Venous thromboembolism in the trauma patient

Deep vein thrombosis (DVT) is a common complication amongst patients who sustain major trauma. Whilst DVT may result in long-term morbidity, it is the potential for the fatal consequences of acute pulmonary embolism (PE) that remain a significant cause for concern in the severely injured patient. The incidence and risk factors for venous thromboembolism (VTE) are discussed. The aetiology of thrombus formation in trauma is reviewed in depth.Multiple methods of thromboprophylaxis exist, both pharmacological and mechanical. Inferior venal caval filters, on the other hand, aim to prevent the emboli from DVTs that have already formed lodging within the pulmonary vasculature. All modalities have potential advantages and disadvantages.The likelihood of DVT can potentially be predicted by scoring systems, whilst numerous methods of DVT detection can be employed. Once DVT has been diagnosed, treatment should be commenced.Major trauma patients may sustain a vast array of injuries, and prevention and treatment of VTE in specific injury patterns are reviewed. However, further evidence in the form of multi-centre, randomized controlled trials must be obtained before a standardized protocol for thromboprophylaxis in major trauma can be produced.     

Construction of a Traditional Chinese Medicine syndrome-specific outcome measure: The Kidney Deficiency Syndrome questionnaire (KDSQ)

ABSTRACT: BACKGROUND: Development of Traditional Chinese Medicine (TCM) syndrome-specific outcome measures is needed for the evaluation of TCM syndrome-specific therapies. We constructed a Kidney Deficiency Syndrome Questionnaire (KDSQ) for the evaluation of the common TCM syndromes Kidney-Yin Deficiency Syndrome (KDS-Yin) and Kidney-Yang Deficiency Syndrome (KDS-Yang) in middle-aged women with menopausal symptoms. METHODS: KDS-Yin and KDS-Yang were traditionally defined by expert opinion were validated by exploratory factor analysis (EFA) and structural equation modeling (SEM). Content validity was tested by EFA on a sample of 236 women from a seminar and SEM on another sample of 321 women from a postal survey. Other psychometric properties were tested on 292 women from the seminar at baseline and two systematically selected sub-samples: 54 who reported no changes in discomforts 11-12 days after the baseline and 31 who reported changes in discomforts 67-74 days after the baseline. All participants completed the KDSQ, the Greene Climacteric Scale and the standard 12-item Short Form Health Survey. RESULTS: The EFA and SEM established the measurement models of KDS-Yin and KDS-Yang supporting content validity of the KDSQ. Internal consistency was good (Cronbach's Alpha larger than 0.70). Construct validity was supported by theoretically-derived levels of correlation with the established external measures. Test-retest reliability was strong (ICCagreement: KDS-Yin, 0.94; KDS-Yang, 0.93). The KDSQ was responsive to changes over time as tested by effect size and longitudinal validity. CONCLUSIONS: The KDSQ was a valid and reliable measure for KDS-Yin and KDS-Yang in Hong Kong Chinese middle-aged women with menopausal symptoms.     

Hepatic Steatosis Assessment with Ultrasound Small-Window Entropy Imaging

Nonalcoholic fatty liver disease is a type of hepatic steatosis that is not only associated with critical metabolic risk factors but can also result in advanced liver diseases. Ultrasound parametric imaging, which is based on statistical models, assesses fatty liver changes, using quantitative visualization of hepatic-steatosis–caused variations in the statistical properties of backscattered signals. One constraint with using statistical models in ultrasound imaging is that ultrasound data must conform to the distribution employed. Small-window entropy imaging was recently proposed as a non–model-based parametric imaging technique with physical meanings of backscattered statistics. In this study, we explored the feasibility of using small-window entropy imaging in the assessment of fatty liver disease and evaluated its performance through comparisons with parametric imaging based on the Nakagami distribution model (currently the most frequently used statistical model). Liver donors (n?=?53) and patients (n?=?142) were recruited to evaluate hepatic fat fractions (HFFs), using magnetic resonance spectroscopy and to evaluate the stages of fatty liver disease (normal, mild, moderate and severe), using liver biopsy with histopathology. Livers were scanned using a 3-MHz ultrasound to construct B-mode, small-window entropy and Nakagami images to correlate with HFF analyses and fatty liver stages. The diagnostic values of the imaging methods were evaluated using receiver operating characteristic curves. The results demonstrated that the entropy value obtained using small-window entropy imaging correlated well with log₁₀(HFF), with a correlation coefficient r?=?0.74, which was higher than those obtained for the B-scan and Nakagami images. Moreover, small-window entropy imaging also resulted in the highest area under the receiver operating characteristic curve (0.80 for stages equal to or more severe than mild; 0.90 for equal to or more severe than moderate; 0.89 for severe), which indicated that non–model-based entropy imaging—using the small-window technique—performs more favorably than other techniques in fatty liver assessment.     

