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Background and Purpose: This study was undertaken to validate a clinical score of vascular origin in patients with acute transient visual disturbances (TVDs) without diplopia., Methods: We conducted a prospective study in an ophthalmology emergency department and a transient ischemic attack (TIA) clinic. Patients underwent clinical evaluation including a tailored questionnaire, brain, vascular, and ophthalmologic investigations, and 3-month follow-up. TVDs were classified according to vascular or nonvascular origin by three independent experts based on all clinical, cerebrovascular, and ophthalmologic investigations, but blind to the questionnaire results. A clinical score was derived based on clinical variables independently associated with a vascular origin, and was externally validated in an independent cohort., Results: An ischemic origin of TVD was found in 45% (67/149) of patients in the derivation cohort. Age and six questions were independently associated with an ischemic origin. A nine-point score (≥70 years old = 2; monocular visual loss = 2; black or white vision = 1; single episode = 1; lack of headache = 2; diffuse, constricted, altitudinal, or lateralized visual loss pattern on drawings = 1) showed good discriminative power in identifying ischemic origin (c-statistic = 0.82) and was replicated in the validation cohort (n = 130, 25% of ischemic origin, c-statistic = 0.75). With a score ≥ 4, sensitivity was 85% (95% confidence interval = 68-95) and specificity was 52% (95% confidence interval = 41-62). In both cohorts, ophthalmologic evaluation found a vascular cause in 4% and was noncontributive in 85%. After 3 months, no patients had a stroke, TIA, or retinal infarct., Conclusions: Our score may assist in predicting a vascular origin of TVD. Ophthalmologic evaluation, when not readily available, should not delay the neurovascular evaluation., (© 2021 European Academy of Neurology.)

Background: Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses., Objective: To assess the risk of relapsing-remitting multiple sclerosis (RR-MS) worsening after YFV., Methods: Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS., Results: 128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) ( p  = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53-3.30, p = 0.54)., Conclusion: These results suggest that YFV does not worsen the course of RR-MS.

Objectives: Mauritania is a highly endemic region for hepatitis B (HBV) and delta (HDV) viruses. No data are available on HDV's impact on the severity of liver disease in consecutive HBV-infected patients in Africa. This study evaluated the degree of liver fibrosis in a cohort of chronic HBV carriers., Methods: Three-hundred consecutive HBV-infected Mauritanian patients were checked for HDV infection via the detection of anti-HDV antibodies (Ab) and viral RNA. HBV- vs. HBV/HDV-infected patients were compared by physical examination, biological analyses, and the APRI (aspartate aminotransferase to platelet ratio index) and FibroMeter tests for determination of liver fibrosis., Results: More than 30% of the patients had anti-HDVAb. Among these, 62.2% were HDV-RNA positive. Co-infected patients were older (>8-years) than HBV-mono-infected patients. They had more liver tests abnormalities and clinical or ultrasound signs of liver fibrosis. APRI and FibroMeter scores were also significantly increased in these patients. In multivariate analysis, beyond HDVAb, male gender and HBV-VL >3.7 log IU/mL were the only markers linked to significant liver fibrosis., Conclusions: In Mauritania, HDV co-infection worsens liver disease, both clinically and biologically, as confirmed by the APRI and FibroMeter tests. These tests may be useful for the management of delta hepatitis, which is a major health problem in Mauritania., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

The development of medicinal products is subject to quality standards aimed at guaranteeing that database contents accurately reflect the source documents. Paradoxically, these standards hardly address the quality of the source data itself. The objective of this work was to propose recommendations to improve data quality in three fields (pharmacovigilance, pharmacoepidemiology and clinical studies). The analysis was focused on the data and on the critical stages presenting critical quality problems, for which the current guidelines are insufficiently detailed, unsuitable and/or poorly applied. Finally, recommendations have been proposed, mainly focused on the origin of the data and its transcription., (© 2013 Société Française de Pharmacologie et de Thérapeutique.)

