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Biomedical subjects

G Brunner

Publications and source records attributed to G Brunner.

At least 37 records · Page 2Linked to original sources
PubMed1989

[Portal hypertension and chronic arsenic exposure. A differential diagnostic challenge].

We are reporting on a 62 year old female patient with portal hypertension (splenomegaly, esophageal varicosis) without signs of liver cirrhosis, who was hospitalized for sclerotherapy of her esophageal varices. Physical examination showed up palmar- and plantar hyperkeratosis and Morbus Bowen or basalioma-like skin lesions++. Anamnestic evaluation revealed, that the patient's psoriasis had been treated with arsenic for many years. This kind of treatment may have induced intraluminal proliferation and obliteration of the portal vein's endothelium, thus being the etiologic factor responsible for noncirrhotic portal hypertension in this patient.

Arsenates↗
PubMed1989

[Treatment of acute stomach ulcer with H2 receptor antagonists. A direct therapy comparison with 300 mg nizatidine nightly and 2 times 150 mg nizatidine with twice daily 150 mg ranitidine].

In this endoscopically controlled, double-blind study involving 242 patients with acute benign gastric ulcer, it was shown that the selective inhibition of nocturnal gastric acid secretion with 300 mg nizatidine administered on retiring represents an effective and reliable form of therapy. After four weeks of treatment, 90% of the patients receiving 300 mg nizatidine, no longer experienced nocturnal pain, in comparison with 83% receiving 2 X 150 mg nizatidine daily (n.s.). The total healing rates after four weeks were 60% in the patients receiving 300 mg nizatidine, 60% in those on 2 X 150 mg nizatidine daily, and 58% in those receiving 2 X 150 mg ranitidine daily. After eight weeks, the respective figures rose to 85%, 84% and 84%. Clinically relevant side effects were observed in none of the three groups. With a dose on retiring of 300 mg nizatidine, it is possible to accelerate the healing of a benign gastric ulcer, simply by the nocturnal suppression of gastric acid production, and, during the day, preserving physiological gastric function, thus avoiding the possible risks of protracted hypochlorhydria.

Adolescent↗
PubMed1989

Application of capillary isotachophoresis to the analysis of glutathione conjugates.

An analytical capillary isotachophoretic method has been applied for the quantitative assay of reduced glutathione (GSH) conjugates produced by the cytosolic enzyme GSH S-transferase. The donor molecule GSH in reduced and oxidized (GSSG) forms and the GSH conjugates of at least two electrophilic acceptors can be assayed in a single analysis. This technique also permits the quantitative assay of further metabolites of GSH conjugates including mercapturic acids. The total analysis time was of the order of 30 min. The sensitivity of the method is sufficient for the accurate detection of 0.15 nmol GSH conjugate of 1-chloro-2,4-dinitrobenzene and p-nitrobenzyl chloride, 0.2 nmol GSH conjugate of 1,2-epoxy-3-(p-nitrophenoxy)-propane and 0.15 nmol GSH. The present method is simple, accurate and does not require radioactively labelled compounds or separate analytical procedures.

Animals↗
PubMed1989

Induction of urokinase activity and malignant phenotype in bladder carcinoma cells after transfection of the activated Ha-ras oncogene.

In order to characterize further the previously observed induction of a highly metastatic phenotype in mouse bladder carcinoma cells by Ha-ras transfection, we studied production of plasminogen activator, in vitro invasiveness, and the potential for lung colonization of these cells. The parent carcinoma cells produced predominantly tissue-type plasminogen activator. Out of 13 clones of ras-transfected cells tested, 8 secreted quantitatively elevated levels of plasminogen activator (up to 3.5-fold) as compared to the control transfectants. The plasminogen activator activity in cell lysates was maximally increased 3-fold, the surface-associated activity increased 2.5-fold. The secreted plasminogen activator of cloned ras-transfected cells was characterized to be predominantly of the urokinase type (71.3% compared to 20.5% with the parental BL cells). Thus, in addition to the quantitative augmentation of plasminogen activator production and secretion in a large fraction of the ras-transfected cell population, a significant qualitative shift from tissue-type to urokinase-type has been observed. In addition, ras-transfection augmented the capacity of the cells for invasion into Matrigel in a double-filter in vitro assay as well as their ability to colonize the lungs of syngeneic animals. These malignant properties of the transfected cells might be responsible for their highly metastatic behaviour induced by ras transfection.

Animals↗
PubMed1989

Enzymatic detoxification using lipophilic hollow-fiber membranes: III. Oxidation reactions of sulfides.

