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E Köhler

Publications and source records attributed to E Köhler.

At least 73 records · Page 4Linked to original sources

Circulating somatostatin. Physiological regulator of pancreatic function?

The present study was designed to determine whether somatostatin is released into the circulation in sufficient amounts to regulate exocrine and endocrine pancreatic function and to evaluate the possible role of somatostatin as a hormonal regulator of the pancreas. Mean plasma somatostatin levels (SLI) increased from 11 +/- 2 pmol liter-1 to peak concentrations of 18 +/- 2 in six healthy male volunteers after a steak meal (P less than 0.05). Infusion of somatostatin inhibited hormone-induced exocrine pancreatic secretion and suppressed cerulein-stimulated pancreatic polypeptide (PP) secretion, but did not significantly change arginine-stimulated insulin and glucagon release at mean plasma somatostatin concentrations within the range seen after a meal. The amount of somatostatin released after a meal thus was of sufficient magnitude to inhibit exocrine pancreatic function and PP release. On the other hand, basal and arginine-stimulated glucagon and insulin secretions were not significantly affected by these plasma concentrations of intravenous somatostatin suggesting that the exocrine pancreas might be more sensitive to somatostatin than the islet cells. We conclude that somatostatin in concentrations within the range seen after a meal is a potent inhibitor of stimulated acinar cell function in man. The findings support the hypothesis that somatostatin acts as a true hormonal regulator.

Adult↗

Effect of a new somatostatin analogue on pancreatic function in healthy volunteers.

We studied the effect of four graded doses of SMS 201-995, a synthetic octapeptide somatostatin analogue (27, 80, 240, and 720 ng/kg/h) on the basal and secretin-plus-cerulein-stimulated exocrine pancreatic function and pancreatic polypeptide (PP) release in five healthy volunteers. Duodenal fluid secretion and bicarbonate output under basal and stimulated conditions were not significantly affected by any dose of SMS. The basal and stimulated enzyme secretion were decreased in a non-dose-dependent manner by all SMS doses used in the study and showed a 75% inhibition of the secretin-plus-cerulein-stimulated trypsin and amylase output. The cerulein-stimulated PP release was significantly suppressed by all four SMS doses. SMS appears to be a strong inhibitor of pancreatic enzyme secretion, at the same time affecting the PP release.

Adult↗

Effect of circulating somatostatin on exocrine pancreatic secretion in conscious dogs.

We determined the effects of exogenous somatostatin-14 (100 and 200 ng/kg/h; mimicking postprandial somatostatin concentrations) on pancreatic responses to a background infusion of secretion in combination with graded doses of CCK-8 in conscious dogs with chronic gastric and duodenal fistulas. The lower dose of somatostatin-14 (S-14), which produced S-14 plasma levels lower than measured after a meal, did not change basal or stimulated pancreatic secretion. The upper dose of S-14, which produced plasma S-14 concentrations slightly above the postprandial range, caused inhibition of pancreatic fluid and protein secretion to low doses of CCK-8 (p less than 0.05). The inhibition was surmountable with higher doses of CCK-8. We interpret these data as indicating that circulating S-14 is not an important hormonal regulator of exocrine pancreatic secretion.

Animals↗

What is the maximal effective dose of caerulein in stimulating pancreatic secretion in man?

The pancreatic exocrine secretory response to increasing doses of exogenous caerulein with and without a background infusion of secretin was studied in 5 healthy volunteers. Caerulein over a full range of doses (2.3-37 pmol/kg/h) produced increasing enzyme secretion up to 18.5 pmol/kg/h, whereas 37 pmol/kg/h was clearly supramaximal and caused submaximal enzyme release. We conclude that maximal pancreatic enzyme secretion is achieved with lower caerulein doses than generally used in pancreatic function tests.

Adult↗

Human pharmacological effects of SMS 201-995 on gastric secretion.

