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K Beckh

Publications and source records attributed to K Beckh.

At least 37 records · Page 2Linked to original sources

Effects of selective phosphodiesterase 3 inhibition in the perfused liver of the rat after endotoxin treatment.

1. This study was designed to investigate the role of rat phosphodiesterase 3 (RPDE3) in regulation of liver metabolism in sepsis. We studied the effects of the phosphodiesterase 3 inhibitor (PDI), enoximone, alone and in combination with regulating factors of hepatic carbohydrate metabolism and bile secretion in the perfused liver of rats treated 4 h earlier with endotoxin. In addition, cyclic AMP and cyclic GMP levels were determined in the effluate and bile by radio immunoassay methods. 2. After endotoxin treatment, infusion of enoximone at three concentrations (1 microM, 10 microM) resulted in an increased glucose output from -1.4 +/- 0.9 to 7.8 +/- 2.5 mumol l-1 20 min-1. Bile acid-independent bile flow increased also, in a dose-dependent manner. 3. In untreated livers, cyclic AMP release increased in the effluate from 1000 +/- 73 fmol g-1 min-1 to 1710 +/- 143 fmol g-1 min-1 when enoximone (10 microM) was administered. In bile from untreated livers, the level of cyclic AMP was also significantly increased by enoximone. After endotoxin treatment, the enoximone (10 microM) effect on cyclic AMP levels in effluate and bile was greatly reduced. Levels of cyclic GMP in the effluate and bile appeared unchanged in the presence of enoximone. 4. During co-infusion of glucagon (1 nM) and enoximone (10 microM), cyclic nucleotide levels in the effluate and bile of livers after endotoxin treatment were determined. In the effluate, cyclic AMP release increased from 827 +/- 144 fmol g-1 min-1 to 17802 +/- 2821 fmol g-1 min-1 when glucagon was administered. The presence of enoximone enhanced cyclic AMP further to 41696 +/- 920 fmol g-1 min-1. The same changes in cyclic AMP release were found in bile. Levels of cyclic GMP in the effluate and bile were not significantly affected by the administration of glucagon and the PDI. 5. Glucose release was determined during glucagon, sympathetic nerves stimulation and phenylephrine administration in the presence and absence of enoximone. The addition of enoximone to glucagon increased glucose release by 8.2 +/- 2.8 mumol g-1 20 min-1, without alteration of lactate balance. The PDI enhanced the glycogenolytic effects of nerve stimulation and of phenylephrine, accompanied by a reduction in lactate production. 6. Enoximone significantly enhanced the bile acid independent bile flow after glucagon, nerves stimulation and after administration of phenylephrine. Bile acid secretion was unaffected by the PDI. The vasoconstrictor effect of nerve stimulation was reduced by the PDI. 7. We conclude that endotoxin treatment reduces the ability of the PDI, enoximone, to increase cyclic AMP release in the perfused liver. The significant increase in cyclic AMP release after stimulation with glucagon and enoximone favours the view that RPDE3 is involved in the degradation of cyclic AMP in the liver after exposure to endotoxin. Additionally, the inhibition of the RPDE3 results in glucose release, vasodilatation and choleresis in endotoxin pretreated livers.

Animals↗

Intrahepatic high-grade malignant non-Hodgkin lymphoma in a patient with chronic hepatitis C infection.

A 61-year-old white female with chronic hepatitis C virus (HCV) infection first diagnosed in 1994 was admitted with two newly discovered lesions in the liver suspected to represent hepatocellular carcinoma. The alpha-1-fetoprotein (AFP) level was within normal limits and there was neither clinical nor sonographic evidence of liver cirrhosis. Fine needle aspiration, however, showed an high-grade malignant centroblastic non-Hodgkin lymphoma (NHL). Staging failed to confirm extrahepatic involvement. Both a cryoglobulinemia and HIV infection were ruled out. Although the coincidence of HCV infection and NHL is not well recognized, recent studies have indicated an increased incidence of NHL and hepatitis C in up to 38% of patients with cryoglobulinemia. In these patients, the diagnosis is always one of a low-grade lymphoma. Based on its lymphoproliferative characteristics, an etiologic role for HCV in the development of NHL has been discussed, though the exact pathogenesis remains unclear.

Biopsy↗

The role of nitric oxide in hemodynamic and metabolic alterations induced by prostaglandin F2 alpha in the perfused rat liver.