A lipophilic hollow-fiber membrane preparation that was previously described for glucuronidation and sulfation reactions was used for the enzymatic oxidation of sulfides. Endogenous and exogenous toxins in buffer solution or in serum or blood of intoxicated animals were circulated through the internal lumen of lipophilic hollow fibers. Native liver microsomes of the rabbit were circulated on the outside of the hollow fibers. Lipophilic toxins accumulate in and penetrate through the lipophilic membrane and the toxins are oxidized by the mixed function oxygenase system of liver microsomes. The oxidized products cannot rediffuse to the donor side. The endogenous toxin dimethylsulfide (DMS) was converted on the enzyme side to dimethylsulfoxide (DMSO) and small amounts of dimethylsulfone, which are hydrophilic and nontoxic substances. Other sulfide compounds, ethylmethylsulfide (EMS) and s-butylmethylsulfide (BMS), have also been converted to their oxidized forms. The enzymatic clearance of the hollow-fiber module for DMS in in vivo experiments in the rabbit was found to be 1.30 nmol/h/mg protein/cm2 hollow-fiber surface. The transmembranous enzymatic clearance of the in vitro oxidation reactions of DMS, EMS, and BMS in buffer solutions (open circuit) were measured, respectively, as 1.63, 3.45, and 5.16 nmol/h/mg protein/cm2 hollow-fiber surface. This technique allows the enzymatic oxidation of sulfur compounds with liver microsomes in vitro and in vivo without immunological hazards, and it is suited for artificial liver support.

Animals↗
PubMed1989

Omeprazole in the long-term management of patients with acid-related diseases resistant to ranitidine.

A total of 143 patients with peptic ulceration of the duodenum, stomach or oesophagus, who did not respond to 3 or more months high-dose treatment with ranitidine (450 mg or more daily), were admitted to oral treatment with omeprazole, 40 mg/day. In 94.4% of the patients, ulcers healed within 2-6 weeks. After healing of their ulcers, 122 patients were admitted to long-term maintenance treatment with omeprazole, 40 mg/day; 91 patients have been on the drug for 1-5.5 years. During maintenance therapy with omeprazole, 40 mg/day, no relapses (verified by endoscopy) have yet occurred and no drug related adverse effects have been observed. There were no significant changes in routine laboratory tests in any patients, including 27 with concomitant liver cirrhosis. Serum gastrin levels were already elevated approximately 2-fold during the initial high-dose ranitidine treatment and rose a further 2-fold at 2-3 months of omeprazole treatment. Thereafter, no further increase of serum gastrin was observed even after 5.5 years of continuous observation. Volume density of G and D cells in the antral mucosa did not change significantly. The volume density of argyrophilic cells in the oxyntic mucosa was 0.73 +/- 0.1% before the start of omeprazole treatment and 0.85 +/- 0.09% after 17-24 months of continuous treatment with omeprazole (ns). In antrectomized patients the volume density was lower (0.23 +/- 0.04%). No clusters of argyrophilic cells were observed in any of the groups. In a control group of patients with gastrinoma the volume density of these cells was higher (1.3 +/- 0.23%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1989

Quantitative studies of gastric endocrine cells in patients receiving long-term treatment with omeprazole.

A total of 36 patients with chronic gastric or oesophageal peptic ulceration (including 6 with antrectomy), resistant to high-dose ranitidine treatment for at least 3 months, were successfully treated with omeprazole 20-60 mg/day, for periods up to 3 years. Fasting serum gastrin levels were monitored at regular intervals during therapy and multiple gastric mucosal biopsies were taken during gastroscopy every 3-6 months. Gastrin levels increased significantly during the first 6 months of therapy from a mean of 81.5 to 206 pg/ml; a slight decrease was observed thereafter. There was no significant increase in the volume density of argyrophilic cells in the oxyntic mucosa. No clusters of endocrine cells were found in the oxyntic mucosa and no change of G-cell volume density occurred in the antral mucosa under therapy. Omeprazole therapy did not result in any changes in gastrin levels or oxyntic argyrophilic cells in the antrectomized patients. It is concluded that the moderate hypergastrinaemia observed during long-term omeprazole treatment in man does not induce hyperplasia of argyrophilic cells in the oxyntic mucosa.

Biopsy↗
PubMed1989

Enzymatic detoxification using lipophilic hollow-fiber membranes: IV. Glutathione conjugation reactions.

