Perturbation of CD4+ and CD8+ T-cell repertoires during progression to AIDS and regulation of the CD4+ repertoire during antiviral therapy.

The T-cell antigen receptor (TCR) repertoire was studied longitudinally by analyzing the varying lengths of the beta chain CDR3 hypervariable region during the course of HIV-1 infection and following combination antiretroviral therapy. Drastic restrictions in CD8+ T-cell repertoire usage were found at all stages of natural progression and persisted during the first six months of treatment. In contrast, significant CD4+ T-cell repertoire perturbations were not found in early stages of infection but correlated with progression to AIDS. Out of ten patients presenting with pretreatment perturbations, normalization of the CD4+ repertoire was observed in eight good responders, but not in two cases of unsuccessful therapy. These results indicate that, besides CD4+ cell count rise, an efficient control of HIV replication may allow qualitative modifications of the CD4+ repertoire balance.

Neurosarcoidosis: signs, course and treatment in 35 confirmed cases.

Thirty-five cases of biopsy-proven sarcoidosis with neurologic manifestations are reported. Neurosarcoidosis was the presenting symptom in 31% of cases and the only clinical manifestation in 17%. Mean follow-up time was 48 months. Central nervous system involvement was observed in 37% and meningitis in 40% of patients. Other manifestations were cranial nerve palsies (37%), peripheral neuropathy (40%), and myopathy (26%). Multiple neurologic manifestations were present in 51% of cases. All but 4 were treated with corticosteroids. Another immunosuppressive agent or cerebral irradiation was added in 6 and 2 patients, respectively. Complete recovery was observed in 46%, improvement in 46%, 4% remained stable, and 4% worsened. There were no deaths. We advocate treating neurosarcoidosis with corticosteroids as early as possible. If the patient's condition worsens, additional immunosuppressive agents or cerebral irradiation is warranted.

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

Resting energy expenditure in human immunodeficiency virus-infected patients: comparison between patients with and without secondary infections.

Resting energy expenditure (REE) was measured in 165 malnourished patients with human immunodeficiency virus infection and compared with that of 31 control subjects. Of these patients, 129 had no symptoms of secondary infections (NI), whereas 36 had evolving secondary infection (I) despite a body temperature < 38 degrees C. Mean REE was 11% higher in the NI group than in the control group (P < 0.05); it was 34% higher in the I group than in the control group (P < 0.001) and 21% higher than in the NI group (P < 0.01). In all cases the best predictive variable for REE was the fat-free mass (FFM) (r = 0.77, P < 0.001 in NI; r = 0.70, P < 0.001 in I; r = 0.78 in the control group. The REE-FFM ratio was 152.5 +/- 1.2 and 207 +/- 5.4 kJ.kg-1.d-1 in the NI and I groups, respectively. A high energy expenditure may be a harbinger of secondary infection in acquired immunodeficiency syndrome and may participate in accelerated weight loss.

The VIRGO study: nevirapine, didanosine and stavudine combination therapy in antiretroviral-naive HIV-1-infected adults.

The virological and immunological efficacy of the triple regimen containing nevirapine (once or twice daily), didanosine (once daily) and stavudine, in antiretroviral-naive patients infected with HIV-1, was evaluated in an open-label, prospective, non-randomized, multi-centre, 52-week study. The first 60 patients (VIRGO I) received nevirapine as the standard dose, 200 mg twice daily; the subsequent 40 patients (VIRGO II) received nevirapine at a dose of 400 mg once daily. All patients received 400 mg of didanosine once daily and 40 mg of stavudine twice daily, adjusted for body weight. At baseline, the median CD4 cell count and plasma viral load (pVL) were 414 cells/mm3 and 4.59 log10 copies/ml in VIRGO I, and 412 cells/mm3 and 4.87 log10 copies/ml in VIRGO II. Using an intent-to-treat, 'non-completer equals failure', analysis, 78% (95% CI, 68-88%) of patients in VIRGO I and 68% (95% CI, 53-83%) of those in VIRGO II had a pVL <500 copies/ml at 24 weeks; the proportions achieving a pVL of <50 copies/ml were 62% (95% CI, 50-74%) and 50% (95% CI, 35-65%), respectively. The week 24 median CD4 cell count increase was 168 cells/mm3 (VIRGO I) and 139 cells/mm3 (VIRGO II). At week 52, 39/45 (87%) of VIRGO I patients had pVL <500 copies/ml and 30/45 (67%) <50 copies/ml. Of the 100 patients, 44 experienced grade 2 to 4 adverse events; 20 permanently discontinued study medication because of an adverse event. Combination therapy with the three reverse transcriptase (RT) inhibitors stavudine, once-daily didanosine and either once- or twice-daily nevirapine could be considered as an alternative option for first-line antiretroviral therapy.

