Application of the 'Spiking' method to the measurement of low dose radiation (≤ 1Gy) using alanine dosimeters.

Alanine dosimeters are limited in radiotherapy by poor sensitivity at low doses (< 5Gy). A set of alanine dosimeters were 'spiked' with a large dose of radiation, (~30Gy, 6MV X-rays) and additional doses ranging between 0.5 and 10Gy. The radical yield was measured by Electron Paramagnetic Resonance (EPR) spectroscopy, and after subtraction of the contribution from the "spike" dose, a linear correlation between the radiation dose and the area of the central EPR signal was obtained for doses between 0.5 and 10Gy (regression value of 0.9890), and for the central peak's amplitude (regression value of 0.9895). Overall, this method is easy to perform, requires no complex EPR signal analysis, and offers much potential to extend the current usage of alanine dosimeters in radiotherapy.

New roles of filopodia and podosomes in the differentiation and fusion process of osteoclasts.

The cytoskeleton mediates various cellular processes such as differentiation and fusion, including in the filopodia and podosomes. However, apart from cell migration and formation of the sealing zone, little is known regarding the changes and related regulatory mechanisms of the cytoskeleton and additional roles of the filopodia and podosomes during the differentiation and fusion of osteoclasts. The cytomorphology and cytoskeleton of osteoclasts in the differentiation process were evaluated using tartrate-resistant acid phosphatase staining and immunofluorescence staining. Moreover, the expression levels of Rho GTPases and enzymes related to osteoclast differentiation and bone resorption were detected by quantitative reverse transcription-polymerase chain reaction. We detected 3 types of filopodia in osteoclast precursors and only 1 type of filopodia in undifferentiated cells. Mature osteoclasts were completely devoid of filopodia. Interestingly, cell fusion was highly specific, and the fusion initially occurred to the filopodia. Confocal images revealed that F-actin and microtubules significantly differed among fused cells. These results suggest that filopodia and podosomes not only play important roles in cell migration and the formation of sealing zones but also in the pre-fusion selectivity of 2 cells and the movement direction of the cell nucleus and cytoplasm during the fusion process. In addition, cdc42v1, RhoU, and RhoF regulate the formation of 3 types of filopodia during various stages of differentiation, while Rac1, Rac2, and filament A may be associated with cell selectivity during the fusion process.

A clinical case-control study on the association between mannose-binding lectin and susceptibility to HIV-1 infection among northern Han Chinese population.

Mannose-binding lectin (MBL) is a key molecule of the innate immune system and a competent to bind carbohydrates of a variety of microorganisms, resulting in complement activation and opsonophagocytosis against various pathogens. However, there is no systemic investigation on the MBL's role in innate immune responses against HIV-1 infection among northern Han Chinese. This study investigated the association between MBL and HIV-1 infection susceptibility among northern Han Chinese. A total of 91 HIV-1 infected patients and 91 HIV-1 seronegative healthy individuals were recruited. Six polymorphisms of MBL2 gene were genotyped by pyrosequencing. The quantitative measurement of serum MBL concentration and MBL complex activity were performed by ELISA. The CD4+ T-cell counts were determined by flow cytometry. The plasma viral loads of 91 HIV-1 infected patients were determined by bDNA method. The results show that there is an association between MBL and HIV-1 infection susceptibility among northern Han Chinese. The individuals with B variant, low serum MBL concentration and low MBL complex activity are more susceptible to HIV-1 infection.

Stroke risk factor, pattern and outcome in patients with cancer.

OBJECTIVE: To investigate risk factors, stroke pattern and outcome in stroke patients with cancer. METHODS: A retrospective review of all stroke patients with cancer (n = 69) admitted to Bankstown-Lidcombe Hospital, Sydney, Australia, between January 1999 and December 2004 was conducted, and comparison made to age- and gender-matched non-cancer stroke patients admitted to the same hospital during the same period. RESULTS: Vascular risk factors did not significantly differ between cancer and non-cancer groups. There was a trend towards greater risk of intracerebral haemorrhage in the cancer group vs the non-cancer group. Previous deep vein thrombosis was more common, and prothrombin time and activated partial thromboplastin time were prolonged in the cancer group vs the non-cancer group. More patients died in hospital in the cancer group vs the non-cancer group. CONCLUSIONS: Coagulation disorders are more likely to be seen in stroke patients with cancer, and patients with cancer have a higher in-hospital post-stroke mortality.