Background: In Mauritania, some authors have described a possible high prevalence of hepatitis delta virus (HDV) infection in the 1990s in studies of small-size samples., Objectives: The aims of our study were to assess the prevalence of HDV in HBsAg positive blood donors in Mauritania, to identify the main risk factors for HDV transmission and to analyze genetic diversity of HDV strains., Study Design: From October 2008 to December 2009, 11,100 consecutive blood donors were considered in this study. Among them, 1700 (15.3%) were HBsAg positive and 455 accepted to participate in this study. Demographic, epidemiological, ethnical, clinical and biological data were recorded. HDV screening, i.e., antibodies (HDVAb) and RNA (HDV-RNA) detection, was performed for all of them as well as HDV and HBV genotyping., Results: Ninety/455 (19.78%) donors were HDVAb positive and HDV-RNA was detectable in 56 (62.2%) of them. HDV infection was significantly associated with older age, number of marriages, military profession, residence in the desert and a history of hospitalization. The HDV genotypes of the circulating strains were HDV-1 (89.3%) and HDV-5 (10.7%)., Conclusion: HDV is highly endemic in Mauritanian blood donors indicating that a high number of them will develop chronic hepatitis, cirrhosis or hepatocellular carcinoma. Associated risk factors support nosocomial transmission of HDV. These data underline the need to reinforce HBV vaccination in newborns and in blood donors without HBV markers, together with screening for HDV in HBV-infected individuals., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: New techniques and instrumentation for arthroscopic management of shoulder instability require accurate measurement tools to investigate possible clinical improvements. The aim of the study was to assess the self-administrated Western Ontario Shoulder Instability Index (WOSI), which is a subjective quality of life measurement tool specific to shoulder instability, and also to validate this score by comparison with the Walch-Duplay score, which is the gold standard score used in Europe. These two scores had never been compared., Methods: Forty-eight patients, who underwent arthroscopic surgery for anterior shoulder instability, were evaluated using the WOSI and the Walch-Duplay score at 42.7 months' follow-up. The correlation between these two scores was investigated., Results: The WOSI significantly correlated with the Walch-Duplay score (global score, and specific items of pain, stability, return to activity). The standard correlation coefficient was 0.8 and the Lin correlation coefficient was 0.65. The WOSI did not correlate with the mobility item of the Walch-Duplay score., Discussion: The WOSI was found to correlate with the Walch-Duplay score. However, the WOSI was more sensitive than the Walch-Duplay score for the assessment of patient satisfaction. It is likely that both self-administrated questionnaires and physical examinations are complementary for an accurate investigation of the functional objective and subjective outcome after shoulder stabilization surgery., Type of Study: Retrospective. Level IV., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: The aim of this study was to document in real life the characteristics and management of hepatitis C patients treated with pegylated interferon-α2a and ribavirin, and the efficacy of treatment (sustained virological response [SVR])., Methods: This observational study enrolled hepatitis C patients initiating pegylated interferon-α2a and ribavirin treatment., Results: A total of 2,066 patients were included, of which 70% were treatment-naive, 53% had genotype (G) 1 and 38% G2 or G3 infection, and 35% had an F3-F4 Metavir score. In total, 18% of patients treated for 24 weeks and 39% of patients treated for 48 weeks prematurely stopped treatment, mainly because of side effects. The SVR rate (intent-to-treat population) was 39%: 43% in naive patients and 31% in treatment-failure patients. In the complete case analysis population, this was 49%: 54% in naive patients and 37% in treatment-failure patients. Among naive patients, the SVR rate was 42% in G1 carriers and 69% in G2 or G3 carriers. The SVR rate was 69% in naive G1 patients without fibrosis (F0; versus 44% in F1-F2 versus 31% in F3-F4; P<0.001). In naive patients, G2 or G3, low viral load (<800,000 IU/ml) and age ≤40 years were predictive factors for SVR. In treatment-failure patients, low viral load, no or low fibrosis stage (F0-F1) and no treatment modification were predictive factors of SVR., Conclusions: In patients treated in a real-life setting, adherence to therapy, SVR rates, predictive factors of SVR and safety results were close to those observed in randomized trials. A high SVR in G1 naive patients with no fibrosis warrants further study and might suggest earlier treatment.

