Development of a Simple Model of Extrinsic Denervation of the Small Bowel in Mouse

Small bowel transplantation (SBT) is associated with poorly understood enteric dysfunction. The study of SBT in mice is hindered by the technical difficulty of orthotopic SBT in the mouse. Our aim was to develop an easy preparation of extrinsic denervation of the entire jejunoileum in mice as a model of orthotopic SBT. All neurolymphatic tissues accompanying the superior mesenteric artery (SMA) and vein (SMV) were ligated just distal to the middle colic vessels. The SMA and SMV were then stripped of investing adventitia, and the mesentery to jejunum and colon were transected radially. Jejunum and colon were not transected and reanastomosed. To confirm extrinsic denervation 1, 3, and 6 months later, segments of small bowel were stained for protein gene product 9.5 (PGP9.5) and tyrosine hydroxylase (TH). Tyrosine hydroxylase immunoreactive intensity was then quantified using a semiquantitative analysis. Immunohistochemical fluorescence showed persistence of PGP9.5 immunoreactivity confirming enteric nerves in jejunoileum; however, there was no TH immunoreactivity in jejunoileum in denervated mice despite the expected preservation of TH immunoreactivity in the still-innervated duodenum at 1 month. At 3 months, sparse immunoreactivity for TH was present, and by 6 months, reinnervation of TH-containing nerves appeared similar to controls. Quantification of intensity at each time-point further confirmed this trend. This technique in the mouse accomplishes a complete extrinsic denervation of jejunoileum early postoperatively (1 and 3 months); reinnervation occurs by 6 months. This is an easily learned murine model of orthotopic SBT. Presented at the American Gastroenterological Association during Digestive Disease Week in Los Angeles, CA, as a poster presentation on May 23 2006. Abstract published in GastroenterologyE 2006; 130:A604.     

Program Directors' Views of the Effect of Managed Care on Substance Abuse Programs in Southern California

This article reports the results of semi-structured interviews with substance abuse treatment (SAT) program directors (PDs) regarding the ways SAT is being influenced by managed care (MC), plans for future SAT, and strategies for decreasing costs of care. It compares findings to an earlier survey of 50 SAT PDs.

Interviews were conducted in 20 SAT programs to gather information about treatment delivery since the advent of MC, including PD responsibilities, funding source, treatment intensity, location, duration, and methods of treatment. Open-ended responses were used to gather information about current and future plans in providing SAT, and awareness of new types of treatment being planned by organizations impacted by MC.

PDs reported changes in SAT secondary to MC such as decreased treatment length, limiting of inpatient and outpatient services, and delayed treatment secondary to benefit determination. Political and economic constraints were seen as barriers to providing adequate and effective services. SAT being subsumed by mental health was viewed as problematic along with an emerging split between alcohol abuse and drug treatment. A positive emerging treatment trend was the development of targeted programs for special need groups.

PDs revealed a variety of strategies that have promoted necessary adaptations to economic and political influences within the structure of managed behavioral care. Strategies such as varying treatment length, modality, and subspecialty care reflected necessary adaptations to diverse market needs.

Managed care continues to have a tremendous impact on the delivery of SAT services. While MC has helped to contain costs, negative outcomes are decreased availability of appropriate care and overtaxing of units that have survived MC cut backs. However, special need programs have allowed SAT programs to specialize, expand, and even flourish in today's competitive SAT market. Interviews with PDs reinforced the need for maintaining quality and diversified SAT services in today's MC environment.     

Reproductive characteristics of a precocious vaccine line (Rt3+15) of Eimeria tenella in embryonating chicken eggs

Coccidiosis of chickens, caused by species of Eimeria (Protozoa, Apicomplexa), is an intestinal disease of major economic importance worldwide. In the present study, the reproductive characteristics of a precocious line (designated E. tenella Rt3+15) from Australia were investigated in chicken embryos and the implications of the findings briefly discussed.     

Chronic lower extremity ischemia: a human model of ischemic tolerance.

BACKGROUND: Ischemic preconditioning (IPC) has been found in animals to have a protective effect against future ischemic injury to muscle tissue. Such injury is unavoidable during some surgical procedures. To determine whether chronic ischemia in the lower extremities would imitate IPC and reduce ischemic injury during vascular surgery, we designed a controlled clinical study. PATIENTS AND METHODS: Two groups of patients at a university-affiliated medical centre with chronic lower-extremity ischemia served as models of IPC: 6 patients awaiting femoral distal bypass (FDB) and 4 scheduled for aortobifemoral (ABF) bypass grafting for aortoiliac occlusive disease. Seven patients undergoing elective open repair of an infrarenal abdominal aortic aneurysm (AAA) were chosen as non-IPC controls. Three hematologic indicators of skeletal-muscle injury, lactate dehydrogenase (LDH), creatine kinase (CK) and myoglobin, were measured before placement of the proximal clamp, during surgical ischemia, immediately upon reperfusion, 15 minutes after and 1 hour after reperfusion, and during the first, second and third postoperative days. RESULTS: Baseline markers of skeletal-muscle injury were similar in all groups. In postreperfusion samples, concentrations of muscle-injury markers were significantly lower in the 2 PC groups than in the control group. For example, at day 2, LDH levels were increased by about 30% over baseline measures in the elective AAA (control) group, whereas levels in the FDB and ABF groups remained statistically unchanged from baseline. Myoglobin in controls had increased by 977%, but only by 160% in the FDB and 528% in the ABF groups. CK levels, in a similar trend, were 1432% higher in the control group and only 111% (FDB) and 1029% (ABF) in the study groups. Taken together, these data represent a significant level of protection. CONCLUSIONS: Patients with chronic lower-extremity ischemia suffered less severe ischemic injury after a period of acute ischemia than those with acute ischemia alone. Ischemic preconditioning is one proposed mechanism to help explain this protective effect.     

