Search results for "Cod"

Extremely High Mutation Rate of HIV-1 In Vivo.

2015

Rates of spontaneous mutation critically determine the genetic diversity and evolution of RNA viruses. Although these rates have been characterized in vitro and in cell culture models, they have seldom been determined in vivo for human viruses. Here, we use the intrapatient frequency of premature stop codons to quantify the HIV-1 genome-wide rate of spontaneous mutation in DNA sequences from peripheral blood mononuclear cells. This reveals an extremely high mutation rate of (4.1 ± 1.7) × 10−3 per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes …

Maintenance treatment for opioid dependence with slow‐release oral morphine: a randomized cross‐over, non‐inferiority study versus methadone

2012

Aims To compare the efficacy of slow-release oral morphine (SROM) and methadone as maintenance medication for opioid dependence in patients previously treated with methadone. Design Prospective, multiple-dose, open label, randomized, non-inferiority, cross-over study over two 11-week periods. Methadone treatment was switched to SROM with flexible dosing and vice versa according to period and sequence of treatment. Setting Fourteen out-patient addiction treatment centres in Switzerland and Germany. Participants Adults with opioid dependence in methadone maintenance programmes (dose ≥50 mg/day) for ≥26 weeks. Measurements The efficacy end-point was the proportion of heroin-positive urine samp…

Model-based approach to describe G-CSF effects in carboplatin-treated cancer patients.

2013

Granulocyte colony-stimulating factor (G-CSF) is often used in cancer patients receiving cytotoxic drugs to prevent or reduce high grade neutropenia. We propose a pharmacokinetic/pharmacodynamic model to describe myelotoxicity in both G-CSF treated and non-treated patients that shall increase our understanding of G-CSF effects. The model was built from absolute neutrophil counts (ANC) obtained in 375 carboplatin-treated patients, 47 of whom received G-CSF. It includes some prior information on G-CSF taken from the literature. Simulations were performed to understand differences in G-CSF effects and explore the impact of G-CSF formulation. Our model well described the data in all patients. M…

Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Grou…

2010

Background: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. Patients and methods: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. Results: Multivari…

Frequency, indications, outcomes, and predictive factors of opioid switching in an acute palliative care unit.

2007

The aim of this study was to prospectively evaluate the frequency, indications, outcomes, and predictive factors associated with opioid switching, using a protocol that had been clinically applied and viewed as effective for many years. A prospective study was carried out on a cohort of consecutive cancer patients who were receiving opioids but had an unacceptable balance between analgesia and adverse effects, despite symptomatic treatment of side effects. The initial conversion ratio between opioids and routes was as follows (mg/day): oral morphine 100=intravenous morphine 33=transdermal fentanyl 1=intravenous fentanyl 1=oral methadone 20=intravenous methadone 16=oral oxycodone 70=transder…

Utility of CT in the diagnosis of pancreatic fistula after pancreaticoduodenectomy in patients with soft pancreas.

2009

OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of routine performance of CT on postoperative day 7 in patients at high risk of pancreatic fistula after pancreaticoduodenectomy. MATERIALS AND METHODS: Two radiologists analyzed images from CT examinations of 50 patients with soft pancreas 7 days after pancreaticoduodenectomy. Pancreatic fistula was defined at CT as a fluid collection close to the pancreaticogastric or pancreaticojejunal anastomosis. Clinicobiologic criteria for the diagnosis of pancreatic fistula were drain output of any measurable volume of fluid on or after postoperative day 3 that had an amylase content more than three times the serum …

Morphine versus oxycodone in pancreatic cancer pain: a randomized controlled study.

2010

Objective: According to experimental findings, oxycodone (OX) could have some advantages over morphine (MO) in clinical models of visceral pain. It was hypothesized that OX could have some advantages over MO in terms of efficacy and dose escalation in pancreatic cancer pain. Methods: Sixty patients with pancreatic cancer with a pain intensity rating of 4/10 who required opioids were included in the study. Patients were randomized to receive 30mg/d of sustained release oral MO or sustained release oral OX (20mg/d). Opioid doses were increased according to the clinical needs. Daily doses of opioids, pain and symptom intensity were recorded at admission (T0) and at weekly intervals for the sub…

Pharmacokinetics, pharmacodynamics, and safety of moss-aGalactosidase A in patients with Fabry disease.

2019

Moss-aGalactosidase A (moss-aGal) is a moss-derived version of human α-galactosidase developed for enzyme replacement therapy in patients with Fabry disease. It exhibits a homogenous N-glycosylation profile with >90% mannose-terminated glycans. In contrast to mammalian cell produced α-galactosidase, moss-aGal does not rely on mannose-6-phosphate receptor mediated endocytosis but targets the mannose receptor for tissue uptake. We conducted a phase 1 clinical trial with moss-aGal in six patients with confirmed diagnosis of Fabry disease during a 28-day schedule. All patients received a single dose of 0.2 mg/kg moss-aGal by i.v.-infusion. Primary endpoints of the trial were safety and pharmaco…

No Association Between Genetic Polymorphism at Codon 129 of the Prion Protein Gene and Primary Progressive Multiple Sclerosis

2011

Polymorphism of the Complement C8A and -B Genes in Two Families with C8β Deficiency and Neisserial Infections

1994

Serum samples from members of two Italian families with complement C8 beta deficiency were studied by SDS-PAGE under nonreducing conditions and by IEF. The proband of family I had suffered from two episodes of purulent meningitis and two of her uncles had suffered from only one episode, while the proband of family II had suffered from three different episodes. In contrast to previous findings, where C8 beta deficiency was cosegregating with C8A (alpha-gamma) allotype A, the proband of family II had the C8A allotype B. In addition, in one of her sons a novel variant of the C8 beta chain was detected. Studies at the DNA level in family I, using a recently described PCR system, demonstrate the…