[Lymphoproliferative syndromes after renal transplantation]. / Syndromes lymphoprolifératifs après transplantation rénale.

UNLABELLED: Following kidney transplantation, lymphoproliferative disorders (LD) are encountered at a frequency of 1%. The onset of these LD is correlated with the degree of immunosuppression. The mortality is elevated (> 50%) especially in late forms. Since 1984 we have performed two hundred and seventeen kidney transplantations. The patients received sequential quadruple-drug immunosuppressive therapy: antilymphocyte globulin (ALG), azathioprine, corticosteroids and cyclosporine. A diagnosis of LD was established in ten patients, four were of early onset (within twelve months of transplantation) and six late (after five to nine years). Rejection occurred in two patients, one of which was steroid resistant requiring ALG. Three LD arose from the graft hilum, four had a voluminous tumor mass with extranodal sites: the graft (1), stomach (2), gingiva (1), meninges (1), and bone marrow (1). Histologically there were eight cases of large-cell B lymphoma, 1 mononucleosis-like LD, and a MALT lymphoma. A search for EBV was positive seven times. Treatment consisted of decreasing immunosuppressive therapy only (1), combined with antiviral treatment (1), or with surgical removal of the graft (3), and/or chemotherapy (5). Nine patients are still alive, in complete remission, graft loss occurred in four cases. CONCLUSION: In our series, we found a high frequency of LD. Despite 4 LD with a voluminous tumor mass and unfavorable histological prognosis requiring chemotherapy, all the LD in our series had a favorable outcome.

Heparinase III limits rat arterial smooth muscle cell proliferation in vitro and in vivo.

Heparinase III degrades heparan sulfate proteoglycans, which are co-receptors for growth factors that stimulate arterial proliferation. We assessed the ability of locally-delivered heparinase III to limit medial vascular smooth muscle cell proliferation induced by balloon catheter injury in rat carotid arteries. Whereas vehicle-treated arteries showed 12% of smooth muscle cells proliferating after 2 days, heparinase III (0.022-5.7 mg/kg) treated arteries showed 0.8-4%. Chemically-inactivated heparinase III did not limit proliferation. In isolated rat A10 vascular smooth muscle cells, heparinase III (1 IU/ml) inhibited both PDGF-BB and bFGF mediated increases in proliferation and migration. These results suggest that heparinase III can limit proliferation by affecting heparan sulfate proteoglycan binding growth factors following arterial injury.

Determinants and mechanisms of flecainide-induced promotion of ventricular tachycardia in anesthetized dogs.

BACKGROUND: Class IC antiarrhythmic agents such as flecainide are known to have potentially significant ventricular proarrhythmic actions, but the underlying mechanisms are incompletely understood. While some studies have reported proarrhythmia in both healthy dogs and dogs that previously have had a myocardial infarction (MI), there are no published, controlled studies comparing proarrhythmia in healthy dogs vs in dogs with MI. In addition, the concentration dependence of proarrhythmia is unknown and the electrophysiological changes associated with proarrhythmia are not well established. METHODS: We administered successive loading and maintenance infusions of flecainide until ventricular tachyarrhythmia or death occurred in 13 healthy dogs and 19 dogs with 72-hour-old MIs (MI dogs). Ventricular proarrhythmia, defined as reproducible ventricular tachycardia absent under control conditions and occurring in the presence of flecainide, was observed in 4 of 13 healthy dogs (31%) and 15 of 19 MI dogs (79%, P = .02), and drug-induced spontaneous ventricular tachycardia occurred in 8 of 19 MI dogs but in no healthy dogs (P = .007). Activation data at the time of proarrhythmia were available for 11 MI dogs and provided evidence for reentry in 9, with a complete epicardial reentry circuit identified in 4 dogs and a partial circuit in 5. While flecainide slowed ventricular conduction in both the longitudinal and transverse directions, there were no significant differences between overall drug-induced conduction changes in MI dogs compared with healthy dogs. However, in 7 MI dogs for whom activation data were available during ventricular pacing at concentrations comparable to those causing proarrhythmia, flecainide induced a new arc of block in 6 of 7, whereas an arc of block was never observed in the absence of proarrhythmia. Conduction block was induced transverse to fiber orientation in a rate-dependent fashion and was caused by a regionally-specific effect of the drug. No differences were noted between refractory periods proximal and distal to the site of block. CONCLUSIONS: Prior MI strongly predisposes dogs to flecainide proarrhythmia, which occurs in the majority of such dogs in a concentration-related way. In most cases, activation data suggest that anisotropic reentry around a localized arc of rate-dependent transverse conduction block underlies proarrhythmia. These results provide insights into the conditions and mechanisms underlying the ability of flecainide to promote the occurrence of ventricular tachycardia.

