[Association of acquired Willebrand's disease, monoclonal gammopathy and angiodysplasia of the small bowel: a rare indication of high-dose intravenous immunoglobulins]. / Association maladie de Willebrand acquise--gammapathie monoclonale--angiodysplasie du grêle: une indication rare des immunoglobulines intraveineuses á forte dose.

Acquired von Willebrand's disease associated with a monoclonal gammopathy and angiodysplasia of the gut is a rare disorder. It is sometimes complicated by chronic intestinal bleeding and severe anemia, that is poorly responsive to usual treatments. We report such a new case that has been revealed by anemia, and characterised by the absence of the high-molecular weight multimers. The correction of the hemostasis defect and of anemia were related to the reappearance of the high-molecular weight multimers, that was achieved only after high-dose intravenous immunoglobulin courses. The perfusions were performed every 3 weeks for 2 years without loss of efficiency, that could be explained by the dissociation of immunoglobulin-von Willebrand's factor complex.

Plasma DNA as a marker of cancerous cell death. Investigations in patients suffering from lung cancer and in nude mice bearing human tumours.

Plasma DNA that circulates mainly as mononucleosomes is a cell death marker. Its significance and prognostic value in cancer as compared to other tumour markers was investigated in 68 patients hospitalised for lung cancers. Prognostic values of the various studied parameters were evaluated using the Cox's model. The cellular origin of plasma DNA was further investigated in nude mice transplanted with human lung adenocarcinoma. Plasma DNA concentrations were increased in cancer patients as compared to normal subjects (P < 0.01). They were higher in patients with extended (Stage 4) disease than in patients with limited stage disease (P < 0.05). Plasma DNA concentrations, serum lactate dehydrogenase activities and neuron-specific enolase concentrations were correlated all together in small cell lung carcinoma (SCLC) and in non-SCLC. Similar relationships were found between survival and each of these three cell death/tumour markers (P < 0.02-0.005). Plasma DNA from mice bearing human tumour hybridised with both mouse and human plasma DNA, while plasma DNA from endotoxin-injected mice hybridised only with mouse plasma DNA. In conclusion, in patients suffering from lung cancer, plasma DNA as well as LDH and NSE represent cell death markers that are correlated with survival. At a time when apoptosis pathways appear to be potential targets for cancer therapy, plasma DNA is a cell death/tumour marker that should be taken into account in studying the cancerous process in human diseases.

Plasma DNA as cell death marker in elderly patients.

Plasma DNA increases where cell death occurs in vivo. To investigate its significance in elderly patients, plasma DNA was assayed in 79 institutionalized patients over 68 years of age. The patients were divided into two groups: group I comprises 39 patients suffering from various acute or chronic illnesses; group II comprises 40 patients without chronic disease, and free of any clinical or biological symptoms of any infectious or inflammatory process. Plasma DNA was higher in group I than in group II (p < 0.0001) and in group II than in a control group of middle-aged subjects (p < 0.05). In group I, increase in plasma DNA concentration was found in various pathological situations associated with cell death phenomena, including infections, cancers with metastasis, hepatitis, irreversible cardiac failure, severe respiratory insufficiency and thrombophlebitis. Plasma DNA concentrations were not correlated with erythrocyte sedimentation rate, fibrinogen concentration, hemoglobin concentration or leukocyte count. In group I, as well as in the overall population, survival after 1 month was significantly reduced in patients with increased concentrations of plasma DNA. In conclusion, plasma DNA as a marker of cell death phenomena occurring in vivo, could be helpful for follow-up and management of elderly patients.

Quantitation of blood plasma DNA as an index of in vivo cytotoxicity.

Cell death triggers the release into extracellular spaces of products of chromatin catabolism, particularly of DNA. A sensitive DNA assay has been used to investigate in the mouse whether the quantitation of plasma DNA may be used as an index of in vivo cytotoxicity. It has been found that toxic doses of bacterial lipopolysaccharide, HgCl2, CCl4, cyclophosphamide and hydroxyurea, are responsible for the release of extracellular DNA in plasma, in a dose dependent relationship. In conclusion, quantitation of extracellular DNA may be used for investigating in vivo cell death phenomena induced by toxic agents and drugs. Such a method could be applied to toxicological studies in animals and man.

Extracellular DNA in blood and urine as a potential marker for cytotoxicity and nephrotoxicity in the mouse.

Cell death releases products of chromatin catabolism, particularly DNA, which can be measured by a DNA assay (using the nick translation reaction) as a marker of toxicity. Conditions for blood and urine collection have been established for quantitation of extracellular DNA in mice. Toxic doses of lipopolysaccharide (5 mg/kg) and HgCl2 (3.2 mg/kg) release DNA to plasma and urine. Increase in urinary DNA is observed 24 hours after a single injection (5 mg/kg) of gentamicin. Quantitation of extracellular DNA can be used to investigate the occurrence of cell death in vivo and applied to toxicological studies, in animals and man.

[Does extracellular DNA play a pathogenic role in the development of lupus glomerulonephritis?]. / Le DNA extracellulaire joue-t-il un rôle pathogène dans le développement des glomérulonéphrites lupiques?

Anti-DNA antibodies play a pathogenic role in the development of lupus nephritis. The role of extracellular DNA in the pathophysiology of lupus diseases is still controversial. It is possible that anti-DNA antibodies are elicited by antigens which cross-react with DNA and that they play their pathogenic role through direct binding on cell membrane or tissue components. Alternatively, experimental and clinical studies suggest that extracellular DNA might be involved in the induction of anti-DNA antibodies and that they might be pathogenic through the formation of immune complexes. Recent studies done on circulating DNA led to propose the hypothesis that cell death phenomena might play a major pathogenic role in the induction of auto-immune reactions and/or in the development of kidney lesions in lupus diseases.