Objective: To describe the evolving epidemiology, management, and risk factors for death of invasive Candida infections in intensive care units (ICUs)., Design: Prospective, observational, national, multicenter study., Setting: One hundred eighty ICUs in France., Patients: Between October 2005 and May 2006, 300 adult patients with proven invasive Candida infection who received systemic antifungal therapy were included., Interventions: None., Measurements and Main Results: One hundred seven patients (39.5%) with isolated candidemia, 87 (32.1%) with invasive candidiasis without documented candidemia, and 77 (28.4%) with invasive candidiasis and candidemia were eligible. In 37% of the cases, candidemia occurred within the first 5 days after ICU admission. C. albicans accounted for 57.0% of the isolates, followed by C. glabrata (16.7%), C. parapsilosis (7.5%), C. krusei (5.2%), and C. tropicalis (4.9%). In 17.1% of the isolates, the causative Candida was less susceptible or resistant to fluconazole. Fluconazole was the empirical treatment most commonly introduced (65.7%), followed by caspofungin (18.1%), voriconazole (5.5%), and amphotericin B (3.7%). After identification of the causative species and susceptibility testing results, treatment was modified in 86 patients (31.7%). The case fatality ratio in ICU was 45.9% and did not differ significantly according to the type of episode. Multivariate analysis showed that factors independently associated with death in ICU were type 1 diabetes mellitus (odds ratio [OR] 4.51; 95% confidence interval [CI] 1.72-11.79; p = 0.002), immunosuppression (OR 2.63; 95% CI 1.35-5.11; p = 0.0045), mechanical ventilation (OR 2.54; 95% CI 1.33-4.82; p = 0.0045), and body temperature >38.2 degrees C (reference, 36.5-38.2 degrees C; OR 0.36; 95% CI 0.17-0.77; p = 0.008)., Conclusions: More than two thirds of patients with invasive candidiasis in ICU present with candidemia. Non-albicans Candida species reach almost half of the Candida isolates. Reduced susceptibility to fluconazole is observed in 17.1% of Candida isolates. Mortality of invasive candidiasis in ICU remains high.

Objective: Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines., Study Design: Prospective, observational, French multicenter study (October 2005-May 2006)., Patients and Methods: Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis., Results: One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida., Conclusion: The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines.

Most of the published works so far have aimed at finding genes associated with multiple sclerosis (MS) susceptibility. Very few studies have attempted to correlate disease features with DNA variants. In a well-characterized sample (651 patients) representative of multiple sclerosis natural history, we engaged a comprehensive study of the role of human leukocyte antigen (HLA) in the course of the disease. We investigated the role of HLA-DRB1*15 allele in samples stratified according to severity evaluated by the Multiple Sclerosis Severity Score (MSSS), time to reach EDSS 6.0 and disease type. We found that HLA-DRB1*15 genotype does not influence MS severity even among patients presenting with a given type of the disease. However, we show for the first time that HLA-DRB1*15 allele modulates the course of MS for relapsing-remitting (RR) onset patients likely by precipitating the secondary progressive (SP) phase.

Context: Care-related pain includes pain occurring during transportation, movement, diagnostic imaging, physical examination, or treatment. Its prevalence has never been assessed in a large adult inpatient population., Objective: To identify the procedures likely to induce or increase pain in hospital patients, attempting to separate the most painful from those reported as most frequently inducing pain., Design: A single-day cross-sectional survey conducted in two large French teaching hospitals, including all hospitalized patients, free of communication problems. One third was randomly selected and interviewed about the painful episodes that had occurred or were associated with the procedures performed during the previous two weeks. Patients were interviewed using a structured questionnaire., Results: Six-hundred-eighty-four patients were randomly selected. Six-hundred-seventy-one painful events were reported in 55% of the patients, with an average of 1.8 events/patient. Fifty-two percent of the painful events were associated with procedures performed by non-medical staff; 38% of the painful episodes occurred during procedures involving vascular puncture and 24% during patients' mobilization. In 57% of painful procedures, pain was rated as severe or extremely severe. The most painful procedures were invasive procedures, other than vascular and non vascular punctures (74% of severe and extremely severe painful episodes). Maximum pain intensity was rated higher for procedures that were repeated than for those experienced only once (62% versus 53%, p=0.02)., Conclusion: This survey gives new insight into our daily practice. Proper management of care-related pain should be a major concern of all hospital staff to improve the quality of our health care.

We investigated the influence of age at disease onset on timing of the progressive phase in 957 patients with multiple sclerosis (MS). Age at onset powerfully predicts the probability of developing a primary progressive form of the disease. Moreover, age at onset strongly determines the time to conversion to secondary progression for patients presenting with a relapsing form. This suggests that age at onset strongly influences the neurodegenerative component of MS.

