Biological tissue adhesive for mesh-application in pigs: An experimental study

Background Tissue damage during herniotomy may attribute to postoperative complications including chronic pain, bleeding and infection. Thus the aim of this study was to evaluate a due and simple operative procedure with intraperitoneal application of mesh with glue in an experimental model prior to use in humans.Method Laparoscopic insertion of a mesh was performed in three pigs. The meshes were fixed with a collagen glue. The pigs were sacrificed after 8 weeks and macroscopic and microscopic evaluation of the meshes, were performed.Results The intraperitoneal placed meshes did not migrate through the study period, and there was no sign of inflammation in surrounding tissue or adhesions around the meshes.Conclusions If these findings can be applied to human inguinal herniotomy, this may lead to significant fewer complications including development of acute and chronic pain, formation of seroma and infection. Furthermore the operation technique is very simple.     

Quality of implementation: developing measures crucial to understanding the diffusion of preventive interventions

As prevention programs become disseminated, the most serious threat to effectiveness is maintaining the quality of implementation intended by the developers. This paper proposes a methodology for measuring quality of implementation in school settings and presents data from a pilot study designed to test several of the proposed components. These methods included assessments of adherence, quality of process, the positive or negative valence of adaptations, teachers' attitudes and teachers' understanding of program content. This study was conducted with 11 teachers who had varying degrees of experience who taught Life Skills Training. Observation and interview data were collected during visits to schools. Results suggest that quality of implementation can be measured through observation and interview. Teachers varied in adherence and quality of program delivery. All teachers made adaptations to the program. Experienced teachers were more likely to adhere to the curriculum, deliver it in a way that was more interactive and engaging to students, communicate the goals and objectives better, and make positive adaptations. The field can use these findings as the basis for exploring strategies for measuring and improving quality of implementation.     

The evolving role of staging laparoscopy in the treatment of colorectal hepatic metastasis

HYPOTHESIS: Laparoscopy is an increasingly important tool in the staging and treatment of hepatic malignancies. This study evaluates the effect of staging laparoscopy (SL) using intraoperative ultrasonography (IOUS) on the regional treatment of isolated hepatic colorectal metastasis. DESIGN: Analytic cohort study. SETTING: Tertiary care center. PATIENTS: Consecutive patients who have a colorectal metastasis confined to the liver and selected for surgical regional treatment. INTERVENTIONS: All patients underwent preoperative evaluation followed by SL/IOUS. Operative plans were based on preoperative imaging and were either carried out or altered intraoperatively according to SL/IOUS findings. MAIN OUTCOME MEASURE: Effect of SL/IOUS on surgical management. RESULTS: Between September 1996 and May 2004 one hundred fifty-two SL/IOUSs were performed in 136 patients (77 males and 59 females), who had a mean (SD) age of 63 (11) years. Data sets were complete in 138 events. All patients had isolated hepatic disease as defined by preoperative computed tomography in 152 (100%) and positron emission tomography in 107 (70%). Staging laparoscopy/IOUS identified surgically untreatable disease in 34 events (25%) because of peritoneal metastases (n = 15), nodal involvement (n = 11), diffuse hepatic disease (n = 5), no identifiable disease (n = 2), and untreatable disease (n = 1). Laparoscopic treatment events included radiofrequency ablations (n = 78), hepatic artery pump implantations (n = 40), resections (n = 26), and combined procedures (n = 37). Overall, SL/IOUS changed the treatment plan in 66 (48%) of 138 of events. This includes 32 (23%) of 138 events in which SL/IOUS findings significantly altered the actual procedure performed relative to the preoperative plan. Three minor complications occurred in the SL/IOUS-only group with a mean (SD) hospital stay of 1.3 (1) days. CONCLUSION: In the regional management of isolated colorectal hepatic metastasis, SL/IOUS avoids unnecessary laparotomies and influences definitive surgical intervention in a substantial proportion of patients.     

Evidence of an association between the Arg72 allele of the peptide YY and increased risk of type 2 diabetes

We tested the hypothesis that variants in the gene encoding the prepropeptide YY (PYY) associate with type 2 diabetes and/or obesity. Mutation analyses of DNA from 84 patients with obesity and familial type 2 diabetes identified two polymorphisms, IVS3 + 68C>T and Arg72Thr, and one rare variant, +151C>A of PYY. The common allele of the Arg72Thr variant associated with type 2 diabetes with an allele frequency of the Arg allele of 0.667 (95% CI 0.658-0.677) among 4,639 glucose-tolerant subjects and 0.692 (0.674-0.710) among 1,326 patients with type 2 diabetes (P = 0.005, odds ratio 1.19 [95% CI 1.05-1.35]). The same polymorphism associated with overweight (25 < or = BMI < 30 kg/m2) (P = 0.018, 1.15 [1.02-1.28]). In quantitative trait analyses of a population-based sample of 6,022 subjects, the Arg allele was associated with an increased plasma glucose level 2 h after an oral glucose tolerance test (OGTT) (P = 0.03), an increased area under the curve for the post-OGTT plasma glucose level (P = 0.03), and a lower insulinogenic index (P = 0.01). In conclusion, the common Arg allele of the PYY Arg72Thr variant modestly associates with type 2 diabetes and with type 2 diabetes-related quantitative traits.     