The cumulative occurrence of resistance mutations in the HIV-1 protease gene is associated with failure of salvage therapy with ritonavir and saquinavir in protease inhibitor-experienced patients.

Salvage therapy with ritonavir (RTV) and saquinavir (SQV) failed to achieve virological and immunological improvement in 24 HIV-infected patients who discontinued triple therapy with RTV or indinavir (IDV) because of failure or intolerance to treatment. Changes in the HIV-1 protease gene sequence were analyzed prospectively in 14 patients. No primary protease mutation was found prior to the use of protease inhibitors. After 7 months of treatment with IDV or RTV, primary resistance mutations at codons pol 46 and/or pol 82 were observed in 11 of 13 patients. After 16 weeks on RTV-SQV, novel primary mutations related to SQV emerged in 7 of 13 patients, together with an increase in the number of secondary resistance mutations. Our observations indicate that the cumulative occurrence of resistance mutations in the protease gene was associated with failure of antiretroviral therapy. The presence of mutations to a first protease inhibitor may represent a risk factor for the failure of a subsequent treatment with a second line protease inhibitor.

Life expectancy in hospitalized patients with AIDS: prognostic factors on admission.

In the course of the inevitable hospitalizations of AIDS patients, many difficult questions concerning curative and palliative approaches to care have to be answered. In order to guide these strategies, we conducted a prospective study to identify those variables which can be easily quantified on admission which might be predictive of patient outcomes. Between 1 June 1990 and 25 April 1991, 140 consecutive hospitalizations of 83 AIDS patients were recorded. Demographic, clinical, and biological data were collected within 48 hours of admission. Probable (p <0.10) or definite (p <0.05) factors contributing to a higher mortality included type of opportunistic infections, serum albumin level, total lymphocyte count, weight, CD4 cell count, and neurological manifestations. In the multivariate proportional hazards model, two factors were significantly and independently predictive of lower survival: body weight less than 90% of ideal body weight and neurologic manifestations. The probability of survival was significantly affected by the number of predictive factors present on admission, and patients were significantly more likely to die when these latter two factors were present concomitantly. These factors might be useful to define the optimal mode of care for hospitalized AIDS patients, considering both patients' wishes and an objective assessment of the prognosis.

[4 new cases of neuromyositis, one of them associated with HTLV-I infection]. / Quatre nouvelles observations de neuromyosites, dont un cas associé à une infection par HTLV-I.

Neuromyositis is a very rare type of polymyositis where, beside the usual muscular manifestations, there are signs of peripheral neuropathy which can be found at clinical, electromyographic and/or pathological examination. We have seen between 1983 and 1990 four cases of neuromyositis. The neurological disorder was an axonopathy in two cases which is usual in neuromyositis; in the other two cases, there was a polyradiculoneuritis which seems to be very rare in this syndrome. In the four patients the disease was particularly severe and unresponsive to treatment. One of our patients had HTLV-I infection diagnosed by polymerase chain reaction amplification and in situ hybridization, while the serological test was negative. To our knowledge only three cases of HTLV-I associated neuromyositis have been reported in the literature.

[Bacterial endocarditis on prosthetic valves]. / Endocardites infectieuses sur prothèses valvulaires.

Bacterial endocarditis is a rare, but often lethal, complication of cardiac valve replacement. The endocarditis is called "early" when it occurs within 2 months of the operation, and "late" when it develops after that period. Contamination of the prosthesis with bacteria may occur intra-operatively or post-operatively. The clinical diagnosis is often difficult in early endocarditis when another focus of infection is present and in late endocarditis in the absence of fever and positive blood cultures. Isolation of the pathogen from blood cultures is essential to the diagnosis and treatment. Therapeutic surgery now has wider indications than formerly. The incidence of this dangerous complication can only be reduced by well-planned and well executed prophylactic measures.

[Tuberculosis and systemic diseases. Apropos of 16 cases]. / Tuberculose maladie et maladies systémiques. A propos de 16 cas.

