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Biomedical subjects

M Kazatchkine

Publications and source records attributed to M Kazatchkine.

At least 37 records · Page 2Linked to original sources

Treatment of mixed cryoglobulinemia with recombinant interferon alpha and adjuvant therapies. A prospective study on 20 patients.

In order to evaluate the efficacy of interferon alpha (IFNa) in mixed cryoglobulinemia (MC), a prospective multicenter clinical trial was conduced in April 1992. It consisted of treating 20 clinically symptomatic MC patients with IFNa for 26 weeks. Hepatitis C virus (HCV) infection was detected in 16 patients. A complete or partial clinical remission was obtained in 12 patients (60%). Eleven of these 12 responders (91.6%) experienced a clinical relapse less than 12 months after the end of therapy. Side effects were noted in 10 patients (50%). It was concluded that subcutaneously administered IFNa does not provide long-term remission.

Adrenal Cortex Hormones↗

[Desensitization to trimethoprim-sulfamethoxazole in patients with HIV infection].

OBJECTIVE: To evaluate the safety and efficacy of an in-patient oral desensitization regimen in HIV- infected patients hypersensitive to trimethoprim-sulfamethoxazole (TMP-SMX). METHODS: TMP-SMX was given orally once a day using incremental doses every day, starting with 0.4 mg TMP/2 mg SMX at day 4 and achieving a full dosage of TMP-SMX (80 mg/400 mg) at day 5. Success was defined as clinical tolerance of the final dose for more than 10 days following completion of the procedure. RESULTS: Desensitization was successfully completed in 29 of 30 patients. A transient rash occurred in one patient during desensitization and resolved without need for discontinuation of the desensitization protocol. The procedure failed in one patient who experienced sustained moderate cutaneous reaction with fever on day 5. CONCLUSIONS: Our results suggest the safety and efficacy of an inpatient oral desensitization regimen in 30 HIV-infected patients who had experienced cutaneous reactions to trimethoprim-sulfamethoxazole (TMP-SMX). Specific desensitization to TMP-SMX allows to circumvent the limitations towards effective prophylaxis of PCP that are dependent on the occurrence of cutaneous reactions to the drug.

Acquired Immunodeficiency Syndrome↗

[Lipoprotein anomalies in HIV infections].

Alterations in lipid parameters occur during many acute infections. Different studies suggest that variations in lipid parameters can be used as markers of the progression of human immunodeficiency virus (HIV) infection. Hypocholesterolemia is observed in asymptomatic HIV+ subjects, then hypertriglyceridemia appears in patients with AIDS. Several hypotheses have been raised concerning the potential causes and consequences of these modifications. Cytokine effects on different enzymes of lipid metabolism, studied in vitro and in vivo, are thought to be partially responsible for the dyslipidemia. Hypertriglyceridemia could participate in cachexia and dementia could be facilitated by the changes in cholesterol metabolism. The use of the lipid parameters is proposed in HIV positive subjects, especially during anti-viral treatment.

Cholesterol↗

[Splenic infarction in a HIV-infected patient. Apropos of a case and review of the literature].

Incomplete ischemia of the celiac trunk due to arterial thrombosis occurred in a patient infected with the HIV. Ischemia led to infarct of the spleen and pancreatitis. Endoluminal desobstruction of the arterial trunk then medical management after exploratory laparoscopy were successful without splenectomy. The causes, diagnostic methods and treatments for splenic infarction in HIV-infected patients are discussed with a review of the literature.

Acquired Immunodeficiency Syndrome↗

Role of laparoscopic surgery in the management of acute abdomen in the HIV-positive patients.

Emergency open laparotomy in patients infected with HIV is accompanied by high mortality. The authors investigated the potential role of a laparoscopic approach for the management of acute abdomen in such patients. Prospectively, 10 patients with HIV disease (9 with AIDS) underwent laparoscopy for acute abdomen. The treatment was exclusively laparoscopic in 6 patients. A conversion to laparotomy was necessary in 4 patients but through guided elective incision in 3 of them. The postoperative course was uneventful in all patients but 1, who died. We advocate a laparoscopic approach, when feasible, as an initial step in the management of acute abdomen in HIV-positive patients.

Abdomen, Acute↗

[Managing of an innovation in health care: the case of polyvalent intravenous immunoglobulins at the Assistance-Publique-Hôpitaux de Paris].

Managing new innovations in medicine is a particularly timely subject. There is an abundant history concerning over expectations resulting from the development of new treatments or diagnostic procedures, some shown to be less effective than promised, others even found to be dangerous. A new aspect to the question is the importance of economic pressures which require rational investment decisions when diffusing innovating technologies. In 1991, the Commission for the evaluation and diffusion of innovating technologies (CEDIT) at the University Hospitals of Paris (Assistance Publique-Hôpitaux de Paris) developed a programme aimed at better managing the distribution and use of polyvalent intravenous immunoglobulins (IgIV), a new promising therapeutic tool with both a high cost and a certain number of risks. The programme was designed to assist prescribers in elaborating better therapeutic strategies and to help hospital managers rationalize expenditures for IgIV. The results of this experience are presented here together with certain conclusions concerning the way management decisions can be applied to the diffusion of an innovation in health care.

