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Five boys, examined because of continued vomiting, were found to have a peculiar annular narrowing of the lumen of the gastric antrum. The roentgenographic appearance was almost uniform from case to case. The narrowing in all four cases examined histologically was caused by gross thickening of the antral wall by local granuloma formation. Four boys were later shown to have chronic granulomatous disease of childhood; the unoperated child was already known to be suffering from this disease. In one child the granulomatous narrowing of the antrum was the first manifestation of the disease. Crohn's disease of the antrum, peptic ulcerative disease, eosinophilic granuloma, and eosinophilic gastritis had been considered in these cases before the correct diagnosis was made. The nitro-blue tetrazolium (NBT) test should be used in obscure lesions of the antrum, especially when there is annular narrowing of that structure in boys. In children with chronic granulomatous disease and antral narrowing, proper antibiotic therapy may make surgical intervention unnecessary. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy, or transient apical ballooning syndrome, is a recently recognized form of transient left ventricular dysfunction that is presumably caused by stress. Takotsubo cardiomyopathy can clinically resemble an acute coronary syndrome. Reported cases have been preceded by emotional stress or medical illness. Herein, we report a fatal case of takotsubo cardiomyopathy that followed a dobutamine stress test. We believe that the dobutamine infusion led to stress-induced cardiomyopathy with a dynamic left ventricular outflow tract obstruction. To our knowledge, there is only 1 other report of an association between dobutamine infusion and the development of takotsubo cardiomyopathy. [ABSTRACT FROM AUTHOR]

Background: Value-based analysis (VBA) is a management strategy used to determine changes in value (quality/cost) when a usual practice (UP) is replaced by a best practice (BP). Previously validated in clinical initiatives, its usefulness in complex systems is unknown. To answer this question, we used VBA to correct deficiencies in cardiac surgery at Memorial Healthcare System., Study Design: Cardiac surgery is a complex surgical system that lends itself to VBA because outcomes metrics provided by the Society of Thoracic Surgeons provide an estimate of quality; cost is available from Centers for Medicare and Medicaid Services and other contemporary sources; the UP can be determined; and the best practice can be established., Results: Analysis of the UP at Memorial Healthcare System revealed considerable deficiencies in selection of patients for surgery; the surgery itself, including choice of procedure and outcomes; after care; follow-up; and control of expenditures. To correct these deficiencies, each UP was replaced with a BP. Changes included replacement of most of the cardiac surgeons; conversion to an employed physician model; restructuring of a heart surgery unit; recruitment of cardiac anesthesiologists; introduction of an interactive educational program; eliminating unsafe practices; and reducing cost., Conclusions: There was a significant (p < 0.01) reduction in readmissions, complications, and mortality between 2009 and 2013. Memorial Healthcare System was only 1 of 17 (1.7%) database participants (n = 1,009) to achieve a Society of Thoracic Surgeons 3-star rating in all 3 measured categories. Despite substantial improvements in quality, the cost per case and the length of stay declined. These changes created a savings opportunity of $14 million, with actual savings of $10.4 million. These findings suggest that VBA can be a powerful tool to enhance value (quality/cost) in a complex surgical system., (Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Value is an economic utility defined by quality and cost, with the maximum benefit achieved by improving quality and reducing cost simultaneously. Health care systems are using value-based analysis to identify the best practices (BPs) that accomplish this goal., Study Design: We chose a clinical condition, deep venous thrombophlebitis (DVT) to test this hypothesis by identifying the BPs available in the literature; determining the usual practice for DVT prophylaxis at each of 8 hospitals (ie, community, tertiary, and a university hospital) in an integrated system; measuring clinical outcomes (mortality and morbidity) for each hospital; determining cost for each treatment algorithm in each hospital; and measuring the savings opportunity if a single BP was used by all of the hospitals., Results: The literature suggests that the BPs for DVT prophylaxis consist of sequential compression devices for short-stay procedures; unfractionated heparin for inpatient procedures, and low molecular weight heparin for thrombotic events. Four of the hospitals were using these BPs; the others relied on sequential compression devices and low molecular weight heparin for prophylaxis. Outcomes were identical and value-based analysis suggested a savings opportunity of nearly $4 million if a single BP was adopted., Conclusions: There were substantial variations in the type of DVT prophylaxis used by the hospitals with no difference in outcomes. A single BP increased value and resulted in savings of $1.5 million, with a savings opportunity of nearly $4 million., (Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Zinc Finger Nucleases (ZFNs) have tremendous potential as tools to facilitate genomic modifications, such as precise gene knockouts or gene replacements by homologous recombination. ZFNs can be used to advance both basic research and clinical applications, including gene therapy. Recently, the ability to engineer ZFNs that target any desired genomic DNA sequence with high fidelity has improved significantly with the introduction of rapid, robust, and publicly available techniques for ZFN design such as the Oligomerized Pool ENgineering (OPEN) method. The motivation for this study is to make resources for genome modifications using OPEN-generated ZFNs more accessible to researchers by creating a user-friendly interface that identifies and provides quality scores for all potential ZFN target sites in the complete genomes of several model organisms., Description: ZFNGenome is a GBrowse-based tool for identifying and visualizing potential target sites for OPEN-generated ZFNs. ZFNGenome currently includes a total of more than 11.6 million potential ZFN target sites, mapped within the fully sequenced genomes of seven model organisms; S. cerevisiae, C. reinhardtii, A. thaliana, D. melanogaster, D. rerio, C. elegans, and H. sapiens and can be visualized within the flexible GBrowse environment. Additional model organisms will be included in future updates. ZFNGenome provides information about each potential ZFN target site, including its chromosomal location and position relative to transcription initiation site(s). Users can query ZFNGenome using several different criteria (e.g., gene ID, transcript ID, target site sequence). Tracks in ZFNGenome also provide "uniqueness" and ZiFOpT (Zinc Finger OPEN Targeter) "confidence" scores that estimate the likelihood that a chosen ZFN target site will function in vivo. ZFNGenome is dynamically linked to ZiFDB, allowing users access to all available information about zinc finger reagents, such as the effectiveness of a given ZFN in creating double-stranded breaks., Conclusions: ZFNGenome provides a user-friendly interface that allows researchers to access resources and information regarding genomic target sites for engineered ZFNs in seven model organisms. This genome-wide database of potential ZFN target sites should greatly facilitate the utilization of ZFNs in both basic and clinical research.ZFNGenome is freely available at: http://bindr.gdcb.iastate.edu/ZFNGenome or at the Zinc Finger Consortium website: http://www.zincfingers.org/.