Prevalence of antibodies to hepatitis C virus among patients with leprosy in several African countries and the Yemen.

The prevalence of anti-HCV was determined in 1,309 leprosy patients and a control group of 1,469 subjects from 6 sub-Saharan African countries and the Yemen. Sera found positive by an initial second generation ELISA were subjected to 3 additional confirmatory tests. The anti-HCV prevalence in leprosy patients (7.1%) was significantly higher than in the control group (2.6%). HCV seroprevalence increased with age in both the control and leprosy groups. No statistically significant difference could be found between anti-HCV prevalence and the several clinical forms of leprosy among patients. The results of this study indicate a high degree of exposure or chronic carriage of hepatitis C among leprosy patients.

[Systemic signs of primary Gougerot-Sjögren syndrome. 48 cases]. / Signes systémiques du syndrome de Goujerot-Sjögren primitif. 48 observations.

Forty-eight patients with primary Sjögren syndrome are documented together with the results of their baseline investigations. The majority of patients were female (44 out of 48) and mean age was 63.2 years. Common clinical features included 20 parenchymal lung disease, among which 4 had interstitial pulmonary fibrosis and 2 lymphocytic interstitial pneumonitis, 12 neurologic manifestations, 16 Raynaud's phenomenon, 12 arthritis, and 3 gastrointestinal involvement. Haematological features occurred in 15 patients and another autoimmune disease was encountered in 13 cases. These extraglandular manifestations were the dominating reasons for hospital referral in 43.5% of cases, the sicca syndrome were most often only mentioned by the patients after special questioning which explain considerable delay before the diagnosis.

Modulation of flecainide's cardiac sodium channel blocking actions by extracellular sodium: a possible cellular mechanism for the action of sodium salts in flecainide cardiotoxicity.

Sodium salts reverse the clinical cardiotoxicity of class 1c antiarrhythmic agents, but the underlying mechanisms are unknown. We studied the modulation of flecainide's action by changes in extracellular sodium concentration ([Na+]e) produced by isotonic substitution of choline for sodium. Increasing [Na+]e by 25 mM attenuated the depressant effects of 3.2 microM flecainide of Vmax in canine cardiac Purkinje fibers, whereas decreasing [Na+]e enhanced drug action. The voltage dependence of Vmax was shifted by flecainide (activation potential for 50% decrease in Vmax, V50: -77.4 +/- 3.5 mV at 3.2 microM flecainide) compared to control (V50: -73.7 +/- 2.8 mV, mean +/- S.D., P < .05). Increasing [Na+]e in the presence of flecainide returned V50 toward control (-75.8 +/- 3.1 mV, P < .05 vs. flecainide at normal [Na+]e). Increased [Na+]e shifted the flecainide concentration-response curve to the right (EC50 19.0 microM) compared to normal (EC50 14.6 microM) and low (EC50 10.8 microM) [Na+]e. [Na+]e modulated the concentration-dependent displacement by flecainide of [3H]batrachotoxin-A-benzoate, with increased [Na+]e shifting the binding curve to the right and decreased [Na+]e shifting it to the left compared to normal [Na+]e. There was a strong linear correlation (r = 0.99) between flecainide's EC50 for Vmax depression and its IC50 for [3H]batrachotoxin-A-benzoate displacement at various [Na+]e. We conclude that [Na+]e modulates flecainide's interaction with the sodium channel. Sodium's ability to displace blocking drug from the sodium channel may underlie the efficacy of sodium salts in treating flecainide toxicity, and could play a similar role in antagonizing cardiotoxicity of other class 1 compounds.

Prevalence of hepatitis C virus antibodies in the general population and in selected groups of patients in Limoges, France.

