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L Knutson

Publications and source records attributed to L Knutson.

45 records · Page 3Linked to original sources

Duodenal mucosal bicarbonate secretion in man. Stimulation by acid and inhibition by the alpha 2-adrenoceptor agonist clonidine.

A multi-channel small diameter tube was used to study the secretion of bicarbonate by 3 cm long segments of the proximal duodenum isolated between balloons. The tube had an outer diameter of 5.3 mm and two central and four smaller, peripheral channels. Measurements of infused phenol red, 14C-PEG and vitamin B12 and of trypsin activity were performed to rule out contamination of the perfusate by gastric and pancreatic secretions. Basal secretion of bicarbonate by the duodenal mucosa in healthy subjects varied between 135 and 220 mumol/cm of intestine per hour. Perfusion of the lumen with acid (100 mM HCl for five minutes) increased the secretion to greater than 400 mumol/cm/h and the alpha 2-adrenoreceptor agonist clonidine (150 micrograms iv) decreased the HCO3- secretion by 70 mumol/cm/h. Clonidine simultaneously reduced the mean arterial blood pressure and plasma noradrenaline concentration, but did not affect the plasma glucose or adrenaline concentration. Duodenal bicarbonate secretion is important in the protection of this mucosa against acid discharged from the stomach. Increased sympathetic activity may, by inhibiting the bicarbonate secretion, decrease the protection in proximal duodenum in man and facilitate ulceration.

Adult↗

A new technique for segmental jejunal perfusion in man.

A multichannel tube with two occluding balloons was developed for measurements of the secretion of different endogenous substances into a defined segment of the small intestine. The tube was inserted under fluoroscopic guidance with the aid of a guide wire and was in position in the proximal jejunum after 45-90 min. The overall success rate of the complete procedure was 90%. The system prevented contamination of the perfusate from gastric and pancreatic secretion. Major dilution of the intestinal secretion was avoided due to high recovery of the perfusion fluid. The jejunal secretion rates of high and low molecular weight substances, i.e., albumin, beta 2-microglobulin, hyaluronan, and histamine, were tested. The recovery of the effluent fluid and the volume marker 14C-PEG 4000 exceeded 95% and was also stable over the perfusion period. The mean secretion rates in 23 healthy controls of albumin (635 micrograms/cm/h), beta 2-microglobulin (0.87 microgram/cm/h), hyaluronan (1061 ng/cm/h), and histamine (70 ng/cm/h) were also stable during the perfusion period. Ten healthy controls were studied under steady state conditions for 3 h. The concentrations in jejunal perfusion fluid relative to serum levels were for albumin 0.06%, indicating the degree of passive leakage from the plasma compartment to the intestinal lumen. The appearance of the low-molecular weight protein beta 2-microglobulin in perfusion fluid was on average 3% of its circulating levels, suggesting that the concentrative transport from plasma is dependent on the molecular size. The jejunal fluid concentrations of histamine and hyaluronan exceeded their respective concentrations in plasma, indicating that local intestinal secretion/synthesis is mainly responsible for their appearance in jejunal fluid. In summary, the technique is simple, rapid, atraumatic, safe, and reproducible and, potentially, can accurately reflect biochemical processes in the small intestine.

Adult↗

Increased risk of cancer in siblings of Alaskan native patients with nasopharyngeal carcinoma.

Alaskan Natives (Eskimos, Indians, Aleuts) are at increased risk of developing nasopharyngeal cancer (NPC) and there is family clustering of NPC. This study reviewed the total cancer experience of relatives of NPC patients and found that siblings of Eskimo NPC patients had a nearly threefold risk. No cancer family syndrome was identified and the cancers diagnosed in the siblings were similar to those seen in the general Alaskan Eskimo population.

Adult↗

Effects of leukotriene D4, the antagonist L-649-923, and arachidonic acid on duodenal bicarbonate secretion in the rat in vivo.

Prostaglandins of the E type stimulate bicarbonate secretion by the duodenal mucosa and inhibit gastric acid secretion, effects that have been related to their anti-ulcer activity. Leukotrienes constitute a more recently discovered branch of the arachidonic acid cascade, and C4 and D4 have been suggested to be ulcerogenic in the stomach. We have studied the effects of luminal administration of leukotriene D4 and the leukotriene C4/D4 antagonist L-649-923 on duodenal mucosal alkaline secretion in the anaesthetized rat. Leukotriene D4 (10(-8)-10(-6) M) had no significant effects, but the antagonist dose-dependently increased the bicarbonate secretion and also transiently increased the transmucosal electric potential difference. The precursor arachidonic acid (10(-7)-10(-6) M) caused a small increase in secretion. The increase in bicarbonate secretion in response to 10(-3) M of the antagonist was of about the same magnitude as that observed with 10(-5) of prostaglandin E2, and it was abolished by pretreatment with the cyclooxygenase inhibitor indomethacin. The gastroduodenal protective effects of L-649-923 in vivo may reflect an increase in mucosal prostaglandin production rather than leukotriene antagonism.