It has been proposed that thiamine deficiency after gastric bypass surgery in obese patients results from prolonged nausea and emesis. We hypothesized that thiamine deficiency is induced by altered gut ecology. This report includes 2 retrospective studies of obese patients who underwent Roux-en-Y gastric bypass surgery at our institution from 1999 to 2005. In the first study, 80 patients (52 women and 28 men) had measurement of whole-blood thiamine diphosphate level and serum folate level. In these 80 patients, 39 (49%) had thiamine diphosphate levels less than the lower limit of the reference range, and 28 (72%) of the 39 had folate levels higher than the upper limit of the reference range, an indicator of small intestinal bacterial overgrowth. In 41 patients with normal thiamine levels, only 14 (34%) had folate levels higher than the upper limit of the reference range (chi(2) test, P < .01). In the second study, 21 patients (17 women and 4 men) had thiamine diphosphate levels less than the lower limit of the reference range and abnormal glucose-hydrogen breath tests, consistent with small intestinal bacterial overgrowth. Fifteen patients received oral thiamine supplements, but repeated thiamine levels remained low in all 15. Nine of these patients then received oral antibiotic therapy; repeated thiamine levels were found to be normal in all 9 patients. These results support the hypothesis that small intestinal bacterial overgrowth results from altered gut ecology and induces thiamine deficiency after gastric bypass surgery in obese patients.

Obesity is an increasing health problem, not only in developed countries but also all over the world. In addition to the focus on food intake and energy expenditure, current studies suggest two other important influences on adult body weight: birth weight and postnatal rate of growth. A common procedure in laboratory animal studies to examine the relationship of low birth weight and adult obesity is maternal nutrient restriction, but maternal undernutrition is not the basis for the majority of obese individuals in developed countries. We have thus developed a new mouse model for human obesity referred to as 'the crowded uterine horn model'. By removing one ovary from a female CD-1 mouse, the female produces a litter of about 13 pups in one uterine horn, resulting in crowding and a 4-fold difference in placental blood flow among foetuses in a litter. Restricted placental blood flow results in intrauterine growth restriction (IUGR); these animals show a 2-fold increase in body weight during the week after weaning, while macrosomial foetuses that go through a very small amount of growth during the same postnatal period. Male mice categorized as IUGR or macrosomic at birth both are obese in adulthood. This pattern of changes in body weight throughout life in male mice mirrors findings from epidemiological studies of human foetuses with IUGR and macrosomia who become obese, and thus may provide a new model that reflects the condition of people in developed countries who become obese.

Takotsubo cardiomyopathy, or transient apical ballooning syndrome, is a recently recognized form of transient left ventricular dysfunction that is presumably caused by stress. Takotsubo cardiomyopathy can clinically resemble an acute coronary syndrome. Reported cases have been preceded by emotional stress or medical illness. Herein, we report a fatal case of takotsubo cardiomyopathy that followed a dobutamine stress test. We believe that the dobutamine infusion led to stress-induced cardiomyopathy with a dynamic left ventricular outflow tract obstruction. To our knowledge, there is only 1 other report of an association between dobutamine infusion and the development of takotsubo cardiomyopathy.

