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The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors.A cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (15). Logistic regression models were used to investigate factors associated with RI.The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/microL and HIV plasma viral load (VL) was50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6-4.3)], age50 years (OR=9.8: 7.4-13.0) and 40-50 years (OR=1.9: 1.5-2.4), body mass index (BMI)22 kg/m(2) (OR=3.3: 2.7-4.3) and tenofovir exposure (OR=1.4: 1.0-1.9 for1 year and OR=1.5: 1.2-2.0 for1 year). Advanced RI (CC60 mL/min) was associated with age50 years (OR=5.6: 2.9-10.9) and 40-50 years (OR=2.2: 1.1-1.4), BMI22 kg/m(2) (OR=1.5: 1.0-2.4), hypertension (OR=2.5: 1.4-2.5) and indinavir (IDV) exposure1 year (OR=2.3: 1.5-3.6).This survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.

The human neurotropic JC virus (JCV) is responsible for progressive multifocal leukoencephalopathy (PML), an infectious demyelinating brain disease with major morbidity and mortality, usually refractory to treatment. We describe a PML in a 67-year-old woman with a destructive polyarthritis associated with anti-JO1 antibodies treated with corticosteroids. Although glucocorticoid therapy was maintained, administration of cidofovir improved the neurological condition. Our observation demonstrates the expanding clinical importance of JCV in systemic rheumatic diseases, particularly when immunosuppressive agents are used, and neurological symptoms or white matter changes on central nervous system imaging should arouse the suspicion of PML.

Objective The aim of this study was to evaluate the effect of hydroxychloroquine (HCQ) on fetal preterm delivery and intrauterine growth restriction (IUGR) in a cohort of pregnant women with systemic lupus erythematosus (SLE). Methods Over an 11-year period (January 1, 2001 to December 31, 2011), all women with SLE and admitted to deliver after 22 weeks of gestation to Bordeaux University Hospital (France), were retrospectively enrolled in the present study. The population was then split into two groups based on the treatment they received: HCQ exposed (HCQ+) versus HCQ non-exposed (HCQ−) group. Results 118 pregnancies were included, 41 in the HCQ+ group and 77 in the HCQ− group. The rate of adverse fetal outcome was significantly lower in the HCQ+ group ( p = 0.001), particularly in terms of preterm delivery, 15.8 % versus 44.2 % ( p = 0.006), and IUGR, 10.5 % versus 28.6 % ( p = 0.03). No adverse outcomes were reported in the HCQ+ group. Conclusion HCQ reduces neonatal morbidity in women with SLE by significantly decreasing the rate of prematurity and intrauterine growth restriction.

Resume Les nouvelles strategies therapeutiques visant a ameliorer la prise en charge des patients infectes par le virus de l'immunodeficience humaine font en partie appel a des molecules et a des concepts anciens, developpes depuis la decouverte du syndrome de l'immunodeficience acquise. C'est ainsi que le premier antiretroviral apparu sur le marche, la zidovudine, un temps delaisse, est a present reincorpore dans les tritherapies pour diminuer l'emergence de la mutation de resistance K65R induite par certains inhibiteurs nucleosidiques de la transcriptase inverse. De meme, le concept d'inhibition de l'entree du VIH dans les cellules cibles, developpe avec les CD4 recombinants solubles, a ete repris avec les inhibiteurs de fusion comme l'enfuvirtide ou les molecules en cours de developpement comme BMS-488043 et SCH-D. Enfin, la monotherapie, abandonnee lors de l'avenement des tritherapies plus puissantes, pourrait a nouveau etre envisagee avec l'inhibiteur de protease booste, lopinavir/ritonavir.

The aim of the present study was to better characterize the expansion of double-negative (DN) T cells in vivo in AIDS patients and to ascertain the discrepant response of an immunodepressed immune system towards two distinct mycobacterial infections. In a large cohort of HIV-1 seropositive patients with low CD4(+) T cell counts (

Idiopathic thrombotycopenic purpura (ITP) is an autoimmune disorder in which circulating autoantibodies react with target antigens on the platelet membrane. In order to identify the autoimmune response in ITP, two MAIPA (Monoclonal Antibody (MAb) Immobilization of Platelet Antigen) assays (MAIPA I and MAIPA II) were performed on sera from thrombocytopenic patients. In the classic MAIPA assay (MAIPA I), control platelets were incubated simultaneously with human serum and a mouse MAb to a platelet glycoprotein. In MAIPA II, the control platelets were incubated first with the human serum and then, after washing, with the selected mouse MAb. A positive MAIPA I test but a negative MAIPA II has been shown to result from the presence of serum antibodies recognizing mouse MAb to platelet glycoproteins used in the assay. We compared the frequency of such 'anti-mouse' antibodies in patients with thrombocytopenia associated or not with other autoimmune states and in healthy donors with a normal platelet count. Statistically significant differences were found in the incidence of anti-mouse antibodies between patients and healthy donors. Furthermore, the identity of the targeted mouse MAbs varied in sera from the patients. The detected anti-mouse antibodies may include anti-idiotypic antibodies produced against cross-reactive idiotypes shared by human and mouse anti-platelet antibodies.