In the liver prostaglandins have been shown to be potent regulators of portal blood flow, carbohydrate metabolism and bile secretion. It is not known whether these effects represent a direct action of prostaglandins, and it has been suggested that nitric oxide (NO) might be a critical mediator for prostaglandin induced hepatic events. We have studied whether nitric oxide formation or inhibition alters the action of prostaglandin F2 alpha (PG F2 alpha) in a single-pass liver perfusion model. The liver of untreated rats (constitutive NO-synthase) or after pretreatment with endotoxin (inducible form of NO-synthase) was perfused at a constant pressure via the portal vein. Effluate were collected in 1-min intervals and bile in 5-min intervals. In both groups the addition of PG F2 alpha (10 microM) to the perfusate for 5 min resulted in a significant increase of glucose and lactate production, and in a significant decrease in portal blood flow (-0.56 +/- 0.04 ml/g per min), in bile flow (-60.7%) and in bile acid release (-60.6%). Inhibition of NO synthase by adding NG-monomethyl-L-arginine (L-NMMA, 100 microM) to the perfusate did not affect any of the alterations induced by PG F2 alpha. Substitution of the endogenous substrate for the NO synthase L-arginine (500 microM) in the perfusate completely prevented the hemodynamic alterations induced by PG F2 alpha in endotoxin pretreated livers and limited the flow reduction (0.15 +/- 0.04 ml/g per min) in the untreated group. The substitution of L-arginine in the perfusate of endotoxin pretreated livers raised nitrite (from 1.5 +/- 0.3 to 3.6 +/- 0.7 nmol/g per min) and urea release (from 65 +/- 25 to 294 +/- 68 nmol/g per min), but had no effect on any of the other metabolic parameters and bile secretion. We conclude that PG F2 alpha increases glucose and lactate production in the perfused rat liver and decreases portal flow bile secretion. The metabolic effects induced by PG F2 alpha appear to be independent of NO mediation and hemodynamic alterations. Portal flow alone can be influenced by endogenous NO formation.

Animals↗

Effect of extracorporeal shock-wave lithotripsy on gallbladder emptying in patients with solitary and multiple gallbladder stones.

In a prospective study, we investigated the effect of extracorporeal shock-wave lithotripsy (ESWL) on gallbladder contractility and on fasting and residual gallbladder volume in patients with solitary and multiple gallbladder stones with stone densities < 100 Hounsfield units (HU) and adequate gallbladder function. Twenty-five patients (seven males and 18 females, mean age 48.5 +/- 11.7 years) treated with ESWL were assigned to either group I, consisting of 13 patients with solitary stones < 20 mm diameter, or group II, including patients with two to three stones and maximum stone diameter of 30 mm. ESWL was performed with the MPL 9000 lithotripter. Gallbladder ejection fraction was determined using the method of Dodds after a 12-hr fast and following application of a standard stimulative meal. Gallbladder volume was measured by ultrasound over 90 min at 10-min intervals before ESWL, then at 1, 30, 120, and 210 days after ESWL. At 24 hr after ESWL, residual gallbladder volume increased in group I from 7.4 ml to 13.9 ml (P = 0.0567) and in group II from 6.5 ml to 20.2 ml (P = 0.0076). Thereafter, residual volumes returned to pre-ESWL levels. In group II, post-ESWL fasting volumes were significantly increased over initial values at all time intervals. Correspondingly, only at 24 hr after ESWL, ejection fractions decreased from 73.1% to 64.9% in group I and from 76.5% to 62.7% in group II. No statistically significant differences in gallbladder contractility between the two groups were observed at any point of the follow-up period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diagnosis of Echinococcus multilocularis infection by reverse-transcription polymerase chain reaction.

Alveolar echinococcosis is a life-threatening parasitosis occurring in countries in the Northern hemisphere. The diagnosis of an Echinococcus multilocularis infection is routinely performed by radiological techniques and by the detection of specific antibodies in the sera of infected patients. However, because serodiagnosis fails in 5%-10% and radiological techniques are difficult to interpret in some cases, we developed a polymerase chain reaction for the detection of echinococcal-specific messenger RNA from fine-needle biopsy specimens. This technique was applied to the diagnosis of alveolar echinococcosis in a 20-year-old seronegative woman. Detection of messenger RNA not only allowed the diagnosis of echinococcal disease but also proved to be a reliable measure for determining the efficacy of an antiparasitic therapy.

Adult↗

Enhancement of hepatic glucose release and bile flow by the phosphodiesterase-III-inhibitor enoximone in the perfused rat liver.