Diffusion of Innovation↗

[Idiopathic CD4 lymphocytopenia].

In healthy adults the CD4+ lymphocyte count in circulating blood is remarkably stable over a prolonged period. In patients infected with the human immunodeficiency virus (HIV) CD4 counts drop off sharply and can be used as a predictive marker of midterm outcome. However certain case reports of patients with out HIV infection, some reported as early as 1983, have led to a much publicized search for another immunosuppressive retrovirus. In reality no evidence of any such virus has been found and the Centers for Disease Control and the World Health Organisation have now defined the syndrome of idiopathic CD4 lymphocytopenia which includes a CD4 count below 300/mm3 or less than 20% of total lymphocytes in at least two successive counts without anti-HIV antibodies and without a known cause of immune deficiency or immunosuppressor treatment. The syndrome is extremely rare and although only recently identified, is probably not new. No endemic zone is known and there is no evidence of inter-human transmission. The clinical presentation is different from HIV infection. Although patients are susceptible to opportunistic infections, CD4 counts have relative stability and no hypergammaglobulinaemia occurs. Idiopathic CD4 lymphopenia is probably a primary immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗

Immune modulating effects of intravenous immunoglobulin (IVIg) in autoimmune diseases.

Administration of intravenous immunoglobulins (IVIg) have now been reported to be beneficial in a large number of autoimmune diseases, whether mediated by autoantibodies or by T cells. We have proposed that the immunoregulatory effect of IVIg in autoimmune diseases is dependent on the selection of recipient's immune repertoires by variable (V) regions of infused immunoglobulins. Thus: (a) IVIg contains antibodies reactive with idiotypes of natural and disease-related autoantibodies and surface immunoglobulins of B cells; IVIg also contains antibodies reactive with idiotype, framework and constant regions of the beta chain of the alpha beta T cell receptor; (b) infusion of IVIg results in transient or long-lasting suppression of specific autoantibody clones in vivo and in stimulation of a distinct subset of B cells reactive with F(ab')2 fragments of IVIg; (c) infusion of IVIg alters the general "architecture" of the network as assessed by studying the kinetic patterns of spontaneous fluctuations of natural autoantibodies in serum; (d) infusion of normal mouse Ig in healthy adult mice selects expressed immune repertoire by removing late pre-B and B cells in the bone marrow, mostly those expressing D proximal VH genes, and by activating distinct subsets of B cells and CD4+ T cells in the spleen; and (e) infusion of IVIg results in a modulation of synthesis and release of cytokines. Although dependent on the V-region reactivities (composition) or injected preparations, these effects probably also require that the infused immunoglobulin contains an intact Fc moiety. This review focuses on autoimmune and inflammatory diseases in which IVIg therapy has been beneficial. Recent recommendations from a committee of experts for IVIg therapy have been pointed out.

Adjuvants, Immunologic↗

Revisited indications for bone marrow examinations in HIV-infected patients.

We reviewed the indications for and the results of bone marrow examination (BME) from HIV-infected patients as an attempt to improve its diagnostic yield. One-hundred-and-eight bone marrow specimens from 90 patients during a 3-year period were examined. A cytological, histological and microbiological study was carried out on the specimens. Forty-three evaluable examinations (40% of total) performed for cytopenia showed normo- or hypercellularity in 33 (77%). Fifty bone marrow specimens were cultured for mycobacteria with a yield of 42% when the indication was persistent fever. Positive cultures yielded Mycobacterium avium complex in 8 out of 12 patients. Twenty-seven patients had both culture and biopsy; granulomas were associated with all the positive (10/10) and with 1 out of 17 negative cultures (chi-square test: p < 0.001). A bone marrow involvement with lymphoma was found in 2 out of 6 patients with previously diagnosed lymphoma, and biopsy revealed a lymphoma in 2 patients. Morphological bone marrow examination should be associated with other techniques in order to appreciate bone marrow production. Bone marrow biopsy is useful for the investigation of persistent fever since granulomas suggestive of disseminated mycobacteria are frequent and allow a treatment to be initiated before microbiological confirmation and antibiotic susceptibility test.

Adolescent↗

Regulation by sulphonate groups of complement activation induced by hydroxymethyl groups on polystyrene surfaces.

Reducing the complement-activating capacity of a polymer surface is important in improving its blood compatibility. Polystyrene surfaces bearing hydroxymethyl (CH2OH) groups activate the alternative pathway of complement. This activation depends strongly on the density of the groups. Polystyrene surfaces bearing sulphonate (SO3-) groups adsorb proteins, resulting in an apparent activation. Polystyrene surfaces bearing both types of groups in close proportions are not activators in human serum, due to the adsorption of a protein of the alternative pathway, which has a protecting effect, not found when a polymer surface bearing hydroxyl groups is mixed in serum with another polymer surface bearing SO3- groups. In the presence of purified proteins of alternative pathway, C3 convertase activity can be created on each of these surfaces by deposition of C3b, but their susceptibility to inactivation by regulatory proteins H and I depends on the types of chemical groups present on the surface and whether the surfaces were passivated or not before C3b deposition.