Hydroxyurea (HU) or hydroxycarbamide is an antimetabolite chemotherapy frequently used in the treatment of chronic myeloproliferative disorders. This treatment is usually well tolerated but a few cases of fever induced by the molecule have been reported in the literature. The aim of the study was to describe the clinical and biological characteristics of HU induced fever.We performed a cross sectional study of patients treated with HU and followed-up in an internal medicine department between 2006 and 2012. We added our cases of HU induced fever with those reported in the literature (Pubmed and Cochrane databases) since 1981.We identified 38 cases of HU induced fever, including our 4 cases. The mean age was 65±10.9 years and the sex-ratio 1/2. The fever appeared after a median duration of treatment of 21 days and was usually high (40°C) but clinically well tolerated. A biological inflammatory syndrome (CRP: 131±92 mg/L) was constant and one third of the patients also presented with hepatitis or lung disease. A probabilistic antibiotic treatment was introduced for 34% of the patients. For the half of the patients, HU-reintroduction test was performed, and was positive for all the patients but one. As soon as HU was withdrawn, the fever disappeared in a median of 24 hours.HU induced fever is unusual. Clinical presentation is very stereotyped. When this adverse effect is suspected, an infectious disease must first be ruled out. If infection is excluded, HU has to be stopped.

Rifabutin, 600 mg/day, was compared with a placebo in the early treatment of culture-proven Mycobacterium avium bacteremia in patients with AIDS. Following 14 days' treatment, bacteriological success, defined as a negative culture or a reduction in the number of CFU of M. avium organisms per milliliter of blood by a factor of > or = 0.5 log from the baseline, was observed in 7 of 10 (70%) evaluable rifabutin patients and in 1 of 13 (8%) evaluable placebo patients (P = 0.002). Rifabutin is active against M. avium as a single agent and can make a significant contribution to combination regimens for the treatment of disseminated M. avium infection in AIDS patients.

Large granular lymphocyte leukemia (LGL) is a hematologic disorder characterized by a monoclonal expansion of large lymphocytes containing azurophilic granules with a T CD3(+)CD57(+) or Natural Killer (NK) CD3(-)CD56(+) phenotype. The World Health Organization (WHO) classification identifies three entities: the T LGL, the chronic lymphoproliferative disorder of NK-cells, and the aggressive NK-cell leukemia. T LGL and chronic lymphoproliferative disorder of NK-cells are indolent diseases frequently associated with cytopenias and a wide spectrum of auto-immune manifestations. Neutropenia can lead to recurrent bacterial infections, which represent an indication of initiating a treatment in most of the cases. Immunosuppressive therapies are usually used in this context. In contrast, aggressive NK-cell leukemia follows a fulminant course with a poor prognosis because patients are refractory to most of the treatments. There is now a considerable interest in the pathophysiology of the disease with the perspective of new therapeutic options.

Bone marrow necrosis is a very rare condition which is characterized by a necrosis of hematopoietic progenitors, adipocytes and reticulin network.We report a 62-year-old woman admitted to an intensive care unit for an essential thrombocytemia associated with bone marrow necrosis complicated by septic shock and progressive multi-organ failure. To our knowledge, this is the second case reported in the literature. The clinical presentation of bone marrow necrosis includes non-specific symptoms such as fever, bone pain and sometimes a clinically significant medullar insufficiency syndrome. Biology can reveal cytopenias, elevated LDH and alkaline phosphatase serum levels. The diagnosis is confirmed by bone marrow trephine biopsy. Bone marrow necrosis is classified as extensive if more than 50% of the bone marrow biopsy show necrosis. Haematological malignancies (particularly leukaemia), and solid malignant tumours (particularly gastro-intestinal or lung cancers) represent up to 90% of aetiologies and must be actively researched. Also, sickle cell disease and catastrophic anti-phospholipid syndrome must also be investigated. Essential thrombocytemia remains an exceptional cause of bone marrow necrosis.Overall the prognosis of bone marrow necrosis is poor unless appropriate and intensive treatment, especially for sickle cell disease in which complete medullar regeneration has been observed.

