No increase in carcinogen-DNA adducts in the lungs of monkeys exposed chronically to marijuana smoke.

Rhesus monkeys exposed to marijuana smoke either 7 or 2 days/weeks (HI and LO groups, respectively), or ethanol-extracted marijuana smoke for 7 days/week (EM) or sham treatment (SH) for 1 year were sacrificed 7 months following the last exposure. Pulmonary levels of carcinogen-DNA adducts were determined. Although mean or median adduct levels were not statistically different, 15 of 22 adduct measures were highest in the EM group and lowest 12 of 22 times in the SH group. The levels of aromatic carcinogen-DNA adducts seem no higher in the lungs of animals exposed to marijuana smoke than in untreated animals. Ethanol-extracted marijuana may have effects greater than marijuana itself.     

Ciprofloxacin-induced acute interstitial nephritis.

Acute renal failure is a complication attributed to numerous medications. Few cases linked to the newer fluoroquinolones have been described. We report a case of acute interstitial nephritis confirmed by renal biopsy that developed in a patient within days of starting ciprofloxacin therapy. A review of the literature reveals common clinical manifestations of this rare adverse effect. Clinicians should be aware of this potential complication of ciprofloxacin use.     

The association between meningitis and dural puncture in bacteremic rats.

Clinicians have long been concerned that performance of spinal anesthesia during a period of bacteremia may result in the subsequent development of meningitis. In order to determine whether such an association exists, percutaneous dural puncture was performed in 40 animals during a period of Escherichia coli bacteremia. Twenty-four hours later, spinal fluid was obtained for final analysis by surgically draining the cisterna magna. Twelve animals had E. coli recovered from the surgically drained spinal fluid. Only animals with a circulating bacterial count of at least 50 CFU/ml developed meningitis. Microscopic examination of the brains and spinal cords of animals with infected cerebrospinal fluid showed evidence of central nervous system infection. Bacteremic animals not undergoing percutaneous dural puncture always had sterile spinal fluid (n = 40). Cisternal puncture in the absence of bacteremia did not result in infection (n = 30). Treatment with a single dose of gentamicin before the dural puncture eliminated the risk of meningitis after dural puncture in 30 bacteremic animals. These results demonstrate that dural puncture is associated with the development of meningitis in rats, provided the animals are bacteremic at the time of the puncture. However, antibiotic treatment before the dural puncture appears to eliminate this risk.     

TRACP Influences Th1 pathways by affecting dendritic cell function.

TRACP, a marker of osteoclasts, is also expressed by cells of the immune system. We identified a novel function for TRACP in the dendritic cell. DCs from TRACP knockout mice have impaired maturation and trigger reduced Th1 responses in vivo. We postulate that TRACP has an important role in the presentation of antigens to T cells. INTRODUCTION: TRACP is highly expressed by osteoclasts, activated macrophages, and dendritic cells (DCs). Knockout mice lacking TRACP have an intrinsic defect in osteoclastic resorption and macrophages that display abnormal immunomodulatory responses and cytokine secretion profiles. Our aim in this study was to investigate the significance of TRACP in the inductive phase of the immune response by examining dendritic cells from TRACP(-/-) mice. MATERIALS AND METHODS: Maturational state and function of leukocyte subsets in mice was assessed by flow cytometry. The ability of the immune system to respond to nonspecific activation and to specific antigen was assessed by delayed type hypersensitivity and the presence of isotype-specific serum antibody in vivo and T-cell proliferation and cytokine production in vitro. RESULTS: The ability of lipopolysaccharide (LPS) to upregulate MHC II and CD80 in DCs from TRACP(-/-) mice was reduced compared with wildtype mice, although production of IL-10 by DCs from TRACP-deficient animals was increased. T- and B-cell responses not involving antigen presentation (anti-CD3, TNP-ficoll) were normal in TRACP(-/-) mice, but responses to T-dependent antigens were impaired. Specifically, TRACP(-/-) mice had defective delayed hypersensitivity responses to picryl chloride and reduced proliferative responses to ovalbumin compared with wildtype mice. In response to ovalbumin, but not anti-CD3, T cells from TRACP(-/-) mice produced less interferon-gamma (IFN-gamma), but there was no difference in IL-4 production: TRACP(-/-) mice also produced less ovalbumin (OVA)-specific IgG2a after immunization. CONCLUSIONS: The finding that DCs from TRACP(-/-) mice have impaired maturation and defective Th1 responses shows that TRACP is important for polarizing responses in na?ve T cells to antigen-presented dendritic cells.     

