Evaluation of the impact of information about treatment-related risks in patients receiving blood-derived or recombinant medications.

The aims of the study were to evaluate the impact of a written information about treatment related risks in patient receiving blood derived or recombinant medications. Haemophiliac patients and patients with constitutional or acquired immune deficiencies are concerned by this treatment and these information. Our objectives are to evaluate the efficacy of the written information, the knowledge of the patients about these medications and the psychological, emotional impact if these information. The study is based on questionnaires which specified how the patient treat bleeding episodes, their knowledge about viral safety of blood products, the patient's perception of his or her health status and relationship with the physician. Psychological and emotional status are evaluated with the Hospital Anxiety and Depression Scale. The results show the difficulty to inform patients: if the information generate only limited anxiety in patients with haemophilia or immune deficiencies, we observe that the delivery of a written information got a mediocre effect on overall knowledge. We think that this information must be appropriate for patients and be communicated orally within the patient-physician relationship.

Plasma exchange and interferon-alpha pharmacokinetics in patients with hepatitis C virus-associated systemic vasculitis.

UNLABELLED: Different types of vasculitis have been reported in association with hepatitis C virus (HCV) infection, i.e. type II mixed cryoglobulinemia and polyarteritis nodosa (PAN). Therapeutic approach of such severely symptomatic patients include interferon-alpha (IFN) plus plasma exchange (PE). There are no data on IFN pharmacokinetic changes related to PE. PATIENTS AND METHODS: We studied 7 HCV-infected patients (mean age: 57 years) presenting with symptomatic type II mixed cryoglobulinemia (n = 5) or biopsy-proven PAN (n = 2). All patients underwent subcutaneous IFN therapy with concomitant PE. Serum IFN concentration was measured in serial samples on days with and without PE. RESULTS: Without PE, IFN C(max )(range: 100-750 IU/ml) was obtained 3-6 h after subcutaneous injection, followed by a 3- to 9-hour plateau. IFN concentration declined subsequently reaching a residual concentration 24 h after injection, ranging from 20 to 40 IU/ml. PE performed 6 h after IFN administration resulted in increased IFN clearance in that the concentration-time IFN-alpha area under the curve decreased from 3,005 IU x h/ml (1,563-4,614) on days without PE to 2,142 IU x h/ml (973-4,123) on day with PE. CONCLUSIONS: In patients with HCV-associated vasculitis, PE increase IFN clearance. Combined IFN-alpha and PE therapy schedule have to be further studied to optimize its biological activity.

A new approach for rapid detection and typing of serum monoclonal components.

When used independently, none of the routine methods to explore serum monoclonal components (MC), including: serum protein electrophoresis (SPE), immunoelectrophoresis (IEP), kappa to lambda ratio (KLR) and immunofixation (IFE), provides a comprehensive quantitative and qualitative identification of the MC. In the past few years the concept of 'protein profile', based on immunonephelometric quantifications of serum proteins, has become widely used. It consists of a qualitative and quantitative graphic representation of numerous serum proteins including immunoglobulins. Aim of study was to develop a multidimensional model based exclusively on protein profiles labeled the protein profile prediction method (PPPM) to improve routine MC detection and typing. Serum samples from 127 hospitalized patients and 99 healthy blood donors were submitted to all of the following: SPE, IFE, KLR and a protein profile (which included IgM, IgA, IgG, kappa and lambda chain detections and quantification). The presence of a MC using IFE was chosen as the gold standard. Healthy donors and patients were randomly divided into two groups defined as testing and validation groups. A logistic model was designed based on the protein profiles of the testing group leading to the determination of a threshold value (called Z(r)) for MC detection. It was then tested to detect MC in the validation group. Using IFE, 73 MC were found in the 127 hospitalized patients. Using the threshold value for MC detection of Z(r)=1.86, the PPPM showed greater sensitivity (94.6%) in detecting a MC compared to either SPE (64.8%) or KLR (89.2%). This result was obtained without diminished specificity (80.8%). The association of SPE or KLR to PPPM did not significantly increase the sensitivity of the PPPM. In the validation group, for samples which had a high predictive probability of a MC using PPPM, the correct MC typing was identified in up to 77% of sera using PPPM only. These results may be interesting in helping to determine when supplementary IFE analysis is required to qualitatively analyze a MC. PPPM allows MC detection with great sensitivity. The immune protein profile dramatically increases the sensitivity of either SPE and/or KLR in detecting MC and may also allow heavy and light chain typing.

Hemolytic and uremic syndrome after heart transplantation.

