Reduced oxygen stress promotes propagation of murine postnatal enteric neural progenitors in vitro.

BACKGROUND: Neural stem and progenitor cells of the Enteric Nervous System (ENS) are regarded as a novel cell source for applications in regenerative medicine. However, improvements to the current ENS cell culture protocols will be necessary to generate clinically useful cell numbers under defined culture conditions. Beneficial effects of physiologically low oxygen concentrations and/or the addition of anti-oxidants on propagation of various types of stem cells have previously been demonstrated. In this study, we tested the effects of such culture conditions on ENS stem and progenitor cell behavior. METHODS: Enteric neural progenitor cells were isolated from postnatal day 3 mouse intestine and propagated either as monolayers or neurosphere-like bodies. The influence of hypoxic culture conditions and/or anti-oxidants on enteric cell propagation were studied systematically using proliferation, differentiation and apoptosis assays, whereas effects on gene expression were determined by qRT-PCR, western blot, and immunocytochemistry. KEY RESULTS: Both hypoxic culture conditions and anti-oxidants supported a significantly improved enteric cell propagation and the generation of differentiated neural cell types. Enteric neural progenitors were shown to be specifically vulnerable to persistent oxidative stress. CONCLUSIONS & INFERENCES: Our findings are consistent with previous reports of improved maintenance of brain stem cells cultured under reduced oxygen stress conditions and may therefore be applied to future cell culture protocols in ENS stem cell research.

Secondary complications and subjective well-being in individuals with chronic spinal cord injury: associations with self-reported adiposity.

STUDY DESIGN: This is a cross-sectional study. OBJECTIVES: To examine the associations between adiposity, secondary complications and subjective well-being (SWB) in individuals with spinal cord injury (SCI). SETTING: Parkwood Hospital (London); Hamilton Health Sciences-Chedoke Site and McMaster University (Hamilton); Toronto Rehabilitation Institute, Lyndhurst Centre (Toronto); and St Mary's of the Lake Hospital and Queen's University (Kingston), Ontario, Canada. METHODS: A total of 531 men and 164 women (N=695) enrolled in the Study of Health and Activity in People with Spinal Cord Injury (SHAPE-SCI) completed the Secondary Health Complications Survey, SF-36 pain subscale, Satisfaction with Life Scale (SWLS) and the Patient Health Questionnaire-9 (PHQ) during a telephone interview. Body mass index (BMI) measurements were obtained from a subsample of the SHAPE-SCI participants (n=73) during a home visit. RESULTS: Controlling for covariates, individuals who reported being overweight were more likely to have a history of overuse injuries and fatigue, experienced a greater impact of overuse injuries and fatigue, had greater pain and depressive symptoms, and had lower satisfaction with life than individuals who did not report being overweight. BMI was only associated with an increased likelihood of reporting spasticity. CONCLUSION: Self-reported overweight status was associated with an increased prevalence of certain secondary complications and lower SWB. Future prospective studies should examine whether reductions in adiposity are associated with changes in the prevalence and the impact of secondary complications and SWB.

Physical activity and subjective well-being among people with spinal cord injury: a meta-analysis.

STUDY DESIGN: Meta-analysis of cross-sectional, quasi-experimental and experimental studies. OBJECTIVE: To determine if there is an association between physical activity (PA) and subjective well-being (SWB) among people living with spinal cord injury (SCI). METHODS: Literature searches were conducted using multiple databases (Embase, CINAHL, Medline, PsychINFO and SPORTDiscus) to identify studies involving people with SCI that included a measure of PA and at least one measure of SWB (for example, symptoms of depression, life satisfaction, mood). Relevant data were extracted from the studies and subjected to meta-analysis. RESULTS: A total of 21 studies were retrieved yielding 78 effect sizes and a total sample size of 2354. Overall, there were statistically significant, small- to medium-sized effects for the relationships between PA and SWB (broadly defined), PA and depressive symptoms, and PA and life satisfaction. Studies using experimental and quasi-experimental designs yielded larger effects for SWB (broadly defined) and life satisfaction, than studies using nonexperimental study designs. CONCLUSIONS: There is a small- to medium-sized positive relationship between PA and SWB among people with SCI that holds across a wide range of measures and operational definitions of these constructs.

