[General practice and internal medicine. The fighting with shared issues]. / Médecine générale, médecine interne. Des combats aux enjeux partagés.

The training of the primary care physicians has been neglected for long by the French medical faculties that, since 1958, favoured the hyper-specialization of their students. The initiative of a few primary care physicians supported by some academic internal medicine physicians allowed changing this situation gradually. Commitment of a training period in primary care practice and then the involvement of teaching general medicine physicians in the course of the theoretical training were essential to this shift. Following three decades of reforms that lead to recognize general medicine as a sub-specialty, an acknowledged academic course of general medicine is eagerly expected for 2009 with the first appointments of professors of general medicine with tenure. The general internists who share the same objective of global patient care are determined to support this academic course that they will welcome within the French National Council of Universities. This academic course will have to comply with the same teaching and research requirements than the other medical subspecialties.

[Autoimmune hepatitis in a HIV-HCV co-infected patient: diagnostic ant therapeutic difficulties]. / Hépatite auto-immune chez une patiente co-infectée VIH-VHC: difficultés diagnostiques et thérapeutiques.

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic inflammatory hepatic disorder, characterized by hypergammaglobulinemia and autoantibodies. In some cases, AIH can be associated with another liver disease; such as the hepatitis C-AIH overlap syndrome, which diagnosis and treatment may be delicate. EXEGESE: We report a type 1 AIH case in a HIV-HCV co-infected woman. AIH remission and HCV eradication were obtained with prednisone and interferon plus ribavirine. AIH relapse appeared with corticosteroid withdrawal and a new remission was obtained with immunosuppressive treatment associating prednisone and azathioprine, without opportunistic infection. CONCLUSION: This case illustrates diagnostic and therapeutic difficulties of hepatitis C-AIH overlap syndromes in an HIV-infected patient. To our knowledge, it is the first AIH case report in a HIV-HCV co-infected patient.

[Hepatitis C-autoimmune hepatitis overlap syndrome: five new cases]. / Association hépatite auto-immune et hépatite virale C: cinq nouvelles observations.

PURPOSE: The hepatitis C-Autoimmune hepatitis overlap syndrome is an uncommon condition whose management can be difficult in both diagnosis and treatment. PATIENTS AND METHODS: Five cases of hepatitis C and autoimmune hepatitis overlap syndrome, brought by a retrospective study, are reported. Hepatitis C was proven by a positive HCV viral load and the autoimmune hepatitis was proven by characteristic immunological and/or histological features. RESULTS: All patients were female, the mean age at diagnosis was 54.2 years (+/-6.6), only one patient had a history of autoimmune disease (autoimmune thyroiditis). Four patients had significant autoantibodies levels (over 1/320) and 4 had a high serum gammaglobulin level (over 1.5 times the upper normal limit). Liver biopsy showed characteristic features of autoimmune hepatitis in all cases and characteristic features of chronic HCV infection in 3 cases. Corticosteroid and/or immunosuppressive treatment was given as a first line therapy in 4 cases while an antiviral treatment has been tried in 4 cases with a good viral response in 2 of them. Corticosteroid and/or immunosuppressive treatment enhanced HCV viral load in all cases, however a histological improvement was observed in every case in which a control biopsy has been performed (3 cases). CONCLUSION: This study highlights the deciding contribution of the initial histological findings in the diagnosis of such a HCV/autoimmune hepatitis overlap syndrome; it also demonstrates that histological outcome is not necessarily compromised by corticosteroid and/or immunosuppressive treatment.

[Dilated cardiomyopathy and lipid-lowering drug muscle toxicity revealing late-onset Becker's disease]. / Cardiomyopathie dilatée et toxicité musculaire des hypolipémiants: une maladie de Becker de révélation tardive.

