Chronic splenomegaly in Nairobi, Kenya. II. Portal hypertension

Eighty-five patients with chronic splenomegaly and proven oesophageal varices were studied at Kenyatta National Hospital, Nairobi. The major defined groups were hepatosplenic schistosomiasis (24%), cirrhosis (20%) and portal vein occlusion (11%). Hyper-reactive malarial splenomegaly (tropical splenomegaly syndrome) was considered as the cause of oesophageal varices in only one patient. In 26% of cases liver biopsy was non-diagnostic and the extrahepatic portal vein was demonstrated radiologically to be patent. Such patients were thought to be suffering from idiopathic portal hypertension, not previously described elsewhere in Africa. Hepatitis B surface antigen was detected in 12% of controls and in 58% of patients with cirrhosis (p less than 0.001). Some serological marker of previous hepatitis B virus infection was present in 92% of patients with cirrhosis and in 79% of controls. Kamba patients from Machakos and Kitui Districts were significantly more prevalent than expected among these 85 cases of portal hypertension.     

Demonstration of mitral and aortic valves by ultrafast computed tomography

Contrast medium-enhanced ultrafast computed tomography has sufficient spatial and temporal resolution to permit imaging of the mitral and aortic valves. The conventional transaxial planar scan projection is not adequate for this purpose. This communication describes the planar configurations and technique required to image the mitral and aortic valves by ultrafast computed tomography.     

Autonomic regulation of postprandial plasma somatostatin, gastrin, and insulin.

To evaluate the neural regulation of postprandial somatostatin release we studied the effect of blockade of (a) alpha-adrenergic and beta-adrenergic and (b) cholinergic receptors on the plasma somatostatin, gastrin and insulin responses to a standard meal in two groups of five fasting healthy male volunteers. Thymoxamine (0.1 mg/kg iv over two minutes then 10 mg/hour for two hours) and propranolol (0.15 mg/kg iv over two minutes, then 0.75 mg/kg/hour for two hours) were started just before eating while atropine (0.04 mg/kg/im) was given at 15 minutes on completion of the meal. There was a prompt and sustained rise in plasma somatostatin after a control meal in all experiments. This rise was arrested by atropine but not altered by either thymoxamine or propranolol. The plasma gastrin response to a meal was moderately enhanced by thymoxamine and markedly enhanced by atropine. Postprandial insulin release was not affected by alpha- or beta-adrenergic blockade but was abolished by atropine. The effect of atropine on the postprandial plasma somatostatin rise might have been mediated through reduction in gastric acidity or delay in gastric emptying. Hence we gave five fasting male volunteers and intraduodenal infusion of fat emulsion (25 calories in 30 minutes) on two occasions both alone and after atropine. Plasma somatostatin rose during the fat infusion alone and this rise was abolished by atropine. These data suggest that (a) cholinergic but not adrenergic mechanisms are important modulators of plasma somatostatin release after orally ingested and intraduodenally infused nutrients (b) atropine abolishes plasma somatostatin release independently of its effects on gastric acidity and motility and (c) are consistent with the hypothesis that atropine potentiates postprandial gastrin release through reduction of somatostatin mediated inhibition.     

A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease.

BACKGROUND: There is an epidemic of renal failure among Aborigines in the Australia's Northern Territory. The incidence is more than 1000 per million, and is doubling every three to four years. We evaluated the relationship of birthweight to renal disease in adults in one high-risk community. METHODS: We screened more than 80% of people in the community for renal disease, using the urine albumin/creatinine ratio (ACR, g/mol) as the marker, and reviewed records for birthweights. RESULTS: Birthweights were available with increasing frequency for people born after 1956. In 317 adults aged 20 to 38 years at screening, the mean birthweight (SD) was 2.712+/-0.4 kg, and 35% had been low birthweight (LBW, less than 2.5 kg). Birthweight was positively correlated with body mass index (BMI), blood pressure, and diabetes rates, but was inversely correlated with ACR. The odds ratio for overt albuminuria in LBW persons compared with those of higher birthweights was 2.82 (CI, 1.26 to 6.31) after adjusting for other factors, and LBW contributed to an estimated 27% (CI, 3 to 45%) of the population-based prevalence of overt albuminuria. Multivariate models suggest that increasing BMI and blood pressure and decreasing birthweight act in concert to amplify the increases in ACR that accompany increasing age. CONCLUSIONS: LBW contributes to renal disease in this high-risk population. The association might be mediated through impaired nephrogenesis caused by intrauterine malnutrition. The renal disease epidemic in Aborigines may partly be the legacy of greatly improved survival of LBW babies over the last four decades. Disease rates should eventually plateau as birthweights continue to improve, if postnatal risk factors can also be contained.     

Atypical HUS: time to take stock of current guidelines and outcome measures?

European guidelines for the assessment and management of atypical HUS were written in 2009. Since then our understanding of this group of diseases has advanced. Evidence is emerging that eculizumab, a monoclonal antibody inhibiting C5 activation, is effective, and potentially superior to current treatment with plasmapheresis. The evidence base for the benefits of plasmapheresis consists of case series and small reports. Before we embark on a change of management policy it is vital that we set up a system for genetic diagnosis, standardised protocols and a means to collect predetermined outcome measures, so that we do not make the same mistakes with assessment of the effectiveness of eculizumab as we did for plasmapheresis.     

