cagA Status and eradication treatment outcome of anti-Helicobacter pylori triple therapies in patients with nonulcer dyspepsia

The differences in eradication rates reported in clinical trials aiming to cure Helicobacter pylori infection cannot be entirely explained by the type of regimen, bacterial resistance, or lack of compliance. Using data from a clinical trial, a logistic regression model was constructed to determine whether cagA status, assessed by PCR, affects the outcome of eradication. Resistance to clarithromycin (10% of the strains) predicted failure perfectly. In the model (n = 156), a cagA-lacking strain (odds ratio [OR] = 2.2; 95% confidence interval [CI], (1.1 to 4.7), tobacco smoking OR = 3.1; 95% CI, 1.3 to 7.0), and a double dose of proton pump inhibitor in the treatment regimen (OR = 0.3; 95% CI, 0.2 to 0.7) were associated with the treatment outcome. The exact role of cagA in the outcome of H. pylori eradication therapy has not been explored. However, the type of histological lesions which it causes in the gastric mucosa may be implicated. Regardless of the mechanism involved, cagA status is a good predictive marker of eradication outcome.     

Susceptibility ofAlcaligenes denitrificans subspeciesxylos-oxydans to beta-lactam antibiotics

The susceptibility of 56 clinical isolates and two reference strains ofAlcaligenes denitrificans subsp.xylosoxydans to -lactam agents was tested and related to -lactamase activity of the strains. The MICs of 12 -lactams determined by an agar dilution method showed that all the strains were sensitive to imipenem and moxalactam. Forty-one cloxacillin-sensitive -lactamase producing strains were highly susceptible to azlocillin, piperacillin and ticarcillin, and less susceptible to several cephalosporins (cefamandole, cefoperazone, ceftazidime). The 17 remaining -lactamase-producing strains, which were sensitive to clavulanic acid and to a lesser extent cloxacillin, had variable resistance to the penicillins tested and synergy was obtained when these penicillins were combined with clavulanic acid or tazobactam. The choice of agents for treatment of infections with this organism must take into account the susceptibility phenotype of clinical isolates.     

Tuberculous vertebral osteomyelitis in the new millennium: still a diagnostic and therapeutic challenge

In order to determine the clinical features and current prognosis of tuberculous vertebral osteomyelitis, the charts of all patients diagnosed with definite or probable tuberculous vertebral osteomyelitis from January 1983 to June 2002 (n=78) were reviewed. The mean delay to diagnosis was 6.1 months. Sixty-five (83.3%) patients had inflammatory spinal pain, 35 (44.9%) had some neurological deficit, and only 27 (34.6%) had fever. Paravertebral, epidural, and psoas abscesses were detected in 73.1, 65.4, and 24.4% of the cases, respectively. Culture was positive in 48% of the percutaneous biospies and in 61.7% of the open biopsies. After histological findings were included, the diagnostic yield of percutaneous biopsies was 68%. Fifty-five (70.5%) patients required surgical treatment at some stage of the disease. Although no deaths were directly attributable to tuberculous vertebral osteomyelitis and only 5.1% of patients relapsed, the mean overall hospital stay was 69.1±36.9 days, and 30 (38.5%) patients had severe functional sequelae. In conclusion, diagnosis of tuberculous vertebral osteomyelitis requires a high degree of suspicion. Percutaneous biopsy should be undertaken as soon as possible in any patient with compatible symptoms or radiological images in order to initiate suitable therapy.     

The middle collateral artery: anatomic basis for the “extreme” lateral arm flap

The vascularization of the posterolateral area of the arm is supplied by the terminal branches of the deep brachial artery [middle collateral artery (MCA) and posterior radial collateral artery]. Their anatomy has been a field of confusion for a long time. An extended lateral arm flap, named the extreme lateral arm flap, supplied by these branches and dissected as a retrograde island flap has been proposed as an alternative for large compound defects of the distal forearm. We carried out an extensive anatomic study of the extreme lateral arm flap on 69 upper limbs: 54 fresh injected with colored latex, 10 embalmed and 5 radiographed after Micropaque injection. Two origin levels of the MCA were found: a proximal one (37%) above the radial groove, and a distal one (63%) at the level of the groove. The deep brachial artery always bifurcated after the origin of the MCA into a posterior radial collateral artery (PRCA) and anterior radial collateral artery (ARCA). Indeed in our dissections, after the origin of the MCA from the deep brachial artery, there was always a common trunk named the radial collateral artery (RCA) which bifurcated into the ARCA and PRCA. In all dissected arms we always found the MCA anastomosed in a transverse pattern with the inferior ulnar collateral artery (IUCA), contributing to the anastomotic circle of the elbow. This circle represents the unique vascularization source of the reverse extreme lateral arm flap.     

Comparative usage of herpesvirus entry mediator A and nectin-1 by laboratory strains and clinical isolates of herpes simplex virus

The herpesvirus entry mediator A (HVEM/HveA) and nectin-1 (HveC/CD111) are two major receptors for herpes simplex virus (HSV). Although structurally unrelated, both receptors can independently mediate entry of wild-type (wt) HSV-1 and HSV-2 by interacting with the viral envelope glycoprotein D (gD). Laboratory strains with defined mutations in gD (e.g. rid1) do not use HVEM but use nectin-2 (HveB/CD112) for entry. The relative usage of HVEM and nectin-1 during HSV infection in vivo is not known. In the absence of a defined in vivo model, we used in vitro approaches to address this question. First, we screened HSV clinical isolates from various origins for receptor tropism and found that all used both HVEM and nectin-1. Second, we determined the numbers of surface receptors on various susceptible and resistant cell lines as well as on primary fibroblasts derived from an individual with cleft lip/palate ectodermal dysplasia (CLPED1). Although CLPED1 cells can only express a defective form of nectin-1, they allowed entry of wild type and mutant HSV strains by usage of either HVEM or nectin-2. Finally, we compared the ability of HVEM and nectin-1 to mediate entry when expressed at varying cell surface densities. Both receptors showed a direct relationship between the number of receptors and HSV susceptibility. Direct comparison of receptors suggests that nectin-1 is more efficient at promoting entry than HVEM. Overall, our data suggest that both receptors play a role during HSV infection in vivo and that both are highly efficient even at low levels of expression.     