Plasma DNA in patients undergoing hemodialysis or hemofiltration: cytolysis in artificial kidney is responsible for the release of DNA in circulation.

Levels of circulating DNA increase under treatment by an artificial kidney. Using a new assay, levels of plasma DNA are studied in 45 patients during 99 sessions of hemodialysis or hemofiltration. Before the session, plasma DNA levels are increased in 41/99 samples and, among them, in 18/24 samples collected from hepatitis B surface antigen carriers. During the first 3 h of the session, plasma DNA levels increase whatever the method of treatment. At the 30th and 60th minute of hemodialysis, a positive gradient of plasma DNA exists between the output and the input of the artificial kidney. It is concluded that: (1) the increase in plasma DNA is related to the overall procedure of artificial kidney therapy; (2) death of leukocytes in the artificial kidney is responsible for the release and the increase in circulation of extracellular DNA.

Rapidly progressive glomerulonephritis associated with amyloidosis: efficacy of plasma exchange.

This report describes one case of rapidly progressive glomerulonephritis associated with amyloidosis in a 53-year-old woman with rheumatoid arthritis, successfully treated with intensive plasma exchange and immunosuppression. Amyloid deposits were present in all of 20 glomeruli in the kidney biopsy specimen and eight out of nine nonfibrosed glomeruli contained crescents. With intensive plasma exchange and immunosuppressive drugs, renal function improved, and hemodialysis was discontinued. After 2 years, renal function was stable at a moderate level of impairment, but heavy proteinuria persisted.

[Treatment of renal colic with intravenous ketoprofen]. / Traitement de la colique néphrétique par le kétoprofène intraveineux.

In view of the part played by renal prostaglandins in the mechanisms responsible for pain in renal colic, it was worth trying to find out whether nonsteroidal anti-inflammatory agents, which inhibit prostaglandin synthesis, have an analgesic effect of their own. In a double-blind trial the effects of ketoprofen 100 mg administered intravenously alone or associated with noramidopyrine were investigated in 62 patients divided at random into two equal groups. A rapid analgesic effect was observed with no significant difference between the groups. No severe side-effects were recorded. The double-blind method made it possible to confirm that ketoprofen administered alone relieved pain in 97% of the patients (with complete sedation in 45%) and acted within 5 minutes. Owing to their effectiveness and safety nonsteroidal anti-inflammatory drugs (especially ketoprofen) may be proposed as an alternative to conventional treatments of renal colic. But because of their activity they should not be prescribed until a firm diagnosis has been made. The cause of the colic should also be rapidly determined in order to treat it as well as the pain it produces.

Renal side effect of nifedipine.

The possibility of a renal-related side effect from nifedipine has been investigated by comparing the effects on plasma creatinine level of coronary arteriography in two groups of patients: one group treated with nifedipine and the other treated with various drugs but without calcium inhibitor. Results showed a moderate (mean, 13%) but highly significant rise in the 27 patients receiving various drugs but no calcium inhibitor. Plasma creatinine change was not significant (mean, 3%) in the 26 patients treated with nifedipine. In the conditions of this study, this difference could only be related to nifedipine treatment. In conclusion, nifedipine may have exerted a protective effect against radiocontrast media nephrotoxicity, which deserves further investigation.

[Circulating immune complexes and bronchopulmonary cancers]. / Complexes immuns circulants et cancers broncho-pulmonaires.

This study of circulating immune complexes was carried out using a C1q radio-labelled complement fixation test in 162 patients suffering from broncho-pulmonary disease. There were a similar number of positive results in primary cancer (44%) or secondary (53%) in tuberculosis (37%) or other pathologies (64%). With primary causes neither the histological type nor the stage of extension were associated with any particular frequency of positive tests. The diagnostic interest of research into circulating immune complexes thus appears limited. This study shows however, the activation of humoral systems of immunity during the course of broncho-pulmonary diseases, and raises the prospect of qualitative studies into the nature of the antigen implicated and their role in the mechanism of defence of the organism.

Quantification of large C3 fragments as an index of complement activation in mice. I. In vitro studies.

This paper describes a method which enables one to evaluate the mouse C3 activation. It is based on differences of solubility of native and activated C3 molecules in polyethylene glycol. The apparent molecular weights of C3 molecules detected were found to be about 230-240 kilodaltons for native C3 and 210 and 220 kilodaltons, respectively, for the two 'activated' C3 molecules. In vitro studies showed the specificity and the sensitivity of this evaluation.

[Anomalies of human gonadal function in periodic hemodialysis: role of the etiology of kidney failure and the role of iron overload]. / Les anomalies de la fonction gonadique chez l'homme en hémodialyse périodique: rôle de l'étiologie de l'insuffisance rénale, rôle de la surcharge ferrique.

Levels of testosterone, free testosterone, oestrogen, LH, FSH, prolactin were measured in 39 dialysed men. A LHRH stimulation test was performed. This study was analysed in function of the underlying renal disease, the duration of hemodialysis, and serum ferritin levels. In chronic glomerulonephritis serum gonadotrophins concentrations were significantly higher than in chronic interstitial nephritis or polycystic disease. A correlation between prolactin and ferritin was found, which may reflect the pituitary iron overload. Free testosterone levels were significantly lower in patients with gynecomastia (23-29 patients). In fact, the most direct relationship that we found with gynecomastia in dialysed men was with the free testosterone/oestrogen ratio.