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Biomedical subjects

F P Brooks

Publications and source records attributed to F P Brooks.

At least 19 recordsLinked to original sources

Gastric effects of thyrotropin-releasing hormone microinjected into the dorsal vagal nucleus in cats.

We investigated the gastric acid secretory and motility responses to microinjection of thyrotropin-releasing hormone (TRH) into the dorsal motor nucleus of the vagus (DMV) in anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral and corpus contractions were continuously recorded by extraluminal force transducers. TRH dissolved in 200 nl of saline and microinjected unilaterally into the DMV induced a dose-dependent (50-200 ng) increase in gastric acid secretion. The acid secretory response began in the first 15 min collection and lasted 45 min. TRH frequently increased the force of contractions of the antrum and corpus within one minute of microinjection. The minimal effective dose for eliciting increased motility was lower than for inducing acid secretion. These results demonstrate that TRH acts in the DMV of cats to stimulate gastric acid secretion and contractions.

Animals

Gastric effects of TRH analogue and bicuculline injected into dorsal motor vagal nucleus in cats.

We investigated the gastric acid secretory and motility responses to microinjection into the dorsal motor nucleus of the vagus (DMV) of RX 77368, a stable thyrotropin-releasing hormone (TRH) analogue, and bicuculline, a gamma-aminobutyric acid (GABAA) receptor antagonist in ketamine-chloralose-anesthetized cats. Gastric acid output was collected every 15 min through a gastric cannula after saline flush and titrated to pH 7.0. Antral contractions were continuously recorded by an extraluminal strain gauge force transducer. The chemicals were dissolved in saline and unilaterally microinjected in volumes of 200 nl. RX 77368 or bicuculline microinjected into the DMV induced significant dose-dependent (50-500 ng) increases in gastric acid secretion and significant dose-dependent (50-200 ng) increases in the force of antral contractions. In response to both chemicals the gastric acid output increased in the first 15 min and peaked in the second and third collections. RX 77368 (500 ng) had a second greater peak 90 min after microinjection. The motility responses were rapid in onset and lasted 60 min for RX 77368 and 30 min for bicuculline. The minimal effective dose for eliciting increased motility was consistently lower than inducing acid secretion. Electrical stimulation of the DMV with 100 microA, 50-Hz, and 0.2-ms pulse duration increased the force of antral contractions but had no effect on gastric acid secretion. Our results demonstrate that the DMV exerts important control over both gastric acid secretion and motility in cats. TRH exerts a stimulatory influence, while GABAA receptors mediate an inhibitory influence on this vagal control.

Animals

Peptic ulcer--current status.

Important problems currently under study or requiring investigation for better understanding of the pathophysiology and management are reviewed under three major categories: acute peptic erosions and ulcers, gastric ulcer, and duodenal ulcer. In patients with acute erosions and ulcers, we need to identify patients at risk for major bleeds, to prevent lesions induced by anti-inflammatory, non-steroidal drugs, as well as bleeding from stress ulcers, and to perfect and establish the efficacy of endoscopic methods for coagulation of bleeding ulcers. In patients with gastric ulcers, we need to establish the relative importance of gastric acidity and mucosal resistance to ulcerogenesis, to determine factors that influence healing rates, and to uncover the factors responsible for recurrence. In duodenal ulcer patients, we need to determine the relative importance of post-prandial versus interdigestive secretion, the role of pepsin, and the importance of local defense mechanisms such as bicarbonate and mucus secretion, cellular defense, and blood flow. The mechanisms of failure to heal during treatment need attention. The relation of symptoms and clinical course to healing of ulcer craters should continue to be considered, as well as the long-term course of ulcer disease. The consequences of long-term suppression of acid secretion are a potential hazard, and, finally, the prevention of recurrence remains the major clinical problem in duodenal ulcer.

Anti-Inflammatory Agents, Non-Steroidal

Lateral hypothalamic sites in cats for stimulation of gastric antral contractions.

Electrical stimulation through a bipolar electrode introduced into either the left or right lateral hypothalamus of anesthetized cats by means of a stereotaxic instrument elicited stimulus-bound phasic antral contractions in the anesthetized cat's stomach of much greater force than recorded under basal conditions. There was no change in gastric acid output. The response was abolished by bilateral cervical vagotomy or atropine. Stimulation during an intravenous infusion of pentagastrin did not alter the gastric acid secretory response. A hypothalamic vagal and cholinergic excitatory gastric antral motor pathway to the stomach has been demonstrated, independent of an acid secretory response.

Animals

The pathophysiology of peptic ulcer disease.

Heterogeneity is the most important consideration in the pathophysiology of peptic ulcer disease. Acute ulcers and erosions present clinically with gastrointestinal bleeding or perforation. If they heal there is no predictable recurrence. Factors concerned with mucosal defense are relatively more important than aggressive factors such as acid and pepsin. Local ischemia is the earliest recognizable gross lesion. The gastric mucosa is at least as vulnerable as the duodenal mucosa and probably more so. Most drug-induced ulcers occur in the stomach. Chronic or recurrent true peptic ulcers (penetrating the muscularis mucosae) usually present with abdominal pain. Many duodenal ulcer patients report that the pain occurs when the stomach is empty or is relieved by food, and follows a pattern of relatively long periods of freedom from symptoms between recurrences. Approximately 50% of patients experience a recurrence within a year if anti-ulcer medication is stopped. In most western countries recurrent duodenal ulcer is more common than gastric ulcer. Peptic ulcer disease is also more common in men. Recent evidence indicates genetic and familial factors in duodenal ulcer and increased acid-pepsin secretion in response to a variety of stimuli. However, it is also becoming clear that of all the abnormal functions noted, few are present in all subjects and many are clustered in subgroups. In chronic gastric ulcer of the corpus, defective defense mechanisms, such as duodenogastric reflux and atrophic gastritis, seem to be more important than aggressive factors. Nevertheless, antisecretory medications accelerate the healing of such ulcers. It remains to be seen whether prostaglandins, mucus secretion, or gastric mucosal blood flow are impaired in chronic ulcer disease.