Objectives: A high prevalence of chronic hepatitis B has been previously reported in heart transplant recipients in our center. Nosocomial transmission of hepatitis B has been therefore suggested. The aim of the present study was to investigate an outbreak of hepatitis B infection in heart transplant recipients and to to look for nosocomial acquisition of hepatitis B in these patients., Methods: In a retrospective case-control study, review of transvenous endomyocardial biopsy (TEB) procedure, line probe assay and DNA sequencing for characterization of the outbreak isolate genotypes were performed in order to assess the possible risk of nosocomial transmission of hepatitis B in the setting of heart transplantation. Case was defined as a patient negative for HBsAg before heart transplantation and positive after. Controls were matched with cases by date of transplantation and time-interval of HBV infection occurrence in the cases patients., Results: Transmission of HBV was associated with the number of HBsAg positive patients undergoing TEB the same day and in the same ward (OR=1.17, per additional encounter; 95%CI=1.01-1.37, P=0.02) and with the total number of TEB undergone after a HBsAg positive patient (OR=1.43 for additional encounter, 95%CI=0.97-2.1, P=0.056) but not with the number of biopsies. The virological study identified eight different strains. No common devices nor gloves, drapes, or medical solution were shared among patients during TEB. One staff member, but no surgeon, was HBsAg positive. No further case occurred after implementation of control measures., Conclusions: Patient-to-patient transmission during TEB sessions was demonstrated by the virological and the case-control studies. This transmission occurred without evidence of blood contact through vials or devices. There is strong evidence that this transmission may be due to the spread of infective blood droplets on the environmental surfaces and the material during the TEB procedure.

Background: The oral status of people living in precarious conditions is problematic. Although the public universal health insurance should allow better access to care, access to dental care remains a critical issue. The analysis of the patient population of a hospital dental consultation (Groupe Pitié-Salpêtrière, Paris) seemed relevant to evaluate the needs of care and the means to provide it. The principal objectives are: to estimate dental health and needs of this population, to describe their sociodemographic characteristics and to compare them with patients living in common social conditions., Methods: A cross sectional study was conducted from February to June 2003. A medical questionnaire and a dental file record were used. All outpatients coming to the dental consultation, in need of conservative or prosthetic treatment, were included. We analysed the risk factors associated with poor dental health., Results: Three hundred and thirty three questionnaires were analysed: two third were men, 45% were foreigners. More than half of them benefited from a special social health insurance for disadvantaged people or didn't have any health insurance. The comparative analysis of this precarious group vs regular insured people showed significant differences for sociodemographic and oral characteristics. Namely, in the precarious group, a poor dental status was generally observed: more cavities (3.6 versus 2), more absent teeth not replaced (6.8 versus 3.5) and less treated teeth (1.9 versus 3.9)--p < 0.0001. Multivariate analysis showed that main risk factors of poor dental status were to be aged and to be a foreigner., Conclusion: This study stresses the importance of the dental care needs in a context of poor insurance refunding for the costs of dental treatments and the lack of structures able to provide dental care for patients living in difficult social condition. These findings question the organization of the dental care system in France.

Two kinds of meningococcal vaccines are available for invasive meningococcal infections (IMI) prevention, non conjugated polysaccharide vaccines anti A+C or anti A+C+W135+Y and conjugated polysaccharide vaccines anti-C. The last one have the advantage of being effective from 2 months of age. Vaccination should to be used in four circumstances: for subjects remaining in close contact with an IMI case; for pilgrims going to Mecca (A+C+W135+Y vaccine must be used); for travelers to a location with active transmission of IMI and close contacts with local population; in case of "mass" vaccination decided by health authorities. Generalised vaccination of all of one or more age groups has been done for serotype C in some European countries, because of high incidence. Effectiveness of this kind of intervention should be weighted with the risk of immunoselection of another serotype and with the possibility of a spontaneous decrease of the incidence.

