CNS actions of calcitonin gene-related peptide on gastric acid secretion in conscious dogs.

To determine the mechanisms of action of calcitonin gene-related peptide (CGRP) in inhibiting gastric acid secretion, we studied awake male beagle dogs fitted with a chronic intracerebroventricular cannula and a gastric fistula. Synthetic rat CGRP (10 pmol/kg to 10 nmol/kg) given intracerebroventricularly or intravenously significantly inhibited pentagastrin-stimulated gastric acid secretion. CGRP (1 nmol/kg) given intracerebroventricularly decreased acid secretion stimulated by 2-deoxy-D-glucose but not by histamine. CGRP-(1-14), [Tyr23]CGRP-(23-37), and [acetamidomethyl-Cys2,7]CGRP, the linear peptide molecule devoid of the disulfide bridge, did not affect gastric secretion. Ganglionic blockade with chlorisondamine, a vasopressin antagonist, naloxone, and truncal vagotomy did not abolish the gastric inhibitory action of CGRP given intracerebroventricularly. CGRP administered intracerebroventricularly and intravenously decreased gastric acid secretion, but not plasma gastrin concentrations stimulated by an 8% peptone meal. It is concluded that CGRP given intracerebroventricularly or intravenously inhibits gastric acid secretion in conscious dogs; the intact molecule appears to be necessary for biological activity; and inhibition of gastric acid secretion by CGRP in the dog is not mediated by the autonomic nervous system or vasopressin-, opiate-, or gastrin-dependent pathways.

Influence of age on mortality of colon surgery.

The geriatric population continues to grow and surgical decision making is often confused by the effect of aging. This study is part of an ongoing effort to determine surgical risk in the elderly population and to identify the significant factors affecting outcomes which could be used to plan surgical procedures. Records of 163 patients over 70 years of age with elective or emergency surgery (133 patients and 30 patients, respectively) were reviewed. There were 17 deaths. All deaths in a cohort of patients under 70 were examined as well. Ninety-five variables were explored to seek differences between groups. The patients who died, independent of age, were similar. Patients over 70 years of age who died differed from the survivors in many ways, both physiologically and in terms of disease state. Survivors were younger; did not have congestive heart failure; had better hepatic, renal, and pulmonary function; less extensive involvement if malignant disease was present; and fewer postoperative complications. If these factors were removed and only apparently normal physiologic characteristics considered, there were no differences in mortality between the patients over 70 years of age and younger patients. Age was less of a factor than physiologic status.

Total counts of antral gastrin cells: a simple direct method.

A simple technique has been developed to quantitate the gastrin cells (G-cells) from the pyloric antrum of the rat. The antrum was digested in pronase to suspend the epithelial cells. This cell suspension was counted and pelleted. The pellet was embedded in paraffin, sectioned, then labeled using the indirect immunofluorescence technique specific for gastrin. The percentage of G-cells was determined from photographs of fluorescing sections and total G-cell numbers were determined by relating these data to total epithelial cell counts. In 14 rats the average G-cell population totaled 1.03 +/- 0.21 X 10(5) G-cells/antrum. The technique is simple, time-saving and avoids the uncertainties inherent in previous procedures for the estimation of G-cell numbers.

Changing patterns of gastrointestinal bleeding.

This study, a retrospective analysis of 351 patients with acute gastrointestinal (GI) hemorrhage, was undertaken to define patterns of disease and age-related operative and mortality rates and to determine changes over time related to changes in management. One third (116 patients) of the admissions had bleeding esophageal varices. Upper GI hemorrhage accounted for 85% (N = 200) and lower GI hemorrhage for 15% (N = 35). Emergency surgical intervention was required in 90 patients (38%), 40% of the upper and 29% of the lower GI hemorrhage patients. Benign ulcer disease accounted for 86% of the cases requiring emergency surgery and was treated with vagotomy and drainage and/or oversewing. Lower GI bleeding is seen in older patients; it has a lower operative intervention rate and a higher mortality. Stress bleeding as a surgical lesion has disappeared since 1979. A more assertive policy for surgical intervention has decreased operative mortality for all age groups. Bleeding duodenal ulcers are decreasing in incidence while gastric lesions appear to be increasing. These population-specific patterns, different from earlier periods, may have implications for training and patient management decisions.