Background: Resuscitation with racemic lactated Ringer's solution induces cellular apoptosis. This study was conducted to determine if the elimination of D-lactate isomer would attenuate apoptosis in the liver, and to investigate the possible mechanisms., Study Design: Sprague Dawley rats (n=30, 5 per group) were subjected to modified volume-controlled hemorrhage and randomized to the following groups: no hemorrhage (sham); no resuscitation (NR); resuscitation with racemic lactated Ringer's (DL-LR); L-isomer LR (L-LR); ketone (beta-hydroxybuturate) Ringer's (KR); or pyruvate Ringer's (PR). Animals were sacrificed 2 hours later and expressions of proapoptotic proteins (BAD), antiapoptotic (bcl-2) proteins, and poly-ADP ribose polymerase (PARP) cleavage in liver were analyzed by Western blotting. Contribution of the phosphatidylinositol 3-kinase/serine/threonine kinase (PI3k/Akt) pathway was assessed by measuring total and phosphorylated PI3K, Akt, BAD, and endothelial nitric oxide synthase (eNOS) proteins. The terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay was used to detect the apoptotic cells. Liver ATP levels were measured using a luciferase reaction assay., Results: Hemorrhage significantly decreased the hepatic ATP level and resuscitation improved it, but it returned to normal only in the L-isomer lactated Ringer's and ketone Ringer's groups. Expression of proapoptotic proteins was significantly lower in the pyruvate Ringer's and ketone Ringer's groups; L-isomer lactated Ringer's and pyruvate Ringer's resuscitation significantly increased bcl-2 expression. Poly-ADP ribose polymerase fragmentation and total number of apoptotic cells were significantly increased in the racemic lactated Ringer's group. There was no significant induction of Akt activity or changes in phosphorylated BAD, Akt, or eNOS levels., Conclusions: Resuscitation with racemic lactated Ringer's induces hepatic apoptosis, which is decreased if the D-isomer of lactate is eliminated. Apoptosis is reduced even more when lactate is substituted with beta-hydroxybutyrate or pyruvate. The beneficial effects are not through improvements in the energy status or activation of the PI3K/Akt pathway.

Unlabelled: Resuscitation with racemic lactated Ringer's solution (containing equal amounts of D and L isomers of lactate) has been shown to induce pulmonary apoptosis. Substitution of DL-isomer lactate with ketone bodies (beta-hydroxybutyrate, BHB), sodium pyruvate, or L-isomer of lactate decrease this injury without changing the energy status of the tissues or the expression of apoptotic genes. These modified solutions however alter the function of apoptotic proteins through an unknown mechanism. We postulated that DL-LR induces apoptosis by restricting the phosphorylation of key apoptotic proteins., Methods: Male Sprague Dawley rats (n = 30, 5/group) were subjected to a three stage, volume-controlled hemorrhage and randomized to the following groups. 1) No hemorrhage (Sham); 2) Hemorrhage and no resuscitation (NR); 3) Resuscitation with 3x shed blood volume of racemic LR (DL-LR); 4) Resuscitation with 3x shed blood volume of LR containing only the L-isomer of lactate (L-LR); 5) Resuscitation with 3s shed blood volume of pyruvate Ringer's (PR); 6) Resuscitation with 3s shed blood volume of ketone Ringer's (KR). The modified Ringer's solutions were identical to racemic LR except for equimolar substitution of DL-lactate for L-lactate, pyruvate and BHB respectively. Lung tissue was obtained 2 hours later and subjected to Western Blotting. The levels of Akt, Bad, and eNOS (total and phosphorylated) proteins were measured. Finally, the expression of gene coding for protein 14-3-3 was measured using RT-PCR., Results: Resuscitation with DL-LR caused a significant (p < 0.05) increase in the total Bad and a decrease in phosphorylated Bad protein expression in the lung. It also caused an increase in the phosphorylated Akt levels and a decrease in gene coding for protein 14-3-3. These changes were consistent with signaling imbalances that favor apoptosis. Modified LR solutions, on the other hand, did not cause these alterations. Phosphorylation pattern of eNOS supported the involvement of PI3K/Akt pathway in this process., Conclusion: Racemic lactate plays a role in the induction of pulmonary apoptosis by restricting phosphorylation of Bad and eNOS proteins.