In vitro hemocompatibility studies of drug-loaded poly-(L-lactic acid) fibers.

Our objective was to evaluate the hemocompatibility of biodegradable stent fibers, employing a closed-loop circulation system filled with human blood. We also investigated the effects of the anti-inflammatory and anti-proliferative drugs curcumin and paclitaxel, incorporated into stent fibers. Fresh whole blood was circulated in four parallel closed-loop systems: the empty tube circuit (control) and tubes containing either a PLLA fiber coil (PLLA), a curcumin-loaded PLLA coil (C-PLLA) or a paclitaxel-loaded PLLA coil (P-PLLA). The influence of PLLA fiber, alone or loaded with drug incorporated during melt-extrusion, on leukocyte and platelet adhesion and activation was determined by flow cytometry. The effects of blood flow and fiber properties on cell deposition were assessed by scanning electron microscopy (SEM). The flow cytometry results clearly demonstrated that PLLA triggers blood cell activation at the site of deployment, as shown by increases in CD11b, CD62P and leukocyte-platelet aggregates, compared to controls. Curcumin and paclitaxel treatments both significantly reduced leukocyte and platelet activation and adhesion to PLLA fibers, as shown by flow cytometry and SEM. Activated leukocytes and platelets revealed significantly lower CD11b and CD62P receptor binding for C-PLLA compared with PLLA alone, and slightly lower for P-PLLA. Reductions in platelet-leukocyte aggregates were observed as well. In addition, there was less leukocyte and platelet adhesion to C-PLLA, compared with PLLA fiber controls, as shown by SEM. A continuous linear thrombus, composed of platelets, leukocytes, red blood cells and fibrin was occasionally detected along the line of tangency between the coil and the tube wall. Flow separation and eddying, proximal and distal to the line of tangency of coil and tube, is thought to contribute to this deposit. Curcumin was more effective than paclitaxel in reducing leukocyte and platelet activation and adhesion to PLLA stent fibers in this setting. However there was evidence of paclitaxel degeneration during melt extrusion that may have inhibited its effectiveness. Incorporation of the anti-inflammatory and anti-proliferative drug curcumin into bioresorbable stent fibers is proposed to prevent thrombosis and in-stent restenosis.

Is cardiac test availability a significant factor in weekend delays in discharge for chest pain patients?

The authors assessed whether the lack of weekend cardiac test availability significantly contributed to weekend delays in hospital discharge for "low-risk" chest pain patients. Mean lengths of stay were compared for late-week versus early-week admissions. Patients with late-week admissions had a 19% greater length of stay than did patients admitted earlier in the week (2.36 +/- 1.87 vs 1.91 +/- 1.21 days, p = 0.10, with p = 0.015 after adjusting for severity of illness). Cardiac diagnostic tests were ordered for only 4% of study patients. Therefore, the "weekend effect" existed in an environment where cardiac diagnostic tests were infrequently ordered.

Reducing lengths of stay for patients hospitalized with chest pain using medical practice guidelines and opinion leaders.

There are few available data on the effectiveness and safety of medical practice guidelines when used for patient care in the coronary and intermediate care units. The aim of this study was to examine the effect of educating physicians about practice guidelines to promote shorter lengths of stay for "low-risk" patients hospitalized with chest pain. Such guidelines were disseminated to physicians working in a health maintenance organization (HMO) by educational conferences, written memoranda, endorsement by opinion leaders, concurrent written feedback, and nursing-to-physician cues. A total of 208 patients were enrolled in the study. Following implementation of the practice guidelines, hospital lengths of stay were reduced from 2.51 +/- 2.1 to 1.96 +/- 1.3 days (22% reduction, p = 0.03) and intermediate care unit lengths of stay from 33.9 +/- 19 to 28.2 +/- 14 hours (17% reduction, p = 0.02) for patients with low-risk chest pain. The reduction in length of stay for patients with low-risk chest pain exceeded reductions in stay for patients hospitalized with cardiac conditions for which no guidelines were introduced. None of the patients treated according to guideline recommendations had unexpected "life-threatening" adverse events in the 2-week period after hospital discharge (95%, confidence interval 0%, 3%). This study supports the effectiveness and possible safety of practice guidelines to reduce lengths of stay for patients with low-risk chest pain.