The beam position monitor (BPM) for the final focus test beam (FFTB) is newly designed to have 1 μm precision and repeatability within 500 μm from center. The system design and the performance test of the prototype electronics are described.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiorgan involvement characterized by an immune response against nuclear components. SLE patients experience a waxing and waning disease course and exhibit a wide array of clinical manifestations, reflecting the systemic nature of the disease. Environmental triggers such as viruses are likely to act in the context of susceptibility genes, including genes involved in antigen/immune complex clearance, lymphoid signalling, or apoptosis, among several others, explaining why the pathogenesis of this disease remains largely uncovered. The abnormal activation of the innate immunity is central to SLE physiopathology. Dendritic cells activation and unabated secretion of IFN-alpha are the key features of the disease through their involvement in the capture and the presentation of nuclear material to the autoreactive adaptive arm (T and B lymphocytes) leading to the subsequent production of anti-nuclear autoantibodies. In this line, numerous studies have demonstrated the prominent role of immune complexes deposition throughout the body which directly can induce inflammation and tissue damage. However, animal models and recent human studies support the concept that other effector pathways including cytotoxic T-lymphocytes could be involved in SLE pathogenesis through their ability to migrate and/or target specifically different tissues. The aim of this review is not to provide a comprehensive review of the SLE pathophysiology but rather to give an overview of the immunological abnormalities associated to SLE. The treatments that are currently used or that are in development to fight against abnormal immune response in SLE will be detailed. The genetics of SLE is not the scope of this review.

Giant cell arteritis, a large-sized vessel vasculitis, may be associated with musculoskeletal proximal (polymyalgia rheumatica) or distal manifestations. A 68-year-old woman, who had inflammatory pelvic girdle pain, was diagnosed with giant cell arteritis and was successfully treated with corticosteroids. The magnetic resonance imaging and ultrasonography revealed a bilateral bursitis and pelvic girdle enthesopathy. Bursitis is the main anatomic lesion occurring in polymyalgia rheumatica and can be underlined by ultrasonography.

Autoimmune manifestations are common in splenic marginal zone lymphoma (SMZL) and are sometimes the presenting feature of the disease. Autoimmune cytopenia (anemia, thrombocytopenia) are the most frequently reported autoimmune conditions. However, other immunological manifestations may be associated with SMZL.We report a retrospective case series of six patients with SMZL associated with autoimmunity.Auto-immune manifestations were the presenting feature of lymphoma in four cases. Auto-immune manifestations included auto-immune cytopenia in three cases (two hemolytic anemia and one pancytopenia), thyroiditis in two cases, systemic lupus and Still's disease in one case each. Antinuclear antibodies were detected with a titre of 1/250 in three cases, and with a titre of 1/32,000 in the patient with systemic lupus. Testing for DNA antibodies was negative in all cases. Two patients had a circulating lupus anticoagulant, with portal venous thrombosis following splenectomy in one case. One patient had hypogammaglobulinemia. A monoclonal gammopathy was detected in three patients. All patients had spleen enlargement. Immunophenotyping of blood peripheral lymphocyte was typical in five out of the six cases. Bone marrow was infiltrated in five out of the six cases. Diagnosis was obtained by the combination of immunophenotyping and bone marrow histopathology in five cases, and by splenic histopathology in the remaining case. Hepatitis C virus serology was negative in all patient.Autoimmune disease as systemic lupus or Still's disease may be associated with SMZL before its tumoral manifestations are evident. In this mode of presentation, spleen enlargement, hypogammaglobulinemia, monoclonal gammopathy, and multiple autoimmune diseases, should alert the physician.

Neutrophilic disease is characterized by aseptic visceral infiltration by normal polymorphonuclear leukocytes that can occur in any organ. Association with an underlying systemic disease, particularly haematological malignancy or inflammatory bowel disease, is frequent. This may produce a multisystem disorder, but diagnosis is usually based on skin lesions because of their clinical and histological accessibility. Pulmonary manifestations are the most common extracutaneous symptoms but may be misdiagnosed, as in our case report.A 77-year-old woman with IgA myeloma presented with an inflammatory bullous plaque of the leg coupled with fever lasting one week. The clinical and histological examinations were evocative of a neutrophilic dermatosis such as Sweet's syndrome. Significant improvement was initially obtained with systemic corticosteroids and colchicine. The course became complicated by necrotic neutrophilic papulopustular lesions of the upper limbs and pulmonary manifestations, with fever and decline in overall condition occurring the day after administration of erythropoietin. A hypothesis of septic aetiology prompted antibiotic and antifungal therapy, which remained ineffective. The patient died the day after the second erythropoietin injection.This case involved late identification of the aseptic neutrophilic aetiology of pulmonary manifestations. Several factors favouring their appearance and the fatal outcome may be suggested: the existence of a myeloma, association with myelodysplastic syndrome and the possible iatrogenic action of erythropoietin. To the best of our knowledge, this is the first reported case of extracutaneous neutrophilic infiltrate occurring in a patient treated with this haematopoietic hormone.