In this study of hepatitis C virus (HCV) infection prevalence in France, the prevalence of antibodies to HCV (as tested by second generation ELISA, with RIBA-2 confirmation in ELISA 2 positive samples) was found to be low (0.3%) in the healthy general population. HCV infection prevalence increased in the general population in association with African or Asian origin and risk factors such as bisexuality, previous history of transfusion, and intravenous drug abuse. The prevalence of anti-HCV infection was also higher in specific patient groups infected with HIV or a history of transfusion or haemodialysis.

[Chlamydia trachomatis conjunctivitis in adults. Study of diagnostic techniques]. / Place des conjonctivites à Chlamydia trachomatis chez l'adulte. Etude des techniques de diagnostic.

The place of Chlamydia trachomatis in acute or chronic conjunctivitis is certainly underestimated due to the difficulties involved in the diagnosis. Three diagnostic techniques for Chlamydia trachomatis conjunctivitis were compared: conjunctival sac swab for ELISA technique, scraping of the tarsal conjunctiva for direct immunofluorescence and for culture. Two groups of patients were studied: 73 patients with acute or chronic conjunctivitis and 44 asymptomatic patients. 19.2% of the patients in the first group had a positive result with the two techniques and 6.8% of the patients in the second group also had positive results with the same criteria. Our results show that indirect immunofluorescence is the technique most frequently positive, followed by ELISA, while culture remains the most specific but the least sensitive technique. The existence of healthy carriers Chlamydia trachomatis is demonstrated.

[Prevalence of antibodies to the hepatitis C virus in pregnant foreign residents in France]. / Recherche des anticorps contre le virus de l'hépatite C chez les femmes enceintes d'origine étrangère vivant en France.

Blood transfusion and intravenous drug use are the two main modes of transmission of the hepatitis C virus (HCV). Sexual intercourse seems to play a less significant part in transmission of the HCV and data are still lacking on vertical mother-to-offspring transmission. HCV seroprevalence was determined in 1,084 pregnant foreign residents of France living in a single city (Limoges). Antibodies to the HCV were detected in sera using both the first and second generation Abbott ELISA kits. Sera yielding reproducible positive results with either kit were retested with a blocking test (HCV EIA Neutralization, Abbott) and a second generation RIBA (Ortho) for confirmation. For screening, use of tests detecting both nonstructural and structural antibodies improved results noticeably (5 of 16 sera). Use of confirmation tests was found to be indispensable. Overall seroprevalence was 1.47%. However, results varied across geographic regions or origin, ranging from 0% for Europe, 1.9% for North Africa and 1.78% for South-East Asia, to 4.76% for black Africa. These findings demonstrated the potential for mother-to-offspring transmission among women from high prevalence areas. A prospective study in African an Asian women is being considered to evaluate ineffectiveness and transmission using serial serologic tests and viral genome detection by polymerase chain reaction studies (PCR).

Seroepidemiology of human herpesvirus-6 in pregnant women from different parts of the world.

The prevalence of HHV-6 IgG was studied in 11 different countries across several continents: Morocco, Burkina-Faso, Congo, Ivory Coast, Mali, Niger, Senegal, Togo, Ecuador, Martinique, and France. The study group consisted of 550 pregnant women, representative of the general adult population in each country. Antibodies were detected by immunofluorescence assay on HSB-2 cells infected with HHV-6. Each serum was tested at nine dilutions (1:20 to 1:5,120), sera greater than or equal to 20 being considered positive. For the negative antigen control, we used mock-infected HSB-2 cells. Great differences were seen between separate areas: Morocco showed both low prevalence (20%) and a low geometric mean titer (12), whereas sub-Saharan Africa displayed high prevalences (60% to 90%) and variable geometric mean titers (34 to 229). This study revealed a prevalence of 92% for Ecuador, significantly higher than the prevalence for Martinique (50%), yet both countries had very low antibody titers compared with those found in Africa. The prevalence in France (76%) was similar to previous results from other European countries.

Kinetics of use-dependent ventricular conduction slowing by antiarrhythmic drugs in humans.

