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Biomedical subjects

J Descotes

Publications and source records attributed to J Descotes.

At least 253 records · Page 14Linked to original sources
PubMedDate not supplied

Increased production of interferon-gamma, but not IL-4 mRNA, by streptozotocin in the popliteal lymph node assay.

The popliteal lymph node (PLN) assay has been proposed as a tool to predict systemic autoimmune reactions induced by medicinal products and chemicals, the mechanisms of which are poorly understood. To determine whether PLN responses involved Th1 or Th2 cell control, or both, the effects of streptozotocin (STZ), a prototypic immunotoxic compound, were analysed on the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) mRNA by lymph node cells after injection into the hind footpad of C57 BL/6 mice. Streptozotocin induced a dramatic increase in IFN-gamma mRNA production, which correlated with PLN responses as evidenced by augmented weight and cellularity indices. No effect on IL-4 mRNA synthesis was noted. These results suggest that a Th1 response is involved in the PLN response to STZ.

Animals↗
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Compared effects of morphine and nickel chloride on NK cell activity in vitro in rats and monkeys.

The measurement of natural killer (NK) cell activity often is recommended as an endpoint for inclusion in the non-clinical immunotoxicity evaluation of environmental chemicals and pharmaceuticals. To date, most data on the impact of immunotoxicants on NK cell activity have been obtained in the rat. Because non-human primates often are used in the safety evaluation of new medicinal products, there is a need to compare chemically induced changes in NK cell activity between rats and primates. In this study, the in vitro effects of nickel chloride and morphine hydrochloride were investigated on NK cell activity in the rat and the cynomolgus monkey. Despite some species-specific differences in the techniques used, rather similar results were obtained in the two species. At the higher concentration, nickel chloride induced a significant decrease in NK cell activity in the ranges of 21.6-24.3% (rat) and 34.4-42.2% (monkey), depending on the effector-to-target cell ratio used, and morphine hydrochloride induced a decrease in the ranges of 23.7-34.7% (rat) and 59.1-68.0% (monkey). These results suggest that NK cell activity can be used as a reliable endpoint for the assessment of immune effects during safety evaluation studies in the cynomolgus monkey.

Animals↗
PubMedDate not supplied

Responses of the immune system to injury.

Three categories of immunotoxic effects are identified: direct immunotoxicity, hypersensitivity, and autoimmunity. Direct immunotoxicity consists of immunosuppression and immunostimulation. Total abrogation of the immune response (immunosuppression) results in more frequent, severe, and often atypical and relapsing infections and lymphomas. Immunostimulation is associated with febrile reactions, the induction/facilitation of autoimmune diseases and allergic reactions to unrelated allergens, and impaired hepatic drug biotransformation. Hypersensitivity is manifested by a variety of symptoms involving either antigen-specific or non-antigen-specific humoral and cellular adverse responses. Autoimmune reactions are divided into organ-specific and systemic reactions. Because of the involvement of many redundant mechanisms, it is difficult to predict responses of the immune system to a given immunotoxic injury. In laboratory animals, histologic but also functional changes are necessary to show evidence of and to predict such adverse responses.

Animals↗
PubMedDate not supplied

Cefaclor-associated serum sickness-like disease: eight cases and review of the literature.

OBJECTIVE: To describe the clinical features of serum sickness-like diseases (SSLD) in cefaclor-treated patients. DESIGN: Analysis of a case series spontaneously reported to Lyons Pharmacovigilance Center. SETTING: General and hospital practitioners and the French Network of Regional Pharmacovigilance Centers (FNRPC). PATIENTS: All reported cases with a possible causative relationship between cefaclor treatment and SSLD. MAIN RESULTS: Eight cases of SSLD following cefaclor treatment are described. The clinical features included cutaneous reactions, arthralgias, and moderate hyperthermia. In 50 percent of the patients, hospitalization was required because of incapacitating symptoms. The outcome was benign in all cases following discontinuation of the offending drug. All eight cases were reported in children under five years of age. Among 137 cefaclor-associated drug reactions collected by FNRPC, 27 cases of SSLD have been reported; 23 of these patients were younger than five years of age. A literature survey confirmed the higher reporting of SSLD in children with cefaclor compared with other antibiotics and suggested an incidence of 0.024-0.2 percent of SSLD per drug course of cefaclor. CONCLUSIONS: The case reports and epidemiologic studies confirmed the presumed role of age (patients under five years of age) in cefaclor-induced SSLD and the benign outcome despite severe clinical presentations in some reports.

Cefaclor↗
PubMedDate not supplied

Side effects of ranitidine.