A hollow-fiber technique was used in the enzymatic glutathione conjugation of lipophilic toxins. Native enzyme was circulated on the external side of a lipophilic hollow-fiber membrane while the toxin-containing media (blood, plasma or aqueous solution) were circulated inside the fiber. Glutathione conjugation reactions were catalyzed by rat liver cytosol, with a specific glutathione transferase activity of 40 nmol/min/mg protein (acceptor: 1,2-epoxy-3-(p-nitrophenoxy)propane). Clearance rates of 1,2-epoxy-3-(p-nitrophenoxy)propane, phenylglycidether, styrene oxide, cis-9, 10-epoxystearic acid, cis-9, 10-epoxystearic acid methyl ester, 5a, 6a-cholesterol oxide, 16-, 17a-pregnenolone oxide, and p-nitrobenzylchloride were 10.44, 13.37, 32.25, 7.60, 7.31, 3.92, 4.20 and 29.24 nmol/mg protein/h/cm2 hollow-fiber surface respectively. This technique makes possible glutathione conjugation reactions with crude enzyme preparations over long periods without loss of activity from covalent immobilization and without loss of cofactor from (auto)oxidation. The lipophilic membrane ensures the absence of hemolysis, immunological hazards and hormone loss, while elimination of the toxin is not impaired.

Animals↗
PubMed1988

Fibrin autography of plasminogen activator by electrophoretic transfer into fibrin agar gels.

An electrophoretic modification of the conventional fibrin autography that can be used for the detection of plasminogen activators (urokinase type and tissue type) and fibrin-degrading enzymes in complex biological fluids is described. After separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the proteins and the substrate plasminogen are transferred electrophoretically into the fibrin indicator gel, resulting in an efficient transfer of proteinases as well as high resolution and contrast of fibrinolytic zones caused by plasminogen activator activity. Picogram amounts of human urokinase type plasminogen activator (about 0.002 International Unit) are still detectable. The technique is also applicable to reversed fibrin autography for plasminogen activator inhibitors.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

Therapy with omeprazole in patients with peptic ulcerations resistant to extended high-dose ranitidine treatment.

94 patients with peptic ulcerations of duodenum, stomach, and esophagus, who did not respond to 3 or more months high-dose (450 or 600 mg) treatment with ranitidine, were treated orally with 40 mg omeprazole daily. After healing all patients were offered long-term maintenance therapy with the same dose for 5 years. In 75 patients the peptic ulcerations healed within 4 weeks, in 13 patients within 8 weeks, and in 3 patients only after an increase to 60 mg omeprazole daily. In 3 patients the ulcers did not heal. So far 83 patients have entered long-term maintenance therapy. 59 of these patients are on the drug between 1 and 4 years. During maintenance therapy with 40 mg omeprazole no relapses have occurred up to now as demonstrated by endoscopy and no drug-related adverse effects were observed. Routine laboratory tests remained without significant changes in all patients including 18 patients with concomitant liver cirrhosis. Serum gastrin levels were already elevated during the initial high-dose ranitidine treatment (106 +/- 15.4 pg/ml). 4 weeks after the start of omeprazole treatment serum gastrin levels rose to 4 times normal levels (195 +/- 28 pg/ml). Thereafter, no further increase in serum gastrin was observed even up to 4 years of continuous observation. It is therefore concluded that omeprazole is highly effective in healing ranitidine-resistant peptic ulcerations and that omeprazole maintenance therapy with 40 mg omeprazole is safe during the time observed and highly effective in the prevention of ulcer recurrence.

Adult↗
PubMed1988

Long-term omeprazole treatment in man: effects on gastric endocrine cell populations.

36 patients with chronic gastric or oesophageal peptic ulceration (including 6 with antrectomy), resistant to high-dose ranitidine treatment for at least 3 months, were successfully treated with 40-60 mg of omeprazole daily for periods between 1 and 2 years. Fasting serum gastrin levels were monitored at regular intervals during therapy and multiple gastric mucosal biopsies were taken during gastroscopy every 3-6 months. Gastrin levels increased significantly during the first 6 months of therapy from a medium level of 81.5 to 206 pg/ml, a slight decrease was seen thereafter. In 10 patients investigated before the start of the treatment and after 1 and 2 years, the volume density of argyrophilic cells in the oxyntic mucosa increased from 0.43 +/- 0.08 to 0.91 +/- 0.14% during the first year; this change was statistically significant. No further increase was observed thereafter. No such difference could be demonstrated between a larger group of 18 patients investigated before and after 1 year of treatment with omeprazole (0.806 +/- 0.1 vs. 0.93 +/- 0.08%) and between a larger group of 22 untreated patients and 17 patients treated for 17-24 months with omeprazole (0.73 +/- 0.1 vs. 0.86 +/- 0.09%). The volume density of argyrophilic cells found in 8 patients with gastrinoma amounted to 1.37 +/- 0.22%. No clusters of endocrine cells were found in omeprazole-treated patients. The D cell volume density in the antral mucosa decreased significantly during the first months of treatment, but steadily increased thereafter to reach pretreatment values after 17 months. There was no change in G cell volume density under therapy. No changes in gastrin levels or oxyntic argyrophilic cells were observed in the antrectomized patients. It is concluded that the hyperplasia of argyrophilic cells observed in some patients during long-term omeprazole treatment is mediated by hypergastrinaemia.