Human pasteurellosis is, in general, a locoregional infection due to contact with an animal. Systemic infections are rare and endocarditis is exceptionally described. The authors report two new cases of endocarditis due to Pasteurella spp, they then review 29 other published cases. Pasteurella spp. endocarditis presents as an acute form in 64% of cases and affects the aortic as often as the mitral valves. Contact with an animal is documented in 65% of cases. Pasteurella multocida is the most frequent species in this infection. The total death rate is 40% and can reach 57% of cases in case of immunodepression. The bad prognosis of this infection, justifies an early diagnosis and a rapid and adapted but not yet consensual medicosurgical treatment.

"Agranular CD4+ CD56+ hematodermic neoplasm" are rare hematologic neoplasms which were recently shown to correspond to the plasmocytoid dendritic cells.A 83-year-old presented isolated skin lesions purple, infiltrating the dermis. The biopsy has shown a dense dermal infiltration with malignant cells CD4+ CD56+ CD43+. There were no bone marrow involvement and no circulating blood cells. A chemotherapy permitted a clinical remission after six courses. Unfortunately, skin and blood relapses appear four months later. After a short success of chemotherapy by DHAP, the patient died three month later."Agranular CD4+ CD56+ hematodermic neoplasm" is a distinct entity from the cutaneous primary lymphomas. Recently plasmocytoid monocyte cells have been identified as the precursor of the malignant population with the high expression of CD123, IL3 receptor. It is a distinct clinicopathologic entity by its clinical presentation with skin tropism, bone marrow involvement with or without leukemic phase and poor prognosis independent of the kind of treatment and its particular phenotype CD4+ CD56+ CD43+. It would be interesting to use antibodies linked to CD123 in therapeutic because any treatment have efficacity in this disease.

Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto's disease is a rare anatomoclinical entity whose etiology remains unknown. It is mainly reported in young adult female, presenting with cervical lymphadenopathies, fever and asthenia. The diagnosis is based on the histological examination of a lymph node biopsy. The disease course is usually uneventful, but sometimes Kikuchi-Fujimoto's disease can reveal or evolve into a cutaneous or a systemic lupus.We report three new cases of Kikuchi's disease: the first one mimicked a systemic lupus, the second one was associated with a lupus-like rash, and a the last one was a severe case with hemophagocytic syndrome and a primo-infection with Epstein-Barr virus revealing a systemic lupus erythematosus.Clinical and biological follow-up of patients presenting with Kikuchi's disease is necessary to look for an association with a lupus. We discuss the pathogenic links between Kikuchi's disease and lupus.

Extrapulmonary tuberculosis is usually more difficult to diagnose than pulmonary tuberculosis. It often involves inaccessible sites and it is paucibacillary.In this study, we tried to analyze the performance of various bacteriological methods used to diagnose 51 cases of extrapulmonary tuberculosis in an infectious diseases ward.The culture was positive for 55% of patients. The new amplification methods used were very disappointing for the testing of nonrespiratory samples. The sensitivity of PCR was 32% compared to that of diagnostic culture which remains the most sensitive reference method. Liquid media allow for rapid growth and limit the contaminations. The combined inoculation of liquid and solid medium increases the sensitivity and helps to identify the pathogen.

Common variable immunodeficiency (CVID) is an immune defect characterized by primary hypogammaglobulinemia. Most of the time, clinical manifestations that reveal CVID are recurrent bacterial infections, but auto-immune or granulomatous events may occur.This retrospective study was conducted on 17 patients fulfilling the classical CVID definition. Lymphocyte activation level was evaluated in 12 patients through HLA-DR expression on lymphocytes subsets.This study includes 17 patients, 7 men and 10 women. The mean age at the first clinical manifestation is 23 years and the mean age at diagnosis is 39 years. Recurrent upper and lower bacterial respiratory tract infections are common to all patients. Abdominal infection due to Mycobacterium avium-intracellulare complex is found in one patient. Digestive events are dominated by chronic diarrhea caused by giardiasis, nodular lymphoid hyperplasia or villous atrophy. Seven patients developed auto-immune conditions (insulin dependent diabetes, idiopathic thrombocytopenic purpura (ITP), rheumatoid arthritis) and 7 patients have a splenomegaly. Non caseating granulomas in the spleen or in lymph node biopsies are found in 3 patients. Ten patients have a T lymphopenia, 2 have a B lymphopenia, 5 have a CD4/CD8 ratio1, and 6 have T CD4(+) lymphocytes400/mm(3). The study of HLA-DR expression on lymphocytes subsets shows that 7/12 patients have activated T CD4(+) and/or CD8(+) cells and these patients have auto-immune or tumoral manifestations. The other 5 patients do not have activated T lymphocytes but present with infectious events only.Our study allows the separation of patients with CVID according to their T lymphocytes activation level. A patient's classification is necessary to define homogeneous groups of patients to perform genetic and functional studies which will probably reveal heterogeneous molecular abnormalities.