Activities of daily living performed by individuals with SCI: relationships with physical fitness and leisure time physical activity.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To examine patterns of participation in activities of daily living (ADL) and fitness-related factors associated with these patterns among individuals with spinal cord injury (SCI). SETTING: Centre for Health Promotion and Rehabilitation at McMaster University, School of Kinesiology and Health Studies at Queen's University. METHODS: Forty-eight participants completed the Physical Activity Recall Assessment for People with Spinal Cord Injury (PARA-SCI) and a fitness test assessing cardiovascular fitness (VO(2max) and peak power output (Po)). The most commonly reported ADL were extracted from the PARA-SCI data for analysis. RESULTS: Women tended to spend more time participating in domestic and personal care ADL than men. Compared to individuals with tetraplegia, individuals with paraplegia tended to spend more time transferring, cleaning and preparing food and less time wheeling, toileting and dressing. Fitness and participation in leisure time physical activity (LTPA) were associated with certain ADL. Participants with higher levels of fitness spent more time partaking in ADL wheeling and cleaning. Moreover, greater time spent participating in moderate- and heavy-intensity LTPA was positively correlated with time spent engaged in certain ADL. CONCLUSION: By identifying common ADL performed by individuals with SCI, the study findings begin to provide direction for developing strategies to optimize ADL participation. Future research should examine fitness as a way to help individuals with SCI optimize their ADL participation.

Effect of the antiadhesive treatments, carboxymethylcellulose combined with recombinant tissue plasminogen activator and Seprafilm, on bowel anastomosis in the rat.

Abdominal adhesions are a significant cause of increased morbidity, mortality, and cost in patients undergoing abdominal surgery. Carboxymethylcellulose combined with recombinant tissue plasminogen activator (CMC + rtPA) and Seprafilm (sodium hyaluronate/carboxymethylcellulose bioresorbable membrane) have been shown to reduce adhesion formation in animal models. The effect these treatments may have on a healing bowel anastomosis is unknown. Forty-eight rats underwent a laparotomy and the distal colonic segment was transected and an anastomosis of the transected ends performed. Before abdominal closure one of three treatments - CMC + rtPA, Seprafilm, and saline (control) - was placed in the rat abdomen around the anastomosis. A necropsy was performed 75 to 96 hours later and bowel anastomosis adhesions were scored using an adhesion scale. The anastomosis strength was then evaluated using a saline infusion bursting pressure model. No difference was observed in the extent of adhesion formation involving the bowel anastomosis among all groups. No statistically significant difference was found among the groups in the bursting strength of the colonic anastomosis. We conclude that CMC + rtPA and Seprafilm do not significantly reduce colonic bowel anastomosis bursting strength in the rat model.

Energy/temperature diagram and compression behavior of the polymorphs of D-mannitol.

Three modifications of D-mannitol were produced and investigated: mod. I (mp 166.5 degrees C, heat of fusion 53.5 kJ mol(-1)), mod. II (mp 166 degrees C, heat of fusion 52.1 kJ mol(-1)), and mod. III (mp incongruent 150-158 degrees C, heat of transition, III to I 0.2 kJ mol(-1)). The measured densities are 1.490 +/- 0.000 g cm(-3) [95% confidence interval (CI)] for mod. I, 1.468 +/- 0.002 g cm(-3) (95% CI) for mod. II, and 1.499 +/- 0.004 g cm(-3) (95% CI) for mod. III. It was possible to relate the different modifications given in the literature to one of the three pure crystal forms or to mixtures of two or all three modifications. The thermodynamic relationship among the crystal forms is represented in a semi-schematic energy/temperature diagram. From these data we can conclude that mod. III is thermodynamically stable at absolute zero. It is enantiotropically related to mod. I and mod. II. FTIR and Raman spectra, differential scanning calorimetry curves, and X-ray powder patterns of these crystal forms are depicted for doubtless assignment in the future. The water uptake of the three modifications at 92% relative humidity and 25 degrees C is less than 1%. The differences of the heat capacities and the heats of solution between mod. II and III are not significant, whereas mod. I shows small significant differences compared with the other modifications. In addition, compaction studies of these crystal forms were performed by means of an instrumented hydraulic press. The results show that mod. III should have the best tableting behavior under these conditions.