The transmission of viral hepatitis from health care workers (HCW) to patients is of worldwide concern. Since the introduction of serologic testing in the 1970s there have been over 45 reports of hepatitis B virus (HBV) transmission from HCW to patients, which have resulted in more than 400 infected patients. In addition there are six published reports of transmissions of hepatitis C virus (HCV) from HCW to patients resulting in the infection of 14 patients. Additional HCV cases are known of in the US and UK, but unpublished. At present the guidelines for preventing HCW to patient transmission of viral hepatitis vary greatly between countries. It was our aim to reach a Europe-wide consensus on this issue. In order to do this, experts in blood-borne infection, from 16 countries, were questioned on their national protocols. The replies given by participating countries formed the basis of a discussion document. This paper was then discussed at a meeting with each of the participating countries in order to reach a Europe-wide consensus on the identification of infected HCWs, protection of susceptible HCWs, management and treatment options for the infected HCW. The results of that process are discussed and recommendations formed. The guidelines produced aim to reduce the risk of transmission from infected HCWs to patients. The document is designed to complement existing guidelines or form the basis for the development of new guidelines. This guidance is applicable to all HCWs who perform EPP, whether newly appointed or already in post.

To measure the prevalence and intensity of pain in hospitalized patients and to assess the quality of pain management, an exhaustive cross-sectional study was conducted in every department in a university hospital. Patients hospitalized for 24 hours or more completed an anonymous self-report questionnaire. Among the 1,475 inpatients, 998 completed the questionnaire. During the 24-hour period prior to our survey, 55% experienced pain. On 100 mm pain intensity measures, the median maximum pain experienced in the 24 preceding hours was 60 mm and the median pain intensity at the time of the survey was 30 mm. Although pain measured at the time of survey disappeared in only 16% of patients, 79% were satisfied with pain management. Despite a high satisfaction level, the prevalence and intensity of pain were very high. This study provided baseline data on pain in a French hospital and led to the implementation of a program for improving pain management.

We prospectively evaluated serum procalcitonin concentrations in patients who presented to an emergency department (ED) with suspected infectious or inflammatory disease. Of 195 study patients, 68 had final diagnosis of systemic infection, and 24 of those 68 had elevated serum procalcitonin levels (>0.5 ng/mL). The procalcitonin level had a sensitivity of 0.35 and specificity of 0.99 for the diagnosis of systemic infection. In multivariate analysis, the procalcitonin level was the only independent variable associated with this diagnosis; in contrast, the C-reactive protein level was not. All patients with systemic infections who ultimately died had procalcitonin levels of >0.5 ng/mL at admission. Procalcitonin levels were significantly higher in patients who ultimately died of systemic infection than in patients who survived. The optimal procalcitonin threshold for the ED population may be lower than that proposed for critically ill patients. Determination of the procalcitonin level may be useful for screening and prognosis of more-severely ill ED patients.

Background: Malaria antibody detection is a valuable tool in the prevention of transfusion-transmitted malaria in countries with a high proportion of donors with travel exposure to malaria. The immunofluorescent antibody test (IFAT) is still the reference method, but it is not suitable for screening of blood donors. ELISA would be an interesting alternative to the IFAT, but it lacks sensitivity., Study Design and Methods: To evaluate the potential value of a combined screening strategy based on malaria antigen and antibody detection, plasma samples from 203 patients infected with Plasmodium falciparum were tested with an ELISA for the detection of malaria antibodies (Malaria IgG CELISA, Cellabs) and a P. falciparum histidine-rich protein-2 kit (Malaria P.f., ICT Diagnostics) for the detection of malaria antigens., Results: Among patients with positive IFAT results, CELISA had a sensitivity of 71 percent, whereas the combined screening tests (CELISA and Malaria P.f.) had a sensitivity of 88 percent (p < 0.001). Sequential samples from 50 patients were tested. The combined screening tests shortened the detection of seroconversion from 11.4 +/- 1.6 to 5.3 +/- 1.1 days (p < 0.001)., Conclusion: Combined malaria antigen and antibody detection, with methods compatible with mass screening, may constitute an attractive alternative to the IFAT for blood donor screening.