Cold agglutinin disease is a chronic auto-immune hemolytic anemia related to a lymphoproliferative disorder with a degenerative potential and no codified treatment. This rare affection is related to the production of anti-erythrocytes immunoglobulins M. They are responsible of hemolytic crises sometimes severe and vascular acrosyndrom when submitted to cold temperature. Before rituximab, a monoclonal antibody targeted against the B lymphocyte CD20 antigen, no treatment was really efficient.We present 5 patients who have been treated with 4 weekly rituximab perfusions, and then we proceed to a review of the literature concerning the other 23 similar cases.With a good tolerance, the treatment allowed a remission in all the cases (4 partial, 1 complete). Among the 23 observations published, the rate of answer was 21/23 (of which 14 gave completes).Rituximab is an alternative treatment of cold agglutinin disease.

Symptomatic lactic acidosis requiring intensive care is a rare and severe adverse event related to the mitochondrial toxicity of the nucleoside analog reverse transcriptase inhibitors (NRTIs).We retrospectively investigated the clinical and biological features of HIV-infected patients who developed severe lactic acidosis syndrome at the University teaching hospital of Bordeaux and the regional community hospital, during 1996-2000.Nine patients were identified (incidence: 0,9/1000 NRTI treated patient-years), 4 men and 5 women with a median age of 36 years. They had a moderate immunodeficiency (median CD4+ T lymphocyte counts: 197/mm(3)) and only one of them presented a virological failure. The causes of hospital admission were abdominal pain (n = 6), dyspnea (n = 6), asthenia (n = 5), jaundice (n = 4), and vomiting (n = 2). Hepatomegaly was present in 6 patients. Lactic acidosis was found in all cases: median pH: 7.28, bicarbonate: 12 mmol/l, anion gap: 27 mEq/l, plasma lactic acid: 13 mmol/l. Cytolysis (n = 8), cholestasis (n = 6), hepatic failure (n = 4), rhabdomyolysis (n = 4) and pancreatitis (n = 2), were also present. Despite medical intensive care, seven patients died. The only two post-mortem examinations revealed severe hepatic steatosis. Median duration of NRTI therapy was 4 years. At presentation, five patients were receiving lamivudine, five didanosine, four stavudine and three zidovudine. Six patients were coinfected by HCV and/or HBV, four had chronic renal failure and five an immediately preceding infectious disease.The prognosis of lactic acidosis is severe. Nucleosid-analog therapy needs clinical and biological monitoring, specially in patients with comorbidities.

Initially, the SLC (Stanford Linear Collider) damping rings accomplished Robinson instability damping by operating the RF accelerating cavities slightly detuned. In order to run the cavities tuned and achieve damping for Robinson instability and synchrotron oscillations at injection, an active feedback system has been developed. The theoretical basis for the feedback system and the development of the hardware are described. Extensive measurements of the loop response including stored beam were performed. Overall performance of the system is also reported. The measured data did not match what the authors' model had predicted. The measurements did show the expected zero at DC, the first-order cavity pole at 45 KHz, and the second-order beam resonance at the synchrotron frequency. Another pole, and an exponentially increasing phase lag appeared near the synchrotron frequency. >

An electronic system which detects synchrotron oscillations of individual bunches with 4-ns separation is presented. The system design and performance are motivated by the requirements of the proposed B factory facility at SLAC (Stanford Linear Accelerator Center). Laboratory results show that the prototype is capable of measuring individual bunch phases with better than 0.5 degree resolution at the 476-MHz RF frequency. >

The Stanford Synchrotron Radiation Laboratory (SSRL) has built a 3-GeV injector to fill the Stanford Positron Electron Accelerator Ring (SPEAR). The diagnostics and associated instrumentation are discussed. The authors describe the function of the various devices in three different situations: the initial commissioning of the machine when systems were being checked out with very low current; machine physics on and characterization of the injector itself; and the normal operation of the machine as a dedicated injector for SPEAR. The devices considered are the Faraday cup, the current toroids, the insertable screens, the beam position monitors, the Q meter, and the stripline. >

A computer model of the storage ring, including the RF system, wake fields, synchrotron radiation loss, and the bunch-by-bunch feedback system, is presented. The feedback system model represents the performance of a fast phase detector front end (including system noise and imperfections), a digital filter used to generate a correction voltage, and a power amplifier and beam kicker system. The combined ring-feedback system model is used to study the feedback system performance required to suppress instabilities and to quantify the dynamics of the system. Results which show the time development of coupled bunch instabilities and the damping action of the feedback system are presented. >