Tolerance of pupae and pharate adults of Callosobruchus subinnotatus Pic (Coleoptera: Bruchidae) to modified atmospheres: a function of metabolic rate.

Three developmental stages (pupae, early pharate and late pharate adults) of Callosobruchus subinnotatus (Pic.) were investigated for their tolerance or susceptibility to four modified atmospheres. Two of these atmospheres were hypercarbic and two were hypoxic. The hypercarbic atmospheres were found to cause mortality earlier than hypoxic atmospheres. Late pharate adults died earlier than pupae or early pharate adults. Late pharate adults that survived the exposure took a longer time to eclose than the pupae or early pharate adult.Using high resolution microrespirometric techniques, it was possible to record the oxygen consumption rate and CO(2) output of different developmental stages in air. The metabolic rate was determined manometrically as the oxygen uptake rate at an ambient temperature of 25 degrees C. The oxygen uptake rate differed significantly between groups of 20 individuals of different stages (p<0.01; t-test). The lowest rate of oxygen uptake (510.6+/-52.2 &mgr;l g(-1) h(-1)) was recorded in pupae. Higher oxygen uptake rates were found in early pharate adults (668.4+/-45.6 &mgr;l g(-1) h(-1)) and late pharate adults (1171.2+/-45.0 &mgr;l g(-1) h(-1)), and adult beetles (1310.4+/-53.4 &mgr;l g(-1) h(-1)). The patterns of CO(2) release were similar to those of oxygen uptake. CO(2) release was highest in eclosed adults and late pharate adults followed by early pharate adults, and lowest in pupae. The mode of CO(2) release ranged from continuous CO(2) release in pupae to discontinuous CO(2) release in late pharate and eclosed adults. Thus, high metabolic rates, and perhaps, in conjunction with discontinuous CO(2) of late pharate adults are responsible for their higher susceptibility to modified atmospheres than pupae and early pharate adults.

Early laparoscopic Nissen fundoplication for recurrent reflux esophagitis: a cost-effective alternative to omeprazole.

BACKGROUND: Eighty percent of patients treated medically for gastroesophageal reflux disease relapse after treatment. Many of these patients require indefinite treatment with omeprazole to prevent recurrence. Nissen fundoplication has been shown to be effective, safe and cost effective in the management of gastroesophageal reflux disease. We suggest a treatment algorithm, which encourages early surgical intervention in cases of recurrent esophagitis after a previously successful two-month course of omeprazole. METHODS: We have offered laparoscopic Nissen fundoplication since 1993. Patients who received Nissen fundoplication since 1990 were asked to report return to baseline activity, medications, and lifestyle changes. Concurrent chart review of patients treated with omeprazole was conducted to analyze cost. RESULTS: Patients receiving laparoscopic Nissen fundoplication were discharged significantly sooner and spent significantly less time convalescing when compared to those who underwent open Nissen fundoplication. Laparoscopic Nissen fundoplication became cost effective at 1.5 to 2 years when compared to omeprazole. CONCLUSION: Based on cost analysis, patient satisfaction, acceptable complication rate, and efficient use of time and resources, we recommend laparoscopic Nissen fundoplication as the appropriate treatment in patients who develop recurrent esophagitis after a two-month treatment with omeprazole.

Removal of unexploded ordnance from patients: a 50-year military experience and current recommendations.