Classical pathway complement destruction is not responsible for the loss of human erythrocytes during porcine liver perfusion

BACKGROUND: Porcine livers perfused with human blood destroy 85% of human erythrocytes (red blood cells [RBC]) during prolonged extracorporeal perfusion, raising the possibility of a complement-mediated graft-versus-host effect. METHODS: Isolated porcine livers were perfused with fresh human blood. Plasma samples were analyzed for complement production by reverse CH50 analysis and porcine immunoglobulin class and specificity by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Anti-CD59 and anti-decay accelerating factor (DAF) monoclonal antibody were used to investigate whether human complement regulatory proteins inhibit porcine complement. RESULTS: After 64 hr of perfusion of porcine livers with human blood, mean complement activity in the perfusate was 95% of the starting value and increasing, whereas perfusion in the absence of a liver showed a falling complement activity of 28.7%. ELISA demonstrated porcine immunoglobulin (Ig) G and IgM in the xenoperfused human plasma. Whereas in a previous study flow cytometry demonstrated porcine antibodies specific for antigens on human T lymphocytes, in this study, anti-human RBC antibodies were not found. Xenoperfused human plasma did not lyse fresh human RBC. Human complement was consistently more efficient at lysing porcine RBC than was porcine complement at lysing human RBC, and human plasma inhibited the ability of porcine plasma to lyse human RBC, raising the possibility of cross-species complement regulation. Complement regulatory proteins on human RBC were blocked using mouse monoclonal anti-human CD59 and DAF. Blocking CD59, but not DAF, augmented lysis of human RBC by porcine complement. CONCLUSIONS: Human CD59 inhibits porcine complement. The production of porcine complement from xenoperfused porcine livers is unlikely to result in clinically significant injury mediated through the classical pathway of complement activation.     

Management of Anemia in Children Receiving Chronic Peritoneal Dialysis

Little information exists regarding the efficacy, modifiers, and outcomes of anemia management in children with CKD or ESRD. We assessed practices, effectors, and outcomes of anemia management in 1394 pediatric patients undergoing peritoneal dialysis (PD) who were prospectively followed in 30 countries. We noted that 25% of patients had hemoglobin levels below target (<10 g/dl or <9.5 g/dl in children older or younger than 2 years, respectively), with significant regional variation; levels were highest in North America and Europe and lowest in Asia and Turkey. Low hemoglobin levels were associated with low urine output, low serum albumin, high parathyroid hormone, high ferritin, and the use of bioincompatible PD fluid. Erythropoiesis-stimulating agents (ESAs) were prescribed to 92% of patients, and neither the type of ESA nor the dosing interval appeared to affect efficacy. The weekly ESA dose inversely correlated with age when scaled to weight but did not correlate with age when normalized to body surface area. ESA sensitivity was positively associated with residual diuresis and serum albumin and inversely associated with serum parathyroid hormone and ferritin. The prevalence of hypertension and left ventricular hypertrophy increased with the degree of anemia. Patient survival was positively associated with achieved hemoglobin and serum albumin and was inversely associated with ESA dose. In conclusion, control of anemia in children receiving long-term PD varies by region. ESA requirements are independent of age when dose is scaled to body surface area, and ESA resistance is associated with inflammation, fluid retention, and hyperparathyroidism. Anemia and high ESA dose requirements independently predict mortality.Almost three decades after the advent of recombinant erythropoietin, the management of renal anemia has become a recent focus of attention and changing paradigms. Whereas correction of hemoglobin (Hb) levels to near-normal has previously been recommended on the basis of association studies linking more severe anemia to morbidity and mortality with dialysis,^1–3 interventional clinical trials consistently demonstrate that near-normalization of Hb increases the risk of vascular events and mortality in adults receiving maintenance hemodialysis and in those with CKD who are not undergoing dialysis.^4–6 This has prompted ongoing reevaluation and revisions of treatment targets in patients exposed to erythropoiesis-stimulating agents (ESAs).⁷The appropriateness of applying treatment recommendations established in adult hemodialysis populations at high cardiovascular risk and adults with CKD to children undergoing dialysis is questionable because cardiovascular events are far less common in children with CKD. Furthermore, two thirds of children requiring dialysis initially opt for peritoneal dialysis (PD), and there are no systematic studies in the adult PD population to inform the optimal Hb target range in these patients. The risk profile of patients receiving PD may differ from that of the hemodialysis setting because of the absence of dialysis-induced intermittent hemoconcentration and lack of contact activation of the complement and coagulation systems.Further aspects to consider in pediatric anemia management are the greater physical activity of children and the need for optimal cognitive functioning at school.^8,9 The significant physiologic variation of the normal Hb range with age¹⁰ and the relative ESA sensitivity that reportedly increases with age during early childhood are also noteworthy.¹¹The registry of the International Pediatric Peritoneal Dialysis Network (IPPN) prospectively collects detailed clinical, biochemical, dialysis, and medication-related information (including ESA types and doses and modalities of iron supplementation) from a substantial number of children undergoing long-term PD around the world. In-depth analysis of this unique database has allowed us to (1) gain insight into the demographic characteristics of renal anemia and its treatment in the pediatric PD population worldwide, (2) explore the relationship between ESA dose requirements and body dimensions, (3) identify factors contributing to ESA resistance in children, and (4) associate anemia control with patient outcomes.