Nutritional risk and malnutrition determination by anthropometry in cirrhotic children and adolescents

BACKGROUND: The malnutrition is a frequent finding in adults with cirrhosis, but the prevalence of nutritional risk and malnutrition is little known in pediatric patients. AIM: To evaluate through anthropometry the presence of nutritional risk and malnutrition in cirrhotic pediatric patients regularly attended at the Pediatric Gastroenterology Service of "Hospital de Clínicas" of Porto Alegre, RS, Brazil. METHODS: Cross-sectional study with 42 cirrhotic children and adolescents aged between 3 months and 18 years. The nutritional evaluation was made by the determination of the weight/age, height/age, body mass index and triceps skinfold thickness and arm muscle circumference measurements. Patients considered in nutritional risk were < or = -1,28 Z score which corresponds to < or = 10th percentile, and those under -2,0 Z and < or = 3th percentile were in malnutrition status. According to Child-Pugh criteria, 22 patients were classified as A (mild severity), 15 (moderate) B and 5 C (intense). RESULTS: The mean weight/age, height/age and body mass index Z scores were, respectively, - 0,38 +/- 1,4 SD, - 0,83 +/- 1,16 SD and 0,17 +/- 1,3 SD. Patients in nutritional risk were 3/42 (weight/age), 8/42 (height/age), 12/37 (triceps skinfold thickness), 9/37 (arm muscle circumference), 2/38 (body mass index); in malnutrition status were 6/42 (weight/age), 7/42 (height/age), 4/37 (triceps skinfold thickness) and 4/37 (arm muscle circumference) and 3/38 (body mass index). CONCLUSION: The prevalence of nutritional risk was 32.4% and chronic malnutrition was 16.7%. The index which better reflected the nutritional risk in these patients was triceps skinfold thickness. Chronic malnutrition status occurrence was greater in the height/age index.     

Evaluation of tests for microalbuminuria screening in patients with diabetes.

BACKGROUND: The first step in the diagnosis of diabetic nephropathy is to measure albumin in a spot urine sample. The aim of this study was to assess the accuracy of urinary albumin concentration (UAC), urinary albumin-to-creatinine ratio (UACR), and the Micral-Test II in a random urine specimen (RUS) for microalbuminuria screening in diabetes mellitus. METHODS: Two hundred and seventy-eight patients collected 24 h timed urine specimens followed by RUS. Albumin (immunoturbidimetry) and creatinine were measured in protein-negative (Combur-Test) urine samples. Samples were classified as normoalbuminuric [24 h urinary albumin excretion rate (UAER) <20 microg/min; n = 189] and microalbuminuric (UAER =20-199 microg/min; n = 89). Micral-Test II readings were performed in 130 RUS. Receiver operating characteristics (ROC) curves were constructed using UAER as the reference standard. RESULTS: The areas under the ROC curves were similar for UAC (0.934+/-0.032) and UACR (0.920+/-0.035; P = 0.626), but the Micral-Test II had lower accuracy to diagnose microalbuminuria (area = 0.846+/-0.047) than UAC (P = 0.014). The first cutoff point with 100% sensitivity for UAC was 14.4 mg/l (specificity =77.2%), and 15.7 mg/g for UACR (specificity =73.0%). Concerning the Micral-Test II, sensitivity and specificity for the 20 mg/l cutoff point were 90.0 and 46.0%, respectively. The agreement between UAER and the Micral-Test II for microalbuminuria diagnosis was 55.8% (kappa = 0.22; P < 0.001). The cost of diagnosing microalbuminuria was 1.74 dollars(UAC), 2.00 dollars (UACR) and 4.09 dollars (Micral-Test II) per patient. CONCLUSIONS: Measurement of UAC in a RUS was the best choice for the diagnosis screening of microalbuminuria in diabetic patients, considering cost and accuracy.     

In utero gene therapy: current challenges and perspectives.