Background & Aims: We have observed a high prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in heart transplant recipients (HTRs). The aim of this study was to assess the epidemiology, natural history, and clinical and biological characteristics of viral hepatitis in HTRs., Methods: From 1983 to 1992, 874 patients underwent heart transplantation at the Pitié-Salpêtrière Hospital, Paris, France, 459 of whom qualified for analysis. A total of 140 patients had posttransplantation hepatitis B, C, or non-A-E. Sixty-nine patients developed HBV infection, 49 HCV infection, 11 HBV-HCV coinfection, and 11 non-A-E hepatitis., Results: HBV was transmitted nosocomially from patient to patient, most likely during endomyocardial biopsies. HCV was mainly transmitted through blood transfusions or the transplanted organ. Clinical and biological findings after 2 years of follow-up showed that 3 patients with an HBV genotype A precore mutant had severe or subfulminant hepatitis and that patients with HBV and HCV infection always progressed to chronicity. In general, patients had mild alanine aminotransferase level increases, a high level of viral replication, and few severe histologic lesions, except for patients infected by precore HBV mutants. Patients coinfected by HBV and HCV tended to have more severe liver lesions. The survival rate 5 years after transplantation in patients with viral hepatitis (HBV, 81%; HCV, 89%; HBV and HCV coinfection, 100%; non-A-E hepatitis, 73%) was similar to that in patients without liver test abnormalities (76%). The actuarial survival curve was also similar in patients with or without liver test abnormalities., Conclusions: In our experience, histologic liver lesions do not progress rapidly in patients with post-heart transplant infection caused by HBV or HCV. HBV or HCV infection seems to have little impact on the 5-year survival rate of HTRs.

Fulminant and severe viral hepatitis are frequently associated with mutant hepatitis B virus (HBV) strains. In this study, the genetic background of a viral strain causing severe subfulminant outcome in heart-transplanted patients was studied and compared with viral hepatitis B strains that were not linked to severe liver disease in the same setting. A total of 46 patients infected nosocomially with HBV genotype A were studied. Five different viral strains were detected, infecting 3, 9, 5, 24, and 5 patients, respectively. Only one viral strain was found to be associated with the subfulminant outcome and 3 patient deaths as a consequence of severe liver disease. The remaining 43 patients with posttransplantation HBV infection did not show this fatal outcome. Instead, symptoms of hepatitis were generally mild or clinically undiagnosed. Comparison of this virus genome with the four other strains showed an accumulation of mutations in the basic core promoter, a region that influences viral replication, but also in hepatitis B X protein (HBX) (7 mutant motifs), core (10 mutant motifs), the preS1 region (5 mutant motifs), and the HBpolymerase open reading frame (17 motifs). Some of these variations, such as those in the core region, were located on the tip of the protruding spike of the viral capsid (codons 60 to 90), also known in part as an important HLA class II-restricted epitope region. These mutations might therefore influence the immune-mediated response. The viral strain causing subfulminant hepatitis was, in addition, the only strain with a preCore stop codon mutation and, thus, hepatitis B e antigen (HBeAg) expression was never observed. The combination of these specific viral factors is thought to be responsible for the fatal outcome in these immune-suppressed heart-transplant recipients.

The neutralizing activity of anti-V3 monoclonal antibodies (MAbs) and anti-HIV-1 immune sera was tested against HIV-1 laboratory strains and African primary isolates. Neutralization was investigated in Phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cell (PBMC) cultures by means of two distinct viral titer reduction assays. In these assays, virus was detected by means of either p24 antigen measurement using ELISA or HIV provirus synthesis using PCR, respectively. Anti-V3 MAbs and anti-HIV-1 immune sera neutralized efficiently the homologous laboratory HIV-1 strains used for eliciting immune response but showed no neutralizing activity against most primary isolates. The two neutralization assays used provided similar results. However, a PCR-based assay circumvented the limitations due to low levels of virus replication. The mechanism of resistance of the primary isolates to neutralizing antibodies was complex and was not simply predicted by partial sequence determination of the epitopes. This points out the need for reliable neutralization assays of HIV-1 primary isolates in order to evaluate the role of humoral immunity during HIV-1 infection and for future vaccine strategies.

Serum IgG1 levels are selectively increased in patients with chronic hepatitis C virus (HCV) infection. In 15 patients who received interferon (IFN)-alpha therapy, serum levels of immunoglobulin classes and IgG subclasses were measured during treatment and after it was discontinued. In spite of important individual variations, mean IgG, IgG1, IgA and IgM levels decreased during therapy and tended to return to pre-treatment levels afterwards, with no detectable correlation with clinical and biological parameters. These results suggest an effect of IFN-alpha on in vivo immunoglobulin production, in HCV carriers.