METHODS: We analyzed retrospectively 16 patients between 1976 and 1993 (six men, ten women, mean age: 49-year-old) suffering from connectivitis. HIV-negative and receiving corticosteroids, combined for six of them with immunosuppressive therapy, and suffering from tuberculosis. RESULTS: The mean period between first signs and diagnosis was 51 days (3-190 d). Tuberculosis was pulmonary (n = 10) of which 4 miliary, pleurisy (n = 3), lymphadenitis (n = 5). We only observed one meningitis, one otitis and one female genital tuberculosis. Six patients had more than one localisation. Diagnosis was proven bacteriologically eight times, histologically six times and for three patients diagnosis was certain because of efficacy of antituberculosis antibiotherapy. Evolution was always good, with antituberculosis antibiotherapy of maximum 18 months, without sequella. Because rifampicin enzymatic induction, connectivitis worsened in five patients. An increase in corticotherapy was necessary for these five patients. CONCLUSION: This series confirmed the frequently extrapulmonary feature of tuberculosis in immunosuppressed patients, the long delay of diagnosis and the risk of exacerbation of underlying disease with rifampicin.

[1977 mortality rate in HIV-infected patients presenting with hepatitis C cirrhosis. Results of the GERMIVC multicenter survey conducted in French departments of internal medicine or infectious disease]. / Mortalité par cirrhose virale C chez les patients infectés par le VIH dans les services de médecine interne et de pathologie infectieuse en 1997. Enquête multicentrique GERMIVIC. (Groupe d'étude sur le virus C). (Société nationale française de médecine interne). (Société de pathologie Infectieuse de langue française).

PURPOSE: Hepatitis C (HCV) has a high prevalence (10-30%) among human immunodeficiency virus (HIV)-infected patients. However, little information is available regarding the impact of hepatitis C on survival. The objective of our study was to determine the incidence of hepatitis C-related deaths in HIV-HCV co-infected patients. METHODS: The study was a retrospective (1-year), multicenter cohort survey conducted in 63 departments of either internal medicine or infectious diseases in France. It included 26,497 HIV-infected patients, of whom 4,465 (16.8%) presented coinfection due to the hepatitis C virus. The following parameters were studied for the year 1997: total number of deaths, number of deaths related to either AIDS, cirrhosis, hepatocellular carcinoma, or other causes. RESULTS: Among the 26,497 patients, 543 deaths (incidence: 2%) were observed in 1997; 543 deaths were due to AIDS (incidence: 1.7%), 36 to cirrhosis and/or hepatocellular carcinoma (incidence: 0.13%), and 48 (incidence: 0.18%) to another cause. In the subgroup including 4,465 HIV-HCV-coinfected patients, 29 deaths (incidence: 0.64%) were due to either HCV-related cirrhosis or hepatocellular carcinoma. These results were compared with those of a previous similar survey conducted in 1995, before the era of highly active antiretroviral therapy. The only significant difference is the dramatic regression of deaths due to AIDS. CONCLUSION: The impact of hepatitis C virus on the mortality among HIV-infected patients whose follow-up took place in departments of either internal medicine or infectious diseases in France was very low in 1997. The expected increase in the life span in these patients could modify these results in the future, due to recent improvements in the HIV infection treatment.

[Leiomyosarcoma of the superior vena cava: diagnosis by endovascular biopsy]. / Leiomyosarcome de la veine cave superieure: diagnostic par biopsies endovasculaires.

We report the case of a 69-year-old woman with leiomyosarcoma of the superior vena cava presenting with acute superior vena cava syndrome (SVCS). CT and MRI failed to fully characterize the endovascular process. Percutaneous endovascular biopsy, followed by metallic stent placement to treat the SVCS, confirmed the diagnosis. Symptoms resolved within 48 hours and surgical resection of the tumor was performed one month later. Unfortunately the patient died two weeks later because of intracranial hemorrhage.

[Agranulocytosis in acute hepatitis B in an HIV seropositive patient]. / Agranulocytose au cours d'une hépatite B aiguë chez un patient séropositif pour le VIH.