Background: Resuscitative fluids induce distinctive changes in leukocyte functions: incubation with colloid Dextran increases production of reactive oxygen species and adhesion, whereas exposure to hypertonic saline (HTS) inhibits "oxidative burst" and phagocytosis. In hypertonic saline Dextran (HTD), the hypertonic component determines the leukocyte functional behavior and subsequently activation response. We investigated whether leukocyte gene expression is analogously affected., Methods: Whole blood from eight volunteers was diluted and incubated for 30 min at 37(o)C in 6.0% Dextran-70, 7.5% HTS, and 7.5% HTD. Total leukocyte RNA was extracted and used to synthesize biotinylated cDNA probes. Each probe was individually hybridized to a cDNA array to simultaneously measure the expression of 23 genes involved in inflammation, cell migration, and apoptosis., Results: Leukocytes incubated with Dextran-70 demonstrated greater than a 6-fold (p < 0.05) increase in the expression of interleukin-8, growth-regulated oncogenes alpha and beta, L-selectin, superoxide dismutase, tumor necrosis factor-alpha (TNF-alpha), and mitogen-activated protein kinase 3. The expression profile induced by HTS was not significantly different from that of unstimulated blood, except for prominent induction of only three genes. HTD attenuated the expression of Dextran-70 upregulated genes, although the level of their expression was higher than in HTS-treated leukocytes., Conclusions: Hypertonic resuscitation fluids diminish the expression of immune activation-associated genes. Hypertonic component of HTD determines the leukocyte gene expression profile.

Many algorithms have been developed for patients with acute lower gastrointestinal hemorrhage (ALGIH). Their clinical usefulness is not readily apparent. It is important first to observe patterns in admission, triage, and management to formulate hypotheses as to how outcomes might be affected. We reviewed patient charts with the diagnosis of gastrointestinal hemorrhage from June 1998 to January 2001. Patients with ALGIH were entered into a database. We defined patients as having ALGIH if presentation included melena or hematochezia. Patients with hematemesis, bloody nasogastric aspirate, or occult fecal blood were excluded. Observations were made on 420 patients. Seventy-six per cent of patients were admitted to the medical service. Lower endoscopy was the first diagnostic method in 33 per cent. Medical management comprised 52 per cent of first management strategies. Surgeons used angiography (3% vs 1%) or surgery (25% vs 5%) more than other services. Fourteen per cent of patients managed with endoscopy, 16 per cent medically, 17 per cent with surgery, and 67 per cent with interventional radiology required two or more subsequent packed red blood cell transfusions. Mean admission Acute Physiology and Chronic Health Evaluation II score was 9.2 whereas that for those with mortality was 13.5. We conclude that the construction of a database will allow for formation and testing of hypotheses in managing ALGIH.

Objective: Rising costs and lowered reimbursements make value essential if laparoscopic cholecystectomy (LC) is to be offered to patients without condemning providers to financial loss. We hypothesize that our protocol increases this value. Once practiced, operative time, complications, and patient satisfaction compare with those of the typical method., Methods: We prospectively randomized 50 consecutive patients equally to control or experimental LC according to our protocol. Equipment costs, operative time, conversions, complications, pain, and return to work were compared. The student's t test was used for comparisons., Results: Mean disposable equipment costs were 173.00 dollars +/- 43.45 dollars and 434.42 dollars +/- 50.54 dollars for the study and control groups, respectively (P < .0001). Mean operative times were 67.26 +/- 15 and 70.60 +/- 19 minutes, respectively., Conclusions: The "bare bones" protocol is safe. It has a short learning curve, demonstrates a cost advantage over the common method, and requires no additional operative time. Pain, time to return to work, and satisfaction are equivalent.

Given that interleukin (IL)-10 (IL-10) serves as a potent down-regulator of specific proinflammatory cytokines we reasoned that its administration should improve outcome in situations in which the biological response to a severe inflammatory challenge is the critical determinant of survival. To test our hypothesis we administered IL-10 in the setting of lethal pancreatitis to determine its effect on proinflammatory cytokine production and survival. We divided Sprague-Dawley rats into three groups. Controls (Group 1, n = 5) received a sham laparotomy. We induced pancreatitis in Group 2 (n = 9) and Group 3 (n = 9) via laparotomy and intrapancreatic infiltration of one mL of 5 per cent sodium taurocholate. Group 2 was treated only with saline, whereas Group 3 was treated with 10,000 units of IL-10 (in saline) at 30 minutes, 3.5 hours, and 6.5 hours after induction of pancreatitis. Serial blood samples were obtained at 6.5 hours for measurement of amylase, IL-1, and IL-6. The Kaplan-Meier method, Wilcoxon test, and Student's t test were used for analysis. Seven-day survival was 100, 0, and 45 per cent in Groups 1, 2, and 3, respectively. Production of amylase, IL-1, and IL-6 was lower in the IL-10-treated group (Group 3) compared with the group treated with saline alone (Group 2, P < 0.05). We conclude that administration of IL-10 in the setting of otherwise 100 per cent lethal experimental pancreatitis significantly reduces production of amylase, IL-1, and IL-6 and improves survival.