Improving emergency obstetric care in Mozambique: the story of Sofala.

OBJECTIVE: The 5-year project in the province of Sofala was designed to improve access, quality and utilization of emergency obstetric care (EmOC) by strengthening rural hospitals and health centers and ultimately the health system's capacity to respond to emergencies more quickly and effectively. METHODS: Implementation consisted of attention to infrastructure, human resource development, transportation and communication systems, and management. Specific management aspects that were targeted for improvement included: supportive supervision, logistics for supplies, equipment and drugs, record keeping, monitoring and evaluation, and quality improvement techniques such as maternal death audits. RESULTS: Access to EmOC improved with an increase in the number of fully functional EmOC facilities from 4 to 18. The number of women with obstetric complications who were admitted for treatment in participating facilities tripled, and the proportion of those women dying declined by half. CONCLUSIONS: Close collaboration and partnership with the provincial health directorate make the sustainability of many results likely while the replication of much of the Sofala model to other provinces is promising for the national strategy to reduce maternal mortality.     

Discovery of potent and selective inhibitors of procollagen C-proteinase for the treatment of fibrotic disorders

Introduction   Fibrosis is a component of many tissue pathologies leading to loss of normal tissue function, primarily due to excessive collagen deposition. Collagen is deposited following cleavage of the C- and N- terminal peptides from the pro-collagen molecule. The cleavage of the globular C-peptide by PCP reduces solubility of the fibrillar collagen molecule, resulting in deposition of insoluble collagen. Increased insoluble collagen deposition is a feature of all organ fibroses, with inhibition of this process, a key potential anti-fibrotic mechanism. The aim of this work was to discover potent and selective PCP inhibitors as experimental, topically applied, anti-fibrotic drugs for clinical evaluation.
Materials and methods   PCP was cloned from human osteosarcoma cells and enzymatic activity demonstrated using a PCP-specific peptide cleavage assay. Activities were confirmed by measuring cleavage of [³H]C-peptide from type-I pro-collagen. A cell-based fibroplasias model was employed to demonstrate compound efficacy using collagen deposition, liberated C-peptide and histological endpoints. The activities of PCP inhibitors in fibroblast and epithelial in vitro cell proliferation and migration assays, and selectivity vs. a panel of MMPs were also determined.
Discussion   In summary, we have identified and characterized potent and selective inhibitors of PCP for progression to clinical studies for investigation as a treatment paradigm for fibrotic disease.  

  Results     

50.

Inappropriate antibiotic use in a tertiary care center in Thailand: an incidence study and review of experience in Thailand.     

Anucha Apisarnthanarak  Somwang Danchaivijitr  Thomas C Bailey  Victoria J Fraser 《Infection control and hospital epidemiology》2006,27(4):416-420

The incidence and patterns of and factors associated with inappropriate antibiotic use were studied in a tertiary care center in Thailand. The incidence of inappropriate antibiotic use was 25%. Admission to the surgical department (adjusted odds ratio, 2.0; P=.02) and to the obstetrics and gynecology department (adjusted odds ratio, 2.0; P=.03) were associated with inappropriate antibiotic use, whereas consultation with an infectious diseases specialist was protective against inappropriate antibiotic use (adjusted odds ratio, 0.15; P=.01).     

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Inappropriate antibiotic use in a tertiary care center in Thailand: an incidence study and review of experience in Thailand.

The incidence and patterns of and factors associated with inappropriate antibiotic use were studied in a tertiary care center in Thailand. The incidence of inappropriate antibiotic use was 25%. Admission to the surgical department (adjusted odds ratio, 2.0; P=.02) and to the obstetrics and gynecology department (adjusted odds ratio, 2.0; P=.03) were associated with inappropriate antibiotic use, whereas consultation with an infectious diseases specialist was protective against inappropriate antibiotic use (adjusted odds ratio, 0.15; P=.01).