INTRODUCTION: The Becker's muscular dystrophy is a genetic myopathy due to mutations of the dystrophin gene, located in the Xp21 region, with a clinical expression usually occurring in young adults. EXEGESIS: We report an atypical case of late onset Becker's muscular dystrophy diagnosed at the age of 57. The patient suffered from mild skeletal muscle involvement revealed by the use of statins and fibrates, associated with severe dilating cardiomyopathy. The DNA analysis showed a deletion of the exons 11-13 in the Xp21 gene. CONCLUSION: The diagnostic of Becker's muscular dystrophy must be considered in all patients with persistently elevated CPK and/or primitive dilated cardiomyopathy, whatever the age of the patient.

[Efficacy and safety of pegylated-interferon plus ribavirin in HIV-infected patients co-infected with hepatitis C virus in clinical practice: a 32 cases observational follow-up]. / Efficacité et tolérance de l'association interféron pégylé-ribavirine chez les patients co-infectés VIH-VHC en pratique clinique: étude observationnelle de 32 patients.

OBJECTIVE: To describe efficacy and safety in clinical practice of pegylated interferon plus ribavirin (INFpeg-Riba) in the treatment of hepatitis C viral infection (HCV) in HIV infected patients. METHODS: Monocentric retrospective study with inclusion of all patients who received at least once INFpeg-Riba before April 1st 2003. All patients were followed up to six months after the end of HCV therapy. RESULTS: Thirty two HIV-positive patients (23 men and 9 women) with chronic hepatitis C treated by INFpeg-Riba were included. The mean age was 43 years. Fourteen patients carried HCV genotype 2 or 3 (43 %) and 18 patients carried genotype 1 or 4 (57%). The Metavir score of fibrosis showed fibrosis F1 (N =3), F2 (N =14), F3 (N =7) and F4 - cirrhosis (N =8). Twenty six patients (81%) were naive for anti hepatitis C drugs. Thirty one per cent of patients were at AIDS stage and 84% were receiving antiretroviral drugs. The mean CD4 cell count was 469 /ml and the plasma RNA HIV was less than 50 copies /ml in 57% of the cases. Adverse events leading to reduction of dose of drugs occurred in 40% and adverse events leading to discontinuation treatment occurred in 12%. A decline of CD4 cell count <200 CD4/ml was observed in 15%. Clearance of HCV-RNA in end of treatment was seen in 46 % and sustained virological response in 34 %. The main predictors of sustained virological response were HCV genotype 2 or 3 (P =0.04) and plasma HIV RNA less than 50 copies/ml (P =0.001). The predictive value of good virological response of a CD4 cell count >350/ml before treatment was very near the statistical significancy (p =0.07). CONCLUSIONS: The efficacy of pegylated interferon plus ribavirin in HIV-HCV co-infected patients is disappointing mainly due to a poor tolerance. In addition to HCV genotype, plasma HIV RNA level and CD4 cell count were essential to predict INFpeg-Riba response and should be taken into account in the process leading to the initiation of such therapy in HIV-HCV co-infected patients.

[Portal vein thrombosis in HIV-infected patients: report of four cases]. / Thrombose portale chez des patients infectés par le virus de l'immunodéficience humaine: à propos de quatre observations.

Portal vein thrombosis (PVT) seems rare among HIV infected patients. Even though, the report of such cases is of great interest because it may help to determine the factors of occurrence. We describe cases of PVT in 4 HIV-infected men, aged 32 - 64. Two of them were co-infected with hepatitis C virus (HCV). The four patients had a history of disseminated mycobacterial infection (one case of tuberculosis, 3 cases of mycobacterium avium complex infection) with abdominal lymphadenitis. Despite HAART, their immunodeficiency was profound (CD4: 65 to 216/mm(3)). At the time of diagnosis, two patients were treated with protease-inhibitor containing regimen: indinavir (one case), ritonavir-saquinavir (one case). PVT was revealed by haematemesis (one case), abdominal pain (ome case), anasarca (2 cases). In three patients, the diagnosis of PVT was confirmed by imagery (echo-doppler or angio- RMI), and for the last patient, PVT was found during the transjugular intrahepatic portosystemic shunt setup. A low level of C protein was diagnosed in one case. Cirrhosis was not found in HIV-HCV co-infected patients. Two patients died early after diagnosis, one patient died 3 years after the onset of symptoms. Various factors may cause the development of a PVT in HIV infected patient. Serious immunodeficiency, opportunistic infections such as tuberculosis and mycobacterium avium complex related infection with abdominal lymphadenitis can further the development of PVT. Protease-inhibitor might have facilitated the process. Due to the severe prognosis of advanced cases, early evocation of diagnosis is needed.