Background: Interleukin-10 (IL-10) counteracts the effects of the proinflammatory cytokines interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF). Experimental data suggest that inhibition of these proinflammatory cytokines improves outcome in sepsis, endotoxemia, necrotizing pancreatitis, and other severe inflammatory states. We hypothesized that the administration of IL-10 would attenuate the release of proinflammatory cytokines after severe hemorrhagic shock., Methods: To test our hypothesis, male Sprague-Dawley rats (N = 20) were divided into control and experimental groups. We induced hemorrhagic shock by removing a sufficient quantity of blood to maintain a mean arterial pressure of 50 mm Hg or less for 120 min. The animals were then resuscitated with shed blood and an equal volume of 0.9% saline. The experimental group received 10,000 units of IL-10 at the initiation of shock. Serum IL-1, IL-6, TNF, and lactate were measured at baseline, after 120 min of shock, and 60 min after resuscitation. The rats were followed for 72 h to calculate survival., Results: Similar levels of hypoperfusion were obtained in both groups as demonstrated by lactate levels and amount of shed blood. The survival rate (70%) was the same in both groups. Serum levels of IL-1 and IL-6 were not significantly different between the two groups, although there was a trend toward IL-6 suppression. TNF, however, was significantly lower in the IL-10-treated group at the end of shock (Wilcoxon test, P < 0. 025)., Conclusion: Administration of IL-10 suppresses the TNF surge observed after severe hemorrhagic shock., (Copyright 2000 Academic Press.)

Previous work from our laboratory demonstrated the feasibility of utilizing placental-derived collagen tissue matrix (CTM) as a bowel wall substitute. We reasoned that this technique would also be suitable in managing intestinal fistulae. To test this hypothesis, we created a chronic cecal fistula in rats and randomly managed some with primary repair and others with CTM replacement. Leak rates, mortality, bursting pressures and histologic scores were similar, suggesting that a chronic fistula can be successfully managed with either a CTM or primary repair., (Copyright 2000 S. Karger AG, Basel.)

Background: Hepatic injury after ischemia/reperfusion is attributed to the development of oxygen free radical (OFR)-mediated lipid peroxidation--a process that can be measured through its byproducts, specifically malondialdehyde. The use of free radical scavengers can offer significant protection against OFR-induced liver injury. We hypothesize that a new potent OFR scavenger, polyethylene glycol-superoxide dismutase (PEG-SOD), can inhibit OFR-mediated lipid peroxidation in hepatic ischemia/reperfusion injury., Methods: Twelve male Sprague-Dawley rats (300-350 g) were subjected to occlusion of the left and middle hepatic arteries and portal veins for 90 min, followed by 120 min reperfusion. PEG-SOD (5000 units/kg) was given intravenously before vascular occlusion and again immediately upon reperfusion to six rats. Normal saline was given to the remaining six rats to be used as a control group. The right hepatic lobe (used as internal control) and left hepatic lobe were harvested separately and tissue malondialdehyde was measured., Results: A marked increase in lipid peroxide was found in the normal saline group after 2 h reperfusion. Treatment with PEG-SOD prevented the rise in tissue malondialdehyde. The mean difference in the malondialdehyde between the left and right hepatic lobes were 13.20 +/- 6.35 and 1.70 +/- 3.65 nmol/g in the normal saline (control) and PEG-SOD groups, respectively. This difference was found to be statistically significant (P < 0.005) using Student's t-test., Conclusions: PEG-SOD can effectively attenuate hepatic ischemia/reperfusion injury by inhibiting OFR-mediated lipid peroxidation.

Background: The effectiveness of enteral feeding in maintaining postoperative nutrition has led some investigators to recommend prophylactic jejunostomy at the time of any high-risk abdominal operation. A failed procedure in this setting weighs heavily on the side of risk without identifiable benefit., Methods: A benefit/risk analysis comparing complication rate, avoidance of parenteral nutrition, and discontinuation of jejunostomy feeding was performed in 92 patients. These patients were judged retrospectively to be undergoing either a prophylactic jejunostomy placed at the time of operation for another serious condition (group A) or therapeutic jejunostomy alone (group B) during a 3-year period (1993 to 1996). Classification as prophylactic or therapeutic was determined by the surgeon's preoperative intent., Results: Avoidance of parenteral nutritional support, a goal of prophylactic jejunostomy, was not achieved in 39% of the patients. Patients in group A had a 5-fold increase in the risk of premature discontinuation of enteral feeds when compared with group B (P < .03). The complication rate was higher in group A (41%) than in group B (26%). Four life-threatening complications occurred in group A; all required reversal of the feeding jejunostomy., Conclusions: This study suggests that the benefit/risk ratio of prophylactic jejunostomy is low. This adds weight to the notion that this procedure be abandoned in favor of other forms of nutritional support.