Animals↗

HCO3- secretion in rat duodenum after treatment with omeprazole and ranitidine.

The bicarbonate secretion by the duodenal mucosa, which is stimulated by luminal acid, is very probably important in mucosal protection against the acid. It was of interest to investigate whether long-term deprivation of the mucosa of this acid stimulus affected the alkali secretion. Sprague-Dawley rats were treated for 4-6 weeks with either omeprazole, 14 mg/kg body weight twice daily, or ranitidine, 300 mg/kg twice daily, by means of gastric intubation. The rate of bicarbonate secretion by the duodenal mucosa was determined in situ by continuous titration. Neither the basal secretion nor the increase in secretion in response to stimulation by prostaglandin E2 or luminal acid (pH 2.0 for 5 or 60 min) differed in treated animals from that in controls that had received placebo (p greater than 0.05). Thus, 4-6 weeks of treatment with omeprazole or ranitidine did not reduce duodenal mucosal bicarbonate secretion in the rat, nor did these drugs diminish the ability of this mucosa to respond to prolonged luminal acidification or luminally administered prostaglandin E2.

Animals↗

Gastroduodenal mucosal secretion of bicarbonate and mucus: physiological control and role in protection.

Bicarbonate secretion by the surface epithelium in the stomach and duodenum maintains a near neutral pH in the mucus gel adherent to the surface in spite of acidities as high as pH 2.0-3.0 in the gastric and pH 1.5-2.0 in the duodenal lumen. This strongly suggests that the alkaline secretion together with the mucus gel provides a first line of protection in the stomach and this may be the main mechanism of defense in the duodenum. The secretion is increased by physiological stimuli such as sham-feeding or the presence of acid in the lumen. Mucosal endogenous production of prostaglandins as well as humoral and neural mechanisms are involved in the control of the secretion.

Animals↗

Tuberculosis of the large bowel. Report of two cases.

Two patients with primary tuberculosis of the ileocecal region and transverse colon were thought to be Crohn's disease or carcinoma of the colon. No pathognomonic symptoms or roentgenographic findings were present, and the diagnosis was made on the basis of histopathological features including the presence of alcohol/acid fast bacilli. In one case human tubercle bacilli were cultured. The involved bowel segments were resected and the patients received antituberculous chemotherapy postoperatively. Although tuberculosis of the colon is very rare it should however be considered in cases of vague bowel dysfunction.

Adult↗

Postoperative gas gangrene in abdomen and in extremity. A comparison in nine cases of clostridial myonecrosis.

Gas gangrene occurred after surgery on an extremity, as a rule highly arteriosclerotic, in 6 patients and after abdominal operations in 3 patients during an 18-month period in 1978-79. The signs of toxemia after abdominal surgery preceded the signs of wound infection by one or two days and the diagnosis in the interval was extremely difficult. In its abdominal form the gas gangrene had such a fulminant course that, when the diagnosis had been established, the outcome was uninfluenced by prompt administration of shock therapy, surgical debridement and antibiotics. All 3 patients died.

Abdomen↗

Jejunal release of prostaglandin E2 in Crohn's disease: relation to disease activity and first-degree relatives.

Patients with Crohn's disease of the distal ileum show increased permeability to hyaluronan and increased release of histamine and complement components in uninvolved parts of the proximal jejunum. These abnormalities are related to disease activity, and are not found in first-degree relatives. Increased synthesis of prostaglandins has been observed in inflamed areas of the intestine in active Crohn's disease. Our purpose was to measure luminal prostaglandin release in patients with active and inactive Crohn's disease and their first-degree relatives. Twenty-four patients with Crohn's disease of the distal ileum (10 in remission and 12 with inflammatory activity) and 17 of their first-degree relatives were included and compared with healthy control subjects (n = 39). Ten centimetres of the proximal jejunum was isolated between balloons as described previously and perfused with a balanced electrolyte glucose-containing solution. Luminal concentrations of PGE2 and albumin were measured and their luminal release was calculated. Luminal release of PGE2 was significantly higher in patients with Crohn's disease than in control subjects [69.7 +/- 11.5 and 34.0 +/- 4.7 pg/cm per h (3.7 +/- 0.6 and 1.8 +/- 0.3 ng/L), respectively, P < 0.01]. The PGE2 levels, however, were not positively correlated to disease activity. Furthermore, there was a modest, but significant increase in luminal PGE2 in first-degree relatives [53.6 +/- 7.0 pg/cm per h (2.9 +/- 0.4 ng/L), P < 0.05]. These changes were not accompanied by significant changes in luminal permeation of albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