A protocol for the acute control of agitation in palliative care: a preliminary report

Agitation is one of the most frequent causes for palliative sedation. It often requires urgent control to avoid negative consequences and even endangerment of all involved, including the patients themselves. A protocol for the control of episodes of agitation was developed, based on a previous experience. The protocol includes a combination of haloperidol and midazolam. The protocol was used 86 times in 27 patients. Each patient was sedated from 1 to 12 times, median 2 times. The median time from the beginning of sedation to the control of agitation was 15 minutes with a range from 1 minute (2 cases) to 3 hours and 5 minutes (only 1 case). In 71 cases (83%), only the first dose was needed. There were no significant complications.     

Serum levels of YKL-40 and hyaluronic acid as noninvasive markers of liver fibrosis in haemodialysis patients with chronic hepatitis C virus infection

Summary.  Hepatitis C virus (HCV) infection is highly prevalent among end-stage renal disease (ESRD) patients undergoing haemodialysis and it is an important cause of morbidity and mortality in this population. The aim of this study was to evaluate the diagnostic value of YKL-40 and hyaluronic acid (HA) as noninvasive markers of liver fibrosis in 185 ESRD HCV-infected patients. Significant liver fibrosis was defined as METAVIR F2, F3 or F4 stages. Significant fibrosis was observed in 45 patients (24%). By univariate analysis, higher levels of YKL-40, HA, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) as well as reduced platelet count were associated with fibrosis. However, by multivariate analysis, only AST ( P  =   0.001), platelet count ( P  =   0.004) and HA ( P  =   0.042) were independently associated with significant fibrosis. For the prediction of significant fibrosis, the areas under receiver operating characterictic curve (AUROC) of the regression model (0.798) was significantly higher than the AUROC of YKL-40 (0.607) and HA (0.650). No difference was noted between the AUROC of the regression model and AST to platelet ratio index (APRI) (0.787). Values <8.38 of the regression model showed a negative predictive value of 94% and scores ≥9.6 exhibited a positive predictive value of 65%. If biopsy indication was restricted to scores in the intermediate range of the regression model, it could have been correctly avoided in 61% of the cases. In conclusion, APRI and a model based on AST, platelet count and HA showed better accuracy than YKL-40 and HA (when used solely) for the prediction of significant fibrosis in ESRD HCV-infected patients.     

The Lustgarten Foundation for Pancreatic Cancer Research 3rd Annual Scientific Conference: "Pancreatic Cancer: From Genes to Treatment"

MEETING NOTES: The Lustgarten Foundation for Pancreatic Cancer Research 3rd Annual Scientific Conference: "Pancreatic Cancer: From Genes to Treatment"     

High-level expression and purification of a recombinant human erythropoietin produced using a baculovirus vector

Conditions presently have been established for the high-level expression and simplified purification of recombinant human erythropoietin produced in Spodoptera frugiperda cells. Expression, as mediated by infection with a recombinant baculovirus, was accomplished in suspension culture using reduced levels of serum and media supplements experimentally determined to provide optimum levels of factor production (500,000 U/L). Purification of this recombinant human erythropoietin to virtual homogeneity (greater than or equal to 99%) was accomplished via a simple three-step procedure involving isocratic elution from DEAE-Sephacel, reverse-phase high performance liquid chromatography (HPLC) on a C4 medium, and the single-step elution of purified hormone from concanavalin A agarose. Overall, an 890-fold purification was accomplished with a recovery of 80% as assayed in vitro. Biologically, this purified erythropoietin is highly active, possessing a specific activity in vitro of 200,000 U/mg protein. Chemically, this erythropoietin (molecular weight [mol wt] 26,200) appears exceptionally uniform in its oligosaccharide constitution (30%) as contrasted with heterogeneously glycosylated erythropoietins derived from mammalian cells (mol wt 30,000 to 38,000; 40% to 50% complex-type oligosaccharide). Thus, human erythropoietin as presently produced in an insect cell line comprises not only an abundant source of highly active, readily purified hormone for studies of its mechanism of action and cell surface receptor, but also represents a uniquely homogeneous form that should prove advantageous for direct structural analyses.     