In suitable candidates, a reduction in gastric capacity to achieve significant weight loss is life-saving. The number and variety of procedures proposed in the last 15 years suggest that the ideal operation is still in evolution. We present a 15-year experience with a single operation designed to avoid the hazards of staple line dehiscence, achieve maximum weight loss, and maintain physiologic homeostasis. From 1979 through 1994, 212 patients, whose age, weight, and number of medical complications were consistent with the criteria for morbid obesity, underwent divided gastric bypass. All patients lost at least 70 lbs, and 95 per cent of the patients lost greater than 100 lbs in 2 years, with an average loss higher than in most comparable series. There were four post operative deaths and three late deaths. Thirteen anastomotic leaks (6%) were successfully managed. Eight patients received nutritional support and antibiotics, and five patients had operative drainage. Eighteen per cent had one or more minor complications. Divided gastric bypass avoids the problem of staple line dehiscence while providing a safe physiologic approach for maximum weight loss in the morbidly obese patient.

Increased concentrations of tumor necrosis factor (TNF) damage normal tissue and produce a shock-like syndrome--changes that can be prevented with anti-body-specific antisera. These findings suggest that TNF-stimulated immunity should protect normal tissue and promote wound healing. To test this hypothesis, 30 Fischer 344 rats (150-200 g) were serially immunized against TNF (20 micrograms/kg). Convalescent sera assayed (micro-ELISA) for circulating antibodies revealed titers (2.54 +/- 0.08 au) significantly higher (P < 0.00001) in immunized animals than in nonimmunized controls (0.11 +/- 0.06 au). Following this, 10 immunized (Group I), 10 nonimmunized (Group II), and 10 control rats underwent partial cecectomy with primary anastomosis. Animals from Groups I and II received TNF (25 micrograms/kg) while controls received saline intravenously on Postoperative Days 1, 3, and 5. Animals were then sacrificed to determine: (1) hydroxyproline content of the anastomosis, (2) mitochondrial respiratory control ratio, and (3) pyruvate dehydrogenase activity of the muscle. We found that (1) exposure to increased concentrations of TNF (Group II) depresses (P < 0.01) biologic markers of wound healing and (2) acquired immunity to TNF (Group I) eliminates this response. In conclusion, acquired immunity to TNF protects the healing intestinal anastomosis from the effects of exposure to increased levels of TNF.

Delayed primary closure has been advocated as the optimal method of management in the presence of wound contamination. The present study was performed to determine whether surgeons have accepted this standard. A total of 918 surgical wounds were evaluated and classified according to the level of contamination and type of wound management used. We found that 150 patients had a Class III or Class IV contaminated wound; however, only 21 per cent were treated with delayed primary closure. The 118 patients treated with primary closure and antibiotics had an aggregate wound infection rate of 27 per cent (Class III-29%; Class IV-24%). Only one (3%) of the wounds managed by delayed primary closure developed an infection. If infection did not occur, there was no difference in the length of stay between patients managed with primary closure and delayed primary closure. However, there was a significantly longer length of stay in the primary closure group if infection occurred. Benefit risk analysis of the patients with contaminated wounds confirmed that in this clinical setting, delayed primary closure remains the optimal method of management for the wound.

Background: Ascites is a common sequela of advanced or recurrent gynecologic malignancies, such as carcinoma of the ovary, fallopian tube, or endometrium. Symptomatic treatment with repeated paracentesis is the initial management after failure of chemotherapy., Study Design: This study was done to evaluate the safety and effectiveness of a peritoneovenous shunt (PVS) in the palliation of these patients with recurrent ascites. A retrospective review of 25 patients having a PVS between 1982 and 1992 was performed., Results: The 25 patients consisted of 21 patients with carcinoma of the ovary, two with primary carcinoma of the peritoneum, one with carcinoma of the endometrium, and one patient with carcinoma of the fallopian tube. The mean weight and abdominal girth decreased after shunt insertion (p < 0.001). Gastrointestinal dysfunction and dyspnea also improved with PVS insertion. There was no change in mean Karnofsky score after placement of a PVS. Two patients died within ten days postoperatively. The median survival period was 80 days and shunt occlusion occurred in four patients., Conclusions: The insertion of a PVS is effective in relieving refractory malignant ascites in gynecologic malignancies. The impact on quality of life requires further study.

