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     

47.

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).     

48.

DRY AFTER-TREATMENT OF INFECTED HANDS     

Hamilton Bailey  F.R.C.S. 《Lancet》1941

     

49.

Surgical Repair of Lacerations and Fistulas of the Parotid Duct          下载免费PDF全文

Bailey HA  Skaff V 《Annals of surgery》1949,129(1):103-108

     

50.

Epidermal growth factor receptor inhibition modulates the nuclear localization and cytotoxicity of the Auger electron emitting radiopharmaceutical 111In-DTPA human epidermal growth factor.     

Kristy E Bailey  Danny L Costantini  Zhongli Cai  Deborah A Scollard  Zhuo Chen  Raymond M Reilly  Katherine A Vallis 《Journal of nuclear medicine》2007,48(9):1562-1570

(111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. METHODS: Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. RESULTS: Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean +/- SD: 35 +/- 4 vs. 24 +/- 5 foci per nucleus, respectively). In clonogenic assays, a significant reduction in the surviving fraction was observed when (111)In-DTPA-hEGF (5 ng/mL, 6 MBq/microg) was combined with gefitinib (1 microM ) compared with (111)In-DTPA-hEGF alone (42.9% +/- 5.7% vs. 22.9% +/- 3.6%, respectively; P < 0.01). CONCLUSION: The efficacy of (111)In-DTPA-hEGF depends on internalization and nuclear uptake of the radionuclide. Nuclear uptake, DNA damage, and cytotoxicity are enhanced when (111)In-DTPA-hEGF is combined with gefitinib. These results suggest a potential therapeutic role for peptide receptor radionuclide therapy in combination with tyrosine kinase inhibitors.     

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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).     

Epidermal growth factor receptor inhibition modulates the nuclear localization and cytotoxicity of the Auger electron emitting radiopharmaceutical 111In-DTPA human epidermal growth factor.

(111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. METHODS: Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. RESULTS: Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean +/- SD: 35 +/- 4 vs. 24 +/- 5 foci per nucleus, respectively). In clonogenic assays, a significant reduction in the surviving fraction was observed when (111)In-DTPA-hEGF (5 ng/mL, 6 MBq/microg) was combined with gefitinib (1 microM ) compared with (111)In-DTPA-hEGF alone (42.9% +/- 5.7% vs. 22.9% +/- 3.6%, respectively; P < 0.01). CONCLUSION: The efficacy of (111)In-DTPA-hEGF depends on internalization and nuclear uptake of the radionuclide. Nuclear uptake, DNA damage, and cytotoxicity are enhanced when (111)In-DTPA-hEGF is combined with gefitinib. These results suggest a potential therapeutic role for peptide receptor radionuclide therapy in combination with tyrosine kinase inhibitors.