Tissue penetration and pharmacokinetics of tigecycline in diabetic patients with chronic wound infections described by using in vivo microdialysis

Tissue penetration of systemic antibiotics is an important consideration for positive outcomes in diabetic patients. Herein we describe the exposure profile and penetration of tigecycline in the interstitial fluid of wound margins versus that of uninfected thigh tissue in 8 adult diabetic patients intravenously (IV) administered 100 mg and then 50 mg of tigecycline twice daily for 3 to 5 doses. Prior to administration of the first dose, 2 microdialysis catheters were inserted into the subcutaneous tissue, the first within 10 cm of the wound margin and the second in the thigh of the same extremity. Samples for determination of plasma and tissue concentrations were simultaneously collected over 12 h under steady-state conditions. Tissue concentrations were corrected for percent in vivo recovery by the retrodialysis technique. Plasma samples were also collected for determination of protein binding at 1, 6, and 12 h postdose for each patient. Protein binding data were corrected using a fitted polynomial equation. The mean patient weight was 95.1 kg (range, 63.6 to 149.2 kg), the mean patient age was 63.5 ± 9.4 years, and 75% of the patients were males. The mean values for the plasma, thigh, and wound free area under the concentration-time curve from 0 to 24 h (fAUC(0-24)) were 2.65 ± 0.33, 2.52 ± 1.15, and 2.60 ± 1.02 μg·h/ml, respectively. Protein binding was nonlinear, with the percentage of free drug increasing with decreasing serum concentrations. Exposure values for thigh tissue and wound tissue were similar (P = 0.986). Mean steady-state tissue concentrations for the thigh and wound were similar at 0.12 ± 0.02 μg/ml, and clearance from the tissues appeared similar to that from plasma. Tissue penetration ratios (tissue fAUC/plasma fAUC) were 99% in the thigh and 100% in the wound (P = 0.964). Tigecycline penetrated equally well into wound and uninfected tissue of the same extremity.     

Community-based distribution of misoprostol for treatment or prevention of postpartum hemorrhage: Cost-effectiveness, mortality, and morbidity reduction analysis

Objective

To compare the cost-effectiveness of community-based distribution of misoprostol for prevention with misoprostol for treatment of postpartum hemorrhage (PPH).

Methods

A Monte Carlo simulation depicted mortality and anemia-related morbidity attributable to PPH among 3 scenarios of 10 000 women delivering at home in rural India: (1) standard management; (2) standard management plus 800 µg of sublingual misoprostol for PPH treatment; and (3) standard management plus 600 µg of prophylactic oral misoprostol. The model included costs of drugs, birth attendant training, and transport for women who did not respond to misoprostol.

Results

Misoprostol lowered mortality by 70% and 81% in scenarios 2 and 3, respectively. Scenarios 2 and 3 raise costs by 6% and 35%, respectively. Incremental cost per disability-adjusted life year (DALY) saved is estimated at $6 and $170, respectively.

Conclusion

Both interventions were more effective at decreasing mortality and anemia than standard management. The most efficient scale-up plan would focus initially on increasing coverage with the treatment strategy ($6 per DALY).     

IPS Empress 2全瓷修复的临床特点

全瓷材料可以提高前牙修复体的自然、逼真效果,它克服了金瓷修复体不透光、颈缘效果差的缺点。但全瓷材料的挠曲性能低,且不能承受过大的抬力,因此仅限于一个单位的修复。最近一种新的全瓷材料(IPS Empress2)由于强度高,可用于前牙多个单位桥的修复,它具有极好的美观性能,高度半透明,边缘完整,它的可蚀刻性增加了与牙齿的粘接,     

Cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia are correlated with Sokal risk scores and duration of therapy but not trough imatinib plasma levels

Cytogenetic and molecular responses to standard-dose imatinib (IM) were correlated with trough IM plasma levels for 78 patients with chronic myeloid leukemia (CML) after a minimum of 12 months of IM therapy. The mean trough IM plasma level was 1065 ng/ml (range, 203-2910). There was no correlation of mean plasma trough IM levels and complete cytogenetic response (CCR) at 1 year (CCR 1010 ng/ml vs no CCR 1175 ng/ml P=.29) or major molecular response (MMR) (MMR1067 ng/ml vs no MMR 1063 ng/ml P=.74) after a median of 1298 days of IM therapy. CCR and MMR did correlate with Sokal risk scores with the odds of achieving CCR or MMR for a low risk vs high risk score of 10.8 (95% CI 2.2-53.5) and 6.4 (95% CI 1.4-29.4), respectively. Furthermore, a longer duration of IM therapy also was associated with a greater likelihood of achieving MMR (P=.02).     

CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers

CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed in >or=50% of pancreatic, gastric and intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that a panel of established hepatocellular, pancreatic and gastric cancer cell lines expressed CD133 at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human CD133 antibody (AC133) conjugated to a potent cytotoxic drug, monomethyl auristatin F (MMAF), effectively inhibited the growth of Hep3B hepatocellular and KATO III gastric cancer cells in vitro with IC(50) values of 2-7 ng ml(-1). MMAF induced apoptosis in the cancer cells as measured by caspase activation. The anti-CD133-drug conjugate (AC133-vcMMAF) was shown to internalise and colocalised with the lysosomal marker CD107a in the sensitive cell lines. In contrast, in the resistant cell line Su.86.86, the conjugate internalised and colocalised with the caveolae marker, Cav-1. Addition of ammonium chloride, an inhibitor of lysosomal trafficking and processing, suppressed the cytotoxic effect of AC133-vcMMAF in both Hep3B and KATO III. Anti-CD133-drug conjugate treatment resulted in significant delay of Hep3B tumour growth in SCID mice. Anti-CD133 antibody-drug conjugates warrant further evaluation as a therapeutic strategy to eradicate CD133+ tumours.     

A principal calling: professionalism and health care services

As heath care professionals, our "product" is clinical service. We demonstrate professionalism by attitudes, knowledge, and behaviors that reflect a multi-faceted approach to the standards, regulations, and principles underlying successful clinical practices. The issues facing practitioners who work in health care environments are complex, forming an infrastructure for conducting clinical and business operations. Issues discussed include: clinical quality and outcomes management; patient safety and medical errors; accreditation and compliance. A thorough knowledge of these topics forms the context within which we integrate our services with the larger health care community. In this age of accountability, inquiry, introspection and integrity are the keys to professionalism. LEARNING OUTCOMES: As a result of this activity, the reader will be able to: (1) discuss basic points related to the complex requirements and issues facing clinical practitioners today; (2) understand the components of "professional" practice within the health care community; (3) integrate quality management, regulatory compliance, and accreditation standards into every clinical practice. Profession: A calling requiring specialized knowledge and often long and intensive academic preparation; a principal calling, vocation, or employment. Professionalism: The conduct, aims, or qualities that characterize or mark a profession or professional person. -Webster's New Collegiate Dictionary.     

Anatomic M-mode echocardiography: A new approach to assess regional myocardial function--A comparative in vivo and in vitro study of both fundamental and second harmonic imaging modes.

OBJECTIVE: To evaluate the accuracy of anatomic M-mode echocardiography (AMM). METHODS: Eight phantoms were rotated on a device at different insonation depths (IDs) in a water beaker. They were insonated with different transducer frequencies in fundamental imaging (FI) and second harmonic imaging (SHI), and the diameters were assessed with conventional M-mode echocardiography (CMM) and AMM with the applied angle correction (AC) after rotation. In addition, left ventricular wall dimensions were measured with CMM and AMM in FI and SHI in 10 volunteers. RESULTS: AC had the greatest effect on the measurement error in AMM followed by ID (AC: R2 = 0. 295, ID: R2 = 0.268; P <.0001). SHI improved the accuracy, and a difference no longer existed between CMM and AMM with an AC up to 60 degrees. In vivo the limit of agreement between AMM and CMM was -1.7 to +1.8 mm in SHI. CONCLUSION: Within its limitations (AC < 60 degrees; ID < 20 cm), AMM could be a robust tool in clinical practice.