BACKGROUND: Retained unexploded ordnance in a patient presents the surgeon with unique emotional and technical challenges. This report is a compilation of data to determine management strategies for these potentially catastrophic injuries. METHODS: All identified military cases from World War II to the present were reviewed. Cases were reviewed for site of injury, type of munition, personnel and equipment precautions, and outcome. Interviews were conducted with available involved surgeons. RESULTS: Thirty-six patients were identified with retained ordnance. Four were moribund upon arrival and died before operation. All of the remaining 32 patients survived the removal of the unexploded ordnance. Thirteen injuries involved the trunk, 4 involved the head and neck, and 18 involved extremities. The majority of missiles (51%) were 40-mm projectiles. No incident was identified in which a round exploded during transportation, preparation, or removal. Explosive Ordnance Disposal assistance was available to the surgical team for all but one patient during and after the Vietnam War. Measures used to reduce the chance of premature explosion are discussed. CONCLUSIONS: Isolation of the operating room and protection of personnel and equipment are essential. Patients should be triaged in the delayed category, because most are not morbund on arrival and all patients operated on survived. Explosive Ordnance Disposal expertise should be used. Knowledge of and adherence to several basic principles will protect personnel and equipment while permitting optimal patient care.

Comparison of antiadhesive treatments using an objective rat model.

Intraperitoneal adhesions are a significant problem (increased morbidity, mortality, and cost) for patients undergoing abdominal procedures. Although a variety of approaches (e.g., fibrinolytic agents, anti-inflammatory drugs, or barrier/separation methods) have been used with some success in preventing adhesions, a comparison of these different modalities has yet to be performed in a model that objectively measures intraperitoneal adhesion formation. Our objectives were to establish an objective, reproducible model of intraperitoneal adhesion formation and to establish efficacy of different treatment modalities in decreasing the strength and extent of intraperitoneal adhesions. In this two-part study, a rat model establishing an objective measure of both the strength and extent of intraperitoneal adhesions was used to compare different treatment modalities. Fibrinolytic agents [recombinant tissue plasminogen activator (rtPA), streptokinase, and urokinase], anti-inflammatory drugs (dexamethasone and tolmetin sodium), and barrier methods [sodium carboxymethylcellulose (CMC), and sodium hyaluronate] and a control group were compared in the first phase. In the second phase, the two most successful agents (rtPA, CMC) were compared both alone and in combination against a commercially available barrier agent (Seprafilm) and a control group. In the first phase of the study, rtPA was the only agent that had a statistically significant effect in decreasing the strength of adhesions. CMC was the only agent that demonstrated a decrease in the extent of adhesions, and the difference tended toward significance. In the second phase, the combination of rtPA and CMC showed a significant decrease in both the strength and extent of adhesions when compared with those of the control group. This decrease was also observed in the group treated with Seprafilm, which showed no difference from the rtPA + CMC group. We conclude that, in this reproducible adhesion model, only the combination of rtPA + CMC and Seprafilm significantly reduced both the strength and the extent of intraperitoneal adhesions.

Biliary dyskinesia: a study of more than 200 patients and review of the literature.

The diagnosis and treatment of biliary dyskinesia, defined as symptoms of biliary colic in the absence of gallstones, remains controversial and has been the subject of several previous retrospective reviews. The diagnosis and treatment of biliary dyskinesia based on the CCK-HIDA scan, and the outcome with cholecystectomy for billary dyskinesia, are reviewed. We add more than 200 cases of cholecystectomy for biliary dyskinesia, and compare our results with those of previous reports. We retrospectively reviewed 295 patients with biliary dyskinesia who underwent cholecystectomy at three military hospitals between 1988 and 1995. All patients had symptoms consistent with biliary colic and preoperative evaluations that revealed no evidence of cholelithiasis. Pathology specimens were reviewed for cholelithiasis and pathologic changes. Data were retrieved by chart review and clinic evaluation of new patients. Individual follow-up of each patient was attempted. Follow-up was achieved in 218 of the 295 patients for a rate of 74%. The mean duration of follow-up was 506 days with a range of 22 days to 6 years. Two hundred patients (92%) had CCK-HIDA scans with an ejection fraction (EF) >=<50%. Eighteen patients (8%) had an EF >50% but did have reproduction of their symptoms with CCK injection. In the group with an EF <50%, 94.5% were improved or cured with cholecystectomy. In the group with an EF >50% and pain reproduction, the improved or cured rate was 83.4%. CCK-HIDA scans are useful for diagnosing biliary dyskinesia and predicting improvement after cholecystectomy. Patients presenting with biliary dyskinesia and an EF <50% on CCK-HIDA scan have 94% improvement or resolution of their symptoms after cholecystectorny. CCK-HIDA scans should be employed early in the evaluation of billary colic with no evidence of cholelithiasis (i.e., with a normal ultrasound scan). When test results are abnormal, cholecystectomy should be performed, since the results in this setting approach those of cholecystectomy for stone disease (>90% cured/improved). In the current climate of cost containment, these excellent results would obviate the need for extensive and expensive medical testing before surgical therapy is recommended.