Pros and cons of parietal cell versus truncal vagotomy.

The reliability of parietal cell vagotomy as a primary procedure for duodenal ulcer is still questioned by many, and several surgeons advocate pyloroplasty in certain subgroups. Since the opening of our hospital in 1972, a randomized, prospective study has been under way. Sixty-seven patients were randomized into three groups: truncal vagotomy and Jaboulay pyloroplasty (Group 1), parietal cell vagotomy and Jaboulay pyloroplasty (Group 2), and parietal cell vagotomy without drainage (Group 3). The overall operative mortality was zero, with an 18 percent morbidity. Postoperative Congo red testing revealed truncal vagotomy to be a more reliable vagotomy, with 25 percent of Group 1 patients noted to have some degree of incomplete vagotomy compared with 36 percent of patients in Group 3 (p less than 0.05). The ulcer recurrence in Group 1 was 4 percent, in Group 2 18 percent, and in Group 3 10 percent. No dumping or diarrhea was noted in Group 3 compared with Group 1 in which 4 percent of patients had dumping and 17 percent had diarrhea and Group 2 in which 14 percent of patients had dumping and 23 percent had diarrhea (p less than 0.05). The higher incidences of recurrence and postoperative side effects obviously related to the pyloroplasty made parietal cell vagotomy with pyloroplasty the least desirable operative procedure. Parietal cell vagotomy is technically a more difficult procedure, but if performed satisfactorily, results in greater patient satisfaction, with 81 percent of the patients symptom-free compared with 63 percent of those who had truncal vagotomy and pyloroplasty.

Impact of choice of anesthetic with vagotomy testing.

Incomplete vagotomy is the most important cause of recurrent ulcer disease. Despite this, intraoperative vagotomy testing has not gained widespread acceptance. We used a technique with Congo red, a nontoxic azine dye that turns black (pH, 3.0) intraoperatively. The vagolytic effects of various general anesthetics has been shown. We found that halothane, used as a general anesthetic, combined with pentagastrin administration as a vagally synergistic stimulant, produced the most reliable, safe, and reproducible result when using Congo red intraoperatively.

The congo red test to determine completeness of vagotomy: clinical application.

Over the past 5 years, we have evaluated the Congo red test for vagal competence as to its reliability under varied clinical conditions both intraoperatively and postoperatively. Our technique has been useful and accurate in approximately 200 patients. Insuring completeness of vagotomy during the operation has been of use in 42 patients uncovering an unsuspected incomplete vagotomy in 4. In a series of 31 patients with recurrent ulcer symptoms, the documentation of the cause as well as the presence of the ulcer is possible with one simple maneuver--endoscopy. Furthermore, the test has been utilized postoperatively in over 100 patients to determine the longevity of a negative test as well as the clinical sequelae of apositive study. With a trend to more selective vagal section and a continuing significant incidence of recurrent ulceration, we are convinced that the congo red test is an important adjunct to the surgical care of ulcer patients.

Operative mortality in general surgery.

The operative mortality in over 7,000 consecutive cases at a Veterans Administration Medical Center is defined. The mortality in elective procedures is low by most standards and is usually associated with a malignant disease. Older patients appear to have an increased operative mortality. Sepsis is the major factor in death after elective and emergency procedures. Age is a critical factor associated with mortality in this population. Preexisting disease (pulmonary, cardiac, hepatic, and malignant) plays a role in determining outcome. Despite these factors it is possible to achieve excellent operative mortality results in a hospital with a commitment to resident training. An aggressive diagnostic and therapeutic approach is considered reasonable to support these patients with multisystem disease. This often includes the extensive use of expensive resources such as preoperative hospitalization with nutritional support and prolonged stays in the surgical intensive care unit postoperatively.

Recurrent hiatal hernia repair: A potential surgical dilemma.

We studied 96 patients who underwent hiatal hernia repair; 17 of these patients had secondary repair. Nor mortality existed for elective first-time repairs. whereas there was a 17.6% mortality and a 46% morbidity in secondary repairs. No clear differences were noted with the type of repair used. Thirty-five percent of those having a recurrent hiatal hernia repair later had another recurrence. Reoperation for recurrent reflux esophagitis is more of a risk than is often thought. This information should be heavily weighed during preoperative decision making.