BACKGROUND: During the course of acute hepatitis B, hematology disorders are common though they are generally mild and occur early. Agranulocytosis is exceptional and occurs late in the disease course. CASE REPORT: We report a case of agranulocytosis which developed 3 weeks after onset of acute hepatitis B in an HIV-positive patient. Peripheral and central hematological disorders led to the diagnosis. Agranulocytosis developed during the cytolytic phase of the primary hepatitis B infection and regressed after administration of hematopoietic growth factors. DISCUSSION: It is sometimes difficult to establish the causal effect of hepatitis B in the development of agranulocytosis in patients with an HIV co-infection who are on a multiple drug regimen and subject to multiple bacterial, viral or parasite infections.

[Transmission modes of hepatitis C virus]. / Modes de transmission du virus de l'hépatite C.

SITUATION IN FRANCE: The prevalence of hepatitis C virus (HCV) infection in the French population is estimated at 1%, a level similar to that in other western countries. USUAL CONTAMINATION ROUTES: Epidemiological studies, together with gene typing, have made it possible to distinguish transmission modes. A history of intravenous drug abuse or transfusion is found in 60 to 80% of all subjects infected by the HCV. Other documented modes of contamination include hemodialysis, organ transplantation, accidental occupational-related puncture and mother-infant transmission. OTHER ROUTES: Sexual or intra-familial nonsexual transmission is uncommon and related to the length of exposure and the stage of HCV infection in the "source" subjects. Cases of HCV transmission have been reported during medical procedures. Currently the mode of of transmission is unknown in 20 to 40% of the cases.

[Hepatitis C virus infection in internal medicine and infectious diseases departments in France. Preliminary results of a national epidemiological survey]. / Infection par le virus de l'hépatite C dans les services de médecine interne et les services de pathologie infectieuse en France. Résultats préliminaires d'une enquête épidémiologique nationale.

OBJECTIVES: In order to know the number and the main clinical features of patients with hepatitis C virus (HCV) infection, we conducted a national epidemiological study of patients followed in Internal Medicine and in Infectious Diseases departments in France. METHODS: For each patient with HCV infection seen between 13/03 and 13/04/1995 (in- or out-patients), a chart was completed. RESULTS: The response rate was about 30% with 2002 charts being analyzed. There were 59% males and 39% females, with a peak of frequency between 25 and 40 years, including 1241/2002 (62%) patients. Most patients were of French origin (85.7%). We found that 1436/2002 (72%) patients came from provinces of southern France and Paris. In 10% of cases the diagnosis was made during the study period. A route of transmission was identified in 86.4%, mainly drug abuse 60.4% and blood product transfusion 19.3%. At the time of diagnosis, main clinical features were: no symptom 47%, liver biological abnormalities 52%, cirrhosis 7.4%, cryoglobulinemia 2.7%, auto-immune disease 3%, hepatocellular carcinoma 0.85%. We frequently found a viral co-infection: HIV 56.1%; HBV 22.2%. A confirmation RIBA test was done in 67.8%, measurement of viremia in 33.4%, genotyping in 6.7% and liver biopsy in 28.7% of cases. Finally, 407 (20.3%) patients received a specific anti-HCV treatment. CONCLUSION: These preliminary results underscore: 1) the large percentage of the population with HCV infection followed outside of hepatogastroenterology departments in France. 2) the high probability that the HCV epidemic is underestimated as we noted 10% of new diagnosis during the study period. 3) the requirement for a multidisciplinary approach for these HCV patients.

[Arterial embolism of the limbs in infectious endocarditis of the heart valves]. / Embolie artérielle des membres au cours des endocardites infectieuses sur valves natives.

Nine cases of infective endocarditis (IE) on native valves, complicated by arterial embolism of the limbs (AEL), were collected between June 1974 and October 1988 (prevalence 4.3 percent). Among the 11 AEL recorded, 9 involved the lower limbs and 2 the upper limbs. The diagnosis, suspected in patients with acute ischaemia (n = 6), transient (n = 1) or pseudophlebitic (n = 1) pain, or discovered by systematic pulse examination (n = 3), was confirmed by Doppler ultrasound (n = 3), angiography (n = 2) or oscillometry (n = 4). AEL occurred 2.8 weeks on average after the onset of treatment; it appeared 6 months after the end of treatment in 1 case and preceded the diagnosis of IE by 1 to 6 weeks in 3 cases. The causative organisms isolated in 7 cases were: non-haemolytic streptococci (n = 4), Staphylococcus aureus (n = 1), Haemophilus parainfluenzae (n = 1) and enterococcus (n = 1). Vegetations were found in 6 of the 7 patients explored by echocardiography. Two cases of embolism of the femoral artery required embolectomy. Effective heparin anticoagulation was obtained in only one patient. Six patients underwent valve replacement in the acute phase of endocarditis. After a mean follow-up period of 32 months (range 3 to 120 months), only one patient has symptoms (claudication of the left upper limb); 5 patients are asymptomatic with a reduced (n = 5) or abolished (n = 2) pulse. Three embolisms have left no sequelae. Altogether, AEL are not uncommon in infective endocarditis. They rarely influence the functional prognosis and are detected by systematic palpation of the pulses. Anticoagulation in effective doses is discussed. Attempts at removing the obstruction should be made only in cases with poorly tolerated proximal embolism. In patients with multiple or recurrent embolic accidents, valve replacement may be considered.

