Biomechanical performance of a braided absorbable suture

Lactomer and Polyglactin 910 sutures are both made of copolymers of lactide and glycolide. Biomechanical performance tests demonstrated superior handling characteristics of the Lactomer sutures. Using sutures comparable in size and knot construction, the Lactomer sutures exhibited knot holding force superior to the Polyglactin 910. Moreover, the low knot rundown forces encountered by the Lactomer sutures facilitated construction of secure knots that failed by breakage rather than by slippage.     

The effect of spatial parameters on oscillatory movement displacement thresholds

Earlier work has established that oscillatory movement displacement thresholds (OMDT) are a form of hyperacuity. There is speculation that the mechanism determining OMDT, like motion perception in general, involves direct motion sensing at high temporal frequencies of oscillation and spatial localization processes (from which motion is inferred) at low temporal frequencies, which are both hyperacuities in their own right. OMDT were determined, for three experienced observers, over the temporal frequency range 1-15 Hz, for three stimulus lengths and three stimulus widths. Both decreasing stimulus length and decreasing stimulus width increased OMDT at all temporal frequencies. Furthermore, the resulting functions consistently exhibit a "kink" in the temporal frequency midrange. The results are interpreted as evidence that there are two subsystems involved in the analysis of visual motion with the kink indicating the transition where one system begins to predominate over the other.     

Cyclosporine metabolism by P450IIIA in rat enterocytes--another determinant of oral bioavailability?

Cyclosporine is converted to its major metabolites (M-17, M-1, and M-21) in human liver by enzymes belonging to the P450IIIA subfamily. These enzymes are also present in rat and human enterocytes; however, the possibility that CsA is metabolized in enterocytes has not been previously investigated. We therefore directly compared metabolism of 3H-CsA in microsomes prepared from liver and jejunal enterocytes. M-17, M-1, and M-21 were the major CsA metabolites produced by enterocyte microsomes. This metabolism appeared to be catalyzed by P450IIIA, because pretreatment of rats with the P450IIIA inducer dexamethasone significantly increased the rate of CsA metabolism in enterocyte microsomes and preincubation of enterocyte microsomes with anti-P450IIIA IgG inhibited the production of CsA metabolites by greater than 95%. To determine if enterocyte P450IIIA metabolizes CsA in vivo, rats were pretreated with the P450IIIA inducer dexamethasone, the P450IIIA inhibitor erythromycin, or vehicle alone. At laparotomy, 2 mg/kg of 3H-CsA was injected into a sealed loop of jejunum, and after collection of the mesenteric venous blood draining this segment for 45 min, the production of M-17 and M-1 was measured. In the control group, a mean of 3.9% of the recovered radioactivity was found as M-1 and M-17. In the rats pretreated with dexamethasone, a mean of 8.4% of the radioactivity was found as M-1 and M-17 (P less than 0.05 relative to control) and this decreased to 2.3% in the group pretreated with erythromycin (P = 0.08 relative to control). We conclude that P450IIIA in jejunal enterocytes readily metabolizes CsA. Furthermore, the metabolism of CsA by enterocytes in vivo is substantial and likely contributes to "first pass metabolism" of orally administered CsA. Our observations provide novel hypotheses to explain some important drug interactions and interpatient differences in CsA dosing requirements.     

Adenovirus-mediated gene therapy to liver grafts: successful gene transfer by donor pretreatment

BACKGROUND: We have previously shown excellent adenoviral (Ad) gene transfection to transplanted liver grafts with the clamp technique (CT) where viral vector was delivered ex vivo and trapped in cold preserved liver grafts. In this study, we adopted a new gene therapy approach to achieve early transgene expression by donor pretreatment with viral vector and compared the efficacy of these two methods by using Ad vector encoding enhanced green fluorescent protein (AdEGFP) marker gene. METHODS: AdEGFP (1 x 10(9)plaque forming units) was delivered to the liver grafts by: (1) single intravenous injection to donor Lewis rats 48 hours before harvesting, (2) ex vivo cold infusion into the harvested liver with CT, or (3) a combination of both methods. Liver grafts were stored in University of Wisconsin solution at 4 degrees C for 18 hours and then orthotopically transplanted into syngeneic recipients, and the expression of EGFP was studied. RESULTS: With intravenous pretreatment of donor liver grafts, EGFP-expressing cells were detected as early as 3 hours after transplant, and moderate expression was seen by 12 hours. In contrast, EGFP was not detected until 12 to 24 hours after transplant with CT. High levels of EGFP-producing cells were seen with each technique at 7 days ( approximately 30% transfection efficiency). A combination of both methods did not enhance infectivity. Liver preservation injury was comparable between groups. CONCLUSIONS: Gene transfer by donor pretreatment with AdEGFP induces early and efficient gene transduction to liver grafts compared with back-table delivery with CT. This method is simple and provides early transgene expression in liver grafts that potentially could be used to deliver genes to decrease preservation injury or rejection.     