Family caregivers making life-sustaining treatment decisions: factors associated with role strain and ease

Although recent studies have focused on life-sustaining treatment (LST) decision-making by families, research has not examined such decision-making as an aspect of ongoing caregiving by family caregivers. This article focuses on factors associated with family caregiver role strain and ease in LST decision-making. Using content analysis, factors were derived from interview data gathered from 17 family caregivers who had made LST decisions for 16 elderly ill relatives. The factors are incorporated in a framework, The Family Caregiving Process in Making LST Decisions for Elderly Ill Relatives, and fall under four key roles--caregiver, elderly ill relative, other family members, and health care providers. Factors affecting the strain and ease felt by family caregivers exist not only during the actual decision-making period, but also arise during the days, months, and years prior to the event and continue on after the LST decisions have been made. Nurses' knowledge of these factors can help nurses decrease family caregiver strain and increase ease during the family caregiver LST decision-making process.     

Cervical adult rhabdomyoma presenting as a rapidly growing mass in a patient with diffuse large B-cell non-Hodgkin’s lymphoma

Background

Adult rhabdomyoma is a rare mesenchymal tumor, which generally grows slowly and is mainly localized in the head and neck area.

Patient and methods

We report the extraordinary case of a rapidly growing adult rhabdomyoma in a 73-year-old man. The patient was treated for diffuse large B-cell non-Hodgkin’s lymphoma with CHOP therapy (doxorubicin, cyclophosphamide, vincristine, and prednisone). Comparison of the respective computed tomography scans showed prominent enlargement of 35% in the tumor mass volume on the right side of the neck within 3 months. The tumor was highly suspicious for lymphoma. Surgical resection was performed.

Results

Histological examination revealed a tumor which was composed of tightly packed polygonal cells with a PAS-positive granular or vacuolated cytoplasm, occasionally with cross-striations. Immunohistochemically, the cells were positive for desmin, myogenin, Myo-D1, but negative for S-100. Due to these characteristic morphologies, adult rhabdomyoma was diagnosed.

Conclusion

This is the first report on an adult rhabdomyoma with a proven rapid enlargement. The possible pathomechanisms are discussed.     

The antiarrhythmic peptide analog rotigaptide (ZP123) stimulates gap junction intercellular communication in human osteoblasts and prevents decrease in femoral trabecular bone strength in ovariectomized rats

Gap junctions play an important role in bone development and function, but the lack of pharmacological tools has hampered the gap junction research. The antiarrhythmic peptides stimulate gap junction communication between cardiomyocytes, but effects in noncardiac tissue are unknown. The purpose of this study was to examine whether antiarrhythmic peptides, which are small peptides increasing gap junctional conductivity, show specific binding to osteoblasts and investigate the effect of the stable analog rotigaptide (ZP123) on gap junctional intercellular communication in vitro and on bone mass and strength in vivo. Cell coupling and calcium signaling were assessed in vitro on human, primary, osteoblastic cells. In vivo effects of rotigaptide on bone strength and density were determined 4 wk after ovariectomy in rats treated with either vehicle, sc injection twice daily (300 nmol per kilogram body weight) or by continuous ip infusion (158 nmol per kilogram body weight per day). During metabolic stress, a high affinity-binding site (KD=0.1 nM) with low density (15 fmol/mg protein) for [125I]di-I-AAP10 was demonstrated. During physiological conditions, specific binding sites for [125I]AAP10 could not be shown. Studies of the effects of rotigaptide on propagation of intercellular calcium waves and cell-to-cell coupling demonstrated that 10 nM rotigaptide produced a small increase in intercellular communication during physiological conditions (+4.5+/-1.6% vs. vehicle; P<0.05). During conditions with metabolic stress, 10 nM rotigaptide produced an increase in coupling measured by both methods. Four weeks after ovariectomy, bone strength of the femoral head was reduced by 20% in vehicle-treated ovariectomized rats, which was completely prevented in both rotigaptide-treated groups. Rotigaptide also prevented decreases in bone mineral. We conclude that the stable analog rotigaptide increases gap junctional communication in osteoblasts in vitro and preferably during conditions with metabolic stress. Rotigaptide further prevents ovariectomy-induced bone loss in vivo. Thus, gap junction modulation may be a promising new target for osteoporosis therapy.     

A novel and selective beta-melanocyte-stimulating hormone-derived peptide agonist for melanocortin 4 receptor potently decreased food intake and body weight gain in diet-induced obese rats

alphaMSH has generally been accepted as the endogenous ligand for melanocortin 4 receptor (MC4R), which plays a major role in energy homeostasis. Targeting MC4R to develop antiobesity agents, many investigators have performed a structure-activity relationship (SAR) studies based on alphaMSH structure. In this report, we performed a SAR study using human betaMSH (5 - 22) (DEGPYRMEHFRWGSPPKD, peptide 1) as a lead sequence to develop potent and selective agonists for MC4R and MC3R. The SAR study was begun with a truncation of N terminus of betaMSH (5 - 22) together with acetylation of the N terminus and amidation of the C terminus of the peptide. Introduction of a cyclic disulfide constrain and replacement of L-Phe with D-Phe afforded a super potent agonist (peptide 5). Furthermore truncation at the C terminus generated a small and potent MC4R and MC3R agonist (Ac-YRcyclo[CEHdFRWC]amide, peptide 6), which exhibited no MC5R and greatly reduced MC1R activity. Molecular modeling of Ac-YRcyclo[CEHdFRWC]amide (peptide 6) revealed that Arg2 in the peptide formed a salt bridge with Glu4. Subcutaneous or intracerebroventricular administration of peptide 6 in rats showed potent in vivo efficacy as evidenced by its effects in reducing energy balance, increasing fat use, and decreasing weight gain in both acute and chronic rat metabolic studies. Furthermore, the antiobesity effect by peptide 6 was manifested only in wild-type but not MC4R-deficient mice, indicating that antiobesity effects of the peptide were attributed largely through MC4R but not MC3R agonist activity of the peptide.