Ranitidine was first marketed in 1981; since then many patients have been treated such that much experience has been accumulated on the safety of this histamine H2-receptor antagonist in the treatment of gastroduodenal disease. A wide array of ranitidine-associated side effects has been described, but infrequently. As so much information is now available, the aim of this review is to assess the weight of evidence for a causal link between ranitidine and the reported side effects. Overall, ranitidine is well tolerated. The incidence of general side effects at less than 2% is very similar to placebo. Headaches, tiredness, dizziness and mild gastrointestinal disturbance (e.g. diarrhoea, constipation and nausea) are among the most frequent complaints, but have very seldom resulted in stopping treatment. Cardiovascular side effects are extremely rare and unpredictable with the usual doses of oral ranitidine (at most 1 in 1 million patients). They mostly comprise sinusal bradycardia and atrioventricular blockade, especially after rapid intravenous administration, receding after cessation of the drug. Clinical studies, however, have not shown a significant pharmacological effect of ranitidine on the cardiovascular system via H2-receptors, even though individual sensitivities cannot be ruled out in a few isolated reports. Ranitidine is unlikely to be directly hepatotoxic: a transient change in liver function tests has been noted in only 1 in 100 to 1 in 1000 patients. Several cases of mixed hepatitis have been reported, but very few were fully documented. The incidence of ranitidine-associated acute hepatitis has been estimated to be less than 1 in 100,000 patients. Neuropsychiatric complications may be less common and clinically quite similar to those reported with cimetidine, i.e. confusion, disorientation, hallucinations, delirium. These side effects have occurred especially in critically ill and multiple-therapy patients, or patients with chronic renal or hepatic failure, so that the direct causal link with ranitidine treatment was often difficult to ascertain. Even though an H2-receptor-mediated effect is an attractive hypothesis (since similar complications were noted with other H2-receptor antagonists), other mechanisms have been suggested to play a role, e.g. cholinergic or histaminic effects. The overall incidence of neuropsychiatric complications is probably markedly less than 1%. White cell injury (i.e. agranulocytosis) appears to be the most frequent haematological complication, even though case reports are very few and poorly documented.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Cells↗
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Clinical toxicity of interleukin-2.

Interleukin-2 (IL-2) is increasingly used to treat patients with cancers refractory to conventional treatment. Flu-like syndromes are extremely frequent but usually mild. A variety of skin complications (mostly erythema and mucositis) have been reported. Life-threatening skin reactions have also been described. Acute reactivation of psoriasis can also occur. Immediate hypersensitivity reactions have so far not been described, but IL-2 treatment has been shown to predispose to acute hypersensitivity reactions to iodine-containing contrast media. Hypothyroidism is the major endocrine complication and antithyroid antibodies have been detected in approximately 50% of patients. Neurological and psychiatric disturbances with moderate or severe mental status changes are common and sometimes treatment-limiting. The occurrence of peritumoural oedema in patients with brain metastases can also be a major practical problem. Musculoskeletal disorders are transient and resolve spontaneously. The vascular leak syndrome is the most frequent and severe complication of IL-2 of which weight gain, generalised oedema, hypotension and impaired renal function are the main features. Even though a damaging effect on vascular endothelium cells by various cytokines released by activated lymphoid cells or mediated by non-lymphocyte-dependent factors has been proposed to be involved, the mechanism remains unclear. Other cardiovascular injuries, possibly life-threatening, including myocarditis, angina pectoris and myocardial infarction, can occur during the first days of treatment. Supraventricular arrhythmias are the most common rhythmic disorder. Decreases in myocardial contractility and haemodynamic pattern similar to those of septic shock have been encountered in most cases. Acute renal dysfunction is common but resolves with symptomatic management. Intrahepatic cholestasis with hyperbilirubinaemia is observed in most patients but permanent liver damage has not been described. Several cases of pancreatitis have been reported. Anaemia, thrombocytopenia, lymphocytopenia and eosinophilia are frequent and occur in most if not all patients. Some data suggest a high incidence of infectious complications, particularly in patients with surgically tunnelled catheters, but marked flu-like syndromes may be confounding. Finally, death directly related to IL-2 treatment has been noted in less than 1% of all patients. Investigations are under way to minimise IL-2 toxicity with varying dose regimens and combined treatments.

Cardiovascular Diseases↗
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Effects of variations in time and dose of diazepam injection on delayed hypersensitivity.

Administration of diazepam was suggested to exert immuno-suppressive properties in mice. In the present study, we explored the time and dose-dependence of diazepam effects on delayed hypersensitivity to sheep erythrocytes in Balb/c mice. DTH response was only depressed when diazepam was injected shortly after immunization and this effect on DTH induction was found with doses of 4 and 8 mg/kg ip while lower doses (0, 5, 1 and 2 mg/kg) remained ineffective.

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