Over the past few years, considerable progress in prenatal diagnosis and surgery combined with improvements in vector design vindicate a reappraisal of the feasibility of in utero gene therapy for serious monogenetic diseases. As adult gene therapy gathers pace, several apparent obstacles to its application as a treatment may be overcome by pre- or early postnatal treatment. This review will examine the concepts and practice of prenatal vector administration. We aim to highlight the advantages of early therapeutic intervention focusing on diseases that could benefit greatly from a prenatal gene therapy approach. We will pay special attention to the strategies and vectors that are most likely to be used for this application and will speculate on their expected developments for the near future.     

Sequence-based protein structure prediction using a reduced state-space hidden Markov model

This work describes the use of a hidden Markov model (HMM), with a reduced number of states, which simultaneously learns amino acid sequence and secondary structure for proteins of known three-dimensional structure and it is used for two tasks: protein class prediction and fold recognition. The Protein Data Bank and the annotation of the SCOP database are used for training and evaluation of the proposed HMM for a number of protein classes and folds. Results demonstrate that the reduced state-space HMM performs equivalently, or even better in some cases, on classifying proteins than a HMM trained with the amino acid sequence. The major advantage of the proposed approach is that a small number of states is employed and the training algorithm is of low complexity and thus relatively fast.     

Selenium metabolism in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Selenium is an essential trace element for living organisms. In many publications, researchers express concern about a possible Se deficiency in patients with end-stage chronic renal failure (ESCRF) undergoing continuous ambulatory peritoneal dialysis (CAPD). However, in a number of published articles, the data provide no evidence that patients under CAPD develop Se deficiency. OBJECTIVE: We investigated Se metabolism in ESCRF patients on CAPD. SETTING: The study was carried out at the Department of Propaedeutic Surgery, Athens University; the Laboratory for Material Analysis of the Nuclear Physics Institute; and the State General Hospital, Athens, Greece. PATIENTS AND METHODS: The study group included 24 patients on CAPD treatment, 14 ESCRF patients, and 17 healthy controls. We measured the Se and Fe content of serum, blood, and erythrocytes. We also measured hematocrit, serum total proteins and albumins, and Se in dialysate effluent. RESULTS: As compared with healthy subjects, the ESCRF and CAPD patients exhibited reduced serum concentrations of Se. However, considering the difference in hematocrit values, the total serum-transported Se per liter of blood was close to normal. Erythrocyte Se proved normal for both groups. The measured Se in the spent effluent indicates that patients under CAPD receive approximately 100 microg Se from their daily diet, as normal subjects do. The Se measurement data from the effluent indicate that 90% of the Se carried by the serum is bound to albumins and that only the remaining 10% is in the form of low molecular weight selenate, free to pass the peritoneal membrane. Of the 24 CAPD patients studied, 4 patients (all women) showed extremely low Se serum levels. Data suggest that those low levels are more likely due to the significantly lower serum albumin levels in the 4 patients than to an insufficient dietary intake. CONCLUSIONS: Data from the present experimental work suggest that patients undergoing CAPD receive the necessary quantities of Se from their regular diet. The data contradict statements in the relevant literature that CAPD patients develop Se deficiency.     

Disseminated intravascular B-cell lymphoma: clinicopathological features and outcome of three cases treated with anthracycline-based immunochemotherapy

The purpose of this study was to evaluate the use of combination anthracycline-based immunochemotherapy in intravascular lymphoma (IVL). This is an extremely rare, disseminated, and aggressive extranodal CD20(+) non-Hodgkin's lymphoma (NHL) with poor outcome following anthracycline-based chemotherapy. From a population of 700 newly diagnosed patients with NHL who were registered and followed up at our unit between 1990 and 2005, three cases (0.4%) have been classified as IVL. Among the patients, there were two men and one woman, with a median age of 52 years. We have assessed the clinicopathological characteristics, response to therapy, and outcome. All patients presented with systemic symptoms and disseminated disease. All patients received anthracycline-based chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab (immunochemotherapy). Complete remission was achieved in all three patients, and currently all remain progression free with a follow-up of 24-45 months. In conclusion, anthracycline-based immunochemotherapy induces durable remissions in patients with IVL, an ultimately fatal disease, suggesting that the clinical course of this disease may be altered with immunochemotherapy.     

