Single dose cephalosporin prophylaxis in high-risk patients undergoing surgical treatment of the biliary tract.

During June 1985 through October 1986, 292 patients considered to be at high risk for having postoperative complications develop underwent cholecystectomy and were evaluated in a multicenter, randomized, prospective, double-blind study. Risk factors included age greater than 70 years, acute cholecystitis within the previous six months, obstructive jaundice, obesity and diabetes mellitus. One gram of cefamandole was administered intravenously to 144 patients and 148 patients received 1 gram of cefotaxime intravenously 30 minutes prior to skin incision. Culture-proved bactibilia was found in 55 patients and 11 of the patients had choledocholithiasis. Of the risk factors considered to place patients at high risk for postoperative infectious complications, obesity and acute cholecystitis proved to be the more common. However, age greater than 70 years, diabetes mellitus and obstructive jaundice were more significant risk factors predisposing to bactibilia. The most common organisms isolated from the bile and gallbladder intraoperatively were Staphylococcus, Streptococcus and Klebsiella species along with enterococcus, Escherichia coli and diphtheroids. Clinically significant postoperative infections occurred in eight patients, including six patients in the cefamandole group and two patients in the cefotaxime group. Antibiotic concentrations were measured in the serum, muscle, subcutaneous fat, gallbladder and bile, with cefamandole showing statistically significant greater concentrations in bile, gallbladder and muscle tissue. There was no statistical significance between the postoperative infection rates, total period of hospitalization or total hospital charges for each group. Therefore, there is no significant advantage between a single prophylactic dose of cefamandole versus cefotaxime for high-risk patients undergoing biliary tract operation.

Introduction of bias in residency-candidate interviews.

We have developed, as part of our resident applicant ranking process, a computerized weighted scoring system incorporating, among other variables, the interview score (IS). This study was undertaken to test the IS as a dependent variable when the applicant file is available during the interview. Over a 3-year period, each of two faculty members interviewed 133 candidates in a "blinded" fashion (file unavailable) or 290 candidates with an "open" file. The mean discrepancy between paired interviewers (1 to 10 scale) was 1.34 +/- 0.10 for the blinded group versus 0.93 +/- 0.06 for the open group (p less than 0.001). Individual and multiple regression analysis were used to test the IS as a dependent variable in the open group, with the blinded group as a control. In each instance (except clerkship grades), the IS correlated more closely with other parameters (p less than 0.05) in the open group. Correlation coefficients were 0.27 (blinded) and 0.64 (open) for weighted scores combining all parameters (p less than 0.001) and 0.39 (blinded) and 0.65 (open) for multiple linear regression analysis (p less than 0.001). We conclude that the IS is significantly influenced if other objective variables are at hand, thus deflating the actual weight of the interview. To accurately quantify the value of the interview, a correction factor must be applied, or, more appropriately, the interview must be conducted blindly.

Endoscopic sclerosis of the gastric cardia for prevention of experimental gastroesophageal reflux.

Surgical anti-reflux therapy appears to involve the muscles of the proximal gastric cardia and those of the lower esophageal sphincter. In an experimental canine reflux model, we injected sclerosant solution into the submucosa of the proximal gastric cardia, hypothesizing that the subsequent fibrotic reaction might exert an anti-reflux effect. Reflux was induced by atropine infusion, and the amount of reflux was quantitated by pH monitoring. Endoscopic sclerosis was effective in preventing reflux induced by high-dose atropine. Because the length and pressure of the lower esophageal sphincter were unaffected by endoscopic treatment, reflux prevention was possibly related to enhancement of the gastric component of the reflux barrier.

Fibrosis of gastric cardia after endoscopic sclerosis. Mechanism for control of experimental reflux?

Endoscopic sclerosis of the gastric cardia (ESGC) prevents experimental gastroesophageal reflux (GER) without changes in lower esophageal sphincter (LES) pressure and length. This study was performed to define the histologic appearance of the esophagus and stomach one year after ESGC. Four dogs were studied one year after ESGC with morrhuate sodium; ESGC had been performed at six sites, 1-3 cm distal to the esophagogastric junction. All animals had stable weight and eating habits at sacrifice. Light microscopy of the cardia and LES included morphometry of wall thickness (mm) and assessment of fibrosis (- to ). The esophagus had minimal changes; the gastric cardia had focal fibrosis, maximal on the greater curve, without any change difference in wall thickness. ESGC results in fibrosis of the gastric cardia, without significant changes in the esophagus. These changes prevent GER, possibly by preventing the initiation of a reflux event.

The effect of mild stress on DMH-induced colorectal cancer.