New assays for the screening of anti-HCV antibodies are regularly proposed for registration. The evaluation of new tests is based on the measurement of their intrinsic value: sensitivity and specificity. To assess the sensitivity of a test, it is very important to be able to obtain sera samplets tested with a "Gold Standard", which is, for HCV, RNA detection. Sensitivity is defined as the ratio of the number of true positive to the number of true positive added to the number of false negative samples. The problem is to define the samples to be tested. It is methodologically impossible to use a serological test for samples selection. The Gold Standard might be performed on samples from the general population or more easily from risk groups. The estimation of the precocity is more difficult. The constitution of an acute hepatitis panel is of interest an the follow up of risk groups has to be encouraged. The estimation of the number of samples needed depends on the required precision in the sensitivity measurement. The confidence interval (CI) decreases when the number of samples tested increases and when the sensitivity is high. The important questions are opposite: if the test is positive what is the probability for the patient to be really positive? (positive predictive value PPV), and, if the test is negative, what is the probability for the patient to be non-infected? (negative predictive value: NPV). The NPV depends on the prevalence of HCV infection in the tested population and on the sensitivity of the test. PPV increases with the prevalence rate and the specificity. Regarding these results, one may suggest that donor screening assays and tests used for diagnose HCV infection in patients may be evaluated with different strategies. Regarding blood donors screening, sensitivity is the most important parameter, the best strategy is to eliminate risk groups, and then, to perform very sensitive assays on negative samples. On the other hand, for patients diagnosis, specificity (avoid false positive results) is more important. The best strategy is to select patients at risk from clinical findings and then, to perform a specific test. Screening strategies for the general population have to take into account these two different strategies.

The overlapping region of gag and pol genes of human immunodeficiency virus type 1 (HIV-1) also called transframe region, contains the frameshift locus from gag to pol. This region encodes both the protein p6, the function of which remains unclear, and a putative transframe protein covently linked to the N-terminus of the viral protease within Gag/Pol protein precursor. We have investigated the variability of the transframe region among nine HIV-1 isolates obtained from Congolese AIDS patients. Nucleotide sequences were determined using the polymerase chain reaction and the direct sequencing of amplified products. The sequences of Congolese isolates markedly differed from one another and from other reference HIV-1 strains by both insertion-deletion events and numerous base substitutions. Several putative cleavage sites of precursor polypeptides were modified. When compared to consensus ones the amino acid sequences of p6 protein were very different among divergent HIV-1 isolates, except for a limited group of 10 conserved amino acids.

Nine isolates of HIV-1 obtained from Congolese AIDS patients were amplified by the polymerase chain reaction (PCR) using primer pairs and oligomer probes derived from the HIV-1 LAV-BRU (BRU) sequence. When compared to BRU, two isolates exhibited a significant decrease of PCR efficiency with a given primer pair. Moreover, the DNA amplified from two other isolates did not hybridize with the corresponding probe despite efficient PCR. Base substitutions were detected in the regions of proviral genomes involved in oligonucleotide annealing and were assumed to be responsible for the failure of both amplification and probing. Our data confirm that the genetic variability of HIV-1 may reduce the efficiency of PCR as a diagnostic procedure, especially in the case of African isolates.

Twenty-nine patients with the AIDS Related Complex (ARC) were studied retrospectively. Cotton-wool spots (CWSs) were the main ophthalmological finding, present in 9 patients (31%) at this stage of the disease. The CWSs were asymptomatic and were therefore discovered during a routine examination. The proportion of patients with significant weight loss was greater among ARC patients with CWSs than among those with normal fundi. Leukocyte counts were found to be significantly lower (p = 0.03, odds ratio 10.0 [1.24 to 80.4]) among ARC patients with CWSs. Lymphocyte counts and the CD4/CD8 ratio were also found to be diminished in these patients. Among the nine patients with CWSs during ARC, seven developed major opportunistic infections or HIV (Human Immunodeficiency Virus) related neoplasias during the following months (3.8 +/- 3.5 months). These findings are consistent with a poorer prognosis for HIV infected patients who have CWSs.

