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Biomedical subjects

C T Bombeck

Publications and source records attributed to C T Bombeck.

At least 37 records · Page 2Linked to original sources

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.

Animals↗

The floppy Nissen fundoplication. Effective long-term control of pathologic reflux.

In 1976 we defined a technique of "floppy" Nissen fundoplication (FNF) that prevented experimental pathologic reflux without preventing gaseous eructations or vomiting (normal reflux) when appropriate. This report describes the one- to eight-year follow-up of the 77 patients operated on since that time. The FNF has been completely effective in preventing pathologic reflux in 75 of 77 patients and has been partially effective in two others who are now subjectively asymptomatic. Adverse side effects were reported by two patients, one with gas-bloat and one with inability to belch or vomit. The lower esophageal sphincter pressure of patients postoperatively was increased to low normal values from a mean of 8.94 +/- 1.66 to 14.31 +/- 0.7 mm Hg (normal, 21.2 +/- 4.2 mm Hg). Since FNF does not cause greatly increased lower esophageal sphincter pressure, the inference that the FNF prevents reflux by altering the physiology of a reflux event is supported. In conclusion, the floppy fundoplication has been an effective operation with a low incidence of adverse side effects and without a tendency for late failure.

Adult↗

A unique late mechanical complication of jejunoileal bypass.

The consequences of jejunoileal bypass include not just metabolic derangements, though the frequency and severity of these problems have led to the procedure being abandoned in the treatment of morbid obesity, but a variety of mechanical complications as well. In this report, a new mechanical complication is presented: Intussusception of the defunctionalized ileum into the sigmoid colon, an intussusception caused by malignant lymphoma of the ileum. Because the patient had pain but no evidence of obstruction, the ileal tumor was fortuitously discovered during flexible sigmoidoscopy.

Adult↗

Regulation by histamine of cAMP-dependent protein kinase in guinea-pig stomach.

The present investigation describes experimental conditions under which histamine stimulates cAMP-dependent protein kinase in the guinea-pig stomach. A histamine-responsive cAMP-dependent protein kinase was shown to be present in the soluble fraction obtained after a low speed centrifugation of the stomach homogenate. There was a small, but detectable stimulation of protein kinase activity and cAMP formation when tissue was incubated with histamine. This response to histamine was highly pronounced in the presence of a phosphodiesterase inhibitor. Protein kinase activation was assessed by measuring protein kinase activity ratio (activity -cAMP/+cAMP). Results indicate that protein kinase activity ratios reflect cAMP tissue levels. Binding of free cAMP by charcoal lowered both cAMP levels and protein kinase activity ratio, but histamine activation was still evident. Results suggest that only a portion of intracellular cAMP, probably in a bound form, is actually responsible for protein kinase activation, and the large accumulation of cAMP in the presence of a phosphodiesterase inhibitor probably does not reflect physiological levels.

1-Methyl-3-isobutylxanthine↗

Glycerokinase activity in human adipose tissue as related to obesity.

The activity of the enzyme glycerokinase is low in mammalian adipose tissue, but high in certain forms of genetic obesity in rats and mice. This study was undertaken to determine if obese human subjects had higher glycerokinase activity than normal-weight subjects. Seventy-three randomly selected patients undergoing abdominal surgery were studied. Subcutaneous and omental adipose tissue was removed during surgery and the activity of the enzyme glycerokinase was measured in vitro under optimal conditions. The following observations were made: (1) the mean activity, when expressed per microgram DNA, was significantly (P less than 0.05) higher in obese subjects at both sites, yet no direct correlation to the degree of obesity was found; (2) the individual activity in morbidly obese patients undergoing gastroplasty correlated inversely with the rate of postoperative weight loss (r = -0.58, P less than 0.05); (3) glycerokinase activity was directly related (r = 0.59, P less than 0.01) to the rate of spontaneous glycerol release, and inversely related (r = -0.51, P less than .025) to the stimulation in glycerol release by norepinephrine; (4) the ratio glycerokinase/lipoprotein lipase in omental adipose tissue correlated with the degree of obesity (r = 0.43, P less than 0.05); (5) in nondiabetic male obese adults, the glycerokinase activity in subcutaneous adipose tissue inversely correlated with age (P = 0.05) and (6) the glycerokinase activity had two apparent Km values in three obese patients, in which it was studied kinetically. It is concluded that a small subsection of the obese population have a high potential for glycerol phosphorylation. In these individuals, weight loss is more difficult since they tend to reutilize the glycerol formed by lipolysis and net glycerokinase activity in their adipose tissue may reflect variations in lipid turnover.