Regulation of activin receptor-interacting protein 2 expression in mouse hepatoma Hepal-6 cells and its relationship with collagen type Ⅳ

AIM: To investigate the regulation of activin receptor-interacting protein 2 (ARIP2) expression and its possible relationships with collagen type Ⅳ (collagen Ⅳ) in mouse hepatoma cell line Hepal-6 cells.METHODS: The ARIP2 mRNA expression kinetics in Hepal-6 cells was detected by RT-PCR, and its regulation factors were analyzed by treatment with signal transduction activators such as phorbol 12-myristate 13-acetate (PMA), forskolin and A23187. After pcDNA3-ARIP2 was transfected into Hepal-6 cells, the effects of ARIP2 overexpression on activin type Ⅱ receptor (ActRII)and collagen Ⅳ expression were evaluated.RESULTS: The expression levels of ARIP2 mRNA in Hapel-6 cells were elevated in time-dependent manner 12 h after treatment with activin A and endotoxin LPS, but not changed evidently in the early stage of stimulation (2 or 4 h). TheARIP2 mRNA expression was increased after stimulated with signal transduction activators such as PMA and forskolin in Hepal-6 cells, whereas decreased after treatment with A23187 (25.3% ± 5.7% vS 48.1% ± 3.6%, P ＜ 0.01). ARIP2 overexpression could remarkably suppress the expression of ActRIIA mRNA in dose-dependent manner, but has no effect on ActRIIB in Hepal-6 cells induced by activin A. Furthermore, we have found that overexpression of ARIP2 could inhibit collagen Ⅳ mRNA and protein expressions induced by activin A in Hapel-6 cells.CONCLUSION: These findings suggest that ARIP2 expression can be influenced by various factors. ARIP2 may participate in the negative feedback regulation of signal transduction in the late stage by affecting the expression of ActRIIA and play an important role in regulation of development of liver fibrosis induced by activin.     

Radioimmunoassay of motilin

A radioimmunoassay method of motilin was developed in our laboratory and was validated in dogs with a platinum monopolar electrode in the duodenum. We confirmed that a bolus infusion of 0.3 M tris-buffer solution or 0.1 N HCl solution in the duodenum produces a significant rise in plasma immunoreactive motilin (IRM) concentrations. This coincided with a marked increase in the percentage of spike potentials on slow waves of the duodenum, similar to phase III of interdigestive myoelectric-activity (MA). A possible relationship between plasma IRM and interdigestive MA of canine duodenum was studied. It was found that cyclic changes occurred in the fasting plasma IRM concentrations in dogs. While the peak motilin concentration was always observed in phase III, the lowest concentration of motilin was found in phase I of interdigestive MA in the duodenum. In dogs with the electrodes in the duodenum and jejunum, the peak IRM concentration did not correlate with phase III of interdigestive MA in the jejunum. A dose of synthetic porcine motilin, 0.06 g/kg/hr, which produced the plasma IRM concentration comparable to the peak fasting motilin concentration, could induce an identical phase III in the duodenum. These observations indicate that there is a relationship between cyclic changes in plasma IRM concentrations and interdigestive MA of the duodenum. It is suggested further that motilin is a hormone which may play an important role in inducing phase III of interdigestive MA in the duodenum.This work was supported by the Gastrointestinal Research Fund at The Genesee Hospital.     

Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu

Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies, including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.