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Biomedical subjects

E Haglind

Publications and source records attributed to E Haglind.

At least 55 records · Page 3Linked to original sources

Value of a risk questionnaire in screening for colorectal neoplasm.

The value of a postal questionnaire and of Hemoccult II (Smith Klein Diagnostic Inc., Sunnyvale, California, USA) testing in screening for colorectal neoplasms was compared. In the questionnaire, the subjects were asked about previous treatment for colorectal neoplasm and rectal bleeding during the previous 6 months, specified as to type. All participants were asked to perform Hemoccult II blood testing over 3 days. Of 13,759 randomly selected subjects 9040 (66 per cent) performed the test and returned the questionnaire. Three hundred and fifty-four subjects with a positive Hemoccult II test and/or a proven previous colorectal neoplasm had a full assessment including double-contrast enema and rectosigmoidoscopy to 60 cm. Eighteen carcinomas and 61 adenomas were thus diagnosed. The population was followed for from 20 to 29 months, during which time rescreening was undertaken. An additional 34 subjects with carcinomas and 90 with adenomas were identified during this period. A significant correlation between the presence of a colorectal neoplasm and a previous history of colorectal neoplasm, a positive Hemoccult II and a previous history of bright red bleeding but not dark bleeding was found. The possibility of diagnosing a neoplasm was two, four and 19 times higher in a subject with a previous history of bleeding, a history of colorectal neoplasm, or a positive Hemoccult II respectively. Screening by faecal occult blood testing, therefore, at the moment seems to be the best and only practicable method.

Adenoma↗

Failure to deduce a peptide inhibitor of Na,K-ATPase from the gene coding for the catalytic alpha-subunit of Na,K-ATPase.

It has been proposed (Bost et al. 1985, Blalock & Bost 1986, Smith et al. 1987) that the DNA strand opposite the one coding, for example, for a hormone or a neurotransmitter codes for its receptor protein. This proposal was tested with regard to the possibility of deducing a peptide inhibitor of Na,K-ATPase from the known gene of the catalytic alpha-subunit of the enzyme. Three such peptides, deduced from presumed extracellular domains of the catalytic alpha-subunit, were tested in vitro and in vivo with regard to their effects on Na,K-ATPase activity. No effect on the enzyme could be demonstrated.

4-Nitrophenylphosphatase↗

Radical production during in vivo intestinal ischemia and reperfusion in the cat.

Free radical formation was studied with electron spin resonance during 2 h of intestinal ischemia in the cat, at a blood flow less than 5 ml.min-1.100 g-1, followed by 30-min reperfusion. A modification of the spin trapping technique was used to stabilize highly reactive free radicals. The rate of secondary radical formation was 0.32 +/- 0.06 mumol.min-1.100 g intestine-1 before ischemia and increased to a maximum of 0.66 +/- 0.09 mumol.min-1.100 g-1 during the first minutes of reperfusion (mean +/- SE, n = 5). This could be prevented either by maintaining intestinal blood flow at 8-15 ml.min-1.100 g-1, by administering allopurinol before and during ischemia, or by perfusing the intestinal lumen with an O2-saturated buffer solution during ischemia, resulting in maximum rates of radical production during reperfusion of 0.37 +/- 0.04 (n = 6), 0.33 +/- 0.04 (n = 5), and 0.39 +/- 0.13 mumol.min-1.100 g-1 (n = 5), respectively. The results demonstrate that free radicals are produced in the intestine during reperfusion after a period of reduced blood flow below a certain critical level, and that inhibition of xanthine oxidase and prevention of hypoxia will eliminate this radical production.

Animals↗

Screening and rescreening for colorectal cancer. A controlled trial of fecal occult blood testing in 27,700 subjects.

All inhabitants of the city of Göteborg who in 1982 were between 60 and 64 years of age (27,700) were randomly divided into a test and a control group. The 13,759 subjects in the test group were invited to perform Hemoccult II (Smith Kline Diagnostic, Sunnyvale, CA) fecal occult blood testing over 3 days and to repeat the testing after 16 to 22 months. At the first screening 9,040 (66%) completed the test, and 7,770 (58%) completed the test at the second screening. In the first screening the test group was divided into two subgroups in which the tests were rehydrated and unhydrated before development. All tests were rehydrated in the second screening; 1.9% and 5.8% of the tests were positive in the unhydrated and rehydrated subgroups, respectively. The number of diagnosed neoplasms in the first screening was significantly larger (P less than 0.01) in the rehydrated group compared to the unhydrated group, 50 and 24 neoplasms, respectively. Sixteen of 61 carcinomas in the test group were found in the interval between the two screenings, 19 of the carcinomas at the second screening, and ten among the nonresponders. Rehydration of the Hemoccult II test is a necessity. Significantly more carcinomas (61) were found in the test group compared to the control group (20). There was a trend toward favorable tumor staging in the test group compared to the control group.