Femoral venous flow dynamics during intraperitoneal and preperitoneal laparoscopic insufflation.

BACKGROUND: Laparoscopic herniorrhaphy may be performed using an intraperitoneal or a preperitoneal approach. Anecdotal and experimental evidence indicates that alterations in lower extremity venous flow, which occur during intraperitoneal laparoscopic insufflation, may be associated with an increased risk of deep vein thrombosis. However, no study has directly compared femoral venous flow during intraperitoneal insufflation with that during preperitoneal insufflation. METHOD: In eight consecutive patients undergoing laparoscopic herniorrhaphy under general anesthesia, flow through the common femoral vein was evaluated with B-mode and color flow duplex. Pre- and intraperitoneal pressures were standardized to 10 mm Hg, and respiratory tidal volumes were standardized to 10 cc/kg. Flow measurements were taken at end expiration. Flow through the common femoral vein was measured after induction of anesthesia, during intraperitoneal insufflation, during preperitoneal insufflation, and between insufflations to ensure return to baseline. RESULTS: All patients in the study were males. Their mean age was 59 years. Mean flow in the common femoral vein was essentially identical at baseline (138 ml/min) and during preperitoneal insufflation (135 ml/min). Alternatively, mean flow in the common femoral vein was significantly reduced during intraperitoneal insufflation (65 ml/min, p = 0.02). CONCLUSIONS: Flow in the common femoral vein is significantly reduced during intraperitoneal insufflation. However, flow in the common femoral vein is not affected by preperitoneal insufflation. These data suggest that laparoscopic preperitoneal inguinal hernia repair may pose as less a risk of thromboembolic complications than laparoscopic intraperitoneal inguinal hernia repair.

Efficacy of a dry fibrin sealant dressing for hemorrhage control after ballistic injury.

OBJECTIVE: To determine if a dry fibrin sealant dressing (DFSD) will provide superior hemostasis when compared with regular gauze in a ballistic injury animal model. DESIGN: A nonsurvival randomized goat study. SETTING: A federal biomedical research institute. SUBJECTS: Eighteen anesthetized Angora goats. INTERVENTIONS: Uncontrolled hemorrhage was induced by a complex ballistic extremity injury. Control of hemorrhage was achieved by applying and holding pressure with the DFSD or regular gauze for 2 minutes. The dressings were left in place for 1 hour. MAIN OUTCOME MEASURES: Total blood loss, mean arterial pressure, ballistic injury, and mortality were recorded after 1 hour. RESULTS: The injuries were equivalent for the 2 groups. No animal mortality was seen. After 1 hour, the mean (+/-SEM) blood loss was 124+/-64 mL in the DFSD-treated group and 377+/-64 mL in the gauze dressings-treated group (P=.01). Twenty minutes after injury, the mean arterial pressure was 95.0 mm Hg (+/-SEM, +/-4.7 mm Hg) in the DFSD-treated group and 70.0+/-5.0 mm Hg in the gauze dressings-treated group. The difference persisted for the remainder of the study (P=.01). CONCLUSION: The DFSD was superior to gauze in decreasing blood loss and maintaining blood pressure while retaining the simplicity of standard dressing application.

Implications of new dry fibrin sealant technology for trauma surgery.