The inhibition of pentagastrin-stimulated-(3 micrograms kg-1 h-1) gastric acid secretion by various doses of intravenous and subcutaneous SMS 201-995, a somatostatin analogue, was investigated in healthy volunteers by means of gastric aspiration, using phenol red as a volume marker. The intravenous doses were compared with the standard dose of somatostatin-14, 3.5 micrograms kg-1 h-1. Similarly, SMS 201-995-induced inhibition of gastric acid secretion was compared with that of exocrine pancreatic secretion assessed by gastroduodenal aspiration. The results can be summarized as follows: SMS 201-995 is a potent inhibitor of gastric acid secretion, exerting near maximal inhibition at a dose of greater than or equal to 0.56 micrograms kg-1 h-1. Near maximal inhibition equals that achieved with SST-14 (3.5 micrograms kg-1 h-1). Pancreatic enzyme secretion appears to be strongly inhibited by lower doses of SMS 201-995 than gastric secretion. Single subcutaneous injections of SMS 201-995 produce an inhibition of gastric acid secretion lasting for many hours. Near maximal inhibition was obtained with a dose of 100 micrograms.

Adult↗

The frequency of islet cell surface antibodies and antibody-dependent cell-mediated cytotoxicity (ADCC) of mononuclear cells in HLA-typed patients with high diabetes risk.

To evaluate the significance of ICSA as a prognostic marker for the development of type I diabetes we investigated 66 subjects with first degree relatives of type I (47) and type II (9) diabetes as well as subjects with anamnestical data suggestive of diabetes. Patients were studied for glucose tolerance (oGTT) and IRI-response, ICSA (indirect fluorescence of living rat islet cell suspensions), ADCC (specific 51Cr-release of serum pretreated neonatal rat islets elicited by mononuclear cells) and HLA-antigens. 23 subjects revealed normal glucose tolerance, 17 impaired glucose tolerance and 26 had a prevoius abnormality. The incidence of ICSA varied between 46 and 53 per cent, that of positive ADCC between 22 and 56 per cent, both being highest in subjects with IGT. 87 per cent of all patients revealed diabetes associated HLA-antigens. We found no correlation of ICSA with glucose tolerance, IRI-response, ADCC and HLA-antigens. In conclusion it can be said that ICSA are present in a high percentage in patients with high diabetes risk but their predictive role as a marker for the manifestation must be elucidated in follow-up studies.

Adolescent↗

Impaired hormonal regulation of lipolysis and the interference with adenosine in adipose tissue from hyperglycemic sand rats in vitro.

Sand rats (Psammomys obesus) developed in response to different food intake various states of hyperglycemia and hyperinsulinism. 12 normo- and 10 hyperglycemic animals were selected by means of a weekly control of plasma glucose and plasma insulin over a period of 12 weeks after separation from the mother. During this time also the development of body weight gain was checked. In both groups of rats the hormonal regulation of glycerol release by incubated adipose tissue was investigated. In any case, the fat tissue from hyperglycemic sand rats showed a lower lipolytic responsiveness to noradrenaline stimulation than that of their normoglycemic controls. This correlates well with previous results in hyperglycemic sand rats in which the catecholamine-stimulated cAMP production was disturbed (Knospe and Köhler 1981). Degradation of released adenosine by addition of adenosine deaminase significantly enhanced the noradrenaline action on glycerol release in both groups of sand rats. Even though the noradrenaline-stimulated lipolytic activity of adipose tissue from normo- and hyperglycemic animals was enhanced in the presence of adenosine deaminase, the hormone resistance of adipose tissue from hyperglycemic sand rats was nevertheless not abolished. The theophylline-mediated adenosine receptor blockade gave further evidence that particularly endogenous adenosine released during incubation of adipose tissue from sand rats inhibited the noradrenaline action on lipolysis. The antilipolytic action of insulin on glycerol release is negligibly low in normoglycemic as well as hyperglycemic sand rats. The degradation of adenosine by adenosine deaminase failed to improve the insulin action. Adenosine addition completely blocked the stimulating effects of noradrenaline on glycerol release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Antibody-dependent cell-mediated cytotoxicity of mononuclear cells against Langerhans islets of Wistar rats in normal man and in patients at diabetes risk.