Two cases of hemolytic and uremic syndrome in heart transplant recipients are reported. Among solid organ transplantations, this complication mainly occurred in renal transplantation and only 1 case was reported in heart transplantation in the literature. Cyclosporine was the only etiologic factor found. The renal outcome was severe with end-stage renal failure and no recovery of the renal function despite stopping cyclosporine, corticoids and plasma exchange.

Oxidizability of atherogenic low-density lipoprotein subspecies in severe familial hypercholesterolemia: impact of long-term low-density lipoprotein apheresis.

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) plays a key role in the pathophysiology of atherosclerosis. LDL-apheresis, which involves direct removal of plasma LDL from circulating blood, is an efficient treatment of homozygous familial hypercholesterolemia (FH). METHODS: We evaluated impact of long-term LDL apheresis treatment on the atherogenicity of the major LDL subclasses (light, LDL1, and LDL2, density [d] 1.018-1.030 g/mL; intermediate, LDL3, d 1.030-1.040 g/mL, and dense LDL, LDL4 and LDL5, d 1.040-1.065 g/mL) separated by density gradient ultracentrifugation in severe FH patients. Therefore, we compared the oxidative resistance as well as the chemical and physical properties of each LDL subpopulation in the FH group with those in the corresponding LDL subfractions from normocholesterolemic control subjects. RESULTS: Both intermediate and dense LDL subfractions were significantly more resistant to copper-mediated oxidation in FH patients treated regularly by LDL-apheresis than their counterpart controls. The lag phases for LDL3, LDL4, and LDL5: 63.9+/-11.6, 55.8+/-1.2, and 47.2+/-6.5 min. in FH patients were significantly longer than those of the corresponding subfractions in normocholesterolemic controls (P <.01 for LDL3 and LDL5, P<.005 for LDL4). This protective effect was reflected in the delayed formation of biologically active lipid oxidation products such as oxysterols, lipid hydroperoxides, dienes, and dienals in the intermediate and dense LDL subfractions of FH patients. These findings may result from lower "seed" contents of lipid hydroperoxide (LOOH) detected as dienes in plasma LDL from apheresis-treated FH patients; indeed, baseline LOOH/diene contents in all 5 LDL subclasses from FH patients were significantly lower than those of the corresponding subclasses in normolipidemic subjects (P<.0005). On the other hand, the enhanced oxidative resistance of both intermediate (LDL3) and dense (LDL4 and LDL5) LDL subpopulations in FH patients could not be accounted for by any consistent modification in chemical composition or in lipophilic antioxidant content, although minor differences were observed between patients and controls in unsaturated fatty acid profile. In contrast, sphingomyelin content was enriched in FH LDL subclasses, potentially resulting in reduced penetration of the hydrophilic surface layer of LDL by oxygen radicals. CONCLUSION: We conclude that low concentrations of preformed lipid hydroperoxides and dienes, together with surface sphingomyelin enrichment, can account for the enhanced oxidative resistance of intermediate (LDL3) and atherogenic dense LDL (LDL4, LDL5) induced by long-term LDL apheresis in severe FH patients.

[LDL-apheresis therapy, methods and indications]. / Traitement par LDL-aphérèse, techniques et indications.

A SEVERE DISEASE: Homozygote hyper cholestrolemia is a very severe disease with an extremely high atherogenic potential. The risk of sudden death starts at about the age of 10 years and mortality reaches nearly 100% at 20 years. In this homozygote autosomal dominant disorder, serum cholesterol rises above 6 g/l due to a total deficiency of LDL-receptors. LDL-APHERESIS: The treatment of choice, LDL-apheresis, is an aggressive treatment. Drug regimens and palliative surgery have little or no effect. Liver transplantation is highly effective but compromises long term prognosis. LDL-apheresis, indicated in case of drug resistance, can be used to clear atherogenic LDL particles extracorporally. Currently it is the most effective means of lowering serum cholesterol in these patients and avoid potential cardiovascular complications. SEVERAL TECHNIQUES: The most specific techniques are also the most costly. These techniques allow treating whole blood or previously separated plasma. Such specific techniques are indicated in children. Compared with other European countries such as Germany, the development of these techniques has been retarded in France due to the lack of financing by the national health insurance system.

[The plasma antioxidant status and trace elements in patients with familial hypercholesterolemia treated with LDL-apheresis]. / Statut plasmatique en antioxydants et en oligoéléments de patients atteints d'hypercholestérolémie familiale traités par LDL-aphérèse.

