From genotype to phenotype--behavior of the transgenic rat TGR(mRen2)27 as an example

Transgenic techniques provide a tool to generate animals that differ from the wild-type by one or more genes, either by introducing foreign genes (transgenic animals) or by specific mutations of genes (knock-out animals). Most transgenic and knock-out animals are mice and not rats. The frequent use of rat models in the behavioral laboratory, however, will require the increasing application of transgenic techniques in this species. This paper reviews behavioral data from our laboratory as an example of characterizing the behavioral phenotype of a particular transgenic rat, the TGR(mRen2)27 rat. By describing the anxiogenic profile of this rat we also consider some problems associated with such an analysis, with the intention to raise issues that may also apply to studies of behavior in transgenic animals in general.     

Evaluation of SV40-transformed synovial fibroblasts in the study of rheumatoid arthritis pathogenesis

The SV40 T antigen has been used to generate immortalized cells from rheumatoid arthritis (RA) synovial fibroblasts (RASFs) that are commonly used in lieu of primary RASFs. In the current study, we investigated the effect of stimulation by tissue necrosis factor alpha (TNF-α) and interleukin 17 (IL-17) on primary and immortalized RASFs in order to gauge the appropriateness of the use of immortalized RASFs, the MH7A cell line, in the study of RA pathogenesis. Changes in the levels of secretion and expression of 8 proteins associated with RA upon stimulation were assessed by multiplex immunoassay. IL-17 stimulation had a minimal impact on protein secretion and expression for primary and immortalized cells. Basic fibroblast growth factor (FGF-2) was not detectable for the primary cells but was detectable for the immortalized cells. In contrast, monocyte chemoattractant protein 1 (MCP-1) was detectable for primary cells but was undetectable for immortalized cells. In general, protein expression and secretion by cells stimulated with TNF-α were significantly increased. For primary cells, several proteins were below the limit of detection for unstimulated cells and cells stimulated with IL-17, while levels for TNF-α-stimulated cells were within the detectable range. For the same proteins, expression was observed for immortalized cells, regardless of stimulation, suggestive of constitutive activation of the NF-κB signaling pathway. The current study therefore provides strong evidence that immortalized and primary RASFs differ in regard to protein expression and secretion and therefore may not be appropriate for use in the study of RA pathogenesis.     

Future ophthalmology practice pattern: A survey of Saudi Board of Ophthalmology residents

Purpose

The main purpose of the study was to examine and identify factors that influence the future practice pattern of Saudi Board of Ophthalmology residents as well as their academic goals. This study also aimed to compare the plans and career goals of the current Saudi ophthalmology residents with a former cohort of Saudi ophthalmology residents.

Complications in paediatric liver transplant from Kuwait when transplanted abroad

Background and study aimsSince the introduction of liver transplantation (LTx) in children suffering from liver failure in 1963, many centres around the world have offered this service to children that have no other alternative. The aim of this retrospective study is to analyse the results of paediatric liver transplant in Kuwait over the last decade.Patients and methodsA retrospective chart review was done involving paediatric patients during the time period of 1995–2004. The information collected included patient demographics, indications for liver transplantation, survival of both patient and allograft, and complications.ResultsA total of 16 cases were found and analysed. The mean age was 3.6 years (ranged 5 months–17 years). There were nine boys and seven girls. The most common indications for LTx were biliary atresia and metabolic liver disease. All the liver transplants were done abroad. There were totally nine deceased donor and seven living related cases. The complications were acute cellular rejection in five, hypertension in two, biliary complications in four, cytomegalovirus (CMV) infection in three and post lymphoproliferative disease in two cases. All but one patient are presently alive.ConclusionThe above information demonstrates that LTx in Kuwati children is safe and improves the quality of life for those that would otherwise have no other alternative.     

Perineal approach to vascular anatomy during transobturator cystocele repair

Objective  To evaluate the risk of vascular injury during transobturator approach of cystocele repair.
Design  Dissection of the obturator area by perineal approach was performed after placement of mesh needles used for cystocele mesh repair.
Setting  Surgery school of Paris.
Population or sample  Twenty obturator regions in ten fresh female cadavers.
Methods  Transperineal dissection of the obturator area was conducted in ten fresh female anatomic subjects after inserting anterior Prolift^® needles.
Main outcome measures  The vascular anatomy of the obturator region was mapped. Distances between needles and vascular structures of the obturator area were measured three times and averaged for each side.
Results  The anterior cannula-equipped needle perforated the gracilis and the adductor brevis muscles. The mean (SD) distance to the anterior obturator vessels was 21.2 (1.6) mm on the right side and 20.4 (1.5) mm on the left. The posterior needle perforated the adductor magnus. Its distance to the posterior division of the obturator vessels was 1.8 (1.0) mm on the right side and 1.1 (0.9) mm on the left.
Conclusions  During mesh cystocele repair by transobturator approach, the posterior obturator vessels division seems at risk of injury during the posterior needle insertion.     

The obesity paradox: body mass index and outcomes in patients with heart failure

BACKGROUND: In the general population, obesity is associated with increased risk of adverse outcomes. However, studies of patients with chronic disease suggest that overweight and obese patients may paradoxically have better outcomes than lean patients. We sought to examine the association of body mass index (BMI) and outcomes in stable outpatients with heart failure (HF). METHODS: We analyzed data from 7767 patients with stable HF enrolled in the Digitalis Investigation Group trial. Patients were categorized using baseline BMI (calculated as weight in kilograms divided by the square of height in meters) as underweight (BMI <18.5), healthy weight (BMI, 18.5-24.9, overweight (BMI, 25.0-29.9), and obese (BMI > or =30.0). Risks associated with BMI groups were evaluated using multivariable Cox proportional hazards models over a mean follow-up of 37 months. RESULTS: Crude all-cause mortality rates decreased in a near linear fashion across successively higher BMI groups, from 45.0% in the underweight group to 28.4% in the obese group (P for trend <.001). After multivariable adjustment, overweight and obese patients were at lower risk for death (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.80-0.96, and HR, 0.81; 95% CI, 0.72-0.92, respectively), compared with patients at a healthy weight (referent). In contrast, underweight patients with stable HF were at increased risk for death (HR 1.21; 95% CI, 0.95-1.53). CONCLUSIONS: In a cohort of outpatients with established HF, higher BMIs were associated with lower mortality risks; overweight and obese patients had lower risk of death compared with those at a healthy weight. Understanding the mechanisms and impact of the "obesity paradox" in patients with HF is necessary before recommendations are made concerning weight and weight control in this population.