Antibody-dependent cell-mediated cytotoxicity against pancreatic islets was investigated in 13 newly diagnosed insulin-dependent diabetics, in 38 patients at high risk for the disease and in 20 age-matched healthy controls. For this purpose 51Cr-labeled neonatal rat pancreatic islets incubated with the specific anti-rat islet cell antiserum 339 or with serum of the lymphocyte donors were used as targets. The antibody-mediated cytotoxic activity of mononuclear cells was evaluated from the specific chromium release after 6 h exposure of pretreated islets to the effector cells. The specific cytotoxic effect of mononuclear cells from healthy controls on pancreatic islets pretreated with serum is weak. ADCC mediated by the specific antirat islet cell antiserum is significantly increased in 54% of newly diagnosed diabetics as well as in 32% of patients at high risk for insulin-dependent diabetes mellitus. 46% of the newly diagnosed diabetics were also ADCC-positive when their own serum was used for the pretreatment of islets, regardless of whether they were islet cell antibody- or islet cell surface antibody positive or not. Subsets of mononuclear cells (non E-rosette-forming cells, high affinity E-rosette-forming cells, low affinity E-rosette-forming cells) were prepared and their cytotoxic potential was analysed in patients with positive ADCC test results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[2-dimensional echocardiography].

In the mid-seventies, echocardiographic devices for clinical use have been developed to generate real-time cross-sectional images of the heart with a rate of about 30 frames per second. This technique improved the diagnostic power of M-mode echocardiography by visualizing the chambers, valves and walls of the heart in a variety of planes. Cross-sectional echocardiography provides important information for example in the evaluation of left ventricular function, diagnosis of congenital heart diseases, endocarditis, hypertrophic cardiomyopathies, cardiac tumors and others, that cannot be determined adequately by M-mode echocardiography alone.

Cardiomyopathy, Hypertrophic↗

[Significance of caffeine values in serum, saliva and urine--determination of pharmacokinetic data by non-invasive methods in psychopharmacologic studies].

For psychopharmacological studies with caffeine two reliable non-invasive methods are available in order to determine pharmacokinetic parameters simultaneously with psychometric tests, without any appreciable impairment of the experimental subject. The investigation were performed in 13 healthy volunteers. Caffeine was determined in serum, saliva and urine. The caffeine level in saliva was about 70% of that in serum, corresponding to the percentage freely dissolved in serum. A good correlation was found to exist between elimination half-lives for serum and saliva levels (r = 0.9702) as well as serum and urine values (r = 0.8784). The amount of caffeine excreted in urine in its unmetabolized form was 1.1 +/- 0.2% of the dose administered. Furthermore, the saliva level was seen to represent the serum level on a broad scale. Sixty minutes after oral uptake, saliva levels were falsified due to adsorption of caffeine to the buccal mucosa. The special pattern of the saliva level during the phases of absorption and distribution is discussed.

Administration, Oral↗

Differential diagnosis of hypertrophic cardiomyopathies: typical (subaortic) hypertrophic obstructive cardiomyopathy, atypical (mid-ventricular) hypertrophic obstructive cardiomyopathy and hypertrophic non-obstructive cardiomyopathy.

Previous clinical studies in patients with hypertrophic cardiomyopathies predominantly comprised patients with typical subaortic HOCM and in many other studies patients with 'hypertrophic' cardiomyopathies were investigated; i.e. no distinction was made between patients with the typical obstructive, the atypical obstructive and the non-obstructive forms of hypertrophic cardiomyopathy. In addition, in the more differentiated studies, the differential diagnosis between HOCM and HNCM was based mainly on the presence and absence of the subaortic pressure gradient. This is also true for the clinical characterization of both types of hypertrophic cardiomyopathy. Finally, diagnostic descriptions of atypical (mid-ventricular) HOCM exist only in the form of case reports, i.e. they are not based on observations in a large number of patients. Therefore a comparative study in 353 patients with hypertrophic cardiomyopathies was designed to characterize the clinical picture of patients with HNCM and with atypical HOCM in relation to typical HOCM with special reference to the differential diagnosis. The study revealed a profoundly different diagnostic profile of the three subsets of hypertrophic cardiomyopathies. The distinction between the three subsets may serve as a more differentiated basis for clinical studies related to diagnosis, therapeutic approaches, long-term follow-up observations and prognostic evaluation of patients with hypertrophic cardiomyopathies.

Adolescent↗

[Clinical aspects, course and prognosis of various forms of hypertrophic cardiomyopathy].