Clinical Trials as Topic↗

Liver metabolic effects of intestinal shock and naloxone treatment in the rat.

The liver metabolic response of rats following a standardized intestinal shock, induced by applying a pressure of 120 cm water on the mesenteric vessels for 60 min, was studied. Immediately prior to the release of the pressure on the vessels saline or naloxone was given either as a single injection or as a continuous infusion. After the reperfusion of the intestine no early disturbances in liver metabolism were found as evidenced from the ATP, glucose and lactate levels in liver biopsies taken 15 min following reflow. Within 60 min of reflow reduction of ATP and increases of glucose and lactate levels occurred. There were no major hemodynamic or liver metabolic differences between saline- and naloxone-treated shocked rats. When saline or naloxone was given as a continuous infusion, the changes in liver metabolism were, however, less severe than those observed in the single injection situation pointing toward a non-specific effect of volume replacement rather than a blockade of opioid receptors. Hepatic hypoxia and/or cellular effects of "shock factors" could be mechanisms of pathophysiologic importance for the disturbed liver metabolism in this shock model.

Acid-Base Equilibrium↗

Evidence for the existence of an endogenous inhibitor of Na, K-ATPase in plasma from cats and rats.

Plasma samples from cats and rats were filtered through molecular filters to obtain a concentrate of the plasma molecules with a mass between 500 and 10,000. This concentrate was placed on a gel filtration column and eluted with a Tris buffer. Fractions corresponding to a molecular mass of 1500-2000 exhibited a marked Na,K-ATPase inhibitory 'activity', which was not influenced by heating to 95 degrees C for 10 min or by enzymatic degradation by pronase or trypsin.

Animals↗

Intestinal vascular obstruction shock in the rat. Effect of 2 dextran solutions on blood and plasma volumes, cardioinhibitory activity in blood and pulmonary platelet trapping.

Pathophysiologic mechanisms involved in the dextran effect on mortality in intestinal shock in rats were studied, using a standardized model for intestinal vascular obstruction. Both dextran 70 and dextran 40 (respective mean molecular weights 70 X 10(3) and 40 X 10(3) d) given to shocked rats reduced but did not prevent the cardioinhibitory action of intestinal venous plasma in vitro. Both dextrans prevented platelet trapping in the lungs. Reduction in blood and plasma volumes was found in shocked rats given saline or dextran 40, but not following dextran 70. These differences were found after 120 min, but not after 240 min, when all shocked groups had lower blood and plasma volumes than in non-shocked controls. The results indicate that several mechanisms influence the effect of dextran 70 on mortality of rats in intestinal shock. Previously observed difference in mortality rates after infusion of dextran 70 and dextran 40 could not be explained by mechanisms studied in this series of experiments.

Animals↗

Diagnostic accuracy of double-contrast enema and rectosigmoidoscopy in connection with faecal occult blood testing for the detection of rectosigmoid neoplasms.

Four hundred and fifty-eight consecutive subjects with a positive faecal guaiac test when screened for early detection of colorectal neoplasms were investigated with double-contrast enemas and rectosigmoidoscopy (60 cm). The results of these two methods were compared. The radiologists and endoscopists were unaware of the result of each others' examination at the time of their own investigation. Altogether ten subjects with carcinoma in the rectosigmoid area were found. The radiologists and endoscopists each overlooked four of these ten carcinomas and only four of the carcinomas were diagnosed with both methods. Fifty-six of one hundred and seven adenomas were 1 cm or larger in diameter and located in the rectum or the sigmoid colon. Thirteen of the fifty-six adenomas were missed by double contrast enema and ten by endoscopy and only thirty-three adenomas were diagnosed with both methods. Neoplasms in the rectum and the sigmoid colon are sometimes difficult to diagnose with both radiology and endoscopy. Rectosigmoidoscopy (60 cm) should therefore be used as a complement to double contrast enemas if this method is chosen for investigation of a patient with rectal bleeding.