BACKGROUND: Rate-dependent conduction slowing by class I antiarrhythmic agents has clinically important consequences. Class I drugs are known to produce use-dependent sodium channel blockade. If rate-dependent conduction slowing by class I agents is due to sodium channel blocking actions, the kinetics of conduction slowing should be similar to those of depression of sodium current indexes in vitro. The purpose of the present investigation was to study the onset time course of ventricular conduction slowing caused by a variety of class I agents in humans. METHODS AND RESULTS: Twenty-seven patients undergoing electrophysiological evaluation for antiarrhythmic therapy were studied. Changes in QRS duration at initiation of ventricular pacing at cycle lengths of 400 and 500 msec were used to evaluate the kinetics of drug action. Mean time constants for each drug were similar to values for Vmax depression reported in vitro studies: flecainide, 24.9 +/- 11.6 beats in eight patients (versus 34.5 beats reported for Vmax block); propafenone, 17.8 +/- 6.9 beats in five patients (versus 8.4-20.8 beats); quinidine, 7.0 +/- 2.4 beats in six patients (versus 5.6-6.2 beats); and amiodarone, 3.6 +/- 2.0 beats for eight patients (versus 3.0 beats). Time constants were significantly different among the various drugs tested (p = 0.0002 at a cycle length of 400 msec; p = 0.002 at 500 msec), and there was a strong correlation (r = 0.89, p less than 0.0001) between values obtained at a cycle length of 400 msec and those at a cycle length of 500 msec. No rate-dependent changes in QRS duration were seen at onset of ventricular pacing among eight age- and disease-matched control patients not taking class I antiarrhythmic drugs, including three patients subsequently showing such changes during type I antiarrhythmic drug therapy. CONCLUSIONS: We conclude that class I agents produce use-dependent QRS prolongation in humans with characteristic kinetics for each agent that are similar to the kinetics of Vmax depression in vitro. These results suggest that rate-dependent ventricular conduction slowing by antiarrhythmic drugs in humans is due to use-dependent sodium channel blockade.

[Seroprevalence of hepatitis C in human immunodeficiency virus infected patients]. / Séroprévalence de l'hépatite C chez les sujets contaminés par le virus de l'immunodéficience humaine.

Prevalence of antibodies against hepatitis C virus (HCV) was evaluated using Ortho and Abbott HCV Elisa assays and the Abbott EIA Neutralization assay in 150 human immunodeficiency virus (HIV)-seropositive patients and compared with the prevalence of hepatitis B virus (HBV) and hepatitis D virus (HDV) markers. Overall prevalence of hepatitis C virus antibodies was 29.3%; significant variations were seen across human immunodeficiency virus risk factor subgroups: prevalence was 10.2% in homosexual men, 12.0% in bisexual men, 73.5% in intravenous drug users, 13.3% in blood transfusion recipients, and 16.6% in frequent travellers. Seroprevalence was higher in the 20 to 40 year-old age group and in patients stage II or III according to the Center for Disease Control classification. Prevalence of hepatitis B virus and hepatitis D virus markers (75.7% and 17.5% respectively) was analyzed according to hepatitis C virus marker status; patients with HBcAb were more likely to have antibodies against hepatitis C virus than their HBcAb-negative counterparts. Further studies are needed to investigate the influence of coexposure to human immunodeficiency virus and hepatitis C virus on liver lesions. Data from this study show that coinfection or coexposure is common.

[Maternal-infant transmission of the HTLV-1 virus]. / Transmission mère-enfant du virus HTLV-1.

The virus is transmitted horizontally via the bloodstream or sexual intercourse but vertical transmission is also believed to be a major mode of contamination. Between 20 and 25% of children born to seropositive mothers are believed to be infected and more than 90% of mothers whose children are found to be seropositive are themselves infected. If transplacental route appears to be exceptional or poorly documented, transmission by breast-feeding has been proved by virological, experimental and epidemiological arguments and is a major mode of contamination.

[Prevalence of hepatitis B (Hbs Ag, Hbe Ag, DNA) and delta virus markers, in about 10,000 pregnant women in Limoges (France)]. / Prévalence des marqueurs des virus des hépatites B (Ag HBs, Ag HBe, ADN) et delta, Chez près de dix mille femmes enceintes à Limoges (France).

The risk of perinatal B virus transmission is well known, but is estimated in France on results obtained from blood donors or from urban populations. In the present study, the screening of HBs Ag was carried out during five years (1984-1988), within a sample population of pregnant women (french women: 8,364, immigrant women: 1,206) seen in the university hospital of Limoges. Positive sera for HBs Ag were also tested for the other markers of B virus including specific DNA, and markers of the delta virus. The total seroprevalence of HBs Ag among these women was 0.54%, and was significantly higher in the immigrant women group (2.57%) when compared to that of french women (0.25%). During the same period (1984-1988), the seroprevalence among females blood donor was 0.03%. Among the HBs Ag chronic carrier pregnant women (n = 52), 27% were HBe Ag positive and four of them (31%) had viral DNA in their serum. Viral DNA was found in three women who were HBe Ag negative. Thirteen per cent of the HBs Ag positive pregnant women were infected by the delta virus.