Female↗
PubMed1988

Roxatidine acetate in the long term maintenance of duodenal ulcers.

A non-comparative multicentre study of 105 patients with healed duodenal ulcers was conducted to determine the effect on ulcer recurrence of 6 months' maintenance treatment with roxatidine acetate 75 mg daily. All patients had previously received roxatidine acetate treatment. 31 patients out of 89 had 32 relapsed ulcers after 6 months of treatment, which represents an overall relapse rate of around 30%; the relapse rate in smokers was double that of non-smokers. The overall incidence of epigastric pain did not increase significantly over the period of the trial, although some patients complained of mild pain when they entered the study despite having endoscopically confirmed healed ulcers. At the end of the study continuous poor appetite and pyrosis were reported by 17% and 6% of patients, respectively. Side effects, which included constipation and diarrhoea, were reported by 4 patients, 1 of whom withdrew from therapy. There were no clinically significant changes in laboratory values. Thus, maintenance treatment with roxatidine acetate 75 mg daily proved a safe and effective method of preventing symptomatic duodenal ulcer relapse.

Adult↗
PubMed1988

Comparison of diuretic effects and pharmacokinetics of torasemide and furosemide after a single oral dose in patients with hydropically decompensated cirrhosis of the liver.

In a controlled double-blind randomized clinical trial, the pharmacodynamics and pharmacokinetics of 20 mg torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) (n = 10) and 40 mg furosemide (n = 9) were compared over 24 h after single oral administration to patients with ascites due to cirrhosis of the liver. The overall 24-h excretion of volume and sodium was not significantly different between patients receiving torasemide or furosemide. The diuretic effect of torasemide, however, was longer in duration than that of furosemide. This was in accordance with the pharmacokinetic behaviour of torasemide and furosemide. The serum elimination half-life of torasemide was longer (4.8 h) than that of furosemide (2.2 h) in these patients and also longer than that in healthy volunteers (3 h). The areas under the serum concentration-time curves for torasemide were higher than in healthy subjects by a factor of 2.5. In parallel with the considerably delayed formation of the diuretically inactive metabolite M5, which is formed via the diuretically active metabolite M1, the serum concentration of M1 was increased in these patients. However, the overall excretion of torasemide and the different metabolites was similar compared to healthy volunteers. These results indicate that the pharmacokinetics and metabolism of torasemide depend on liver function. No adverse reaction were experienced in either group.

Administration, Oral↗
PubMed1987

[A chronic destructive non-suppurative cholangitis-like disease picture with antinuclear antibodies (immunocholangitis)].

Three females had suffered, two for many years, from bouts of a liver disease of unknown origin, which clinically, histologically and biochemically fulfills the criteria of chronic destructive non-suppurative cholangitis. None of the patients had antimitochondrial antibodies, but all had antinuclear antibodies at high titres. Two of them are mother and daughter; the latter has two daughters (aged 10 and 12 years), both of whom have antinuclear antibodies at low titres but no abnormal liver function tests. The female family members of the third patient also had antinuclear antibodies in their serum with normal liver enzyme tests. None of the patients was taking any drugs. Contrary to true chronic destructive nonsuppurative cholangitis (primary biliary cirrhosis), in the three patients immunosuppressive treatment with azathioprine (Imurek) and prednisone (Decortin) was successful. It is suggested that the described disease be called immunocholangitis.

Adult↗
PubMed1986

Enzymatic synthesis and chromatographic purification of lignan glucuronides.

Enterolactone, enterodiol and secoisolariciresinol were conjugated with glucuronic acid by solubilized rabbit liver microsomal UDP-glucuronyltrasnferase. The monoglucuronide conjugate of all three substrates was formed and its identity confirmed by nuclear magnetic resonance (NMR) spectroscopy. Analytical high pressure liquid chromatography (HPLC) and NMR spectroscopy indicated conjugation with glucuronic acid to occur at several positions in the molecule. The enzymatic conjugation was monitored by analytical capillary isotachophoresis (ITP). The Km-values for enterlactone, enterodiol, and secoisolariciresinol were calculated to be 0.30, 0.23, and 0.22 mmol/l respectively.

Animals↗