A prospective randomized trial was undertaken to evaluate the influence of routine 72-hour catheter exchange and the use of an implantable collagen cuff in preventing central venous catheter infection in critically ill patients requiring multiple lumen central venous access. Patients were randomized to one of four groups, which determined whether the central venous catheter placed would be removed at 3 or 7 days and whether an implantable collagen cuff would be used or not. Upon removal, cultures of the central line tip, the insertion site, and peripheral blood were obtained. One hundred and fifty-nine catheters were studied in 85 patients during a 14-month period. There were 26 (16.4%) episodes of catheter colonization and four (2.5%) episodes of catheter infection in the entire population. Catheter colonization rates (same organisms cultured from catheter tip and skin site) were 14.5 per cent at 3 days and 18.4 per cent at 7 days. Infection rates (same organism cultured from catheter tip and peripheral blood culture) were 2.4 per cent at 3 days and 2.6 per cent at 7 days. With regard to the use of the collagen cuff, colonization rates were 14.5 per cent with the use of the cuff and 18.1 per cent without the use of the cuff. Infection rates were 5.3 per cent with the use of the cuff and 0 per cent without the use of the cuff. None of these differences reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of calcium and endotoxin were investigated in vivo and in vitro using the A/J, retired white male breeder mouse model. Intravenous administration of increasing calcium doses (3.75, 4.37, and 4.75 mg Ca/g-BW) resulted in increasing serum calcium levels (11.4, 14.4, 15.2, respectively vs. animals not injected, 9.5 mg/dl). Mice injected with E. coli bacterial endotoxin after injection of calcium demonstrated significantly (P less than 0.05) lowered serum calcium concentrations (10.5, 12.1, 12.5, respectively). The magnitude of serum calcium reduction was related to the level just prior to endotoxin administration. Mitochondria were incubated using a Percoll purification step. The effect of pretreating the animal in vivo with calcium, endotoxin or calcium plus endotoxin versus control was investigated in both liver and skeletal muscle. When mitochondria were incubated in medium containing EGTA (free Ca less than 1 X 10(-9)). no significant difference between groups was observed in either (RCR) or mitochondrial calcium content. When mitochondria were incubated in EGTA buffers containing calcium (free Ca approximately 7 X 10(-7) liver, 1 X 10(-7) muscle) significant differences in RCR and mitochondrial calcium content were observed. Liver RCR increased significantly with calcium or endotoxin pretreatment (2.20, 2.43 vs. 1.86). Muscle mitochondrial RCR significantly decreased with calcium administration (5.02 vs. 6.79). Both liver and muscle mitochondrial calcium content significantly decreased (2.54 vs. 27.32, and 6.46 vs. 25.82 nMole Ca/mg mitochondrial protein). Preloading with calcium prevented the decline in mitochondrial calcium content. Findings suggest that the reduction in intramitochondrial calcium content during endotoxemia could be an effector of metabolic derangement specifically through calcium-dependent intramitochondrial enzymes.

The use of epinephrine in cardiac arrest remains an area of continuing controversy. This study was undertaken to characterize the effect of endogenous and exogenous epinephrine on plasma epinephrine levels, and the relationship between plasma epinephrine and norepinephrine and mean arterial pressure and diastolic arterial pressure. Nineteen young swine were anesthetized with ketamine and alpha-chloralose and instrumented with arterial and central venous lines. Ventricular fibrillation was induced by pacemaker. At 5 min post arrest cardiopulmonary resuscitation (CPR) was begun with a mechanical resuscitator. Animals were randomized to receive either saline placebo (n = 9), 0.01 mg/kg epinephrine (n = 5) or 0.1 mg/kg epinephrine (n = 5) via the central venous line. Plasma was drawn for high pressure liquid chromatographic analysis of catecholamines every 2 min. The resuscitation was carried on for 30 min after the arrest. Plasma epinephrine levels differed significantly between treated subjects and controls, as did mean arterial pressure and diastolic arterial pressure. There was a correlation between both mean arterial pressure and diastolic arterial pressure with plasma epinephrine and log epinephrine, but no correlation with plasma norepinephrine. The two doses of epinephrine did not differ in the degree to which they elevated the mean arterial pressure and diastolic pressure. We conclude that the endogenous catecholamine response to cardiac arrest while producing norepinephrine and epinephrine levels many times greater than those in the resting animal, is not sufficient to maintain blood pressure. There is a strong correlation between blood pressure and the log of the plasma epinephrine concentration, but epinephrine concentration alone does not solely account for changes in blood pressure during arrest.

Since 1977, we have managed 56 patients (36 Payne and 20 Scott bypasses) with late (one to 18 years) complications resulting from a jejunoileal bypass. All patients underwent a one-stage conversion of the jejunoileal bypass to a gastric bypass. Patients were classified according to postbypass weight, the need for nutritional support, the type and severity of complication, and the time interval between jejunoileal bypass and the onset of the complication and correction of the complication. There were no operative deaths; one patient died 18 months after surgery of cirrhosis. The complication rate was 34%; however, most complications were minor. Our experience with this procedure has shown it to be highly effective in correcting complications other than polyarthritis. When coupled with nutritional support, it is safe even in malnourished patients.