Scintigraphic detection of pulmonary aspergillosis in rabbits with a radiolabeled leukotriene b4 antagonist.

Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the 111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients. METHODS: Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection. RESULTS: Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for 111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate. CONCLUSION: The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of 111In-DPC11870 were superior to those obtained after injection of 67Ga-citrate.     

Outcomes and presurgery correlates of lumbar discectomy in Utah Workers' Compensation patients

Background contextLumbar discectomy is the most common type of back surgery performed in the United States. Outcomes after this procedure can be variable and it appears that Workers' Compensation patients might be at increased risk for poor outcomes.PurposeTo examine long-term multidimensional outcomes of lumbar discectomy within a cohort of Workers' Compensation patients from Utah and identify presurgical biopsychosocial factors related to poor outcomes.Study design/settingA retrospective cohort study consisting of a review of presurgical medical records and assessment of patient outcomes via a telephone survey. Outcomes were assessed at least 2 years postsurgery.Patient sampleA consecutive sample of 271 workers from Utah who underwent lumbar discectomy from 1994 to 1999. A total of 134 patients were surveyed at the time of follow-up.Outcome measuresPatient satisfaction, Roland-Morris Disability Questionnaire, SF-36v2, and Stauffer-Coventry Index.MethodsA retrospective review of presurgical biopsychosocial variables and outcome assessment via telephone survey was conducted.ResultsWork disability rate for the cohort was 12.7% (17/134). Analysis of patient satisfaction, back pain-related dysfunction, and the Short-Form Health Survey-36 subscales indicated approximately 25% of patients experienced poor outcomes. Older age, number of comorbid health conditions, assigned case manager, litigation, and time delay from injury to surgery were consistently statistically significant predictors (p<.05) of poor outcomes.ConclusionsResults of this study suggest that compensated back surgery patients are at greater risk for poor lumbar discectomy outcomes than noncompensation patients. Presurgery correlates of poor outcomes may be useful in identifying high-risk compensation patients.     

Effects of decreased insulin-like growth factor-1 stimulation on hypoxia inducible factor 1-α protein synthesis and function during cutaneous repair in diabetic mice

Insulin-like growth factor-1 (Igf-1), a critical mediator of tissue repair, is significantly decreased in diabetic wounds. Furthermore, decreased levels of hypoxia-inducible factor 1-alpha (Hif-1alpha) and its target genes are also associated with impaired wound healing in diabetic mice. The aim of our study was to examine whether the reduced levels of Igf-1 are responsible for the reduction in Hif-1alpha protein synthesis and activity in diabetic wounds. We provide evidence that Igf-1 regulates Hif-1alpha protein synthesis and activity during wound repair. In addition, Igf-1 stimulated phosphytidylinositol 3-kinase activity in diabetic fibroblasts, which, in turn, increased activation of the translational regulatory protein, p70 S6 kinase. Moreover, improved healing of diabetic wounds by addition of recombinant IGF-1 protein was associated with an increase in Hif-1alpha protein synthesis and function in vivo.     

Internal Hernias: Clinical Findings,Management, and Outcomes in 49 Nonbariatric Cases

Internal hernia, the protrusion of a viscus through a peritoneal or mesenteric aperture, is a rare cause of small bowel obstruction. We report the clinical presentation, surgical management, and outcomes of one of the largest series of nonbariatric internal hernias. Ten-year retrospective review of patients at our institution yielded 49 cases of internal hernias. Majority of patients presented with symptoms of acute (75%) or intermittent (22%) small bowel obstruction. While 16% of CT scans were suspicious for internal hernia, in no cases the preoperative diagnosis of internal hernia was made. The most frequent internal hernias were transmesenteric (57.0%) and 34 hernias (69%) were caused by previous surgery. All internal hernias were reduced and the defects were repaired. Compromised bowel was present in 22 cases and 11 patients underwent small bowel resection. The mean postoperative hospitalization was 10.9 days. The overall mortality rate from our series is 2%, and the morbidity rate is 12%. Transmesenteric hernias, as complications of previous surgeries, are the most prevalent internal hernias. Preoperative diagnosis of internal hernia is extremely difficult because of the nonspecific clinical presentation. However, if discovered promptly, internal hernias can be repaired with acceptable morbidity and mortality. Poster presentation at Digestive Disease Week, May 22, 2006, Los Angeles, California, USA.