Adipose Tissue↗

Proximal gastric vagotomy versus selective vagotomy with antrectomy: results of a prospective, randomized clinical trial after four to twelve years.

This prospective, randomized study of selective vagotomy with antrectomy (SVA) versus proximal gastric vagotomy (PGV) for patients with duodenal ulcer compares the incidence of recurrent duodenal ulcer and postoperative morbidity during a 4- to 12-year follow-up period. In 46 patients with SVA there were no recurrent ulcers, but 26% of these individuals had serious digestive problems that were not amenable to medical treatment. The 40 patients with PGV had eight recurrent ulcers (20%), but five of these were found in the first 15 patients (33%) compared with three in the 25 patients (12%) who had operations after the need for extensive periesophageal denervation was discovered in the mid-1970s. Most recurrent ulcers were amenable to medical treatment, but 5% of the patients who had PGV had postoperative dysphagia that required periodic bougienage. The data are consistent with several interpretations, depending on the bias of the individual. However, based upon the fact that recurrent ulcers could be managed nonoperatively after PGV versus the lack of effective treatments for postgastrectomy complaints after SVA, it is reasonable to consider wider use of PGV. There are reasons to believe that the variable ulcer recurrence rates after PGV can be explained by subtle differences in operative technique, including those based upon use of the Congo red test for completeness of vagotomy. Unlike SVA, PGV remains an operative procedure in evolution that requires further clinical investigation. At this time either operation can be applied if both the surgeon and the patient have a clear understanding of the possible effects.

Clinical Trials as Topic↗

The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6-hydroxydopamine (6-OHDA) causes selective acute degeneration of the adrenergic nerve terminals--that is, a reversible chemical sympathectomy. The effect of this drug was studied on the insulin-stimulated gastric secretion. Insulin-stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after 6-OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibers in the vagus nerve might have some modulating effect on the insulin-induced gastrin release.

Animals↗

The effect of chemical and surgical sympathectomy on gastric secretion and innervation.

The purpose of this project was to evaluate the effects of chemical and surgical sympathectomy on gastric acid secretion (GAS) and mucosal innervation in the dog. Chemical sympathectomy was achieved with 6-OHDA and surgical sympathectomy was performed by excising the celiac and superior mesenteric ganglia. Gastric biopsies for fluorescence microscopy were taken before and after sympathectomy, as was pentagastrin (PPG) stimulated GAS. Each sympathectomy increased GAS in response to submaximal doses of PPG while simultaneously destroying adrenergic nerve terminals in the gastric mucosa. 6-OHDA caused a complete degeneration of nerve terminals at one week, but regeneration was complete by 9 weeks. The data support the concept that the sympathetic innervation of the stomach is an inhibitor of GAS.

Animals↗

The effect of chemical sympathectomy on insulin-stimulated gastric secretion in dogs.

Administration of 6 hydroxydopamine (6 OHDA) causes selective acute degeneration of the adrenergic nerve terminals, that is a reversible chemical sympathectomy. The effect of this drug was studied on the insulin stimulated gastric secretion. Insulin stimulated (0.15-0.4 IU/kg) gastric acid and pepsin output and serum gastrin was measured before and after 6 OHDA treatment (40 mg/kg) in gastric fistula dogs. Chemical sympathectomy resulted in a highly significant increase in acid and pepsin secretion. However, the hypoglycemic gastrin release was unaltered except the peak response, which showed a significant reduction. These data confirm earlier observations, that the sympathetic innervation of the stomach has an inhibitory effect on gastric secretion in the dog. Furthermore it seems that the adrenergic fibres in the vagus nerve might have some moduling effect on the insulin induced gastrin release.

Animals↗

Action of histamine and 3-isobutyl-1-methylxanthine on cAMP activation of protein kinase in dog gastric mucosa.