A cohort study of nevirapine tolerance in clinical practice: French Aquitaine Cohort, 1997-1999.

We performed a retrospective study to evaluate, under routine circumstances, the tolerance and immunovirological changes associated with antiretroviral regimens that contain nevirapine in 137 patients (88% were antiretroviral experienced). During a mean follow-up of 11 months, 33% of patients reported side effects attributed to nevirapine, and 21% discontinued treatment because of poor tolerance. Administration of antihistamines or corticosteroids at the initiation of treatment was not protective against adverse events (relative risk, 0.82; 95% confidence interval, 0.49-1.38). The proportion of patients with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection who had alanine aminotransferase levels of >100 IU/L increased from 19.4% at baseline to 42.9% at month 12 of follow-up (P=.02). We noticed a significant increase of the proportion of patients with total cholesterol levels of >5.5 mM (P=.02). We have shown that there is a high level of discontinuation of nevirapine therapy in clinical practice and that side effects were not prevented by administration of antihistamines or corticosteroids. Coinfection with HCV or HBV increased the risk of hepatotoxicity, which lead to the cautious use of nevirapine for such patients.

Risk factors for lactic acidosis in HIV-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case-control study.

A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiency virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P<10(-4)), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-infinity], P=.03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4+ T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.

Human immunodeficiency virus type 1 replication within cystic lymphoepithelial lesion of the salivary gland.

Cystic lymphoepithelial lesions of salivary glands (CLLSG) are nodular or diffuse salivary gland enlargements that are observed in patients who tested positive for human immunodeficiency virus type 1 (HIV-1). Two cases of CLLSG are reported. Particular emphasis is placed on the presence of HIV-1 major-core protein (P24), HIV-1 RNA sequences, Epstein-Barr virus (EBV) DNA sequences, and lymphocyte receptor gene rearrangement. Lymphoid alterations consisted of explosive hyperplasia with a prominent follicular reticular dendritic cell (DRC) network and numerous intrafollicular CD8+ lymphocytes. Intrafollicular DRC strongly expressed HIV-1 major-core protein and HIV-1 RNA, indicating that most DRCs actively replicated the HIV-1 virus. The presence of active HIV-1 replication within DRC and the absence of clonal EBV infected lymphoid population strongly suggest that CLLSG pathogenesis is primarily induced by HIV-1. The presence of oligoclonal immunoglobulin gene rearrangements in our cases, however, suggest the need of long-term follow-up of such patients to determine whether CLLSG could be a benign prelymphomatous disease.

The absence of hyperbilirubinaemia is highly predictive of treatment failure in advanced HIV-infected patients treated with indinavir.

In order to determine prognostic factors associated with treatment failure (TF) in advanced HIV-infected patients treated with a regimen including indinavir, a prospective cohort study of 80 patients was set up between 1 March and 31 December 1996. TF time was calculated using the Kaplan-Meier method, from treatment induction to the first of the following events: treatment modification for adverse event or lack of significant virological and/or immunological response, AIDS-defining diagnosis or death. Date of point was 31 December 1998. Multivariate analysis was performed using a Cox model. At baseline, 60% of the patients were AIDS-free, median viral load and CD4+ count were respectively 4.8 log/ml and 79/microl. After a median follow-up of 26 months, 70% of the patients experienced a TF in a median time of 8 months. Seventy-two per cent presented an hyperbilirubinaemia (>2 mg/dl). In multivariate analysis, initial AIDS stage (hazard ratios [HR]=1.94, P=0.04) and digestive intolerance (HR=2.32, P=0.003) were predictive of TF. Conversely, hyperbilirubinaemia was associated with a better outcome (HR=0.35, P<0.0001). These 2 latter parameters very likely reflected patients' treatment compliance.