[Splenectomy can cure thrombocytopenia of systemic lupus erythematosus]. / La splénectomie peut guérir la thrombopénie du lupus.

Between 1976 and 1988, 7 patients with systemic lupus erythematosus (SLE) underwent splenectomy for severe peripheral thrombocytopenia (platelet count below 30,000/mm3) which had resisted corticosteroid therapy (n = 7), high-dose immunoglobulins (n = 4), vincristine (n = 2), danazol (n = 1), cyclophosphamide and plasma exchanges (n = 1). No infective or non-infective complication of splenectomy was observed. One patient died of intracerebral haemorrhage 3 years later, after several recurrences of thrombocytopenia. The 6 survivors have normal platelet counts (more than 150,000/mm3) after splenectomy, over a mean follow-up period of 80 months. Two of these 6 patients never had recurrent thrombocytopenia and have not received any treatment for 17 to 102 months. Four patients are still under prednisone in doses lower than 30 mg/day. Among these, 2 had recurrent thrombocytopenia 2 and 60 months respectively after splenectomy and responded favourably to another course of corticosteroids associated, in one case, with cyclophosphamide. Thus, splenectomy is an effective treatment of the thrombocytopenia associated with SLE. However, the possibility of early or late recurrences makes it necessary to reserve splenectomy to those cases where medical treatment has failed or is contra-indicated.

[Anti-Scl-70 antibodies in systemic scleroderma]. / Anticorps anti-Scl-70 dans la sclérodermie systémique.

We looked for anti-Scl-70 and anti-centromere antibodies in 109 patients (26 men and 83 women). Mean age was 43 +/- 15 years. Forty patients had systemic sclerosis according to ARA criteria. The extension of cutaneous involvement was defined by using Barnett and Coventry criteria: 12 patients were type I (sclerodactyly), 20 type II (acrosclerosis) and 8 type III (diffuse scleroderma). Among the 12 patients with type I, there were 8 cases of CREST syndrome defined as follows: presence of sclerodactyly, Raynaud's phenomenon and 2 of the 3 following criteria: oesophageal dysmotility, calcinosis, telangiectasia. Other organ involvement was recorded. Control patients had idiopathic Raynaud's phenomenon (n = 22), other connective tissue diseases (n = 20), and miscellaneous diseases (n = 28). Ninety-nine patients were prospectively included in this study. Patients' sera were stored at -20 degrees C. Ten previously stored sera obtained from patients with systemic sclerosis were also analyzed. Immunological tests were performed simultaneously and with no information on the diagnosis. When antinuclear antibodies were detected by indirect immunofluorescence, double immunodiffusion and immunoblotting were performed. Anti-Scl-70 antibodies were detected in systemic sclerosis only: 1 of 12 type I, 11 of 20 type II and 4 of 8 type III. One serum negative by immunodiffusion was positive using immunoblotting. We found that the specificity of anti-Scl-70 antibodies for systemic sclerosis was 100 p. 100 and their sensitivity 40 p. 100. There was a correlation between the presence of anti-Scl-70 antibodies and the presence of antinuclear antibodies (p less than 0.05) and the extent of cutaneous involvement (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Prophylaxis of varicella in pediatric staff.]. / Prévention de la varicelle chez le personnel d'encadrement des enfants.

Varicella is an ubiquitous, highly contagious viral disease of childhood which may be severe in non immune adults and pregnant women. Pediatric staff is particularly at risk of nosocomial varicella and susceptible staff should be prospectively idenfitifed by serologic tests. A number of different approaches may be used to prevent disease depending on the at risk population and the preexposure or postexposure status. This article reviews and evaluates the different approaches to the prevention of varicella in pediatric staff.