Adenoma↗

Intestinal vascular obstruction in the cat. Right heart function in a shock model.

Cardiovascular function was studied in a model of intestinal vascular obstruction in cats. To measure right ventricular end diastolic pressure and maximal dP/dt, a tip transducer catheter was placed into the right ventricle. The intestinal vascular obstruction resulted in shock with decreases of blood pressure, cardiac output, and external cardiac work. Small intestinal mucosal lesions were found in all shocked cats. At an increased preload to the heart, right ventricular function was depressed in shocked cats. The model corresponds to one used earlier in the rat, where cardioinhibitory activity in venous blood was found in vitro. In this corresponding model of intestinal shock in the cat a depressed function of the right ventricle of the heart was found in vivo.

Animals↗

Effects of naloxone in intestinal shock in the rat.

The contribution of endogenous opioid peptides to the development of circulatory derangement in severe shock was studied using naloxone. A standardized intestinal shock was induced in rats by applying a pressure of 120 cm water on the mesenteric vessels for 60 min. The rats were then given either saline or naloxone. Mean arterial blood pressure improved and a less severe acidosis resulted in naloxone-treated animals compared to saline-treated. No differences were found in hematocrit, the degree of small intestinal mucosal lesions, or survival rates after 7 days comparing naloxone and saline treatment. Survival time increased after naloxone but not after saline treatment. The results support the hypothesis that endogenous opioid peptides contribute to cardiovascular collapse in intestinal shock.

Acid-Base Equilibrium↗

Mucosal lesions of the small intestine after intestinal vascular obstruction in the rat.

Small intestinal mucosal lesions, characteristically restricted to the villous tissue, have been described in shock states of different types. We have found this type of mucosal lesion in a standardized intestinal ischemia shock in rat. The pathophysiology of the mucosal lesion has been debated. In earlier work we noted a tenfold increase of platelets in the ischemic intestine. The importance of reperfusion and local platelet accumulation for the development of ischemic lesions in the intestinal mucosa was studied. Biopsy specimens taken immediately before and after reperfusion of the ischemic small intestine showed the same degree of mucosal lesion, i.e. total disintegration of the lamina propria. In thrombocytopenic rats subjected to intestinal ischemia, the severity of mucosal lesion was the same as in normothrombocytic rats. The results indirectly support the hypothesis of local villous oxygen deficit as the pathophysiologic mechanism leading to lesions of the small intestinal mucosa in shock.

Animals↗

The role of 5-hydroxytryptamine in the feline response to intravenous infusion of live E. coli.

A standardized septic shock was induced in cats by intravenous infusion of a live E. coli bacteria strain. The bacterial infusion induced a rapid haemodynamic response characterized mainly by a pulmonary arterial hypertension and a late phase characterized by systemic hypotension and hypodynamic circulation. Systemic arterial, pulmonary arterial, portal venous, left atrial pressures, max inspiratory-expiratory pressure difference in the trachea, aortic and intestinal blood flows were monitored. Arterial blood samples were taken for recording the number of circulating platelets and white blood cells and for determining the acid-base balance. The effect of pretreatment with ketanserin, a specific 5-hydroxytryptamine2 (5-HT2)-receptor blocker on these haemodynamic reactions was studied. In short term experiments on non-bacteriaemic control cats, ketanserin prevented the pulmonary hypertension induced by intravenous 5-HT infusions but not the increase in intestinal blood flow. Ketanserin induced a reduction of total peripheral (including intestinal) vascular resistance to blood flow but had no effect on aortic blood flow. After infusion of bacteria, ketanserin pretreated cats were more hypotensive due to a relative peripheral dilatation of the resistance vessels. Ketanserin pretreatment had no effect on the pulmonary vascular reactions, the tracheal pressure difference or the number of circulating platelets or white blood cells. Thus, except for a more pronounced hypotension early after bacterial infusion, ketanserin pretreatment did not influence the haemodynamic response. It is concluded that 5-HT is not of significant importance in the pathogenesis of the haemodynamic reactions following experimental bacteraemia.

Animals↗

The effects of 5-HT blockade in graded intestinal vascular obstruction in the rat.