Objective. Churg-Strauss syndrome (CSS) has been described in association with the treatment of asthmatic patients with leukotriene receptor antagonist. The main mechanism proposed to explain this condition is the unmasking of CSS after the leukotriene receptor antagonist has allowed corticosteroid tapering. Other hypotheses might be proposed. Methods. We describe two patients who developed CSS after starting treatment with montelukast, a new antileukotriene drug. Results. Both patients presented with CSS after 4-5 months of treatment with montelukast. Neither patient received long-term systemic steroids for asthma, but both were on inhaled steroids. One patient had a myocardial involvement and experienced a stroke. Our two patients were treated with systemic steroids and cyclophosphamide. Conclusions. CSS does not appear to relate to steroid tapering in our patients. The other hypotheses are a coincidence or a direct adverse effect of the antileukotriene. Long-term data on these drugs are lacking and leukotriene's role in vasculitis remains to be elucidated.

Since eradication of HIV is unlikely, long-term management of the disease necessitates careful evaluation of the combinations of currently available drugs to determine the most potent and useful rational sequencing of regimens.To determine the antiretroviral efficacy and tolerability of saquinavir soft gelatin capsule (SQV-SGC) plus zalcitabine (ddC) and stavudine (d4T), as first-line treatment in HIV-infected patients.Multicentre, open-label, non-comparative study.Thirty-five asymptomatic, HIV-infected adults with no prior antiretroviral treatment, a CD4 countor =250 cells/microL and baselineor = 5000 HIV RNA copies/mL were included in the study. Patients received SQV-SGC 1200 mg three times a day (tid), ddC 0.75 mg tid and d4T 30 or 40 mg twice a day (bid) for 24 weeks. Plasma HIV RNA, CD4 and CD8 cell counts, HIV reverse transcriptase and protease resistance genotypes, SQV plasma concentration and tolerability were evaluated.At baseline, median HIV RNA (interquartile range) was 4.99 (4.81-5.48) log10 copies/mL, and median CD4 count was 370 (318-504) cells/microL (n = 35). At week 24, the median decrease in HIV RNA was 3.05 (2.19-3.68) log10 copies/mL. A viral load below the level of quantification (200 copies/mL and 20 copies/mL) was achieved in 63% and 34% of patients, respectively (intent-to-treat analysis). The only mutations detected were L90M substitutions in two patients. At week 24, the median CD4 count increased (P0.0001), and CD8 cell counts decreased (P0.0001), relative to baseline. In total, there were five cases of peripheral neuropathy (14%). Mean triglyceride and cholesterol levels remained within normal ranges.Triple therapy with SQV-SGC plus ddC and d4T is a reasonably well tolerated regimen that markedly and rapidly reduces viral load with immunological improvement. This combination is an effective additional therapeutic option, with an efficacy that compares favourably to other triple regimens used in HIV treatment.

Primary non-Hodgkin's lymphoma of the nasal cavity is particular. Pathological characteristics mainly associate a prevalent NK lymphocyte phenotype, a frequent exposure to the Epstein-Barr virus and a poor sensitivity to radiotherapy compared to other lymph node localizations.The authors report the case of a 38-year-old man. The patient had previously presented a chronic maxillary sinusitis. After a diagnosis of Wegener's disease, the poor course under therapy resulted in a nasal lymphoma. Natural killer cell nasal lymphoma was confirmed with a leading biopsy at the same time as a serious clinical outcome. The patient died of septic shock with multivisceral failure.The two differential diagnoses of ulcerative lymphoma of the midface are ulcerative infectious diseases and Wegener's disease. We must not miss this severe disease, with its poor prognosis and variable, though sometimes rapid speed of evolution.