Dynamics of HIV replication in lymphocytes and the efficacy of protease inhibitors

Using a system that allows transfection of resting peripheral blood lymphocytes (PBLs) two questions were addressed: the kinetics of HIV replication from the state of proviral latency, and the impact of different parameters on the efficacy of protease inhibitors to control HIV replication. PBLs were transfected with an infectious full length HIV-DNA harboring a luciferase reporter gene and activated thereafter. Ritonavir was added at different times at doses ranging from to 0.06 to 1 microM. Viral expression was assessed by quantifying luciferase activity in cell extracts and levels of p24 HIV antigen in culture supernatants. After transfection and cell activation, intracellular expression of HIV proteins, as assessed by luciferase detection, occurred within 2 hr. HIV-gag p24 antigen was detected in culture supernatants between 6 and 8 hr post-activation. Ritonavir was effective in blocking viral replication when given within 4 hr following HIV reactivation, but a delay in ritonavir administration or breaches in ritonavir levels after 6 hr from transfection resulted in viral escape. HIV reactivation from proviral latency in PBLs is an extremely rapid process, faster than estimated from previous models. These data stress the need for maintaining effective antiretroviral concentrations to block completely viral replication.     

Cyclosporin A-mediated killing of <Emphasis Type="Italic">Leishmania major</Emphasis> by macrophages is independent of reactive nitrogen and endogenous TNF-α and is not inhibited by IL-10 and 13

Murine macrophages were treated with various doses of cyclosporin A (CsA) to enhance the killing of Leishmania major parasites. CsA reduced the rate of infected cells from 75% in non-treated controls to less than 15% with 1 micro g CsA/ml in a dose-dependent manner. The leishmanicidal effect was also observed when CsA was added 48 h after the infection of macrophages. In contrast, FK506, another structural non-related immunosuppressive drug with antiparasitic activities, showed no effect on the ability of macrophages to kill intracellular Leishmania parasites. Since nitric oxide has been identified as a key molecule for the leishmanicidal function of macrophages, we analyzed the role of this molecule. There was no influence on the leishmanicidal effect of CsA when L- N-(1-iminoethyl)lysine, a potent and selective inhibitor of mouse inducible nitric oxide synthase, was added. Furthermore, the presence of the macrophage-inhibiting cytokines interleukin (IL)-10 and IL-13 simultaneously or prior to CsA did not inhibit leishmania killing, while both cytokines completely prevented parasite killing by macrophages activated with gamma interferon and tumor necrosis factor (TNF). CsA was fully active on macrophages from TNF-receptor p55 knockout mice arguing against autocrine activation by TNF. We therefore conclude that the antileishmanial effect of CsA is independent of effector mechanisms employed by macrophage-activating cytokines.     

Possible effect of gender and season on the length of hospitalisation in unipolar major depressives

BACKGROUND: Seasonal variation as well as gender differences of several phenomena of affective disorders are a common topic of interest. METHODS: The authors analysed the possible effect of season and gender on the length of hospital stay in 529 in-patients with unipolar major depressive episode. RESULTS: Age and menopausal status alone did not influence the length of hospitalisation but there was a statistical tendency (only for females) for the shortest hospital stay in summer, that reached significance in females younger than 50 years. CONCLUSIONS: The results suggest a possible seasonal and gender effect on recovery from major depression. LIMITATIONS: Retrospective nature of the study, lack of systematic assessment of clinical response and no data collection about marital status and living conditions, that also can influence the time of discharge.     

Primary histiocytic sarcoma of the spleen associated with erythrophagocytic histiocytosis

We report an exceptional case of a histiocytic sarcoma presenting as a primary isolated spleen tumor in a 71-year-old woman. The neoplastic cells in the cords and sinuses of the red pulp formed multiple lobulated tumors, which were detected in vivo by ultrasound scan. The medium cells, large cells and the giant cells expressed CD68, a histiocyte-associated marker, lysozyme and S100 protein. All these cells were negative for B- and T-cell markers, cytokeratins, melanosome markers (HMB45) and CD1a (Langerhans' cells). Many tumor cells displayed strong erythrophagocytosis and sometimes lymphocytophagocytosis. In addition, numerous histiocytes with morphology indistinguishable from reactive macrophages also exhibited a strong erythrophagocytosis, and were found in the tumor as well as in the normal splenic parenchyma. Despite multi-agent chemotherapy, the patient suffered from a relapse in the liver, with a rapid fatal outcome. A literature review showed that such a primary splenic presentation with multiple tumors is rare. In contrast, in systemic malignant histiocytosis, secondary spleen involvement occurs more frequently but with diffuse infiltration. The association with a reactive histiocytosis with erythrophagocytosis corresponds to "histiocytic medullary reticulosis", as previously described by Scott and Robb-Smith.