Trauma patients have been bleeding to death for thousands of years. The methods used to control hemorrhage (tourniquets, pressure, bandages, and ligatures) have not changed for 2000 years. Technology now exists to amplify the normal clotting system with human proteins, thus providing almost instant hemorrhage control in the face of bleeding. The increasing body of clinical and animal research and safety data regarding new fibrin sealant technologies is compelling. When combined with the evolving concepts of extended trauma resuscitation, acceptance of this technology will finally add a new method of rapid, easy hemostasis to the armamentarium of the surgeon faced with an unstable hemorrhaging patient. Several important issues remain unresolved, such as optimal thrombin and fibrinogen content, amount of material required for hemostasis, long-term effects, distribution of breakdown products, and role of recombinant proteins. These issues are under active investigation. Despite these unanswered questions, the field of absorbable, off-the-shelf, rapidly active hemostatic agents that do not require refrigeration is an exciting area that should yield significant improvements in the care of injured patients.

Thoracoscopic pleurodesis with minocycline vs talc in the porcine model.

BACKGROUND: Eighteen adult pigs (Sus scrofa) underwent thoracoscopy and were placed into one of three groups: no sclerosant, talc pleurodesis, or minocycline pleurodesis. METHODS: Animals were then sacrificed at matched time intervals. Gross inspection of the pleural cavity estimated percentage of pleural symphysis (>25% was considered substantial) and allowed assignment of a pleurodesis score based on a scale described by Bresticker. Microscopic examination evaluated degree of fibrosis as mild, moderate, or severe. RESULTS: The talc group had significantly better pleurodesis than the minocycline group as determined by (1) the proportion of animals with substantial surface pleural symphysis (5/6 vs 1/6, p < 0.01), (2) a higher pleurodesis score (3 vs 1.3, p < 0.05), and (3) the proportion of animals with moderate fibrosis (5/6 vs 0/6, p < 0. 01). CONCLUSIONS: The authors conclude that instillation of aerosolized talc produces significantly better fibrosis and pleural symphysis than atomized minocycline in this animal model.

An external audit of laparoscopic cholecystectomy in the steady state performed in medical treatment facilities of the Department of Defense.

OBJECTIVE: This study provides the first objective assessment of a complete patient population undergoing laparoscopic cholecystectomy in the steady state. The authors determined the frequency of complications, particularly bile duct, bowel, vascular injuries, and deaths. SUMMARY BACKGROUND DATA: This retrospective study, conducted for the Department of Defense healthcare system by the Civilian External Peer Review Program, is the second complete audit of laparoscopic cholecystectomy. Data were collected on 9130 patients undergoing laparoscopic cholecystectomy between January 1993 and May 1994. METHODS: The study sample consisted of clinical data abstracted from the complete records of 9054 (99.2%) of the 9130 laparoscopic cholecystectomies performed at 94 military medical treatment facilities. RESULTS: Of 10,458 cholecystectomies performed in the Military Health Services System, 9130 (87.3%) were laparoscopic and 1328 (12.7%) were traditional open procedures. Seventy-six medical records were incomplete: however, there was sufficient data to determine mortality and bile duct injury rates. Of the remaining 9054 cases, 6.09% experienced complications, including bile duct (0.41%), bowel (0.32%), and vascular injuries (0.10 percent). The mortality rate was 0.13%. Access via Veress technique was used in 57.6% and Hasson technique in 42.4% of patients. Intraoperative cholangiograms were performed in 42.7% of the cases with a success rate of 86.2%. Eight hundred ninety-two (9.8%) patients were converted to open cholecystectomies. CONCLUSIONS: In the steady state, despite an increase in the percentage of laparoscopic cholecystectomies performed for nonmalignant gallbladder disease, there continues to be minimal complications and low mortality.

Penetrating injury of the vertebral artery: a unique management approach.

We have reported a case of traumatic vertebral artery transection discovered during an emergency neck exploration for penetrating injury with acute hemorrhage. Knowledge of the surgical anatomy of this vessel and awareness of the treatment alternatives that must be considered for its acute injury are important. A cooperative approach between the surgeon, anesthesiologist, and radiologist in this case, using a combination of anesthetic hypotension, surgical tamponade, and angiographic embolization, resulted in a successful outcome in this difficult case.