Comprehension of cell cycle regulation mechanisms has progressed very quickly these past few years and regulators of the cell cycle have gained widespread importance in cancer. This review first summarizes major advances in the understanding of the control of cell cycle mechanisms. Examples of how this control is altered in tumoral cells are then described.The typical mammalian cell cycle consists of four distinct phases occurring in a well-defined order, each of which should be completed successfully before the next begins. Progression of eukaryotic cells through major cell cycle transitions is mediated by sequential assembly and activation of a family of serine-threonine protein kinases, the cyclin dependent kinases (CDK). The timing of their activation is determined by their post-translational modifications (phosphorylations/dephosphorylations), and by the association of a protein called cyclin, which is the regulatory subunit of the kinase complex. The cyclin family is divided into two main classes. The 'G1 cyclins' include cyclins C, D1-3, and E, and their accumulation is rate-limiting for progression from the G1 to S phase. The 'mitotic or G2 cyclins', which include cyclin A and cyclin B, are involved in the control of G2/M transition and mitosis. The cyclins bind to and activate the CDK, which leads to phosphorylation (and then inhibition) of the tumor suppressor protein, pRb. pRb controls commitment to progress from the G1 to S phase, at least in part by repressing the activity of the E2F transcription factors known to promote cell proliferation. Both the D-type cyclins and their partner kinases CDK4/6 have proto-oncogenic properties, and their activity is carefully regulated at multiple levels including negative control by two families of CDK inhibitors. While members of the INK4 family (p16INK4A, p15INK4B, p18INK4C, p19INK4D) interact specifically with CDK4 and CDK6, the CIP/KIP inhibitors p21CIP1/WAF1, p27KIP1 and p57KIP2 inhibit a broader spectrum of CDK. The interplay between p16INK4A, cyclin D/CDK, and pRb/E2F together constitute a functional unit collectively known as the 'pRb pathway'. Each of the major components of this mechanism may become deregulated in cancer, and accumulating evidence points to the 'pRb pathway' as a candidate obligatory target in multistep oncogenesis of possibly all human tumor types.Major advances in the understanding of cell cycle regulation mechanisms provided a better knowledge of the molecular interactions involved in human cancer. This progress has led to the promotion of new therapeutic agents presently in clinical trials or under development. Moreover, the components of the cell cycle are probably involved in other non-cancerous diseases and their role must be defined.

The association between dermatomyositis and cancer is clearly established, but its frequency remains difficult to define.We report the case of an association between a dermatomyositis and a cancer of the piriform antrum. Four months after surgical treatment and radiotherapy, the increased macro-CK level gave us reason to suspect a cancer relapse with pulmonary, hepatic, splenic and renal metastases without progressive clinical signs.Mitochondrial macro-CK detection must evoke the presence of neoplasia with or without metastasis, which would be a poor prognosis, as has been shown in our patient.

Eosinophilic fasciitis (EF) is a scleroderma-like disease of unknown etiology characterized by skin induration, elevated immune globulins, and peripheral eosinophilia. The hallmarks of the chronic cutaneous involvement in this syndrome are inflammation and fibrosis of the fascia. To determine how the inflammatory process in EF may be regulated, we investigated the spontaneous and mitogen induced [lipopolysaccharide (LPS), phytohemagglutinin (PHA) or both LPS+PHA] syntheses of interleukins (IL)-2, 5 and 10, interferon-gamma (IFN-gamma), and leukemia inhibitory factor (LIF) cytokines by peripheral blood mononuclear cells (PBMC) from 4 patients with active EF and compared them to those of 10 healthy individuals.We used a short term whole blood assay and culture supernatants were collected after 24 h to measure the IL-2 and IFN-gamma contents and after 48 h to evaluate IL-5, IL-10, and LIF. Supernatant cytokine concentrations were determined by ELISA.All 4 patients had similar patterns of cytokine secretion. Cytokine production did not differ between patients and controls under basal conditions or when LPS was added to the cultures. In contrast, under PHA or LPS+PHA stimulation, significantly higher amounts of all 5 cytokines were detected in samples from patients compared to those from controls.Overall, our data suggest that EF is characterized by an increased capacity of PBMC to produce IL-5 and IL-10, possibly leading to eosinophilia and immune globulin overexpression. In this context, the simultaneous elevations of type 1 cytokines (IL-2 and IFN-gamma) and LIF production by the same cells may be an attempt by the immune system to limit the exacerbation of a type 2 dominant response.

Pancreatic cancer is responsible for 6,000 deaths per year in France. During the course of the disease, venous thrombosis is common. Conversely, arterial thrombosis is rarely described.We report the case of a 59-year-old patient with pancreatic adenocarcinoma. Treatment by gemcitabine allowed rapid and persistent improvement of the body weight and a prolonged survival (18 months). Sudden complication, i.e. splenic arterial thrombosis, reversed the favorable outcome.Splenic venous thrombosis is a frequent complication occurring in the course of pancreatic cancer. It is easily diagnosed using abdominal computerized tomography. Arterial thrombosis is rarely observed. It might be due to either sporadic, unexpected, occurrence of cases related to the evolution of underlying pathological mechanisms, or to omitted treatment of vascular complications, as until the introduction of new anticancer drugs this disease was considered to be of very poor prognosis.

We describe the case of a teenager who developed fever, arthritis, cutaneous vasculitis and severe pancytopenia 3 weeks after the third vaccination boost with a recombinant hepatitis B vaccine. Bone marrow examination showed paucity of late myeloid elements and, subsequently, maturation arrest. Interferon-gamma (IFN-gamma) production by peripheral blood mononuclear cells from the patient was dramatically increased. An underlying immune predisposition (HLA-DR3) may have indirectly enabled the vaccine to trigger a hepatitis B virus-specific cytotoxic T-lymphocyte response. It is therefore possible that the pancytopenia was induced by a dysregulation of the CD8+ T-cell compartment via increased IFN-gamma production.

