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Biomedical subjects

L M Nyhus

Publications and source records attributed to L M Nyhus.

At least 73 records · Page 4Linked to original sources

Protective role of faecal pH in experimental colon carcinogenesis.

There is epidemiological evidence that populations with alkaline stool pH are at greater risk for colon cancer than populations with acid stool pH. This association was investigated in the laboratory using the rat-dimethylhydrazine colon carcinogenesis model. Rats with acid stool pH, produced by consumption of lactulose or sodium sulphate or both, had significantly fewer colon tumours after injections of dimethylhydrazine (DMH) than rats treated with DMH alone. The results confirm the hypothesis that acidification of the stool can protect against the induction of colon cancer.

1,2-Dimethylhydrazine↗

Stimulated protein kinase activity during acute pancreatitis in rats. Possible mediation by proteolysis, lipolysis, and bile salts.

The rate of protein phosphorylation, as catalyzed by the protein kinase enzymes, was measured in the pancreas of rats with acute experimental pancreatitis. Two different methods were used to induce pancreatitis in rats: retrograde injection of deoxycholate (DOC) into the pancreatic duct, or daily intravenous administration of DL-ethionine. Basal protein kinase activity was elevated in rats with acute experimental pancreatitis. This increase in activity was not dependent on free Ca2+ and did not result from elevated cAMP levels. To assess the possible role of digestive enzymes in protein kinase activation, tissue extracts from healthy controls were subjected to mild treatment with digestive enzymes and DOC. Trypsin, chymotrypsin, phospholipase A, and DOC produced protein kinase activation of a similar magnitude as found in diseased tissue. Results indicate that stimulated protein kinase activity in tissue of animals with acute pancreatitis may arise from the action of digestive enzymes.

Acute Disease↗

A new tube for simultaneous gastric decompression and jejunal alimentation.

A new tube has been devised for simultaneous gastric decompression and jejunal enteral alimentation. The tube is inserted by the nasogastric route intraoperatively. What differentiates this from earlier tubes is the addition of two inflatable balloons that facilitate passage of the tip of the tube through the retroperitoneal duodenum and into the proximal jejunum. Such a device is needed because the advantages of enteral alimentation in the postoperative patient include safety, low cost and significant metabolic benefits.

Enteral Nutrition↗

Vasoactive drugs in acute pancreatitis.

Experimental evidence has shown that pancreatic blood flow is severely diminished during acute pancreatitis, but it is unclear whether a decrease in blood flow is a critical event in the evolution of complications of this disease. When an episode of edematous pancreatitis is complicated by necrosis of part of the gland, there is a risk of both acute and chronic complications, including sepsis, hemorrhage, and abscess. One of the questions that remains is whether the decreases in blood flow alluded to are primary or secondary causes. If primary, treatments that preserve pancreatic blood flow during pancreatitis might have a salutary effect on observed morbidity and mortality. This study determined whether two vasoactive drugs, oxidopamine (6-hydroxydopamine) and dihydroergotamine tartrate, given prior to experimentally induced pancreatitis in rats, affected observed mortality. After oxidopamine treatment, rats had a higher survival rate and greater pancreatic blood flow than untreated controls. The association of greater pancreatic blood flow and reduced mortality did not exclude other possible effects of oxidopamine treatment but was consistent with the hypothesis that vasoactive therapy may have a role in this disease.

Acute Disease↗

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↗

Endoscopic control of upper gastrointestinal hemorrhage with a bipolar coagulation device.

It has been difficult to determine the real efficacy of endoscopic treatment for upper gastrointestinal tract bleeding sites for several reasons. First, since 80 per cent of an unselected group are expected to stop bleeding spontaneously, it is important to focus upon those individuals who continue to bleed instead of a group in whom bleeding would have stopped spontaneously in the majority. Second, it is difficult, if not impossible, to have comparable groups of patients with similar lesions and similar rates of bleeding who can be randomized into different treatment groups. This report describes the use of a bipolar endoscopic coagulation device in 28 patients with active massive upper gastrointestinal tract hemorrhage who represent 10 per cent of the patients with hemorrhage during a one year interval. Endoscopic treatment controlled bleeding initially in 23 of these patients. Another eight patients with recent hemorrhage who were at high risk for recurrent bleeding (visible vessels) had endoscopic coagulation without subsequent hemorrhage. Immediate operations were required in five of the 28 and delayed operations in another four. Mortality in the patients treated by endoscopic or surgical therapy was comparable (20 per cent), but no patient died of hemorrhage. The high mortality in this group of patients is explained by associated illnesses. B-C is as effective as other endoscopic treatments for nonvariceal sources of upper gastrointestinal tract hemorrhage. This modality is relatively cheap compared with other devices, is theoretically less complicated and has minimal risk to the individual patient. Because of these considerations, it is a technique which deserves wider application and may become the endoscopic treatment of choice for control of upper gastrointestinal tract hemorrhage. Patients with endoscopic control of upper gastrointestinal tract bleeding avoid perioperative morbidity, have a lower transfusion requirement and may have a shorter hospital stay than comparable individuals who require operative control of bleeding sites.

Clinical Trials as Topic↗

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↗

Forskolin action on histamine stimulated adenylyl cyclase in parietal cells of rat and guinea pig.

Forskolin causes a concentration dependent stimulation of adenylyl cyclase in rat and guinea pig parietal cells; guinea pig enzyme has higher activity than rat enzyme, both in the absence and presence of forskolin. Forskolin has a potentiating effect on histamine and epinephrine stimulated enzyme activity in rat cells, but only on histamine stimulated activity in guinea pig cells. Cimetidine, an H2-type antihistamine, does not block the stimulatory action of forskolin. It is speculated that quantitative and qualitative differences in hormone receptors may be magnified with forskolin.

Adenylyl Cyclases↗

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↗

Perspective on extra-gastric vagal fibers: should they be preserved when possible?

A number of discoveries have forced both basic scientists and practitioners of medicine to reinterpret their view of the relation of the autonomic nervous system, the brain, and the gastrointestinal tract. There is growing support for the concept of an autonomous enteric nervous system, one which has many participant and regulatory peptide neurotransmitters, but which can apparently function independently of certain afferent or efferent (vagal) connections to the central nervous system. Recognizing the possibility that extra-gastric vagus nerves may serve an essential role in physiologic functions, it is logical to support the concept that these nerves be preserved when possible. Whether operations which spare extra-gastric vagal nerves will pass the test of time remains to be seen.

Autonomic Nervous System↗