A possible association between Chlamydiae psittacci infection and temporal arteritis.

Some arguments are in favor of the role of Chlamydia in the pathogenesis of atherosclerosis and some vasculitis. Illustrating this possible relation, we report the case of a patient developing consecutively a Chlamydia psittacci infection and a temporal arteritis. A 73-year-old woman, with no significant medical history, was hospitalized for constitutional symptoms. Three weeks before, she had described fever and sore throat of two days' duration. Since that time, she had remained exhausted and developed a mild intermittent claudication of the jaws. Clinical examination was poor. A biological inflammatory syndrome was noticed. Chest X-ray revealed bilateral interstitial opacities. The titer of anti-C. psittaci antibodies was significant (positive 1g G at 1/2048). Soon after initiation of doxycycline, a temporal arteritis biopsy was performed, due to the persistence of clinical symptoms and high inflammatory syndrome, conclusive for the diagnosis of temporal arteritis. Corticotherapy was added to antibiotic therapy, resulting in the decrease of inflammatory syndrome and an improvement in the general status of the patient. X-ray opacities decreased in three weeks. Serological control after three months showed a decrease of the titer of anti-C. psittacci antibodies to 1/256, confirming the initial diagnosis of Chlamydia pneumopathy. Our observation could provide one more argument for the role of bacteria-like Chlamydia in the pathogenesis of vascular diseases. Prospective seroepidemiological and molecular biology studies could allow us to clarify the association between Chlamydia infections and inflammatory vasculitis-like temporal arteritis.

[Acute cardiac insufficiency and toxoplasmosis]. / Insuffisance cardiaque aiguë et toxoplasmose.

The authors report the case of a 21-year old, non-immunocompromised girl who presented with severe acute heart failure associated with Toxoplasma infection. The outcome was favourable: cure without sequelae was obtained in a few months with a symptomatic and specific treatment consisting of spiramycin and methylprednisolone. This case is interesting for several reasons. The occurrence of such an acute heart disease is extremely rare in patients with toxoplasmic myocarditis, and so is the presence of a septal focus suspected on the basis of a predominantly septal hypokinesia at echocardiography and of enzymatic changes. The development of an acute heart failure should suggest a diagnosis of toxoplasmic myocarditis, which is rare but important since a specific treatment is available.

[Arterial thrombosis of the arm and hemorrhagic rectocolitis. Report of a case]. / Thromboses artérielles des membres supérieurs et rectocolite hémorragique à propos d'un cas.

Several cases of arterial thrombosis associated with inflammatory enterocolitis affections have been reported. In all but one case reported in the literature the outcome was favorable. A 40 year old woman developed thrombosis of the radial and ulnar arteries during an acute episode of ulcerative colitis. The course of the thrombotic lesions was irreversible and all fingers of the right hand had to be amputated. The corticotherapy as a possible predisposing factor for these thromboses is discussed, but their onset during an inflammatory episode suggests a role for the inflammatory enterocolitis. A thrombocytosis (807,000 platelets/mm3) could have predisposed to their onset, and in this case the hemostatic disturbances and fibrinolysis associated with the ulcerative colitis could have played a major role.

[Aortic aneurysms due to Yersinia enterocolitica: three new cases and a review of the literature]. / Anévrismes aortiques a Yersinia enterocolitica: trois nouveaux cas et revue de la littérature.

