the most frequent symptom (2%). There were severe adverse events in 20 cases (0.36%), with an incidence of 20/430 per subject (4.6%). There were no deaths or life-threatening events. Although the main objective of Phase I studies is to determine the maximum dose tolerated, cause-effect relationships with adverse events are hard to establish, because of the frequency of adverse events with placebo, and because of the limited number of subjects included such studies.
We report a case of splenic artery thrombosis developed in a 54-year old woman after prolonged use of oral contraceptives. The diagnosis of the disease, difficult on clinical grounds, was confirmed by computerized tomography and selective arteriography. The presence of anti-ethinyloestradiol antibodies in the serum is suspected to be a risk factor for thrombosis associated with oral contraception.
Two new cases of eosinophilic ascites and a brief review of 40 cases found in the literature are presented. In three quarters of the cases eosinophilic ascites affects women aged 40 years on average. Because the patients present with a history of allergy (55%), blood hypereosinophilia (69%), associated pleural effusion (11%), gastrointestinal disorders and, above all, eosinophilic infiltrations in the walls of the digestive tract or the serous membranes (63%), this pathology may be regarded as a clinical form or eosinophilic gastroenteritis. The outcome is favourable in 90% of the cases; relapses occur in 26%. Is eosinophilic gastroenteritis and independent pathological entity, or should it be considered a minor clinical form of Chusid's idiopathic hypereosinophilic syndrome? The lack of decisive arguments precludes a firm conclusion.
Ehlers-Danlos Syndrome is a hereditary dysplasia of connective tissue with an abnormality in collagen synthesis. The syndrome consists of increased elasticity and fragility of the skin, increased laxity of the ligaments of the joints and fragility of the blood vessels. It is rarely associated with pregnancy but when it is several problems arise which are demonstrated in our case. Our patient had a type III syndrome (hypermobility of the joints) or a type IV syndrome (echymoses, Sack-Barabas Syndrome). In the literature the following are reported: premature rupture of the membranes with premature delivery, tears, perineal haematomas and type IV ruptures of the great vessels of the uterus. The best way of delivering and anaesthetising the patient are discussed. The prognosis depends above all on the type of the disease (25% of mothers die in type IV disease). Strict rest and Pfannestiel lower segment Caesarean section operation under general anaesthetic allowed us to achieve a favorable outcome for the mother and for her child.
The authors report the observation of one patient in whom the first administration of chemotherapy with fluoro-5 uracil has induced a severe but reversible cardiogenic shock. The latter was preceded by a prolonged, constrictive thoracic pain without myocardial infarction constitution. The cardiac toxicity of fluoro-5 uracil has been well described in the form of anginal pains receding with the discontinuation of the treatment. However, the possible occurrence of arrhythmias, of collapse and even sudden deaths leads the authors to suggest the daily clinical and electrical observation of the patients treated with fluoro-5 uractil.
A 60 year-old man complained of numbness and pain in the right lower limb, suggesting lesions of the fifth lumbar and first sacral roots. Sixteen months later, CT showed a tumor of 3.5 cm at the emergence of the first right sacral root. Microscopic examination disclosed an infiltration of the fibers of the nerve by numerous masses of hyaline eosinophilic material which stained with Congo red and produced green birefringence under polarized light. The persistence of congophilic properties of the amyloid deposits after permanganate pretreatment suggested an immunoglobulin origin (AL). A research of amyloid deposit in others viscera: heart, kidneys, digestive tract, was negative. We believe that this is the first reported case of amyloid pseudo-tumor involving a peripheral nerve.
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The authors report the case of a 21 years old man, with sex-linked agammaglobulinemia, who presents a presumed viral hepatitis, followed two years. The evolution, does yet fear a progressive cirrhosis. About this report and analysis of literature, frequency, evolution and pathophysiologic hypothesis, particularly the lymphocyte T role, are also discussed as the problem of hepatitis prevention of these subjects, who receive gammaglobulin injections.
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