The responses to an exogenous lipid challenge of nonhypermetabolic surgical patients requiring parenteral nutrition and seriously ill septic patients were compared. All patients received a 500-ml intravenous infusion of a 10% lipid emulsion over a 4-hr period. An early elevation of glycerol and triglyceride was noted during the infusion suggesting chylomicron fractionation. Peak triglyceride levels were higher in the septic group but the rate of lipid clearance appeared essentially identical in both septic and nonseptic patients. Lipoprotein lipase levels remained constant and were equal for both groups. Significant late ketone body production was statistically identical in both groups despite depressed albumin levels in the septic group suggesting adequate hepatic ketogenic capacity in septic as well as nonseptic patients.

A patient with a traumatic arteriovenous fistula of the kidney developed encephalopathy with seizures and was unconscious for 48 hours before undergoing a left nephrectomy, excision of a false aneurysm of the left renal artery, and colostomy closure. He has remained in good health for two years following the final operative intervention.

Major alterations in the glucose-mediated regulation of growth hormone are associated with sepsis; however, these alterations are not related to the rate of change in plasma glucose or changes in glucagon, epinephrine levels, or circulating levels of arginine. Alterations in the growth hormone regulatory mechanism occurred among septic patients who manifested severe glucose intolerance which was associated with suppression of insulin production. Inhibition of growth hormone release in these patients may have an adverse effect on amino acid movement, which lends further support to the concept that sustained hyperglycemia in the septic patient is undesirable.

Until recently, the Graham patch was the undisputed method of management for a perforated duodenal ulcer. Results of our experience with 186 patients treated at Wayne State University Affiliated Hospitals from 1970 through 1978 dispute this concept and suggest that a definitive operation is the procedure of choice. One hundred and thirty-seven of the patients were treated with an omental patch, and 47 underwent a definitive operation; 114 of the patients were available for an 18 month follow-up study. It was found that previous ulcer symptoms were not an accurate predictor of the need for a subsequent definitive operation and that mortality was determined by the age and condition of the patient at the time of operation rather than by the choice of operation itself. It is recommended that the perforation itself is an indication for a definitive operation unless the patient is in a state of shock at the time of operation. Vagotomy and pyloroplasty have proved to be safe, reliable, definitive operations in this situation.

Basal glucose metabolism was evaluated in eight stable, infected patients by measuring hepatic glucose production rates in relation to stress endocrine profile and by comparing these data to five injured, noninfected patients. All patients exhibited normal total-body oxygen consumptions and cardiac indices. Fasting basal insulin values were similar in both groups (6 microU/cc) despite a significantly higher plasma glucose level in septic patients (106 +/- 14 mg/dL) compared to nonseptic patients (88 +/- 10 mg/dL). Septic patients exhibited splanchnic glucose production and calculated glucose clearance rates, 53% and 34% higher, than injured nonseptic patients, respectively. In addition, septic patients exhibited a decreased pancreatic insulin secretory response to an intravenous glucose tolerance test as evidenced by a significantly depressed peak insulin value (17 microU/cc) relative to injured patients (77 microU/cc). These findings indicate that insulin suppression is evident in sepsis even in the absence of shock and suggest that sepsis-related basal hyperglycemia does not appear to be associated with peripheral insulin resistance.

Adenosine and the adenine nucleotides have a potent depressant action on cerebral cortical neurons, including identified corticospinal cells. Other purine and pyrimidine nucleotides were either weakly depressant (inosine and guanosine derivatives) or largely inactive (xanthine, cytidine, thymidine, uridine derivatives). The 5'-triphosphates and to a lesser extent the 5'-diphosphates of all the purine and pyrimidines tested had excitant actions on cortical neurons. Adenosine transport blockers and deaminase inhibitors depressed the firing of cortical neurons and potentiated the depressant actions of adenosine and the adenine nucleotides. Methylxanthines (theophylline, caffeine, and isobutylmethylxanthine) antagonized the depressant effects of adenosine and the adenine nucleotides and enhanced the spontaneous firing rate of cerebral cortical neurons. Intracellular recordings showed that adenosine 5'-monophosphate hyperpolarizes cerebral cortical neurons and suppresses spontaneous and evoked excitatory postsynaptic potentials in the absence of any pronounced alterations in membrane resistance or of the threshold for action potential generation. It is suggested that adenosine depresses spontaneous and evoked activity by inhibiting the release of transmitter from presynaptic nerve terminals. Furthermore, the depressant effects of potentiators and excitant effects of antagonists of adenosine on neuronal firing are consistent with the hypothesis that cortical neurons are subject to control by endogenously released purines.