Effect of prolonged hyperdynamic endotoxemia on jejunal motility in fasted and enterally fed pigs

OBJECTIVE: To determine the effects of hyperdynamic endotoxemia on the motility of the small intestine. SUMMARY BACKGROUND DATA: Motility disorders of the gastrointestinal tract are a common complication of sepsis. It has been suggested that gram-negative endotoxin plays a role in the pathogenesis of the accompanying diarrhea frequently observed. METHODS: Pigs were infused with lipopolysaccharide for a 24-hour period. During this fasting period jejunal motility was measured using ambulatory manometry. One and 4 days after cessation of endotoxin, pigs were enterally fed, and again motility was recorded. RESULTS: Hyperdynamic endotoxemia was achieved in this model. Manometric pressure recordings revealed that endotoxin infusion accelerated the migrating motor complex (MMC) migration along the jejunum. Also, a simultaneous increase in MMC cycling frequency was observed in the endotoxin-treated group. Elevated MMC migration velocity and cycling frequency were maintained the following day after endotoxin during feeding and returned to basal values 4 days after endotoxin. CONCLUSIONS: A small dose of continuously infused endotoxin significantly provokes jejunal motility disturbances that may contribute to diarrhea.     

Pyruvate prevents poly-ADP ribose polymerase (PARP) activation,oxidative damage,and pyruvate dehydrogenase deactivation during hemorrhagic shock in swine

The inadequate availability of fuel substrates and sharp decline in cellular ATP have been implicated in a cascade of events associated with cell death and organ failure during hemorrhagic shock (HS). In this in vivo swine model of severe prolonged HS, the effect of exogenous pyruvate administration on various markers of cell damage in brain and liver was examined. Thirty minutes after the start of controlled arterial hemorrhage, 30% sodium pyruvate, 10% saline, or 0.9% saline was administered via jugular vein. Four hours after the initiation of hemorrhage, tissue samples from brain and liver were obtained and examined for the cellular and molecular markers of cellular damage. Results of our study suggest that pyruvate prevents loss of total NAD content, cleavage of poly-ADP ribose polymerase (PARP), and inhibits lipid peroxidation in both the brain and liver of swine during prolonged severe HS. We conclude that there are multiple mechanisms by which pyruvate can possibly prevent cell damage caused during HS.     

Developing meaningful metrics of clinical productivity for military treatment facility anesthesiology departments and operative services

Comparing clinical productivity is important for strategic planning and the evaluation of resource allocation in any large organization. This process of benchmarking performance allows for the comparison of groups with similar characteristics. However, this process is often difficult when comparing the operative service productivity of large and small military treatment facilities because of the significant heterogeneity in mission focus and case complexity. However, in this article, we describe the application of a new method of benchmarking operative service productivity based on normalizing data for operating room sites, cases, and total American Society of Anesthesiologists units produced per hour. We demonstrate how these benchmarks allow for valid comparisons of operative service productivity among these military treatment facilities and how the data could be used in expanding or contracting operating locations. In addition, these benchmarks are compared with those derived from the use of this system in the civilian sector.     

Condom use promotes regression of human papillomavirus-associated penile lesions in male sexual partners of women with cervical intraepithelial neoplasia

Penile HPV-associated lesions are frequently seen in male sexual partners of women with CIN. The natural course and clinical significance of these lesions are unclear. Women with CIN and their male sexual partners were randomized for condom use (condom group n = 68, noncondom group n = 68). Males were screened for the presence of penile lesions, i.e., flat lesions, papular lesions and condylomata acuminata, and of HPV in their penile swabs by PCR testing. Median follow-up time was 13.1 months (range 2.9-57.4). The outcome of our study was clinical regression of penile lesions defined as disappearance of lesions at penoscopy. Potentially prognostic factors, i.e., HPV status, lesion type and age, were studied as well. Outcomes were assessed in 57 men of the condom group and in 43 men of the noncondom group. Condom use shortened the median time to regression of flat penile lesions (7.4 months condom group vs. 13.9 months noncondom group; HR = 2.1, 95% CI 1.2-3.7). This effect was not found for papular lesions (HR = 0.5, 95% CI 0.1-2.8). HPV-negative men showed a significantly shorter median time to regression of flat lesions (3.8 months) compared to men with either HPV-positive status (8.5 months; HR = 0.4, 95% CI 0.2-0.9) or inconsistent HPV status (13.1 months; HR = 0.2, 95% CI 0.1-0.6). Regression of flat penile lesions is HPV-dependent and accelerated by condom use. This effect is probably the result of blocking viral transmission between sexual partners.     