Adsorption↗

The detection of CR1 mRNA and CR1 antigen identifies the presence of immature podocytes in a case of Wilms' tumor (nephroblastoma).

Wilms' tumors (nephroblastomas) are heterogeneous tumors consisting of proliferating epithelial cells in glomeruloid bodies and tubule formations and of proliferating blastemal cells. Using a specific CR1 35S-labeled cDNA probe and CR1 antibodies, CR1 mRNA and CR1 antigen-expressing cells were detected in glomeruloid bodies in one case of Wilm's tumor. The concomitant expression of CR1 mRNA and CR1 antigen and the high level of CR1 mRNA expression that characterize podocytes at an early stage of glomerular maturation in the normal human fetal kidneys indicates that glomeruloid bodies are composed of immature podocytes.

DNA Probes↗

Renal disease associated with HIV infection: a multicentric study of 60 patients from Paris hospitals.

Sixty HIV-infected patients presenting renal symptoms who underwent percutaneous renal biopsies were analysed. According to the CDC classification, 44 patients were staged in group IV, five in group III, and 11 in group II. Patients were divided in two groups according to their ethnic origin (29 black patients and 31 white patients). Risk factors such as homosexuality, multiple transfusions or intravenous drug abuse (IVDA) were identified in all white patients except two, but in only nine (31%) of the black patients. Three main patterns of renal disease were observed: focal and segmental glomerulosclerosis (FSGS) was found predominantly in black patients (23 black patients versus 3 Caucasians, P < 0.001) and was associated with the nephrotic syndrome; immune-complex-type glomerulonephritis (ICGN) was frequent in black and white patients (21% and 52% respectively) including four cases of IgA nephritis all seen in white patients; and 10 cases of lupus-like nephritis (4 black and 6 white patients). The frequent hypergammaglobulinaemia in those patients suggests a pathogenic role of polyclonal B cell activation in ICGN. Interstitial nephritis was present in 48 and 52% of the black and white patients respectively and did not seem related to drug toxicity or superimposed infectious disease. In addition to interstitial nephritis, the coexistence of multivisceral lymphocytic infiltration involving accessory salivary glands, liver and/or lung, found in six patients possibly suggests a virus-induced immune disorder.

AIDS-Associated Nephropathy↗

[Mechanisms of action of intravenous immunoglobulins in the treatment of autoimmune diseases].

Administration of intravenous immunoglobulins (IVIg) has been reported to be beneficial in a large number of autoimmune diseases, whether mediated by autoantibodies or by T cells. Immunoregulatory effect of IVIg in autoimmune diseases is dependent on the interaction of the Fc portion of IVIg with Fc receptor on leukocytes and on the selection of recipient's immune repertoires by variable (V) regions of infused immunoglobulins. Thus: a) IVIg contains antibodies reactive with idiotypes of natural and disease-related autoantibodies and surface immunoglobulins of B cells; IVIg also contains antibodies reactive with idiotype, framework and constant regions of the beta chain of the T cell receptor; b) infusion of IVIg results in transient or long lasting suppression of specific autoantibody clones in vivo; c) infusion of IVIg alters the general "architecture" of the network as assessed by studying the kinetic patterns of spontaneous fluctuations of natural autoantibodies in serum; d) infusion of IVIg results in a modulation of synthesis and release of cytokines. This review points out mechanisms of action of IVIg in autoimmune and inflammatory diseases, focussing on those depending on V region of infused immunoglobulins.

Animals↗

Hypocomplementemic urticarial vasculitis syndrome, Jaccoud's syndrome, valvulopathy: a new syndromic combination.

We describe 3 cases of hypocomplementemic urticarial vasculitis syndrome (HUVS) with Jaccoud's hands deformity and cardiac valve disease (aortic regurgitation, mitral regurgitation, mitral disease). In one case, the valve lesions required valve replacement and later a heart transplant. Valve disease and articular deformities developed 2 and 4 years, respectively, after the onset of HUVS. This as yet undescribed combination of diseases suggests a new syndrome. Pathogenesis of periarticular and cardiac lesions is unknown. The role of Clq and anti-Clq antibody is discussed.

Adult↗

Population dynamics of natural antibodies in normal and autoimmune individuals.

We have measured the quantities of naturally occurring autoantibodies in the serum of normal, unmanipulated individuals. These changes over time following broad-band complex dynamical patterns that are similar in mouse and man. The patterns more likely reflect the network architecture of the natural antibody repertoire, regulating the activation and decay of individual clones. The temporal changes of both disease-specific and nonspecific autoantibodies are consistently modified in autoimmune individuals.

Animals↗