Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients

The objective of this study was to quantitate the improvement in exercise capacity produced in anemic chronic hemodialysis (HD) patients after correction of their anemia with recombinant human erythropoietin (rHuEPO). The maximal exercise capacity and quadriceps strength of 19 anemic HD patients was tested before and after correction of the anemia with rHuEPO. A progressive work exercise protocol (PWET) on a cycle ergometer was used to compare measurements of maximal oxygen uptake (VO2max), maximal heart rate, and subjective assessment of fatigue during the test. Measurements of quadriceps strength were performed before the cycle ergometer studies. At baseline, all patients had reduced VO2max (15.3 +/- 5.4 mL/kg/min) and maximal exercise heart rates (138.5 +/- 23.9 beats/min). rHuEPO increased the mean hematocrit from 21.2% to 35%, and this was associated with a 17% increase (P less than 0.0005) in the VO2max. At any specified work load, rHuEPO treatment decreased heart rate, minute ventilation, and the subjective perception of fatigue. Both isometric and isokinetic measurements of quadriceps strength were improved following administration of rHuEPO. The maximal exercise heart rate was decreased in comparison to the baseline measurements (P less than 0.04), suggesting that in contrast to normal subjects, HD patients stop exercise before oxygen transport limitations are reached. In this unselected group of chronic HD patients, rHuEPO produced clinically significant improvements in both aerobic exercise capacity and isometric and isokinetic quadriceps strength. The improvement in aerobic capacity was substantially less than would have been expected from the correction of a comparable degree of anemia in non-HD patients. None of the 19 treated patients attained the exercise performance level predicted for a sedentary normal subject.     

A comparison of the responses to recombinant human erythropoietin in normal and uremic subjects.

The erythropoietic response to graded doses of recombinant human erythropoietin (epoetin alfa) was assessed in 24 hemodialysis patients by quantitative ferrokinetic studies, and measurement of the reticulocyte count and plasma levels of transferrin receptor protein. These responses were compared to those of 22 normal subjects. Epoetin alfa was given intravenously at 15, 50 or 150 U/kg every other day for four injections. Three patients with chronic renal failure were restudied after renal function was restored following renal transplantation. The results of these three different measurements of erythroid function showed that the acute response to recombinant human erythropoietin was similar in normal subjects and patients with renal failure. We conclude that chronic uremia does not alter the responsiveness to erythropoietin in vivo.     

Calciphylaxis – a topical overview

'Calciphylaxis', a calcification syndrome associated with ischaemic cutaneous necrosis, is acquired naturally in humans in disease states. It is a life and limb-threatening complication, usually observed in patients with renal disease and secondary hyperparathyroidism, but known to occur in the absence of renal or parathyroid disease. The reported mortality rate, which ranges from 60-80%, relates to wound infection, sepsis and organ failure. It is a small-vessel vasculopathy, which is estimated to occur in about 4% of haemodialysis patients. Clinically, violaceous, reticulate areas of cutaneous necrosis and eschar may be evident, particularly in the extremities. In addition to the clinical picture, a raised calcium phosphorous product, an elevated parathyroid hormone level, radiographic evidence of vessel and soft-tissue calcification and the finding of mural calcification affecting small arteries and arterioles on histopathology help to confirm the diagnosis of this entity which generally has a poor prognosis. A high index of suspicion and an active multidisciplinary management approach, with rigorous attention to wound care and prevention of sepsis, are vital in the management of these patients. In this overview, we discuss the pathophysiology, clinical features and associations, risk factors, diagnosis and management issues relating to calciphylaxis.     

The Sigma-trial protocol: a prospective double-blind multi-centre comparison of laparoscopic versus open elective sigmoid resection in patients with symptomatic diverticulitis

Backround  

Diverticulosis is a common disease in the western society with an incidence of 33–66%. 10–25% of these patients will develop diverticulitis. In order to prevent a high-risk acute operation it is advised to perform elective sigmoid resection after two episodes of diverticulitis in the elderly patient or after one episode in the younger (< 50 years) patient. Open sigmoid resection is still the gold standard, but laparoscopic colon resections seem to have certain advantages over open procedures. On the other hand, a double blind investigation has never been performed. The Sigma-trial is designed to evaluate the presumed advantages of laparoscopic over open sigmoid resections in patients with symptomatic diverticulitis.     

Verbal Working Memory and Atherosclerosis in Patients with Cardiovascular Disease: An fMRI study

BACKGROUND AND PURPOSE: Intimal-medial thickening (IMT) of the carotid wall is an accepted peripheral marker of atherosclerosis. It is associated with increased risk for myocardial infarction and stroke, and lower attention-executive-psychomotor functioning. The purpose of this study was to examine the relationship between IMT and brain activity during a verbal working memory (VWM) task in patients with cardiovascular disease (CVD). METHODS: Thirteen CVD patients underwent functional magnetic resonance imaging (fMRI) during a 2-Back VWM task, and B-mode ultrasound of the carotid arteries. IMT was calculated using an automated algorithm based on a validated edge-detection technique. The relationship between IMT and 2-Back-related brain activity was modeled using partial correlations controlling for age and small vessel disease as measured by white matter signal hyperintensities on MRI (WMH). RESULTS: Higher IMT was associated with lower 2-Back-related signal intensity and in the right middle frontal gyrus, independent of age and WMH. CONCLUSIONS: IMT may be one mechanism contributing to brain dysfunction in CVD. The blood oxygenation level-dependent (BOLD) contrast appears to be highly sensitive to peripheral vascular health as measured by IMT. Future studies should examine the sensitivity and specificity of the BOLD response for predicting cognitive decline in CVD.