To characterize the different types of hypertrophic cardiomyopathy [typical (subaortic) hypertrophic obstructive cardiomyopathy (HOCM) (n = 235), atypical (midventricular or apical) HOCM (n = 33), and hypertrophic nonobstructive cardiomyopathy (HNCM) (n = 85)], studies of the clinical picture, course, and prognosis were performed in 353 patients. Clinical picture. There were found to be distinct differences between the diseases in terms of incidence, symptoms, findings at auscultation, carotid pulse tracings, ECG (incidence of abnormal negative T-waves), and echocardiography. Echochardiography proved to be diagnostically less specific than invasive methods, however, and in particular often failed to distinguish between atypical HOCM and HNCM. Clinical course. There was no evidence of a change from one form of hypertrophic cardiomyopathy to the other. The Sokolow-Lyon index in the ECG did not increase in any group. The rate of complications (endocarditis, systemic emboli) varied between 0.61 and 1.28 events per 100 patient years. Only 7.4%-23.5% of patients with HOCM improved as a result of conservative treatment, compared to 83%-87.5% of surgical patients. In addition, the rate of postoperative syncope was reduced by 90%. Prognosis. 90 patients were operated on. Operative mortality in typical HOCM was 4.5% over the last 5 years. If this is disregarded, the cumulative survival rates are significantly higher in surgical patients with typical HOCM than in those treated conservatively. The data confirm surgical treatment to be the therapy of choice in patients with HOCM refractory to conservative treatment. The prognosis seems to be improved by operation.

Adult↗

[Effect of systolic-diastolic displacement of the base of the heart on M-mode echocardiography].

M-mode-beam detects only structures moving in a direction parallel to them. The purpose of this study was to examine those movements of the heart which cannot be recorded by M-mode. We examined ten normals, ten patients with left ventricular volume overload, and ten patients with left ventricular pressure overload by M-mode and two-dimensional echocardiography (parasternal long axis view) simultaneously. We looked at the movement of particular structures during the cardiac cycle. A systolic movement of the base of the heart toward the apex is perpendicular to the M-mode beam and can therefore not be recorded. This shift is marked in patients with volume overload. End-diastolic diameter was measured too far apically in relation to the end-systolic diameter. We measured the amount of this dislocation of the end-diastolic diameter and corrected it. The new end-diastolic diameter was lower than the usual one. The difference was: -2.2 +/- 1.9 mm in normals (p less than 0.02); -6.9 +/- 2.6 mm in left ventricular volume overload (p less than 0.005); and -0.8 +/- 2.2 mm in pressure overload (n.s.). The overestimation of the fractional shortening was 12.4 +/- 13.3% in normals (p less than 0.02) and 21.4 +/- 7.4% in volume overload (p less than 0.005), expressed as a percentage. In conclusion, the static M-mode beam does not cross the same parts of the heart during systole and diastole because of movements of the base of the heart in relation to the beam. Misinterpretations of left ventricular function are the consequence. These depend on the extent of the movements and the configuration of the left ventricle.

Adolescent↗

[Left bundle-branch block: inferences from ventricular septal motion in the echocardiogram concerning left ventricular function].

In left bundle branch block (LBBB) abnormal motions of the interventricular septum (IVS) are well known in echocardiography. We asked: (1) Is it possible to distinguish several kinds of IVS motion in the M-mode echocardiogram and (2) Is there any correlation with clinical data? We analyzed the M-mode echocardiograms of 100 patients in whom LBBB had been diagnosed, either alone or in connection with latent or dilatative cardiomyopathy. All showed a posterior motion of the IVS in early systole. Three kinds of motion could subsequently be identified: anterior (= paradox) (18%, type A), posterior (= normal) (58%, type B), and intermediate (24%, type AB). Group A had a more severe clinical stage of disease than group B (p less than 0.0005); ECG showed a longer QRS complex (p less than 0.0005), X-ray a bigger cardiac-thoracic ratio (p less than 0.0005), and M-mode-echocardiogram larger left ventricular end-diastolic diameters (p less than 0.025). Mean values of group AB fell between those of group A and those of group B. Moreover, ejection fraction at left ventricular angiography was lower in group A (52.0%) than in groups AB (58.0%) and B (62.9%) (A vs B p less than 0.005), and mean pulmonary artery pressure on exertion was higher in group A (43.3 mm Hg) than in groups AB (38.1 mm Hg) and B (28.7 mm Hg) (A vs. B p less than 0.0005). For types A and AB taken together, the likelihood of abnormal pulmonary artery pressure on exertion was 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Bundle-Branch Block↗