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Biomedical subjects

T Vial

Publications and source records attributed to T Vial.

At least 55 records · Page 3Linked to original sources
PubMed1994

Contact sensitization assays in guinea-pigs: are they predictive of the potential for systemic allergic reactions?

Guinea-pig assays have been used extensively to detect contact sensitizers. In contrast, almost no reliable assays are available to detect the potential for low-molecular-weight drugs and chemicals to induce systemic allergic reactions in humans. Based on clinical data, and, to some extent, on recent immunological findings, it is proposed that guinea-pig assays can predict the hazard for systemic allergic reactions in man. Seventy drugs and chemicals were compared from published results in guinea-pig assays and in the clinic. A close correlation was found with 43 substances and a relatively good one with 16 substances. Conflicting results were found with 11 substances only. However, substances known to induce systemic allergic reactions in man were all detected as weak sensitizers, at least in guinea-pigs. Guinea-pig contact sensitization assays may therefore prove useful until more suitable and specific assays are available to predict the risk for systemic allergic reactions.

Allergens↗
PubMed1994

Morphology of popliteal lymph node responses in Brown-Norway rats.

The popliteal lymph node (PLN) assay has been proposed as a tool to predict in rodents those xenobiotics likely to induce autoimmune reactions in humans. To further validate this assay and to study the mechanisms involved, histologic changes in PLNs from rats injected with streptozotocin, diphenylhydantoin, pure acetone, or 50% ethanol were compared to a local graft-versus-host (GvH) reaction. This study suggests that routine histology of PLNs is instrumental to discard primary irritants. In addition, the hypothesis of a GvH-like mechanism in positive PLN responses is supported by the finding that the reference compounds streptozotocin and diphenylhydantoin produced histologic changes similar to a "true" local GvH reaction.

Acetone↗
PubMed1994

Comparison of popliteal lymph node responses in various strains of rats.

Outbred (namely Wistar and Sprague-Dawley) and inbred (Wistar-Furth, Lewis, Fisher 344 and Brown-Norway) strains of rats were screened for their responses to reference compounds in the popliteal lymph node (PLN) assay. Streptozotocin and diphenylhydantoin gave positive responses as evidenced by increased weight and cellularity indices in all strains used whereas procainamide, isoniazid and barbital consistently gave negative responses. Although these findings overall are in agreement with previous investigations involving these compounds, the lack of marked interstrain differences in PLN responses argues against a strong immunogenetically controlled mechanism as could be assumed in presumably auto-immune reactions. The question is raised whether drug-induced side-effects predicted by the PLN assay are basically non-autoimmune as suggested by clinical and immunological findings in man.

Animals↗
PubMed1994

Clinical toxicity of the interferons.

Since their initial description in 1957, the interferons (IFNs) have been increasingly used to treat a wide array of diseases. Acute adverse effects, i.e. 'flu-like' syndromes, hypo- or hypertension, tachycardia, headache, myalgias and gastrointestinal disorders, occur within the first hour or day after starting treatment. They are seldom treatment-limiting and are easily manageable. Sub-acute and chronic effects develop after several days, usually within 2 and 4 weeks of therapy. The most typical is neurological toxicity, including fatigue/asthenia, and behavioural and cognitive changes. Such symptoms may seriously impair quality of life and result in treatment discontinuation. Seizures have seldom been described. Other infrequent central nervous system adverse effects include vertigo, cramp and oculomotor nerve paralysis. Distal paraesthesias and peripheral neuropathy have been reported. IFN-associated autoimmunity is quite rare but a matter of concern. Biological or clinical manifestations usually require several months to become apparent. Autoantibodies have been shown to develop in most patients but have been inconsistently associated with clinical symptoms of systemic lupus erythematosus, rheumatoid-like arthritis and thyroiditis. Both hypo- and hyperthyroidism have been described but are usually reversible. Other infrequent autoimmune reactions include diabetes, pemphigus and worsening of multiple sclerosis. Although several patients present with a pre-existing autoimmune disorder, no predisposing factor has been clearly established. While hypotension and tachycardia are the most frequent acute cardiovascular complications, a few additional cases of cardiac arrhythmias and myocardial ischaemia have been reported after a short course or several weeks of treatment. These latter complications do not appear to be dose-dependent or age-related. Isolated cases of congestive heart failure have also been described. Mild proteinuria has been observed in 15 to 25% of patients, but acute renal toxicity is uncommon. A transient rise in serum aminotransferase levels is frequently noted during the first stage of therapy, especially in patients receiving the highest dosages. Direct hepatotoxicity is extremely rare. Autoimmune hepatitis, which is ill-diagnosed as chronic viral hepatitis, and de novo induction of autoimmune hepatitis, account for the majority of liver diseases. Haematotoxicity is relatively common but mild to moderate, and develops gradually during the first weeks of treatment. Neutropenia is the most common haematological toxicity, but is usually not dose-limiting and resolves rapidly upon drug discontinuation. Myelosuppression, autoimmune and immune allergic haemolytic anaemias and thrombocytopenias have seldom been described. Cutaneous adverse effects comprised nonspecific erythema and hair loss and, less frequently, vasculitis, local ulcerations at the site of injection and exacerbation of psoriasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity.