Intestinal vascular obstruction with an obstruction pressure of 120 cm of water for one hour induces a 75% mortality in rats. The mortality is associated with intestinal mucosal lesions, release of cardiotoxic material to the intestinal venous blood and trapping of platelets in the lungs. The present series of experiments was performed to study the role of released serotonin in the pathogenesis of the circulatory collapse that follows in this shock model. This was done by pretreating rats subjected to standardized intestinal vascular obstruction with Ketanserin, a selective 5-HT2 receptor blocking agent. It was found that Ketanserin reduced the increase in hematocrit otherwise induced but had no significant effect on mortality, trapping of platelets or the intestinal mucosal lesions. It is concluded that serotonin is probably not of significant importance in the pathogenesis of the circulatory collapse following intestinal vascular obstruction.

Animals↗

An evaluation of the functional implications of the intestinal mucosal lesions in shock.

Small intestinal mucosal lesions are reported in clinical shock and are commonly found in experimental shock. Experimental series in which shock is induced by regional intestinal ischemia or IV infusion of live Escherichia coli in cats or by graded intestinal vascular occlusion in rats are described. In all series mucosal damage was related to pronounced hypotension or mortality. In the cat models myocardial dysfunction was demonstrated in vivo by IV volume load and recording of changes in left ventricular filling pressure as related to cardiac performance. Following intestinal ischemia in cats and intestinal vascular obstruction in rats the intestinal venous plasma was found to contain cardiotoxic factors when tested in vitro. It is proposed that the development of small intestinal mucosa lesions in shock tends to further aggravate hypotension by causing intestinal release of cardioinhibitory material.

Animals↗

Graded intestinal vascular obstruction. IV. An analysis of the pathophysiology in the development of refractory shock.

Pathophysiological mechanisms of importance for mortality in shock were studied using different modes of treatment in a standardized intestinal vascular obstruction model. In an untreated series the degree of intestinal mucosal damage, but not the increase in hematocrit, correlated to mortality. The importance of hypovolemia, instability of membranes, and metabolic blockage were studied in several series by giving saline, dextran 40, dextran 70, albumin, methylprednisolone, glucose, and glucose-insulin-potassium. Dextran 70 was the only agent which significantly reduced mortality--from 88 to 58%. This effect was, however, not due to hemodilution nor to prevention of mucosal lesions. In an additional series the effects of dextran 70 on intestinal electrolyte concentration, on pulmonary trapping of platelets, and on cardioinhibitory effects in vitro of intestinal venous plasma were evaluated in comparison with untreated shock. Dextran 70 prevented the electrolyte changes and platelet trapping in the lung, and the cardioinhibitory effect of intestinal venous plasma was reduced. A combination of these mechanisms may be of importance in producing mortality in this shock model.

Animals↗

Graded intestinal vascular obstruction. II. Effects of antibiotic pretreatment in the rat.

This study was performed to elucidate whether bacteria, or products of bacterial origin, could account for the circulatory collapse following a 1-hour intestinal vascular obstruction in the rat. Animals pretreated with clindamycin, in a way previously shown to induce characteristics otherwise found only in germ-free rats, were compared to controls pretreated with saline. Graded intestinal vascular obstruction was applied and four different pressure levels were used. Mortality increased with the applied pressure but there was no difference between the clindamycin-pretreated rats and controls. Hematocrit increased equally in all pressure levels and was not influenced by pretreatment. The amount of fluid lost from the serosal surface of the intestines was not correlated to the pretreatment used, the increase in hematocrit, or mortality. In the higher pressure levels, characteristic microscopic intestinal mucosal lesions were found in both series and the degree of mucosal damage correlated with increase mortality.

Animals↗

Graded intestinal vascular obstruction. III. An analysis of pathogenic mechanisms.

A standardized model allowing graded obstruction of the intestine and its vascular supply was used in rats. Application of high pressures (100 and 120 cm of water) has previously been found to induce high mortality and intestinal mucosal lesions. This study was performed to elucidate the possible importance of nervous depressor reflexes and release of cardiotoxic material in the pathogenesis of the induced circulatory collapse. Denervation of the intestines made the blood pressure reduction during the period of obstruction less pronounced. Intestinal venous plasma obtained following one hour of obstruction with high pressure had a significant inhibitory effect when tested on isolated rabbit papillary muscles as compared to plasma obtained following obstruction with lower pressure. Pretreatment with clindamycin had no effect on this variable. It is suggested that the release of cardiotoxic factors is one pathogenetic factor in the development of the circulatory collapse following intestinal shock.

Animals↗