Acute renal failure can be induced by intravenous administration of immunoglobulins, especially in patients with a predisposition for nephrotoxicity. The onset and resolution of acute renal failure is typically rapid, but in some cases hemodialysis may be needed.We present 2 cases of acute renal failure associated with intravenous immunoglobulin therapy: a 76-year-old man with a history of non-insulin-dependent diabetes mellitus and hypertension and a 77-year-old woman using nonsteroidal antiinflammatory drugs.Intravenous immunoglobulins must be used with precaution in patients with risk factors for acute renal failure. In such patients, renal failure may be avoided by using preparations without sucrose.

Chronic hepatitis C virus (HCV) infection may be associated with numerous immune disorders, with vasculitis including polyarteritis nodosa, or with both. Cryoglobulinemia, which is often present, can also be expressed by vasculitis. We describe 2 cases of Churg-Strauss syndrome (CSS) in patients with HCV infection. We found no previous case of CSS accompanying HCV infection in the literature. The current patients were women aged 40 and 66 years. In both cases, a clinical and laboratory pattern suggesting CSS was found before the HCV infection was discovered. One patient had cryoglobulinemia. One patient was successfully treated with interferon (IFN). The other was treated for 18 months with IFN and corticosteroids. Second-line therapy consisting of IFN with ribavirin was successful. The emergence of HCV infection may have led to an induced form of CSS. The relationship among HCV, cryoglobulinemia, and CSS is not clear, but may be similar to that existing between polyarteritis nodosa and hepatitis B virus. These observations suggest that IFN-alpha therapy may be effective against CSS in HCV infected patients with or without cryoglobulinemia.

The prognosis for survival of patients infected with the human immunodeficiency virus (HIV) who develop non-Hodgkin lymphoma (NHL) usually is considered to be poor. To the authors' knowledge the impact of highly active antiretroviral therapy, recently introduced in HIV disease case management, has not yet been studied in such circumstances.All cases of NHL prospectively diagnosed between January 1986 and December 1997 among patients followed in the Aquitaine Cohort were reviewed. The Kaplan-Meier method and the proportional hazards model were used for statistical analysis.One hundred one NHL diagnoses were validated during the 12-year study period. The median proportional hazards cell count at the time of diagnosis of NHL was 112/mm(3). Histologic findings (Working Formulation classification) were: intermediate grade (N = 23), high grade (N = 61), other (N = 7), and undetermined (N = 10). In 56% of cases, staging classification was Ann Arbor Stage IV. Approximately 73% of patients received a specific NHL chemotherapy. During follow-up, 44% were treated with nucleoside reverse transcriptase inhibitors (NRTIs) alone and 18% with triple therapy including a protease inhibitor (PI). The median survival was 6.0 months. In multivariate analysis, after adjusting for age, year of NHL diagnosis, histologic type, medical center, and transmission category, the following factors recorded at the time of diagnosis of NHL were indicative of an increasing risk of death: CD4+ count/= 50/mm(3) (relative hazard [RH: 2.4, 95% confidence interval [95% CI], 1.2-4.7), hemoglobin/= 10 g/dL (RH: 2.1, 95% CI, 1.1-4.0), and Ann Arbor Stage IV (RH: 2.0, 95% CI, 1.2-3.6). Antiretroviral therapy after the diagnosis of NHL was associated with survival: NRTIs (RH: 0.27, 95% CI, 0.13-0.53) and NRTIs plus PI (RH: 0.08, 95% CI, 0.03-0.21).Although recently introduced and prescribed, antiretroviral therapy including PIs already has improved the survival of HIV-infected patients with NHL significantly.

This review is aimed at defining the frequency, the clinical, biological and radiological presentation and the therapeutic possibilities for AL amyloid arthropathies. The frequency of AL amyloid arthropathy is estimated to be between 2 and 5%. There is usually a bilaterally progressive symmetrical arthritis of multiple joints (predominantly in the upper limb joints) with a chronic evolution. Neurologic or cutaneous symptoms are common. The analysis of synovial fluid sediments is a key test for the diagnosis of amyloid arthropathy. Patients with amyloid arthropathy must be screened for monoclonal gammapathies. The synovectomy is the best symptomatic treatment. A better knowledge of the pathogenesis of amyloid deposits should permit to improve therapeutical strategies.

Group B streptococcal meningitis is unusual in adults. It occurs in patients with a chronic disease.We report a case of group B streptococcal meningitis that occurred in a 32-year-old woman, uncovering inner ear congenital malformation associated with cerebrospinal fluid fistula. There was no recurrent episode of meningitis during a 2-year period following surgical correction of the malformation.Clinical signs suggesting cerebrospinal fluid fistula should be considered in any adult patient with severe group B streptococcal infection.