OBJECTIVE: To show that germander (Teucrium chamaedrys), an herbal medicine used to facilitate weight loss, may be hepatotoxic and to delineate the nature of the injury. DESIGN: Retrospective study. SETTING: Liver units of several centers in the French Network of Pharmacovigilance. PATIENTS: Seven patients who developed hepatitis after germander administration and who had no other cause of liver injury. MEASUREMENTS: Clinical examination, liver function tests, various serologic tests, ultrasonography, and histologic study. RESULTS: Hepatitis characterized by jaundice and a marked increase in serum aminotransferase levels occurred 3 to 18 weeks after germander administration. Liver biopsy specimens in three patients showed hepatocyte necrosis. After discontinuing treatment with germander, jaundice disappeared within 8 weeks and recovery was complete in 1.5 to 6 months. In three cases, germander readministration was followed by the prompt recurrence of hepatitis. CONCLUSION: Germander may be hepatotoxic, which supports the view that herbal medicines are not always as safe as generally assumed.

Acute Disease↗
PubMed1992

Hepatitis associated with amoxycillin-clavulanic acid combination report of 15 cases.

Fifteen cases of hepatitis related to a combination of amoxycillin and clavulanic acid are reported. Most patients were aged 60 years or more and there were more men than women (sex ratio 4:1). The amoxycillin-clavulanic acid had been given at doses ranging from 0.5 to 6 g/day (mean 2 g/day) for seven to 60 days (mean 18 days). In 11 cases, the first symptoms appeared one to four weeks after stopping treatment. Jaundice was observed in all patients and was frequently associated with pruritus. Serum aminotransferase activities were increased in all patients and were generally two to 10 times the upper limit of normal. Serum alkaline phosphatase activity was considerably increased, from two to seven times the upper limit of normal. Histological examination of the liver, performed in seven patients, showed centri- or panlobular cholestasis in all cases, associated with granulomatous hepatitis in one. The prognosis of amoxycillin-clavulanic acid induced hepatitis seemed to be good. None of the patients exhibited biological or clinical features of hepatic failure and the course of the disease was characterised by the resolution of jaundice within one to eight weeks and a complete recovery within four to 16 weeks. Taking into account the number of treated subjects and reported cases, we estimated the risk of developing hepatitis with this drug combination to be very low, probably below 1/100,000. Our data suggest that the risk of hepatotoxicity may be increased in elderly men given lengthy treatment. The association of hepatitis and signs of hypersensitivity may suggest an immunoallergic mechanism of hepatotoxicity in some patients.

Adult↗
PubMed1992

[Hypoglycemia induced by oral hypoglycemic agents. Records of the French Regional Pharmacovigilance Centers 1985-1990].

All 98 cases of sulfonylurea-induced hypoglycemia reported by the 30 regional drug-monitoring centers between 1985 and 1990 were analyzed: 46 with gliclazide, 40 with glibenclamide, 5 with glipizide, 1 with glibornuride and 6 with first-generation sulfonylureas. These cases of hypoglycemia were often serious. The patients were 61% female and their mean age was 78.9 years. The average number of medications being taken was 3.4, but ranged up to 14. The risk factors were: reduced food intake (4.2%), renal failure (4.2%), prescription error (3.2%), voluntary or accidental overdose (5.2%), alcohol (1.1%), suspected drug interactions (50%), unknown (32.6%). The most frequent drug interactions involved miconazole (8 cases), angiotensin-converting enzyme inhibitors (9 cases), lipid-regulating agents (fibrates) (7 cases), co-trimoxazole (trimethoprim-sulfamethoxazole; 5 cases), metformin (4 cases), histamine H2-receptor antagonists (4 cases). The mechanisms of these interactions are discussed.

Administration, Oral↗