Epidemiologic studies suggest that certain psychosocial factors increase the risk of cancer. Yet, animal studies suggest that psychosocial stress inhibits the development of chemically induced tumorigenesis. The purpose of this study was to examine the effect of three different chronic mild stressors on the development of dimethylhydrazine (DMH)-induced colorectal carcinoma in rats. Results of this study show that the development of DMH-induced colorectal carcinoma was not significantly inhibited or altered by each individual stress treatment. Additionally, results indicate that mild stressors can induce neurochemical changes commonly associated with stress, without the confounding effects of more aversive stressors that are likely to compromise the nutritional and physiological status of the animal and thereby alter tumor formation.

Nizatidine suppression of basal gastric acid output: a comparison of two intravenous dosage regimens.

To study the pharmacokinetics and pharmacodynamics of two intravenous nizatidine dosing regimens, serial plasma concentrations and continuous intragastric pH were monitored simultaneously in 10 subjects with a documented history of duodenal or gastric ulcers. A 24-hour gastric pH profile was characterized for a 300 mg daily dose of nizatidine randomly administered both as 100 mg every 8 hours and 150 mg every 12 hours. No significant differences were observed in the mean pharmacokinetic parameters between the two dosing regimens. Pharmacodynamic parameters for the 100 mg every 8 hours versus the 150 mg every 12 hours regimen were not significantly different except for percent of time during the 24-hour study period that the pH was maintained greater than 4 (43.6 +/- 20.7 versus 34.7 +/- 18.3, P less than .05). A significant relationship was demonstrated for both regimens (P less than .05) between the percent time pH greater than 4 and area under the plasma curve for the 24 hour study period. The lack of a significant difference in nizatidine pharmacokinetics between the two dosage regimens suggests a pharmacodynamic cause for the greater cumulative pH effect of the every 8 hour regimen.

Endoscopic sclerosis of the cardia affects gastroesophageal reflux.

Gastroesophageal reflux disease remains a disorder of unknown etiology associated with abnormal function of the lower esophageal sphincter (LES) and other physiological co-factors of the pathologic reflux. Effective operations for reflux are designed to reinforce the anti-reflux barrier and alter the tendency towards abnormal reflux. We have postulated that the most important component of these procedures is the prevention of distraction of the lowermost components of the LES at the onset of a potential reflux episode. Distraction of the LES causes shortening of the effective sphincter mechanism and can initiate experimental reflux events. In this study we used endoscopic sclerosis of the submucosal space at the cardia as a means of reducing distraction of the cardia in the hope that this would reduce abnormal reflux events. Canine gastroesophageal reflux was induced by intravenous atropine and monitored by continuous esophageal pH monitoring. Sclerosis of the cardia prevented gastroesophageal reflux, without measurable effect on the LES pressure or length. Endoscopic sclerosis of the cardia may be a useful technique in the control of human gastroesophageal reflux.

The preperitoneal approach and prosthetic buttress repair for recurrent hernia. The evolution of a technique.

Repair of recurrent groin hernias is associated with a high incidence of repeat recurrences (2-19%). Reported herein is a 10-year experience of the management of recurrent groin hernias through the use of the preperitoneal approach with the addition of a reinforcing prosthetic mesh buttress. Two hundred and three recurrent groin hernias in 195 patients (192 men, three women) were treated between July 1975 and October 1986. The preperitoneal approach to the inguinal region was performed under regional anesthesia to define the nature of the recurrent hernia. Initial experience in a randomized trial between the use of local endogenous tissue repair versus endogenous repair with a prosthetic polypropylene mesh buttress demonstrated superiority of the latter in reducing repeat recurrences of anatomically defined direct or combined recurrent hernias. Pure indirect and femoral recurrences did not mandate mesh reinforcement. Long-term follow-up was available for 115 hernias (56%) in 102 patients (52.3%) over a period of 6 months to 10 years. Eight patients had repeat recurrences a mean of 30 +/- 22 months after repair. Six recurrences (four direct, two indirect) occurred in an early experience, when no mesh was used. Two recurrences (one indirect and one lateral to the mesh) representing 1% of all hernias (1.7% of those followed-up) have occurred after routine use of the mesh buttress, with the last re-recurrence seen in December 1982. Three ventral hernias (1.5%) occurred at the wound of entry, but none have occurred since placement of the mesh was modified to cover this wound. There were five (2.5%) wound infections and one (0.5%) hydrocele with no re-recurrences. It is concluded that the preperitoneal approach to recurrent groin hernias, together with the appropriate use of a reinforcing mesh buttress, is safe, allows anatomic definition of the hernial defect, and is followed by few repeated recurrences. The evolution of this approach during the last 10 years has made it the procedure of choice for the management of all recurrent groin hernias at the University of Illinois College of Medicine.