Evaluation of risk factors in superobese patients submitted to conventional Fobi-Capella surgery

BACKGROUND: Obesity is one of the worlds greatest health problems. The Roux-en-Y gastric bypass is the gold standard treatment for severe obesity. Surgery in obese patients has an acceptable level of morbidity and mortality. The superobese patient, a subcategory of severe obese patients with a high surgical risk has not yet been analyzed as a group. METHODS: A retrospective and prospective cohort study was conducted enrolling 135 patients submitted to Roux-en-Y gastric bypass for treatment of severe obesity at the " Hospital das Clínicas" , Federal University of Pernambuco, Recife, PE, Brazil, between November 1997 and September 2003. The independent variables were possible risk factors of adverse outcomes: age, gender, weight, body mass index, diabetes, hypertension, hypercholesterolemia, sleep apnea, cardiopathy/coronariopathy, pneumopathy or any other co-morbidity. The dependent variables were major complications, minor complications and death. RESULTS: Diabetes (RR = 1.6 and CI = 1.02-2.40) and sleep apnea (RR = 1.8 and CI = 1.18-2.64) were associated to minor complications. Cardiopathy/coronariopathy were associated with major complications (RR = 5.42 and CI = 1.22-2.40) and death (RR = 16.25 and CI = 3.00-87.95). BMI >or=55 kg/m2 was associated with minor complications (RR = 1.58 and CI = 1.04-2.40), major complications (RR = 3.17 and CI = 1.03-9.80) and death (P = 0.007). After logistic regression, the body mass index >55 kg/m2 remained as a strong risk factor of death (OR = 3.6 and CI = 1.05-12.32). CONCLUSIONS: The body mass index >or=55 kg/m2 was the main risk factor for severe complications and death. Other risk factors affecting the outcome were diabetes, obstructive sleep apnea and cardiopathy/coronariopathy.     

Glucose-6-phosphate dehydrogenase aveiro: a de novo mutation associated with chronic nonspherocytic hemolytic anemia

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme abnormality. The clinical phenotype is variable but often predictable from the molecular lesion. Class I variants (the most severe forms of the disease) cluster within exon 10, in a region that, at the protein level, is believed to be involved in dimerization. Here we describe a de novo mutation (C269Y) of a new class I variant (G6PD Aveiro) that maps to exon 8. Mutant and normal alleles were found in both hematopoietic and buccal cells, indicating the presence of mosaicism. The available model of the protein predicts that this lesion lies in proximity to the dimer interface of the molecule. A possible mechanism to explain the severity of the defect is proposed. (Blood. 2000;95:1499-1501)     

Factors associated with the intensity of liver fibrosis in renal transplant patients with hepatitis B virus infection

BACKGROUND: Hepatitis B may show a more aggressive course after kidney transplantation, but the factors associated with the progression of fibrosis in this group have not been identified. OBJECTIVES: To determine the influence of hepatitis B virus (HBV) viral load and host-related factors on the progression of hepatic fibrosis in hepatitis B virus-infected renal transplant recipients. PATIENTS AND METHODS: Renal transplant patients positive for HBV surface antigen (HBsAg) and submitted to a liver biopsy because of evidence of viral replication were included. Patients with advanced fibrosis (METAVIR F3-F4) were compared with patients with mild fibrosis (F0-F2) regarding sex, age, estimated time since infection, post-transplant time, donor type, history of renal transplantation, alanine aminotransferase, anti-hepatitis C virus, HBeAg and quantitative hepatitis B virus-DNA. Logistic regression analysis was applied to identify variables independently associated with more advanced fibrosis. RESULTS: Fifty-five patients (75% men, 41+/-11 years) with a mean post-transplant time of 5+/-4 years were included. HBeAg was detected in 67% of the patients and anti-hepatitis C virus in 35%. The median hepatitis B virus-DNA level was 2.8 x 10(8) copies/ml. Seventeen (31%) patients had advanced fibrosis. Using logistic regression analysis, the only variable that showed an independent association with more advanced stages of fibrosis was post-transplant time (P=0.03, odds ratio: 1.2, 95% confidence interval: 1.02-1.45). CONCLUSION: Hepatitis B virus viral load, although very high, and hepatitis B virus/hepatitis C virus coinfection are not related to the intensity of liver fibrosis in renal transplant patients infected with hepatitis B virus. Post-transplant time was the only factor independently associated with more advanced liver fibrosis, suggesting the influence of immunosuppression on the progression of liver disease in these patients.     

BKCa Channel Activation Attenuates the Pathophysiological Progression of Monocrotaline-Induced Pulmonary Arterial Hypertension in Wistar Rats

Cardiovascular Drugs and Therapy - In the present study, the therapeutic efficacy of a selective BKCa channel opener (compound X) in the treatment of monocrotaline (MCT)-induced pulmonary arterial...