The use of phosphodiesterase-III-inhibitors (PDI) as inotropic substances in the treatment of cardiac failure can be associated with hyperglycaemia. This phenomenon could be caused by hepatic events induced by PDI. The purpose of our study was to investigate the effects of the PDI enoximone on hepatic carbohydrate metabolism and bile flow. In the rat liver perfusion model, hepatic glucose and lactate production, portal flow and bile flow were determined. Administration of enoximone (1, 10, 100 microM) increased hepatic glucose output and bile acid-independent bile flow in a dose-dependent manner. The PDI enhanced the glycogenolytic effects of glucagon (from 15.7 to 38.6 mumol glucose/g/20 min), of epinephrine (from 7.1 to 38.7 mumol glucose/g/20 min), of norepinephrine (from 9.8 to 32 mumol/g/20 min) and of phenylephrine (from 25.5 to 40.8 mumol glucose/g/20 min). Furthermore, lactate production was significantly reduced by enoximone. The effect of epinephrine and phenylephrine on portal flow was blocked or diminished by enoximone administration. In summary, it was shown that the PDI enoximone is able to enhance hepatic glucose production. Bile acid-independent bile flow was increased by the inhibition of phosphodiesterase-III. The effects of enoximone and glycogenolytic hormones on glucose release were synergistic. The vasoconstrictive action of catecholamines was reduced or completely prevented by enoximone. In conclusion, enoximone has glycogenolytic, vasodilatory and choleretic properties in the liver.

Animals↗

[Endoscopic and surgical therapy of hemorrhagic duodenal and stomach ulcer].

The aim of this prospective clinical study was to evaluate whether a combination of the endoscopic hemostasis together with fibrin sealing and consecutive conservative therapy could reduce the frequency of recurrent bleedings, thus the number of operations without adversely influencing the prognosis of the disease. 134 patients admitted to the surgical and medical hospital of the University of Ulm between 1/1990 and 1/1992 with bleeding gastroduodenal ulcers took part in this study. All patients were treated endoscopically by hypertonic saline solution plus epinephrine and fibrin sealant. If initial endoscopic hemostasis was not achieved patients were operated within 6 h after admission. Patients with successful initial endoscopic hemostasis were treated conservatively and underwent control endoscopy after 24 and 48 h. In 23 patients the initial endoscopic hemostasis was not successful, they had to be operated immediately. In 111 patients endoscopic hemostasis was achieved, 20% of these patients had acute bleeding ulcers (Forrest Ia, b), 66% showed stigmata of fresh bleedings (Forrest-IIa bleeding). Primary endoscopic hemostasis was achieved in 85.6% of all patients treated, 14.4% of patients (n = 16) developed a recurrent bleeding during the observation period verified by gastroscopy. Half of these patients had an acute bleeding at the first gastroscopy (Forrest-Ia, Forrest-Ib bleeding). Recurrent bleeding became apparent between day 1 and 6 after admission to the hospital. Two patients refused surgical intervention, the other 14 were operated immediately.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Low pretreatment gallbladder stone densities at computed tomography predict rapid stone clearance following extracorporeal shock wave lithotripsy.

The importance of routine computer tomographic (CT) stone analysis in optimizing the therapeutic outcome after extracorporeal shock wave lithotripsy (ESWL) remains controversial. The aim of the present prospective study was to seek a correlation between CT findings and stone clearance rates after ESWL in 159 patients. One hundred fifty-nine symptomatic patients (116 females, 43 males) with solitary radiolucent gallbladder stones underwent CT for stone analysis before lithotripsy. In Group I (<50 HU, n=104), stone clearance was achieved in 55.8% of patients within 6.11+/- 6.95 months; in Group II (51-100 HU, n = 28), in 50.0% of patients within 11.2 +/- 10.3 months; in Group III (>100 HU, n = 27) in 29.7% of patients within 9.60 +/- 6.96 months. The mean follow-up period was 17.9 +/- 10.0 months. Patients in Group I showed a significantly higher rate of stone clearance than those in Groups II and III (p < 0.001) as well as a significantly shorter time for the achievement of total stone clearance than either of the other groups (p < 0.001). The authors conclude that CT stone analysis provides a more accurate method of selecting patients suitable for ESWL and may be of importance in predicting the expected length of time for achieving complete stone clearance.

Absorptiometry, Photon↗

Direct regulation of bile secretion by prostaglandins in perfused rat liver.

