Treatment of Older Patients with High-Risk Myelodysplastic Syndromes (MDS): The Emerging Role of Allogeneic Hematopoietic Stem Cell Transplantation (Allo HSCT)

MDS are myeloid clonal hematologic disorders that are most commonly diagnosed in the seventh decade of life. Several treatment options are currently available. However, allo HSCT remains the only curative therapy. Unfortunately, despite the higher incidence of MDS in the older population, less than 10 % of patients undergoing allo HSCT for MDS are > 65 years old. In this paper we discuss the various treatment options in older patients with high-risk MDS with particular emphasis on the role of allo HSCT in older MDS patients.     

Applying terrestrial lidar for evaluation and calibration of airborne lidar-derived shrub biomass estimates in Arctic tundra

Monitoring of climate-driven expansion of low-stature shrubs in Arctic tundra can be improved through application of high-resolution remote sensing. However, the destructive nature of harvest sampling that is usually performed for validation of these data is resource intensive and can limit future comparisons by destroying benchmark measurements. We compared aboveground shrub biomass estimates derived from terrestrial laser scanning (TLS) and airborne laser scanning (ALS) with the goal of determining whether TLS data can be used to accurately calibrate ALS estimates of shrub biomass in Arctic tundra. We used a leave-one-out cross-validation calibration of canopy volume against harvested shrub biomass to establish predictive relationships between TLS canopy volume and harvested shrub biomass, and between ALS canopy volume and TLS-derived shrub biomass estimates. TLS produced more accurate predictions of shrub biomass (R² = 0.78; root mean square deviation [RMSD] = 102 g) than did ALS, but the accuracy of ALS-derived shrub biomass predictions was the same whether they were calibrated directly against harvest biomass or against TLS-derived estimates of biomass (R² = 0.62; RMSD = 140 g). Our results suggest that once the initial TLS-harvest relationship is known, TLS can provide valid ground reference data for calibration of ALS-derived estimates of shrub biomass without the need for additional destructive harvest.     

High levels of reactive oxygen metabolites in colon cancer tissue: Analysis by chemiluminescence probe

Reactive oxygen metabolites (ROM) have been postulated to contribute to the development of various carcinomas, including colon cancer. Indeed, the effects of ROM scavengers are being tested for chemoprevention of adenocarcinoma of the colon. However, there has been no evidence to indicate that high levels of ROM are indeed present in cancerous tissue. In this study, we used a chemiluminescence probe to estimate ROM levels in cancerous and neighboring noncancerous colonic tissues from seven patients with colon cancer. Cancerous tissues contained significantly (p < 0.05) more luminol‐enhanced chemiluminescence (4,808 ± 2,282 counts/min/mg protein) than neighboring noncancerous tissues (2,175 ± 1,111). The addition of an ROM scavenger, catalase (2, 4, and 8 μg/ml), to the tissue suspension inhibited chemiluminescence produced by both noncancerous (—74%, —85%, and —71%) and cancerous (—11%, —61%, and — 53 %) tissues. This study shows that colonic cancerous tissue contains high levels of ROM, which may play an important role in the pathogenesis of colon cancer.     

Lung vascular cell heterogeneity: endothelium, smooth muscle, and fibroblasts

The pulmonary circulation represents a unique vascular bed, receiving 100% of the cardiac output while maintaining low blood pressure. Multiple different cell types, including endothelium, smooth muscle, and fibroblasts, contribute to normal vascular function, and to the vascular response to injury. Our understanding of the basic cell biology of these various cell types, and the roles they play in vascular homeostasis and disease, remains quite limited despite several decades of study. Recent advances in approaches that enable the mapping of cell origin and the study of the molecular basis of structure and function have resulted in a rapid accumulation of new information that is essential to vascular biology. A recent National Institutes of Health workshop was held to discuss emerging concepts in lung vascular biology. The findings of this workshop are summarized in this article.     

Efficacy of and tolerance to prolonged release prazosin in patients with hypertension and non-insulin dependent diabetes

The treatment of hypertension represents one of the major elements of the cardiovascular prognosis in type II diabetes. Among antihypertensive drugs, alpha blockers may be interesting because of the absence of unfavourable effects on plasma glucose and lipid levels. OBJECTIVE: The aim of this study was to evaluate the effectiveness and the safety of prazosin osmotic tablet treatment in non-insulin-dependent diabetic patients with mild to moderate arterial hypertension. METHODS: After an initial 4-week-single-blind placebo period, 81 hypertensive subjects (162 +/- 11/96 +/- 5 mmHg) with type II diabetes were included in the study to receive prazosin osmotic tablet (o.t) open-label therapy at the dose of 2.5 mg/day for 12 weeks. After 4 weeks of treatment the dosage of prazosin o.t was increased to 5 mg/day if the diastolic blood pressure remained > or = 90 mmHg. RESULTS: Both supine and standing systolic and diastolic blood pressures were significantly decreased (P < 0.001) with prazosin therapy from 162 +/- 10/96 +/- 5 mmHg in supine and 160 +/- 12/95 +/- 6 mmHg in the upright position, to 149 +/- 15/86 +/- 9 mmHg and 148 +/- 16/86 +/- 9 mmHg respectively at the end of the 12-week-treatment period. There were no significant changes in the glycemic parameters (glycemia, haemoglobin A1c) during the prazosin therapy compared with baseline values. A significant decrease of triglycerides (P = 0.005), total cholesterol (P < 0.001) and LDL cholesterol (P = 0.03) levels was observed during prazosin therapy compared with the baseline measurements, whereas HDL cholesterol remained stable. Only 6% of the patients reported adverse events in relation with the study drug during the active treatment period. CONCLUSION: This study showed a significant decrease of the blood pressure in hypertensive subjects with type II diabetes after prazosin o.t treatment, without any change of glycemic parameters. Moreover, there was a favourable evolution of the lipidic parameters during the study characterised by a significant decrease of triglycerides and total and LDL cholesterol.     

Mechanism of action of the oral direct thrombin inhibitor ximelagatran

Thrombin plays a central role in thrombus formation through its conversion of fibrinogen to fibrin and activation of platelets as well as amplifying its own generation by feedback activation via factors V, VIII, and XI. Consequently, thrombin represents a logical and promising target for therapeutic interventions against arterial and venous thromboembolic disorders. Ximelagatran is the first oral agent in the new class of direct thrombin inhibitors and is rapidly absorbed and bioconverted to the active moiety, melagatran, which inhibits fluid-phase and clot-bound thrombin with similar high potency. Binding to the active site of thrombin is direct and competitive and does not require the presence of co-factors. Inhibition of thrombin generation and platelet activation has been demonstrated in vitro with melagatran as well as ex vivo after oral administration of ximelagatran to healthy human volunteers. Oral ximelagatran dose dependently reduced the total thrombus area in an ex vivo flow chamber model of arterial thrombosis, reflecting the cumulative effect of inhibition of thrombin activity, thrombin generation, and platelet activation. Melagatran has also been shown to reduce thrombin-mediated inflammation in vitro. The combination of antithrombotic and anti-inflammatory activity with the practicality of oral dosing provided by ximelagatran represents an important new option for the treatment of arterial and venous thromboembolic disorders.