Dog gastric mucosa was incubated with histamine, IMX and db-cAMP, and the tissue was analyzed for cAMP content and cAMP-dependent protein kinase activity. Results show that in the absence of IMX, histamine does not produce measurable changes in either cAMP content or protein kinase activity ratios. In the presence of 5 X 10(-5) mol/l IMX histamine elicits a dose-dependent accumulation of cAMP, and this accumulation is reflected in elevated protein kinase activity ratios. When IMX concentration is increased to 5 X 10(-4) mol/l, the histamine effect is more pronounced. Incubation of gastric mucosa with 10(-6) mol/l db-cAMP results in elevated cAMP tissue levels both in the absence and presence of IMX, but protein kinase activity ratio is significantly elevated only in the presence of 5 X 10(-4) mol/l IMX. It is concluded that histamine stimulates cAMP formation and protein kinase activation in dog gastric mucosa, but elevations are detectable only when the phosphodiesterase enzyme is inhibited.

1-Methyl-3-isobutylxanthine↗

A new concept in the surgical treatment of gastroesophageal reflux.

Surgical treatment of gastroesophageal reflux has been thought to depend on the construction of a valve mechanism at the gastroesophageal junction (GEJ). Recently, a silicone prosthesis that does not construct a valve has been introduced, and in preliminary studies in the human, shown to be effective in the treatment of reflux. A precise mode of action has not been demonstrated for the prosthesis. This study was undertaken to investigate the mechanics of the prosthesis and determine its effectiveness in an animal model. Six canine gastroesophageal specimens were excised and the lower esophageal sphincter (LES) simulated by a rubber band placed around the GEJ at a tension calibrated to give 25 mmHg "sphincter" pressure. Circumferential silk ligatures of varying length were then placed on the stomach 3.0 cm distal to the GEJ. With no ligature, the LES opening pressure (LESOP) was 8.0 mmHg, varying to 17.0 mmHg with an 8.0 cm ligature. Further, 24 adult mongrel dogs were randomly divided into four equal groups: controls, circular myomectomy of the LES alone, myomectomy combined with fundoplication, and myomectomy combined with implantation of the silicone antireflux prosthesis. Evaluation included manometry, endoscopy, and histology. Although only the normal sphincter and fundoplication responded physiologically, the prosthesis was just as effective in preventing reflux, as evidenced by reducing acid exposure time of myomectomized dogs from 35.4% to 1.8%, and by preventing endoscopic esophagitis. It was concluded that the silicone antireflux prosthesis acts in the same fashion as the ligature in the model, by interrupting distraction of the LES by gastric wall tension. This concept is an effective method for raising LESOP, treating experimental gastroesophageal reflux, and eliminating the sequelae of reflux. Long-term evaluations of the prosthesis are required.

Animals↗

Comparison of cAMP system in parietal cells from rat and guinea pig.

Adenylyl cyclase activity, cAMP content, and activation of cAMP-dependent protein kinase were measured in rat and guinea pig parietal cells isolated by the same procedure. Incubation of parietal cells with histamine resulted in aminopyrine uptake, stimulation of adenylyl cyclase activity, accumulation of intracellular cAMP, and activation of cAMP-dependent protein kinase. In addition, aminopyrine uptake and the cAMP system were stimulated in rat cells by epinephrine, whereas guinea pig cells were unresponsive to epinephrine. It is suggested that there may be differences between the two species with regard to receptors on the parietal cells.

Animals↗

Comparative accuracy of operative ultrasonography and cholangiography in detecting common duct calculi.

Operative ultrasonography and operative radiographic cholangiography were compared for diagnostic effectiveness with regard to their ability to screen the common bile duct for the presence of calculi. We performed real-time B-mode ultrasonography and cholangiography using two injections of contrast material. In 350 patients, 349 ultrasonic and 285 cholangiographic examinations were performed with technically satisfactory results. The sensitivity, specificity, efficiency, and predictability of a negative test were at a high and comparable level for the two diagnostic procedures. However, the predictability of a positive test for ultrasonography of 91.8% was significantly greater (P less than 0.02) than the predictability of 73.2% for cholangiography. Since predictability of a positive test is based on common duct exploration rather than presumptive evidence of a clinical course, this test may be more valid than the other measures to determine diagnostic effectiveness. The advantages of ultrasonography, which are superior accuracy, favorable image qualities, reduced invasiveness, increased safety, avoidance of contrast material, and lower cost, were contrasted with the problems of ultrasonography, which included a slow learning curve for performance and interpretation of the technique and the limited availability of dedicated ultrasound equipment for surgical operations. We concluded that the advantages outweighed the problems and that operative ultrasonography of the common duct warrants wider application in clinical surgery.

Cholangiography↗

Effect of 3-isobutyl-1-methylxanthine on histamine-stimulated gastric secretion in dogs.