Prostaglandins have been postulated to act as mediators of intercellular communication between liver cell populations in the regulation of liver carbohydrate metabolism. Their role in the regulation of bile secretion is rather unclear. The action of prostaglandins on bile flow and bile acid secretion was studied in the in situ perfused rat liver. Infusion of prostaglandin F2 alpha resulted in reduction of bile flow and bile acid secretion. In addition, portal flow was diminished and glucose output was increased. The parameters were altered in a dose-dependent manner. The effects of prostaglandins D2 and E2 were similar but less potent than those of prostaglandin F2 alpha. To separate the effects on portal flow and bile flow, we used nitroprusside and nifedipine to suppress the hemodynamic changes induced by prostaglandins. In the presence of these substances, the alterations of bile flow and bile acid secretion were even more pronounced. Infusion of inhibitors of prostaglandin synthesis increased bile flow. In conclusion, prostaglandins F2 alpha, D2 and E2 reduce bile flow and bile acid secretion. These effects are independent of hemodynamic changes. Suppression of synthesis of endogenous prostaglandins by inhibitors of prostaglandin synthesis reversed these effects. Prostaglandins are involved in the regulation of bile flow and bile acid secretion.

Animals↗

Low hepatic clearance of peptide YY (PYY) in the perfused rat liver.

The hepatic clearance rate and secretion rate mainly determine peripheral plasma concentrations of regulatory peptides released from the gastrointestinal tract. In the present study hepatic extraction of peptide YY (PYY) during a single passage was investigated in the in situ perfused rat liver excluding modulating actions of circulating hormones. During perfusion of low amounts of PYY (50, 100, 500 pmol l-1), peptide concentrations in the portal vein (5.1 +/- 4.6, 98.1 +/- 2.6, 558 +/- 13.6 pmol l-1) and in the hepatic vein (50.2 +/- 1.4, 88.6 +/- 2.2, 503 +/- 18.1 pmol l-1 was only 22.1%. PYY had no influence on hepatic glucose and lactate production, portal flow as well as bile flow and bile acid secretion at these concentrations. PYY seems to traverse the liver almost intact and reaches the target organs without any significant hepatic extraction. Concomitant studies on metabolic and excretory functions of the liver showed no effect of PYY.

Animals↗

Regulation of bile secretion by sympathetic nerves in perfused rat liver.

Although the biliary system is innervated by the autonomic nervous system, little is known about the regulation of bile secretion by hepatic nerves. In rat liver perfused in situ with constant pressure and erythrocyte-free medium, hepatic nerves were electrically stimulated (20 V, 20 Hz, 2 ms) by a platinum electrode placed around the hepatic artery and portal vein. Nerve stimulation caused a decrease in bile flow, bile acid secretion, and portal flow. The nerve effects on bile secretion were mediated via alpha 1-receptors. In this system, artificial reduction of perfusion flow by 30% led to a similar decrease of bile flow. In perfusion systems with constant flow and erythrocyte-free medium or with constant pressure and erythrocyte-containing medium, the nerve effects were reproduced despite the altered hemodynamics and the increased oxygen supply. In addition, partial inhibition by sodium nitroprusside of the nerve-induced reduction of portal flow had little effect on the reduction in bile secretion. In conclusion, a direct effect on bile formation was suggested. Yet an additional role of a vascular-mediated effect could not definitively be excluded. With the use of inhibitors of prostanoid synthesis the nerve effects on bile secretion were markedly reduced, suggesting a mediating or modulating role of prostanoids.

Animals↗

CCK receptor antagonist loxiglumide alters uptake of CCK in perfused liver and pancreatic acini of the rat.

The aim of the present study was to analyze the effect of the specific cholecystokinin (CCK) receptor antagonist loxiglumide on hepatic and pancreatic processing of CCK-8 and the CCK analogue cerulein. Rat liver perfusion was performed in a non-recirculating system. CCK concentrations were measured by radioimmunoassay in perfusates from the inflow cannula (portal vein) and the outflow cannula (hepatic vein). In rat pancreatic acini, the effect of loxiglumide on internalization and surface-binding of radiolabelled CCK-8 was determined. Cerulein (20 nM, 2 nM) was extracted in a single pass through the liver by 29.7 and 25.4%, respectively. The hepatic uptake of CCK-8 (50 pM, 2 nM) was more than 90 and 89.9%, respectively. Loxiglumide drastically inhibited hepatic extraction of both peptides and reduced internalization of 125I-CCK-8 in pancreatic acini dose dependently by 39-93%. These results demonstrate that the potent CCK receptor antagonist loxiglumide significantly decreased CCK uptake by the liver and pancreas.

Animals↗

Manifestation of acute intermittent porphyria in patients with chronic inflammatory bowel disease.