Recombinant human interleukin-11 prevents mucosal atrophy and bowel shortening in the defunctionalized intestine

BACKGROUND: Mucosal atrophy and bowel shortening are the hallmark of proximal intestinal diversion for extensive necrotizing enterocolitis (NEC) or Thiry-Vella fistulas (TVF), in which the ends of a defunctionalized loop of intestine are exteriorized as stomas. Recombinant human interleukin-11 (rhIL-11) is a pleiotropic cytokine that promotes epithelial regeneration and enhances adaptation after bowel resection. The authors hypothesized that rhIL-11 may prevent mucosal atrophy and bowel shortening in rats with TVF METHODS: After creation of ileal TVF, Sprague-Dawley rats were selected randomly to receive either rhIL-11 or equal volume of 0.1% bovine serum albumin (BSA) subcutaneously daily. On day 14, the TVF were excised and examined morphologically. Enterocyte apoptosis was measured using the TUNEL assay. Mucosal DNA and protein content were measured. RESULTS: Administration of rhIL-11 resulted in a significantly greater weight gain and less shortening of TVF than BSA treatment. TVF from the rhIL-11-treated group showed evidence of hyperplasia and hypertrophy and increased crypt to villus ratio. The BSA group had substantial mucosal atrophy. There was a qualitative decrease in the incidence of apoptosis in the rhIL-11 group. CONCLUSIONS: Recombinant human IL-11 prevents mucosal atrophy and shortening of defunctionalized intestinal loops. It may help reduce the incidence of short gut syndrome in infants with extensive NEC.     

Socioeconomic differences in risk factors for obesity in adolescents in Northern Ireland.

OBJECTIVES. To test for socioeconomic differences in some biological and behavioral risk factors for obesity in a representative and contemporary sample of adolescents. METHODS: Cohort study of 2 016 randomly selected 12- and 15-year-olds representative of Northern Ireland, studied in 2000. We tested for differences in obesity risk factors based on a priori hypotheses between adolescents from affluent (n=487) versus deprived (n=237) families. Potential risk factors were dietary energy and macronutrient intake, habitual physical activity, TV viewing and computer use, and physical fitness. RESULTS: Adolescents of higher socioeconomic status reported significantly lower habitual energy intake (210 kJ/kg/d SD 80 vs. 229 kJ/kg/d SD 91, p < 0.01); significantly higher levels of habitual physical activity (physical activity score 25.9 SD 16.6 vs. 20.9 SD 16.4, p < 0.001), and had significantly higher cardiorespiratory fitness (estimated VO2 max 46.2 ml/kg/min SD 8.4 vs. 43.4 ml/kg/min SD 8.3, p < 0.001). Prevalence of overweight and obesity (BMI >85th percentile) in the cohort was 29.1% and was slightly but not significantly higher in the low (33.8%) versus the high (28.5%) socioeconomic groups. CONCLUSIONS: Differences in some of the biological and behavioral risk factors for obesity exist between adolescents of different socioeconomic status in Northern Ireland. These may help explain the basis of established socioeconomic differences in obesity risk.     

The NHS England 100,000 Genomes Project: feasibility and utility of centralised genome sequencing for children with cancer

Background Whole-genome sequencing (WGS) of cancers is becoming an accepted component of oncological care, and NHS England is currently rolling out WGS for all children with cancer. This approach was piloted during the 100,000 genomes (100 K) project. Here we share the experience of the East of England Genomic Medicine Centre (East-GMC), reporting the feasibility and clinical utility of centralised WGS for individual children locally.Methods Non-consecutive children with solid tumours were recruited into the pilot 100 K project at our Genomic Medicine Centre. Variant catalogues were returned for local scrutiny and appraisal at dedicated genomic tumour advisory boards with an emphasis on a detailed exploration of potential clinical value.Results Thirty-six children, representing one-sixth of the national 100 K cohort, were recruited through our Genomic Medicine Centre. The diagnoses encompassed 23 different solid tumour types and WGS provided clinical utility, beyond standard-of-care assays, by refining (2/36) or changing (4/36) diagnoses, providing prognostic information (8/36), defining pathogenic germline mutations (1/36) or revealing novel therapeutic opportunities (8/36).Conclusion Our findings demonstrate the feasibility and clinical value of centralised WGS for children with cancer. WGS offered additional clinical value, especially in diagnostic terms. However, our experience highlights the need for local expertise in scrutinising and clinically interpreting centrally derived variant calls for individual children.Subject terms: Cancer genomics, Cancer genomics