Grip force control in patients with neck and upper extremity pain and healthy controls

OBJECTIVE: To investigate whether sensory and motor problems in patients with non-specific neck and upper extremity pain can be ascribed to a deficit of sensory-motor integration. METHODS: Grip force control and adaptation were measured in 81 cases, 32 former cases and 39 healthy controls, during repetitive lifting and holding of an object. The object (300 g) was lifted vertically over 20 cm and held for 5s, using the dominant arm (the affected arm in all cases). The object was novel to the subjects when lifted for the first time, and was lifted five times consecutively. Grip forces orthogonal to the object's surface and its vertical acceleration were measured. RESULTS: Cases used significantly higher grip forces than both other groups, while vertical acceleration was not different. After the initial lift, all groups significantly reduced the maximum grip force. CONCLUSIONS: Subjects with neck and upper extremity pain consistently use higher grip forces than controls, but adjust grip forces by a similar amount after the first lift. Compensation of impaired sensory information rather than a general deficit in sensory-motor integration seems to account for these findings. SIGNIFICANCE: Non-specific neck and upper extremity pain coincides with objectifiable changes in control of grip force.     

L-arginine supplementation in hyperdynamic endotoxemic pigs: effect on nitric oxide synthesis by the different organs

OBJECTIVES: Under septic conditions, the protective role of nitric oxide in the organs may become compromised at a time of increased demand as a result of decreased availability of L-arginine. It remains unknown whether supplementation with L-arginine, as a substrate, can modulate organ nitric oxide production. DESIGN: Controlled study with laboratory animals. SETTING: University research laboratory. SUBJECTS: Female crossbred pigs. INTERVENTION: Pigs were challenged with Escherichia coli endotoxin (intravenously) and received intravenous fluid resuscitation for 24 hrs to reproduce a model of long-lasting hyperdynamic endotoxemia. Pigs were infused with either L-arginine or L-alanine intravenously during endotoxin and via the intragastric route after cessation of endotoxin infusion. The effects of L-arginine supplementation on nitric oxide synthesis and the relationships with arginine metabolism were determined with a stable isotope infusion protocol. Also, organ nitrite plus nitrate fluxes were measured. Implantation of multiple catheters enabled in vivo measurements across the hindquarter muscle, the portal-drained viscera, the liver, and the kidneys. MEASUREMENTS AND RESULTS: The isotope conversion method showed that L-arginine intervention significantly increased nitric oxide production by the portal-drained viscera, liver, and kidneys, resulting in elevated whole-body nitric oxide synthesis under endotoxemic and postendotoxemic conditions. Organ nitrite plus nitrate fluxes only tended to increase because of high variance among data. CONCLUSIONS: In this endotoxemia model, supplemental use of L-arginine favored nitric oxide synthesis in various organs.     

Genetic replacement of the adenovirus shaft fiber reduces liver tropism in ovarian cancer gene therapy

Approaches to alter the native tropism of adenoviruses (Ads) are beneficial to increase their efficacy and safety profile. Liver tropism is important with regard to potential clinical toxicity in humans. Ad5/3 chimeras in which the Ad5 knob is substituted by the Ad3 knob, such as Ad5/3luc1, have been recently shown to increase infectivity of ovarian cancer cell lines and primary tumor cells, which express low levels of the coxsackie-adenovirus receptor (CAR), without increasing infectivity of liver cells. A novel strategy to address the problem of liver uptake and improve the tumor/liver ratio is genetic replacement of the Ad fiber shaft. Ad5.Ad3.SH.luc1 is an Ad5-based vector that contains the fiber shaft from Ad serotype 3 but the fiber knob from Ad serotype 5. To compare tumor/liver of Ad5.Ad3.SH.luc1 and Ad5/3luc1 in vivo, we created three different tumor and treatment models of ovarian cancer in mice, simulating intraperitoneal and intravenous administration of tumors. Ad5.Ad3.SH.luc1 displayed the lowest liver tropism of all viruses in all models tested. Intravenous administration of all viruses resulted in higher tumor transduction rates compared to intraperitoneal administration. Genetic shortening of the Ad5 fiber shaft significantly increases relative tumor/liver gene transfer. This could improve the effective tumor dose and reduce side effects, thereby increasing the bioavailability of therapeutic agents.     

Intravesical recurrence after bladder sparing treatment of small cell carcinoma of the bladder: Characteristics,treatment, and outcome

Introduction

Small cell carcinoma of the bladder (SCCB) is a rare and lethal disease. Previously, we and others have reported a bladder sparing strategy with platinum-etoposide-based chemotherapy followed by radiotherapy of the bladder. Little is known on frequency and treatment of intravesical recurrence following this approach. The objective of this study is to describe the incidence of intravesical recurrences and their management.