We report three cases of mycotic aortic aneurysms due to Yersinia enterocolitica. In all cases, serogroups are O:9. The three patients more than 70 year-old men with immunodeficiency underlying conditions allowing bacterial graft (neoplasia, diabetes mellitus, dysimmunitary syndrome, hematologic diseases). The six cases of the literature were clinically, biologically and epidemiologically similar. The strains of Y enterocolitica responsible for septicemia are especially serogroups O:9. This is probably due to particular virulence factors in this serogroup (phagocytosis resistance gene: yopH, ypkA et yop E) (yop: Yersinia outer membrane proteins). The presence of a pYV plasmid (plasmid yersinia virulence), found in Yersinia pathogen strains, lead to bacterial proliferation in the tissues. The authors discuss pathophysiological mechanisms involved in arterial bacterial graft following an Y. enterocolitica infection.

[Hemorrhagic complications of antivitamin K. Report of 75 hospitalized patients]. / Complications hémorragiques des antivitaminiques K. A propos de 75 patients hospitalisés.

Hemorrhagic complications are the most frequent complications of antivitamin K (AVK) treatments and can be life-threatening. We report 75 patients from a University Hospital. They were 40 males and 35 females (median age 74 years, 20-94), and were classified into 3 grades according to clinical picture: grade 1 (no surgery or transfusion, grade 2: surgery or blood transfusion needed, grade 3: death). 43 patients had grade 1 complications, 27 grade 2, and 5 grade 3 complications. The most frequent complications were muscular hematomas (36 patients), sub-cutaneous hematomas (14 patients), digestive bleeding (13 patients), hematuria (12 subjects). Eight patients had intracerebral bleeding, of whom 3 died. The treatment time was very variable (1 to 988 weeks). Only half patients had a prothrombin rate (PR) below 20% but two thirds had an INR above 5. This study showed that PR was a poor predictor of hemorrhagic complications. INR was a better parameter. For 15 patients, we considered that the indication was unadapted or questionable, among whom 2 died. This work suggests that the promotion of AVK prescription rules should go on.

[Upper extremity deep venous thrombosis. 40 hospitalized patients]. / Thromboses veineuses profondes des membres supérieurs: à propos de 40 patients hospitalisés.

Deep venous thrombosis is 50 times less frequent in upper than in lower limbs. Data remain poor in the literature. Forty consecutive patients (24 males, 16 females, mean age: 54.5 years) were retrospectively analysed from 161 subjects who underwent venous explorations of the upper extremity for a 3.5 year period in the same center. Diagnosis of thrombosis was made by duplex ultrasonography (n =37) or phlebography (n =3). Main clinical manifestations were edema (n =36) and pain (n =29). Location of thrombosis was humeral (n =1), axillary (n =2), or sub-clavian (n =37, 2 bilateral). The majority of thrombosis (n =29) were secondary to cancer and venous catheter (n =19, 15 implanted ports), to central catheter alone (n =3) or cancer alone (n =7). The 11 others were associated with thoracic outlet syndrome (n =6) or apparent primary thrombosis (n =5). Thrombophilia was identified in 6 out of these 11. During follow up [mean of 9 months (0,5-36)], two patients developed pulmonary embolism, 14 a post-thrombotic syndrome and 16 patients died. Initial therapy included heparin (n =36) or fibrinolysis (n =4). Upper extremity deep venous thrombosis are mostly associated with cancers and venous catheters. Thrombophilia is frequent in the other cases. Heparin followed by oral anticoagulation is the optimal therapy whose duration depends upon underlying condition. Fibrinolysis has not been useful for preventing post-thrombotic syndrome in our study.

[Isolated involvement of the trigeminal nerve of sarcoidosis origin]. / Atteinte isolée du nerf trijumeau d'origine sarcoïdosique.