Proximal gastric vagotomy with drainage for obstructing duodenal ulcer.

The optimal treatment for obstructing duodenal ulcer is controversial because of questions about the efficacy of proximal gastric vagotomy (PGV) in controlling the primary ulcer diathesis. Impressed with the theoretic advantages of PGV with drainage as a primary treatment for this problem, we have treated 37 suitable patients by this approach. All patients underwent endoscopic examination and barium meal study that proved the diagnosis. PGV, including division of the gastroepiploic nerves as indicated by intraoperative testing, was followed by Jaboulay gastroduodenostomy (18), Finney pyloroplasty (12), Heineke-Mikulicz pyloroplasty (3), anterior hemipylorectomy (2), duodenoplasty (1), and gastroenterostomy (1). No recurrent ulcers were seen during a mean follow-up of 4.6 years. Three patients had mild early dumping at infrequent intervals. Bilious vomiting, alkaline gastritis, and other postgastrectomy complaints were recorded infrequently. PGV with drainage is a good treatment for the obstructing ulcer and does not have as many morbid risks as alternative operative procedures.

Effect of activity-stress on experimental rat colon carcinogenesis: early histopathologic changes and colon tumor induction.

The effect of stress on experimental colon carcinogenesis was investigated in the rat by adapting the activity-stress ulcerogenesis model to the 1,2-dimethylhydrazine (DMH) rat colon carcinogenesis model. Activity-stress was applied intermittently (normal housing conditions alternated with activity-stress conditions on an equal time basis) to DMH-injected rats either throughout the experiment (AS-DMH) or following completion of DMH injections (DMH-AS). The AS-DMH treatment was associated with reduced colonic tumor induction compared with controls, as was to a lesser degree with DMH-AS condition. In a separate study, the early histopathologic effects on the colon of a single DMH injection, an activity-stress treatment, or the combination of both DMH and activity-stress treatments were compared with those of controls. Activity-stress moderated DMH-induced increases in colonic epithelial cell proliferation and nuclear hyperchromia when compared with DMH treatment alone. The findings of activity-stress-associated protection on colon tumor induction and the concordance of these results with quantitative early histopathologic alterations demonstrate that in the rat activity-stress exerts a protective influence in colon carcinogenesis. In addition, these results suggest further that risk modifiers of colon cancer can be assessed in short-term studies that quantify early histopathologic alterations.

Can the use of an endoscopic Congo red test decrease the incidence of incomplete proximal gastric vagotomy?

The endoscopic Congo red test allows accurate and rapid evaluation of the completeness of vagotomy and may result in a lower incidence of postoperative incomplete vagotomy. This report describes 44 patients tested during proximal gastric vagotomy. Evidence of incomplete vagotomy was found in over 95% at the conclusion of the conventional operation. Importantly, the test was a guide to further operative maneuvers which abolished the evidence of incomplete vagotomy upon subsequent testing. The endoscopic Congo red test satisfies the requirements for an ideal test for complete vagotomy: it is easily performed, does not require special equipment, and can be repeated several times if necessary to verify that desired effects have been achieved. The wider use of this test, therefore, appears justified.

Computerized axial manometry of the esophagus. A new method for the assessment of antireflux operations.

This is a presentation of a new manometric parameter of the mechanical competence of the lower esophageal sphincter (LES), the lower esophageal sphincter vector volume (LESVV). It is determined by computer analysis of continuous-pressure measurements during constant speed pullback of a radially oriented 4- 6- or 8-channel manometry catheter across the LES. Patients were studied with this method both before aggressive medical therapy for esophagitis and before and after Nissen fundoplication. LESVV accurately predicted failure of medical therapy and success of the fundoplication. In patients with successful fundoplication, LESVV demonstrated a 100-fold increase in mechanical competence of the LES, even in the absence of increased LES pressure or length, increasing from 113 +/- 63 mm3 to 11357 +/- 3733 mm3.

The influence of physical activity in 1,2 dimethylhydrazine induced colon carcinogenesis in the rat.