Kaposi's Syndrome (K. S.) was defined as a virus induced immunogenic tumour responding to interferon. It can be used as a guideline for therapeutical trials in A. I. D. S. K. S. mortality is 13%. K. S. + O. I. (opportunistic infections) mortality reaches 70% and O. I. mortality is approximately 50%. Therefore treating O. I. is a must but it is not mentioned in the paper. Attempts made to modify immunodepression, usual K. S. treatments, experimental treatments based upon similar pathogenicity (like systemic lupus erythematosus, Hansen's disease, preneoplasia dyskeratosis) were unsuccessful. Trials with alpha recombinant interferon realised at the Sloan Kettering Memorial for Cancer in New York are summarized for 74 patients and are in preliminary interpretation. Our study is based upon 13 cases studied for 14 to 4 months and comes up to the same conclusions using 18 to 36 million units/day for 6 months (6 cases) and 3 to 4 months (7 cases). For 6 full treatments the results are: 2 K. S. were cleaned up after 8 and 3 months follow up, 4 K. S. with O. I.: 3 remissions and then relapses and 1 stabilization, for 7 current treatments: 2 had to be discontinued because of bad tolerance, 1 stabilization and 4 remissions. For all treatments a decrease and a lesser gravity of O. I. can be noted during treatment. Besides flu-like syndromes, main clinical side effects, are: asthenia, general condition impairment, 2 fits were observed for which I.N.F. cannot be clearly incriminated. Daily treatment compelling and surveillance are real drawbacks. Different types of better used interferon will probably yield interesting results (40% regression or improvement).

Serum samples taken from 6,624 blood donors since 1984 to 1987, were tested for Hepatitis B virus surface antigen (HBs Ag) using a microhemagglutination assay and for anti-HIV antibodies by ELISA test. The mean carrier state of HBs Ag was 10.68% and that of anti-HIV antibodies was 6.99%. The association of HBs Ag and anti-HIV antibodies was discovered in 4.84% donors but without correlation for the period of the study.

From January 1984 to June 1985, 20 out of 65 P. falciparum strains isolated in an hospital in Paris were epidemiologically suspect of resistance to chloroquine. 15 of them were submitted to in vitro chemosensitivity tests with several antimalarials drugs. In cases of suspected chloroquine resistance the initial choice of an alternative drug is mainly presumptive and is generally not guided by the in vitro chemosensitivity assay which results are too much delayed. When in vitro assay shows sensitivity to amino-4-quinolines treatment can be modified accordingly. The determination of plasma concentration of drugs are required in any case. However in vitro sensitivity assays would probably appears essential to physicians in cases of resistance to quinine.

Seven patients infected with the filarial worm Loa loa received a treatment by cytapheresis in an attempt to lower the microfilaraemia. Microfilarial levels of between 6,000 and 38,500 ml, before extraction, were reduced, according to the case, by between 47 and 97% (mean 76%). The diethylcarbamazine chemotherapy which followed in 6 of 7 patients showed no sign of any of the serious side-effects which often occur in these type of cases. Due to its practicality and the fact that it is well tolerated, both clinically and biologically, cytapheresis would seem to represent the best method for initially treating loaiasis with high microfilaremia.

We report 15 cases of symptomatic HIV infection seen in Paris between June 1983 and June 1985 in Congolese patients. The first signs were diarrhea, weight loss, fever, pruritus. Disseminated lymphadenopathy was frequent. Twelve patients had AIDS, and the opportunistic infections were: isosporosis, oesophageal candidiasis, cerebral toxoplasmosis, Kaposi's sarcoma, CNS' cryptococcosis, cutaneo-mucosal.

Twenty five patients with peripheral neuropathy at different stages of human immunodeficiency virus (HIV) infection are reported. Cerebrospinal fluid (CSF) findings were available in 17 cases, electrophysiology in all and a neuromuscular biopsy in 11. Of six otherwise asymptomatic HIV+ patients, five had chronic inflammatory demyelinating polyneuropathy (CIDP) and one acute inflammatory demyelinating polyneuropathy (AIDP). CSF showed pleocytosis in all cases. Infiltration of the endoneurium and/or the epineurium by mononuclear cells was seen in biopsies from three cases. These six patients recovered either spontaneously, or with corticosteroids or plasmaphereses. Of five patients with AIDS related complex (ARC), three had distal predominantly sensory peripheral neuropathy (DSPN), one CIDP and one mixed neuropathy. Of 14 patients with AIDS, one had mononeuropathy multiplex and 13 painful DSPN. Electrophysiological studies were consistent with an axonopathy. Nerve biopsies in six cases showed axonal changes but surprisingly associated with marked segmental demyelination in two cases. Cell infiltration was present in nerve samples in two cases. Five patients died within six months after the onset of the neuropathy.