Acute Disease

Effect of diet on gastric secretion.

Meals stimulate gastric acid secretion in man and animals. The lowest pH of gastric content in man, however, occurs during the early morning hours. Protein meals are both effective buffers raising the gastric pH immediately after ingestion and potent stimulants to acid secretion lowering the pH as the meal is emptied. Two methods, intragastric titration and marker dilution methods are available for measuring acid output in man to a meal. Acid secretion is influenced by the appetizing qualities and the chemical and physical characteristics of the meal. In man and cat acid secretion in response to a meal can equal the maximal response to histamine and pentagastrin. In the dog, it exceeds it. Fat delays the acid secretory response. Both the vagus nerves and gastrin are implicated in mediating the response.

Animals

Where is pancreatic research going?

Research on the exocrine pancreas is showing signs of an accelerating rate of advance. After a period of relative inactivity, there is a prospect for major advances in both basic science and clinical areas. Isolated acinar cells and lobules can now be studied in vitro, and electrophysiologic techniques can be applied to individual cells. Hormones acting on the exocrine pancreas have been isolated and purified, and radioimmunoassays are available. "Candidate hormones" are under investigation. Controlled clinical trials of therapeutic agents are being carried out in pancreatic diseases, and a number of new diagnostic techniques are being evaluated. It remains for investigators to propose important new hypotheses that can be tested by these new techniques.

Humans

Vagally induced gastric antral contractions and gastric emptying of a liquid test meal.

The emptying of a liquid test meal from the stomach was studied during, and in the absence of, electrical stimulation of cut ends of a thoracic branch of the vagus in anaesthetized cats. The test meal (154 mmol.1-1 NaCl and 30 mg.1-1 phenol red) was measured by collecting effluent from a duodenal fistula over a 30 min period. The stomach emptied about 60% of the meal under control conditions compared with over 90% during efferent stimulation of the vagus. The increased volumes emptied during efferent stimulation were not accounted for by secretion of gastric acid. Coincident with the vagally evoked antral contractions there was a gush of liquid from the duodenal cannula. Afferent vagal stimulation resulted in an initial marked delay of emptying followed by an acceleration so that the volume emptied after 30 min was similar to that in control experiments. Antral contractions, evoked by efferent vagal stimulation, accelerated the emptying of a liquid test meal from the stomach.

Animals

Adenocarcinoma of the stomach with common variable immunodeficiency syndrome.

Two patients had adenocarcinoma of the stomach in association with common variable immunodeficiency syndrome. There has been an increased prevalence of malignancy in this late-onset immunodeficient state. Similar to five previously reported cases, our patients had gastric carcinoma as a late complication. Further documentation of this association stresses the need for long-term follow-up in this premalignant condition.

Adenocarcinoma

The effect of cholecystokinin-pancreozymin on circulating gastrin levels in man and dog.

Perfusion of the jejunum with a mixture of amino acids (MAA) stimulates cholecystokinin-pancreozymin (CCK) release in man. Since gastrin is normally found in the small intestine, studies were conducted to determine if MAA perfusion had an effect on circulating serum gastrin levels in man. In man, endogenous stimulation of CCK had no effect on gastrin release; however, when CCK was given exogenously (10% pure form), serum gastrin levels were significantly increased. In dogs, the 10% pure CCK given exogenously also significantly increased gastrin concentrations, while the pure CCK octapeptide did not. Cross-reactivity between CCK and the gastrin antibody was minimal and could not be shown to be responsible for the serum gastrin elevations. Neither the physiological release of CCK in humans nor exogenous administration of CCK octapeptide in dogs at a dose equivalent to maximal stimulation of pancreatic secretion in humans significantly altered peripheral venous serum levels of immunoreactive gastrin. Therefore, we conclude that the gastrinemic response of exogenous CCK (10% pure) in man and dog is probably due to an impurity in the CCK preparation; when studying the effects of CCK on the gastrointestinal tract, only the pure CCK or the octapeptide should be used.

Amino Acids

Thrombocytosis in patients with celiac sprue.

In 57% of the patients (12 of 25) seen with celiac sprue, as shown by clinical course and small bowel biopsy, peripheral blood thrombocytosis was present (range: 350,000 to 815,000 platelets per mm(3); mean: 546,000 +/- 44,060 SE). After clinical and histological remission, the platelet counts in these patients fell significantly (range: 188,000 to 300,0000 platelets per mm(3); mean 252,750 +/- 13,211 SE). There was no correlation between thrombocytosis and serum iron, folate, or vitamin B12 levels. Celiac sprue joins inflammatory bowel disease among gastrointestinal disorders as a consideration in the differential diagnosis of thrombocytosis. In these patients, thrombocytosis reflected active disease and was not present during remission. Evaluation of peripheral blood platelets may be useful in the assessment of patients with celiac sprue.

Adult