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamin A and E and beta-carotene. Trace elements such as selenium, zinc and copper are involved in the activity of antioxidant enzymes: glutathione peroxidase and superoxide dismutase. The aim of this work was to determine the antioxidant and trace elements status of patients with very severe hypercholesterolemia and who were treated by dextran sulphate low density lipoprotein apheresis, in comparison with two control populations: one constituted by normocholesterolemic subjects and the other by hypercholesterolemic patients before treatment. Our results showed that, as compared with normocholesterolemic subjects, patients treated by LDL-apheresis were not deficient in vitamin E, beta-carotene and copper but had low plasma levels of selenium, zinc and vitamin A. The low selenium and vitamin A levels were due to the treatment by LDL-apheresis by itself, while the hypercholesterolemia of these patients might have provoked the low plasma levels of zinc. This study pointed out the interest of a supplement of selenium, zinc and vitamin A in patients treated by LDL-apheresis.

Antioxidant status of hypercholesterolemic patients treated with LDL apheresis.

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamins A and E and beta-carotene. Trace elements, such as selenium, zinc, and copper, are involved in the activity of the antioxidant enzymes glutathione peroxidase and superoxide dismutase. The aim of this study was to determine the antioxidant and trace element status of patients with severe hypercholesterolemia who had been treated with dextran-sulphate low-density lipoprotein apheresis in comparison with two control populations, normocholesterolemic subjects and untreated hypercholesterolemic patients. Our results showed that, patients treated with LDL apheresis, compared with normocholesteromic subjects, were not deficient in vitamin E, beta-carotene, and copper, but had lower plasma levels of selenium, zinc, and vitamin A. The low selenium and vitamin A levels were due to the LDL-apheresis treatment, and the hypercholesterolemia might have provoked the low plasma levels of zinc. The study pointed out the potential benefits of supplemental selenium, zinc, and vitamin A in patients being treated with LDL apheresis.

Prévalence des anticorps du virus de l'hépatite C chez des donneurs de sang et des malades transfusés à Cotonou au Benin

Dans une etude prospective; les auteurs ont determine la prevalence des anticorps anti-VHC chez les donneurs de sang; les malades drepanocytaires polytransfuses et non transfuses. La prevalence de portage d'anticorps dans chacun des groupes etait respectivement de 1;4 pour cent; 16 pour cent et 0 pour cent. Le nombre de produits potentiellement contaminants etant de 140 par an; le risque de contamination par le sang est donc eleve. Il est donc important de tout mettre en oeuvre pour la recherche des anticorps anti-VHC chez les donneurs de sang

Blood antioxidants (vitamin E and beta-carotene) in long-term low density lipoprotein apheresis.

We measured vitamin E and beta-carotene in the serum and in circulating lipoproteins in a large population of 15 patients with familial hypercholesterolaemia who were undergoing long-term treatment by low density lipoprotein (LDL) apheresis. The technique used for apheresis was dextran sulphate cellulose adsorption. The results showed that before LDL apheresis, patients had high vitamin E and normal beta-carotene levels in the serum and in the VLDL+LDL fraction. There were no relationships between serum levels of vitamin E and beta-carotene and the duration of LDL-apheresis. Low vitamin E and beta-carotene levels in the HDL fraction could be related to the low HDL concentrations in these patients. Vitamin E/cholesterol ratios were similar to those of the normolipaemic controls whereas beta-carotene/cholesterol ratios were lower. After LDL-apheresis treatment, the ratios in the HDL fraction fell whereas the ratios in the serum and in the VLDL and LDL fraction did not change. This study shows that these patients exhibited no deficiency in either serum of VLDL-LDL of vitamin E or beta-carotene after long-term treatment by LDL-apheresis and that the status of these antioxidants in serum was independent of the duration of treatment.

[Biological efficacy of LDL apheresis in major hypercholesterolemia]. / Efficacité biologique des LDL aphérèses dans les hypercholestérolémies majeures.

Severe hypercholesterolaemia include familial homozygous hypercholesterolaemia and certain heterozygous hypercholesterolaemias which become severe, due to spontaneous non-response to treatment or to iatrogenic side effects. Other causes include an associated overload in Lp(a) or uncontrolled atheromatous disease. Surgical treatment has been replaced by iterative LDL apheresis in these severe forms. Mean cholesterol and LDL cholesterol levels can be reduced by 41 to 63% and 49 to 68% respectively with LDL apheresis. In general, HDL cholesterol is protected in selective LDL apheresis. We observed similar decrease for apo B and LDL cholesterol levels. Fifty percent of the Lp(a) was removed in the 3 groups of patients studied.

[Cholestatic viral hepatitis A in adults. Clinical, biological and histopathological study of 9 cases]. / Hépatite virale A cholestatique de l'adulte. Etude clinique, biologique et histopathologique de 9 cas.