In a retrospective study covering 411 acute intermittent porphyria patients, four cases of a coincidence with Crohn's disease or ulcerative colitis were found. Their courses of disease confirmed that patients with chronic inflammatory bowel disease have a higher risk for acute porphyria manifestation. Both malnutrition (glycopenic induction) and sulphasalazine (drug-induced exacerbation) are known as triggering factors for acute porphyric states. Furthermore, diagnosis of acute intermittent porphyria tends to be much more difficult in such cases, as the acute phases of abdominal pain are likely to be associated with the enteral disease process. A delay of diagnosis and therapy of acute hepatic porphyria, however, may endanger the patient by pareses, which could be irreversible or even lethal. Therefore, whenever there is suspicion of a coinciding acute porphyria, urinary screening tests for porphyria should immediately be performed and, if a coinciding acute hepatic porphyria is diagnosed, porphyrogenic drugs like sulphasalazine should be avoided in treatment of chronic inflammatory bowel disease.

Acute Disease↗

[Percutaneous drainage of liver and splenic abscess].

42 patients with solitary (n = 34) and multiple (n = 8) abscesses of the liver (n = 36) and the spleen (n = 6) were treated with ultrasound guided percutaneous interventions. 38 patients (90%) underwent a total of 97 closed abscess aspirations using needles of 0.9 and 1.3 mm in diameter. In 4 cases (10%) percutaneous catheter drainage was performed. Intravenous antibiotics were used in all cases. Those patients with closed abscess aspiration additionally received local injection of aminoglycosides into the cavity. 40 out of the 42 patients could be treated successfully by percutaneous methods for a cure rate of 95.2%. Percutaneous drainage failure occurred in 2.4%. One patient with multiple liver abscesses and catheter drainage died from myocardial infarction (hospital mortality 2.4%). Complications of ultrasound-guided interventions included two minor bleedings, requiring no therapy, and one pleural empyema (complication rate 7.1%). There were no treatment related lethal complications. These results indicate that abscesses of the liver and the spleen up to 10 cm in diameter can be effectively treated by closed (repetitive) needle aspiration and antibiotic therapy with a relatively low rate of complications. About half of our patients with abscesses of more than 10 cm received percutaneous catheter drainage. On the basis of our experience surgical drainage of liver abscesses and splenectomy in splenic abscesses should be restricted to those cases with percutaneous drainage failure.

Abscess↗

[The coincidence of acute intermittent porphyria and Crohn's disease].

In the course of four weeks, tetraparesis developed in a 28-year-old man with Crohn's disease for the last six years, treated with glucocorticoids and sulphasalazine. The cause was acute intermittent porphyria which had been previously overlooked because of the similar abdominal symptoms of Crohn's disease. Treatment with glucose, propranolol and haemarginate failed to bring about any improvement, but there was a remission of the porphyria. This case demonstrates that diagnosis of acute intermittent porphyria in the presence of Crohn's disease is difficult, and if delayed therapeutic measures in the face of persisting neurological complications are of little benefit.

Acute Disease↗

Activation of glycogenolysis by stimulation of the hepatic nerves in perfused livers of guinea pig and tree shrew as compared to rat: differences in the mode of action.

A study on the metabolic and hemodynamic actions of hepatic nerve stimulation in the perfused liver of guinea pig and tree shrew as compared to rat was performed, since the density of liver innervation was reported to be different. 1) Nerve stimulation resulted in an increase in glucose release and decrease in lactate uptake or in a shift to output as well as a decrease in portal flow in all three species. The change in glucose output was very similar, that in lactate balance and flow was smaller in tree shrew than in guinea pig and rat. Apparently, the metabolic and hemodynamic changes did not reflect the different densities of liver innervation. 2) The overflow of the neurotransmitter noradrenaline into the hepatic vein differed very clearly in the three animals. In the guinea pig and tree shrew the maximal increase in noradrenaline concentration measured in the effluent was about 6-7-fold higher than in the rat. 3) The content of noradrenaline in the liver in vivo was about five-fold higher in the guinea pig and again another four-fold higher in the tree shrew than in the rat. The contents of adrenaline and dopamine were very low in comparison to those of noradrenaline. The different hepatic noradrenaline contents of the three species investigated are in line with the anatomical findings on the different innervation density. 4) Inhibitors of eicosanoid synthesis reduced the nerve stimulation-dependent metabolic and hemodynamic alterations in guinea pig liver as in rat liver indicating a similar mechanism in these species. Apparently, prostaglandins might be involved as mediators or modulators of nerve actions also in the more densely innervated guinea pig liver and not only in the less densely innervated rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