Comparison of hemodynamic and biochemical effects of furosemide by continuous infusion and intermittent bolus in critically ill patients.

Positive fluid balance in critically ill patients is a common problem in the intensive care unit (ICU) often associated with a poor outcome. In addition, clinically important changes in hemodynamic variables have been found to occur after diuretic therapy. This study was conducted to evaluate the safety and relative effectiveness of two diuretic protocols in the ICU. Twenty-two patients in the medical ICU with pulmonary edema or fluid overload and PaO2/FIO2 pressure less than 300, were randomized to diuretic therapy by either continuous infusion or intermittent bolus. Hemodynamic and biochemical measurements were recorded. Protocol-guided diuretic management can be readily and safely implemented in the ICU. Although both continuous and bolus diuretic regimens appear to be equally effective in achieving negative fluid balance, the clinician may consider a continuous infusion of furosemide in the hemodynamically and electrolytically unstable patient to ensure more controlled diuresis with less hemodynamic and electrolyte alteration. From a nursing perspective, a continuous infusion of furosemide is a more efficient means of drug delivery.     

Lipoedema is not lymphoedema: A review of current literature

Lipoedema is a rare painful disorder of the adipose tissue. It essentially affects females and is often misdiagnosed as lymphoedema or obesity. It is globally misdiagnosed or underdiagnosed, and the literature is lacking appropriate guidance to assist clinicians towards this diagnosis. However, the need to recognise this disorder as a unique entity has important implications to establish proper treatment and, therefore, its tremendous effect on patients. Early diagnosis and treatment can turn these patients’ lives upside down. The aim of this review is to focus on the clinical guidance, differential diagnosis, and management strategies. In addition, other aspects of lipoedema, including epidemiology and pathogenesis, are also being discussed here. Lipoedema is distinct from obesity and distinct from lymphoedema, although it might progress to involve the venous and lymphatic system (venolipedema or lympholipedema or both). Late diagnosis can leave the patient debilitated. Management of lipoedema includes weight loss, control of oedema, complex decongestive physiotherapy, liposuction, and laser‐assisted lipolysis. However; there are increasing reports on tumescent liposuction as the preferred surgical option with long‐lasting results. The role of more randomised controlled studies to further explore the management of this clinical entity remains promising.     

Recent attempts at RNAi-mediated P-glycoprotein downregulation for reversal of multidrug resistance in cancer

Multidrug resistance (MDR) is among the major mechanisms leading to failure in chemotherapy of cancer patients. The ATP‐binding cassette proteins are major contributors to MDR, involved in the active efflux of xenobiotics out of cancer cells. Among them, P‐glycoprotein (P‐gp) is the most dominant protein involved in the efflux of drugs. For more than 30 years, scientists have searched for the ideal P‐gp inhibitor to modulate drug resistance activity of P‐gp. This inhibitor should be tissue and cell specific with side effects on other tissues, must not provoke immune responses from the host, should provide sustained inhibition, and must be synthesized readily with low cost. Chemical P‐gp inhibitors tested to date, have shown nonspecific toxic effects limiting their clinical applications. Sequence‐specific P‐gp gene silencing by RNA interference (RNAi) may provide a more effective approach for downregulation of specific protein targets due to high specificity, limited toxicity and immunogenicity, and relative ease in synthesis. RNAi can be implemented by delivery of synthetic small interfering RNAs (siRNAs) or by gene expression of short hairpin RNAs using gene expressing vectors. Specific delivery systems and expression vectors have been designed for this purpose and many researchers have explored their effectiveness for P‐gp downregulation. In this report, we review the efficiency of various methods for siRNA delivery and transfection for P‐gp downregulation in cancer cells for MDR reversal. Novel ideas and observations by different research groups were discussed for future improvement in this essential field. © 2011 Wiley Periodicals, Inc. Med Res Rev     

Review of the role of cigarette smoking in diabetic foot

Diabetic foot ulceration has been a serious issue over the past decades in Asia, causing economic and social problems. Therefore, it is important to identify and reduce the risk factors of diabetic foot. Cigarette smoking has been reported to be associated with diabetes and its macrovascular complications, but the relationship between smoking and diabetic foot ulcers is still unclear. In the present review, we summarize the effects of cigarette smoking on diabetic foot ulcers with respect to peripheral neuropathy, vascular alterations and wound healing. One underlying mechanism of these impacts might be the smoking‐induced oxidative stress inside the cells. At the end of this review, the current mainstream therapies for smoking cessation are also outlined. We believe that it is urgent for all diabetic patients to quit smoking so as to reduce their chances of developing foot ulcers and to improve the prognosis of diabetic foot ulcers.