OBJECTIVES: We report here 9 cases of acute viral hepatitis A leading to hospitalization between June 1989 and October 1992. The main feature was a marked and protracted cholestasis. RESULTS: Jaundice lasted an average of 77 +/- 39 days (range: 30-120) and total serum bilirubin concentrations were 265 +/- 184 mumol/L (range: 51-560). IgM anti-HAV was present in the serum for 6.3 +/- 5.5 months (median: 4, range: 2-19). Histopathological examination of the liver was performed in 6 patients and most showed intralobular cholestasis and portal tract inflammation associated with dystrophy and paucity of bile ducts. Acute renal failure was noted in one patient. In three patients, whose pruritus was not relieved by cholestyramine, plasma exchange was an effective therapy. CONCLUSION: These case reports confirm the severity of viral hepatitis A in adults and emphasize the importance of vaccination.

[Western blotting analysis of cryoglobulins associated with chronic hepatitis C]. / Analyse en western blot des cryoglobulines associées aux hépatites chroniques C.

In a prospective study, a monoclonal component was found in 29/89 (33%) of mixed cryoglobulinemia (MC) associated with hepatitis C virus (HCV) infection, with a IgM in 87% of cases and a Kappa/Lambda ratio at 1.8. HCV RNA anti-HCV antibodies were demonstrated in both MC with and without monoclonal component.

Gd-DOTA: evaluation of its renal tolerance in patients with chronic renal failure.

Gd-DOTA is an intravenous contrast medium used in MRI. The clinical and biological tolerance of Gd-DOTA was studied in patients with chronic renal failure (e.g., those having a glomerular filtration rate of less than 60 mL/min). Twenty patients were randomized into two groups. In the control group, spin-echo (SE) T1- and T2-weighted images of the kidneys were obtained without injection of Gd-DOTA. In the DOTA-group, patients received 0.1 mmol/kg of Gd-DOTA. SE T1-weighted images were obtained before and after injections; a T2-weighted sequence was performed before injection. Clinical data, serum creatinine, and laboratory parameters were estimated before, and 24 and 48 hr after MRI. No adverse reaction was reported after injection of Gd-DOTA. Mean serum creatinine and glomerular filtration rate remained unchanged in both groups. For five patients in the control group and three patients in the DOTA-group the serum creatinine levels increased more than 10% and less than 25%. No evidence of nephrotoxicity was observed with Gd-DOTA in patients with chronic renal failure.

[Comparison between treatments of severe forms of familial hypercholesterolemia by total plasma exchange and selective removal of low density lipoproteins (LDLapheresis)]. / Comparaison des traitements des formes sévères d'hypercholestérolémie familiale par échange plasmatique total et épuration sélective des lipoprotéines de basse densité (LDLaphérèse).

A plasma exchange program for familial hypercholesterolaemia was started in 1982. Ten patients aged from 7 to 58 years were progressively included: 3 had an heterozygous form of the disease with ischaemic heart disease; 3 had an homozygous form with defective low density lipoprotein receptor activity, 4 had a receptor-negative homozygous familial hypercholesterolaemia and had previously undergone portacaval shunt. During total plasma exchange against human albumin (470 sessions in 9 patients) low density lipoprotein cholesterol values, but also high density lipoprotein cholesterol values, decreased by 40 per cent. More recently, 5 patients had selective low density lipoprotein absorption on dextran sulfate column (Liposorber); 90 exchanges were performed. High density lipoprotein cholesterol values decreased by 55 per cent and high density lipoprotein cholesterol values by only 27 per cent. The patients' attitude to treatment was excellent, with less fatigue and better compliance.

Prospective study of HIV I seropositive patients in hemodialysis centers.

A prospective multicenter study was undertaken between February 1985 and August 1986 in 4 hemodialysis centers in the Paris area (France) in order to assess the prevalence of HIV I infection and the risk of transmission of the virus within the centers. A four-month follow-up was carried out in 221 patients undergoing hemodialysis (HD) and in 40 staff members caring for the patients in 2 centers. 62 patients undergoing peritoneal dialysis (PD) and 126 hemodialysis patients who transited through a center (HDT) were screened once. A questionnaire exploring risk factors was completed for each patient and staff member. Sera were tested for HIV I antibodies by ELISA (ELAVIA) and confirmed by Western Blot. Of the 347 HD + HDT patients, 4 were found to be positive. Of the 221 HD patients, 1 multi-transfused hemophiliac and 1 multitransfused Nigerian without other risk factors were positive in the first screening. Another patient seroconverted after transfusion during the study; no other risk factors existed and the donor has not yet been found. One of the 126 HDT patients had received infected plasma. No staff members or PD patients were positive. No transmission within centers, from patient-to-patient or patient-to-staff was evidenced. Although HIV I seems to be less infectious than HBV, precautions to prevent transmission of HIV I in dialysis centers should be maintained.