The effect of IMX on histamine-stimulated gastric secretion has been studied in dogs equipped with gastric cannulas. After determining the histamine dose response, IMX, histamine, and IMX plus histamine were given by a constant intravenous infusion for 3 h, and acid was collected at 15-min intervals. In a separate series of experiments a single dose of 100 mg of db-cAMP was given 1 h after initiation of infusion of IMX, histamine, and histamine plus IMX. Results show that IMX, a potent inhibitor of phosphodiesterase, is a weak stimulant of acid secretion, and augments histamine-stimulated secretion. However, during stimulated acid secretion, there were no significant changes in tissue cAMP levels, Administration of exogenous dib-cAMP did not produce any significant changes in acid secretion in dogs, but did contribute to elevated cAMP levels.

1-Methyl-3-isobutylxanthine↗

Influence of hiatal hernia on lower esophageal sphincter function.

Sliding hiatal hernia has long term been implicated as a cause of lower esophageal sphincter (LES) incompetence and gastroesophageal reflux. The physics of LES function in hiatal hernia were investigated in in vitro and in vivo experiments. In vitro models of sliding hernias were constructed from excised canine gastroesophageal specimens. A "sphincter" was simulated with a rubber band around the gastroesophageal junction. It was found that placement of a ligature "hernia ring" on the stomach increased the opening pressure of the model sphincter. Addition of a tissue "hernia sac" sutured to the esophagus above the sphincter further increased the opening pressure, the protective effect being related to the pressure transmitted from the stomach to the hernia sac. There was no fluid leakage from the hernia sac between the hernia ring and the stomach. In anesthetized dogs (in vivo model) gastric and esophageal pressures were measured during gastric infusion while the LES gas way to reflux. A ligature tied loosely around the stomach to simulate a "hernia ring" and a sliding hernia without a hernia sac increased both the opening and the closing pressures of the LES by 36 +/- 18% and 35 +/- 20% (mean +/- SD), respectively. The opening pressure was increased by a decrease in gastric wall tension at the gastroesophageal junction, which was caused by the decreased radius of the herniated portion of the stomach. Pressure transmitted from the stomach to the hernia sac added to the LES pressure, and thereby further increased the opening pressure of the sphincter. The results explain how gastroesophageal reflux may be prevented in patients with hiatal hernia. It was recognized that the hernia sac may protect the sphincter, provided that it inserts into the esophagus above the LES.

Animals↗

The effect of propranolol on insulin-stimulated gastric secretion in dogs.

The effect of beta-adrenergic blockade on the insulin hypoglycemia-induced gastric secretion was studied. Insulin-stimulated (0.15 IU/kg) gastric acid and pepsin output and serum gastrin were measured before and after beta-adrenergic blockade with propranolol (20 microgram/kg/min intravenous infusion) in gastric fistula and Heidenhain pouch dogs. Insulin injection caused acid and pepsin secretion from the gastric fistula, and both acid and pepsin secretion was significantly increased during beta-adrenergic blockade. Significant gastrin release was observed after insulin stimulation. However, the insulin-induced gastrin release was unaltered by intravenous infusion of propranolol. The Heidenhain pouch did not show any secretion in these experiments. It is concluded that beta-adrenergic blockade augments the hypoglycemia-induced gastric secretion in dogs. Furthermore, it seems that this effect is not dependent on vagally released gastrin.

Animals↗

The lack of effect of propranolol on the intestinal phase secretion in the dog.

Four mongrel dogs were prepared with a Heidenhain pouch, a gastric fistula, and a 90-cm-long Thiry-Vella loop. After recovery, the jejunal loop was perfused for 3 h with either 5% liver extract or with 0.15 M NaCl, and measurements of gastric acid and pepsin secretion and serum gastrin levels were performed. The experiments were repeated during beta-adrenergic blockade induced by intravenous infusion of propranolol in a dose of 20 micrograms/kg/min. As control, propranolol was also given alone without intestinal perfusion. Perfusion of the jejunal loop with liver extract caused a significant acid secretion from the Heidenhain pouch and gastric fistula. In addition, significant pepsin secretion was obtained, but only from the gastric fistula. The serum gastrin levels remained unchanged during intestinal perfusion. Beta-adrenergic blockade did not influence any of these measurements. The results suggest that the intestinal-phase hormone also stimulates pepsin secretion in dogs. Furthermore, it seems that neither the release nor the action of this hormone is controlled by the beta-adrenergic nerves in the gut.

Animals↗