An epidemic of respiratory syncytial virus in elderly people: clinical and serological findings.

In 1984-1985, an outbreak of respiratory syncytial virus (RSV) infection occurred in two geriatric wards. Among 68 patients (mean age +/- SD = 82.5 +/- 12.5 with respiratory signs, 52 had signs caused by RSV infection. Among all patients, the clinical and serological attack rates were 61.2% and 75.0%, respectively. The most frequent clinical presentation was intensive coughing (96.1%) and fever (96.1%) associated with expectorate (63.5%). The duration of the respiratory symptoms was 5 to 7 days. The disease gradually resolved, although in eight (15.4%) patients complications occurred. For periods of up to 1 year after infection, 172 sera were obtained and tested by complement fixation test (CFT), fluorescent assays for titrating specific IgG, IgA, and IgM, and Western blotting. Specific IgM appeared in six (11.5%) of the infected patients and peaked 2 to 6 months after infection, and there was no significant correlation with severity of clinical symptoms. However, higher peak G and A antibody responses were observed in persons with rales (CFT: P = 0.008; IgG: P = 0.042; IgA: P = 0.020), cough (IgG: P = 0.034), sputum (IgG: P = 0.030), dyspnea (CFT: P = 0.024), conjunctivitis (CFT: P = 0.025), and bronchitis (CFT: P = 0.018). The temporal patterns of IgA and CFT results were found to be similar, whereas IgG peaked later, i.e., between 2 and 6 months. The patients with the most severe symptoms had the highest antibody titers obtained by conventional tests and by Western blots. Thus, RSV can be an epidemic pathogen among elderly persons, although this illness is usually mild.

Multicenter evaluation of a new recombinant enzyme immunoassay for the combined detection of antibody to HIV-1 and HIV-2.

A newly developed recombinant antigen-based anti-HIV-1/HIV-2 enzyme immunoassay (Abbott Recombinant HIV-1/HIV-2 EIA) was evaluated against a second generation anti-HIV-1 EIA (Abbott Recombinant HIV-1 EIA). Five thousand and twenty-nine sera from European blood donors and 403 sera from central African blood donors were used in the evaluation, along with four panels and one cohort. The panels included 99 'problem' sera, 733 sera with antibodies to HIV-1 from asymptomatic people and from patients at different disease stages, 25 serial bleeds from five plasmapheresis donors seroconverting for antibodies to HIV-1, and 202 sera with antibodies to HIV-2 collected from healthy and diseased people of European or west African origin. In addition, 734 sera collected from a west African cohort were tested. Using Western blot as the reference standard, the specificity obtained by the recombinant anti-HIV-1 EIA (HIV-i EIA) was 99.90% [99.81-99.99%; 95% confidence limits (95% CL)] with European blood donor sera; 99.50% (98.78-100%) with Central Africa blood donor sera; 92.93% (87.78-98.08%) with 'problem' sera and 99.43% (98.87-100%) with sera from a west African cohort. Using the same samples, the recombinant anti-HIV-1/HIV-2 EIA (HIV-1/HIV-2 EIA) yielded a specificity of 99.84% (99.73-99.95%), 99.50% (98.78-100%), 95.96% (92.00-99.92%) and 98.58% (97.69-99.47%), respectively. All 776 Western blot-confirmed anti-HIV-1 sera were reactive in both EIAs, and the EIA-reactive samples from seroconverting plasma donors were always observed for both assays in the same serial bleed. For HIV-2, the HIV-1 EIA yielded an overall sensitivity of 75.83% (69.93-81.72%) compared with 99.53% (98.58-100%) for HIV-1/HIV-2 EIA. The addition of a recombinant env-protein of HIV-2 to the recombinant env and core proteins of HIV-1 on the solid phase of HIV-1 EIA improved the detection of anti-HIV-2 while preserving the assay's overall specificity and sensitivity for the detection of anti-HIV-1.