Sarcoidosic neurological manifestations are uncommon. Isolated cranial nerve's injury is exceptional. The authors report the case of a 29 year-old woman with a trigeminal nerve tumor. Surgery and anatomopathology led to the diagnosis of sarcoidosic infiltration. No other neurological or extra-neurological localization was found. Cranial fifth nerve injury was observed in 14 cases of the literature. In all cases, trigeminal nerve injury was described as associated with another disease's localization (neurological and/or extra-neurological). This observation seems unusual due to isolated nature of the presentation and complete resolution after surgery. This case illustrated the diagnosis and nosologic difficulties raised by granulomatous lesions, symptomatic or not, in the absence of systemic localization.

Sperm conservation and HIV infection.

In the course of preparing a medico-legal report in civil proceedings instituted by a couple contaminated by HIV, the case of Mr B. was brought to our attention. At the end of 1984 Mr B. had a serious accident in consequence of which he received a number of blood transfusions. The post-transfusion inquiry established blood contamination. Several years later (in 1990), and for reasons closely related to the above accident, Mr B. and his wife were having difficulty in having a child. They decided to resort to intraconjugal artificial insemination (IAI) first through a private laboratory and then through a CSCOS (Centre for the Study and Conservation of Human Ova and Sperm). In 1992 Mr B. and his wife were both found to be HIV positive; the infection was ascribed to the IAI, as the most plausible cause. In the face of such dramatic events, we wondered why neither the laboratory nor the CSCOS had checked whether the couple were HIV positive. Reflecting on this led us: (a) to make an inventory of the different organizations and facilities empowered to manipulate sperm for medically assisted procreation (MAP); (b) to investigate their obligation in terms of the prevention and control of specific diseases.

[Amoebic liver abscess. Study of 20 cases with literature review]. / Abcès amibien du foie. Analyse de 20 observations et proposition d'un algorithme thérapeutique.

PURPOSE: The management of amoebic liver abscess includes antiamoebic drugs combined or not with percutaneous puncture or surgical drainage. This study was to suggest a decision tree for the therapeutic approach of such feature. METHODS: We report a retrospective analysis of 20 imported cases with amoebic liver abscesses admitted at the Department of Tropical Diseases during 1995-1999 at the Bordeaux University Hospital Centre, France, and a review of the literature. RESULTS: The twenty patients were 14 males and 6 females, mainly 20 to 40 years old. The clinical presentation was mainly accounting a painful liver enlargement with hyperthermia. The echographic picture was mostly represented by a unique liver element located at the liver right lobe. They were numerous in an HIV infected patient. Thirteen patients have been treated using a medical therapeutic approach. A percutaneous puncture has been necessary for 4 cases. A percutaneous drainage has been realised for two patients as regard to the persistence of the hepatalgia occurrence. A surgical drainage has been experienced by two patients after a lack of efficacy of a percutaneous drainage, after rupture of an abscess treated medically, respectively. A review of the literature and the analysis of the 20 cases history have been used to determine a therapeutic algorithm. CONCLUSION: The occurrence of immediate complications at onset must indicate a first line surgical drainage procedure. Beside this situation, risk factors for rupture must be assessed (high size abscess, pejorative localization), as well as poor prognosis feature (liver failure, bacteraemia). If no pejorative condition occurs, a first-line exclusive medical approach can be undertaken with a clinical efficacy evaluation at H72. Otherwise, the indication of the percutaneous drainage must be discussed.

[Skin manifestations related to hepatitis C viruses]. / Les manifestations dermatologiques associées au virus de l'hépatite C.

The hepatitis C virus causes both hepatic and extrahepatic disorders, particularly as regards dermatology. The link between essential mixed cryoglobulinemias and the C virus infection has been clearly evidenced., whereas its frequency seems low in other systemic vasculitis such as polyarteritis nodosa. Similarly, the link between C virus hepatopathy and porphyria cutanea tarda is now proven. Lichen planus is also described as being associated with this virus, but further epidemiological studies are required to determine the exact prevalence of lichen in C virus hepatopathy cases. Finally, various cutaneous disorders, such as urticaria, erythema multiforme, dermo-hypodermitis, etc, occasionally arise during acute or chronic hepatitis C.