Proteolysis of cell-surface tissue transglutaminase by matrix metalloproteinase-2 contributes to the adhesive defect and matrix abnormalities in thrombospondin-2-null fibroblasts and mice

Thrombospondin (TSP)-2-null dermal fibroblasts display an attachment defect that results from increased matrix metalloproteinase (MMP)-2 levels in their conditioned media. To investigate the molecular mechanisms responsible for this defect, we analyzed the activity of tissue transglutaminase (tTG) in TSP-2-null dermal fibroblasts and in tissues of TSP-2-null mice. tTG functions as a co-receptor for beta1 and beta3 integrins and stabilizes extracellular matrix proteins by introduction of isopeptide cross-links. Cell-surface tTG activity was reduced in TSP-2-null cells (0.50 +/- 0.05 arbitrary units versus 0.84 +/- 0.07 for wild type; P < or = 0.05), and addition of MMP-2 to the culture medium of wild-type cells caused a 35% reduction in cell-surface tTG activity. tTG was susceptible to proteolysis by MMP-2 in vitro, and addition of the MMP inhibitor TIMP-2 to TSP-2-null cells restored tTG activity (0.3 +/- 0.08 for untreated cells; 0.71 +/- 0.09 with TIMP-2). TSP-2-null mice had reduced tTG activity in skin, as measured by incorporation of fluorescein isothiocyanate-labeled cadaverine, and a threefold increase in acetic acid-extracted dermal collagen. Furthermore, isopeptide cross-links were reduced in both uninjured skin and in excisional wounds of TSP-2-null mice, as determined by morphometric immunohistochemical analysis, indicating that isopeptide cross-links are important for the stabilization of the collagenous matrix in dermis. These findings provide a mechanism for the reduced adhesion of TSP-2-null fibroblasts and an explanation for the increased collagen solubility and fragility of TSP-2-null skin.     

Reversal of Experimental Posthepatectomy Liver Failure in Pigs: A New Application of Hepatocyte Bioreactors

Postoperative liver failure remains a major cause of morbidity and mortality after extensive hepatectomies. This study aims to evaluate the effectiveness of a hepatocyte bioreactor in the treatment of experimental post‐hepatectomy liver failure. Our experimental model included a combination of a side‐to‐side portacaval shunt, occlusion of the hepatoduodenal ligament for 150 min, 70% hepatectomy, and reperfusion. Following the development of liver failure, 12 pigs were randomized into a control group (n = 6) and a treatment group (n = 6). Both groups underwent extracorporeal perfusion through a plasma separation device, a membrane oxygenator, and two parallel bioreactors. In the latter group, the bioreactors were loaded with 10 billion fresh hepatocytes, isolated from a donor pig. Following hepatocyte treatment, all animals were maintained for 24 h under mechanical ventilation, with intravenous fluid and glucose supplementation. Hemodynamic parameters, intracranial pressure, and biochemical parameters were measured. Liver biopsies were obtained during the 24‐h autopsy. The extracorporeal circuit was well‐tolerated hemodynamically. Treated animals had lower intracranial pressure compared with controls (at 24 h, 15 ± 3.1 vs. 22 ± 3.5 mm Hg, P = 0.006). Plasma ammonia in treated animals was lower compared with controls at 12 h (100 ± 29 vs. 244 ± 131 µmol, P = 0.026). Liver histological study showed decreased necrosis and increased regeneration activity in treated animals compared with controls. Treatment through an extracorporeal hepatocyte bioreactor attenuates brain edema and improves histological and functional parameters of the liver remnant of pigs with posthepatectomy liver failure.