Recent epidemiologic findings indicate that relative risk of colon cancer is augmented with increasing proportion of time spent on sedentary occupations, and reduced with occupations requiring high levels of work-related physical activity. Therefore, the influence of exercise on experimental colon carcinogenesis was investigated. Spontaneous running wheel activity was related to incidence of 1,2 dimethylhydrazine (DMH) colon tumor induction. Colon tumor incidence was significantly reduced in animals that were allowed spontaneous wheel activity throughout the period of DMH tumor induction vs standard housed controls (p less than 0.05), indicating that, in the rat, physical activity protects against colon tumorigenesis. Further comparisons reveal a mild positive association (p = 0.07) between activity and incidence of tumors in the left colon. These results are in accord with epidemiologic findings indicating reduced colon cancer risk with increased physical activity. Possible mechanisms for the protective influence of physical activity on tumorigenesis include reduction in fecal pH, body weight and increased antioxidant enzyme activity. To the extent that epidemiologic associations between colon cancer and activity are inclusive of the multidimensional nature of physical activity, animal models such as that utilized in this experiment can be utilized for investigating the etiologic potential, or strength of association in variables that have been epidemiologically associated with colon cancer risk.

Computer-aided oesophageal manometry: prospects and problems.

We describe a method in which computer-aided analysis has been applied to oesophageal manometry, and address some of the major problems which were encountered. The elimination of pressure artefacts caused by respiration and normal cardiac function is necessary in order to define accurately the parameters required from the analysis. The most promising method of solving this signal/noise problem is to include a fast Fourier transform in the analytical program.

Endoscopic Congo red test during proximal gastric vagotomy.

Although proximal gastric vagotomy is widely performed as an elective treatment for duodenal ulcer, the incidence of recurrent ulcer is troublesome. There are several theories to explain recurrent ulcers, and important technical steps should be considered when performing proximal gastric vagotomy. The use of an intraoperative test may allow more accurate performance of the operation and more complete vagotomy of the parietal cell mass. This report describes the use of the endoscopic Congo red test in patients during proximal gastric vagotomy. The test allows rapid and accurate mapping of areas of the stomach with intact vagus and secretory nerves after operative vagotomy, and can be repeated several times if necessary to verify completion of the vagotomy. The use of universally available equipment and the potential for intraoperative and postoperative use are other attractive features of the test. Use of the endoscopic Congo red test provides physiologic evidence that vagus secretory nerve fibers traverse the right and left gastroepiploic nerves, leading us to believe that the gastroepiploic nerves should be routinely divided during proximal gastric vagotomy. In patients with recurrent duodenal ulcer requiring reoperation, the endoscopic Congo red test allows preoperative demonstration of the site of the intact vagal nerve trunks. The endoscopic Congo red test deserves further investigation and wider application during operations for chronic duodenal ulcer.

Distinction of lower esophageal sphincter strength from sphincter competence.

Although an absolute correlation has been impossible to demonstrate, it has long been thought that the manometric magnitude of the lower esophageal sphincter pressure was a good index of lower esophageal sphincter strength, and hence its competence. To study this relationship, 12 adult mongrel cats were surgically fitted with gastric cannulas. The cats were studied by six-lumen, radially-oriented, rapid pullback manometry before and after administration of atropine, and before and after daily perfusion of the distal esophagus with 0.1 N hydrochloric acid. Lower esophageal sphincter strength was determined by the lower esophageal sphincter pressure vector cross-sectional area. This was computed by plotting the lower esophageal sphincter pressure on polar coordinates, and finding the area circumscribed by the vectors. Lower esophageal sphincter competence was determined by measurement of both the intragastric volume and intragastric pressure required to produce gross reflux. Atropine significantly decreased the mean lower esophageal sphincter pressure vector cross-sectional area from 7,963 +/- 2,469 mm Hg to 720 +/- 59 mm Hg (p less than 0.05) and decreased the mean lower esophageal sphincter opening pressure from 30.2 +/- 6.9 mm Hg to 13.2 +/- 4.1 mm Hg (p less than 0.05). However, acid perfusion significantly decreased the lower esophageal sphincter pressure vector cross-sectional area from 6,786 +/- 3,334 mm Hg to 715 +/- 720 mm Hg (p less than 0.05). This indicates that the lower esophageal sphincter has two components, one of which is acid-sensitive and both of which are atropine-sensitive.

Preservation of lower esophageal sphincter asymmetry after acid-induced abolition of the high pressure zone.

Over a decade ago acid abolition of the esophageal high-pressure zone in the cat was described. This finding was inconsistent with other studies demonstrating that the esophagus was impermeable to acid. Because this finding had been used to support the hypothesis of a "vicious circle" in the course of esophagitis, this phenomenon was re-studied in the cat. In ten animals, acid irrigation of the esophagus caused both esophagitis and transient reduction in lower esophageal sphincter (LES) manometric pressures. Despite the reduction in pressures, manometric asymmetry of the LES was preserved and the esophagitis promptly resolved when acid irrigation was stopped. We therefore conclude that although LES pressure may be abolished, this alone is insufficient to produce reflux and esophagitis over the long term. Preservation of asymmetry implies that the multiple exogenous components composing the LES may not be damaged by this insult.