Management of hyperparathyroidism in patients with renal failure.

Patients with hyperparathyroidism of renal failure fall into two categories: those with hypocalcemia and those with hypercalcemia. If medical management fails and operative indications are present--bone pain or fracture, metastatic calcification, progressive hypercalcemia or uncontrolled pruritus--parathyroid exploration should be done. Total parathyroidectomy and autotransplantation is the procedure of choice when hypocalcemia is present and more than one gland (usually all) is enlarged (which is the case in most patients). Parathyroid adenomectomy is the procedure of choice where autonomy of parathyroid function is established or a single gland is enlarged and all others are small; hypercalcemia is present in these patients. In other instances of hypercalcemia associated with advanced renal disease, total parathyroidectomy and autotransplantation should be performed; that is, in patients in whom more than one gland is enlarged or irregular or in whom all glands are not identified. Continued follow-up is necessary to confirm this rationale of therapy.

Mortality and gastrointestinal surgery in the aged: elective vs emergency procedures.

Elderly patients are often viewed as high-risk surgical candidates. Consequently, elective surgery may not be performed, with the result that a potentially treatable disease process may develop into an acute catastrophic event. We question the validity of this approach. In our experience with 1,411 gastrointestinal (GI) surgical procedures performed between March 1972 and September 1979, 23.6% have been in patients older than 70 years of age. The operations were emergent in this age group 19.5% of the time. Despite the advanced age of these individuals, the overall operative mortality for 269 elective procedures was 6.7%. For the 65 patients aged 70 years or older who underwent emergency procedures, the operative mortality was 20%. While elective GI surgery in the elderly has a significant risk, death is almost always the result of an associated disease (pulmonary, renal, or cardiac). Emergency procedures in the elderly indeed carry greater risk, statistically the same as in the 50- to 69-year-old group. Death is frequently related to an acute process complicating a treatable disease.

Biliary obstruction in chronic pancreatitis: indications for surgical intervention.

A syndrome of distal common bile duct obstruction secondary to the fibrotic effects of chronic pancreatitis has been recognized for some time. A group of ten characteristic patients, seven of whom have undergone surgery, is discussed. The diagnostic techniques and surgical procedures are presented, and the results are analyzed. Three patients with the syndrome were not operated upon and one improved spontaneously. The typical patient was a male alcoholic, average age 48 years, with a history of chronic, relapsing pancreatitis and abdominal pain. The most consistently abnormal laboratory value is a markedly elevated alkaline phosphates level. Endoscopic retrograde pancreaticocholangiography and transhepatic cholangiography are the most useful diagnostic procedures. Fifteen per cent of the most useful diagnostic procedures. Fifteen per cent of the patients operated upon required emergent surgery for acute cholangitis and sepsis. Another 29 per cent required prompt intervention for progressive hepatic failure secondary to biliary cirrhosis. The authors advocate an aggressive approach to establish biliary drainage in the presence of acute cholangitis or biliary cirrhosis. If a dilated pancreatic duct can be demonstrated and abdominal pain is the principal problem a direct procedure on the pancreas is needed.

Serotonin as an inhibitor of gastrin.

A dose of exogenous serotonin (0.1 mg/kg/min) previously described to cause maximal acid inhibition, was infused into six chronically awake dogs and significantly inhibited acid output. Integrated basal gastrin output was inhibited from a mean of 232.6 pg-min/ml to 31.6 pg-min/ml (p < 0.05) by serotonin infusion. Antral explantation significantly increased gastrin levels from a mean control level of 163 +/- 71.1 pg/ml to a mean of 991.0 +/- 663.4 pg/ml (p < 0.05). These elevated gastrin levels were then not significantly inhibited by serotonin. The effect of serotonin on gastrin output has not previously been documented. Whereas acid inhibition was uniformly achieved, serotonin inhibited basal gastrin output (integrated gastrin output) but not a stimulated level of gastrin output. Serotonin may be an important 'enterogastrone', and its release may play a role both in acid inhibition and in preventing ulcer disease.