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Biomedical subjects

R Gugler

Publications and source records attributed to R Gugler.

At least 19 recordsLinked to original sources
PubMed2005

[A young diabetic with small-nodule liver cirrhosis, high transferrin saturation and negative HFE test].

HISTORY: A 28 year young female presented to our hospital for further evaluation with recently diagnosed diabetes mellitus, hyperpigmentation of the skin, hepato- and splenomegaly, thrombocytopenia and an elevated transferrin saturation (96 %), but a negative test for HFE gene mutations such as C282Y and H63D. FINDINGS: Using the mini-laparascopic technique we diagnosed a smallnodular liver cirrhosis with an iron overload. DIAGNOSIS AND TREATMENT: This is the clinical presentation of one subtype of the so called Non-HFE-hemochromatosis, the juvenile hemochromatosis (HFE2). Other causes of primary and secondary iron overload have been ruled out. Different from the HFE-positive hemochromatosis (HFE 1) in which the gene defect is located on chromosome 6, the defect in HFE 2 is located on chromosome 1. The underlying genetic defect has been localized within recently identified HJV gene. Phlebotomy is the treatment of choice, to be performed until the ferritin level is lower than 50 microg/l. CONCLUSIONS: If liver cirrhosis is present in hemochromatosis, the overall risk of developing heptatocellular carcinoma is 20 times higher than in the normal population. Therefore it is suggested to perform an ultrasound examination of the liver and an AFP-test every 6 months, whereas an MRI-scan should be performed once a year, as a basis for further treatment options.

Adult↗
PubMed2005

HJV gene mutations in European patients with juvenile hemochromatosis.

A large variety of mutations within the genes encoding hepcidin (HAMP) and hemojuvelin (HJV) have been identified in patients with the severe iron overload disorder juvenile hemochromatosis (JH). The aim of the present study was to evaluate the molecular background of JH in patients from central parts of Europe. Sequence analyses of HAMP and HJV were performed in seven JH patients from six families from Germany, Slovakia, and Croatia. For detection of the G320V mutation in HJV, a rapid polymerase chain reaction-based assay was developed. No mutations were found within the HAMP gene. Six of seven (86%) JH patients carried at least one copy of the G320V mutation within the HJV gene. Four of these patients were homozygous for the G320V mutation. In addition, two novel HJV mutations were identified (C119F and S328fsX337). Taken together, the present study demonstrates that molecular analysis of the HJV gene is a powerful tool for an early and reliable diagnosis of JH. As in affected patients from Greece, the G320V mutation seems to be widely distributed among JH patients from central parts of Europe. Therefore, detection of the G320V mutation could identify the majority of JH cases from these regions non-invasively.

Adolescent↗
PubMed2004

[The elderly patient with esophageal and gastric disease].

UNLABELLED: The increasing percentage of elderly patients in gastroenterology requires special management of this patient group. In gastroesophageal reflux disease symptoms are not different in the older patients, but advanced disease and Barrett's syndrome are more frequently present. Medical treatment is the same as in the young population, and surgical anti-reflux procedures may be applied with identical success rates. The incidence of oral medication-induced esophageal injury in the elderly is high, but is often overlooked. Operative resection procedures in esophageal cancer are carried out in experienced centers without increase in mortality or perioperative complications. A high prevalence of H.p. infection in the elderly is, unfortunately, not followed by more frequent testing for H.p. in these patients or even by eradication treatment. NSAID induced lesions are present more frequently in older age, treatment is however by the same principles as in the young. Also, prevention of NSAID lesions is not performed differently in the elderly. CONCLUSIONS: Elderly patients have similar symptoms in esophageal and gastric disease as younger patients do, but disease states are often more serious. These patients are treated by the same principles and should not be denied chances of curative operative procedures when indication is given. Surgery should however preferably be carried out in specialized centers.

Aged↗
PubMed2004

Interferon alfa2a induction therapy in combination with ribavirin and amantadine for the treatment of naive patients with chronic HCV infection.

Pilot studies have suggested that the addition of amantadine to interferon (IFN) is effective against hepatitis C virus (HCV). Furthermore, IFN induction therapy seems to improve virological response rates. In this open, randomized, multicentre trial we compared safety and efficacy of a triple therapy comprising IFN alpha 2a, ribavirin and amantadine using high induction doses (6 MU IFN alpha daily for the first 6 weeks) against a therapy with standard IFN alpha dosages over the entire treatment period plus amantadine and ribavirin. A total of 158 naive patients with chronic HCV infection were randomized 1:1. Group A (n = 81): induction therapy with 6 MU IFN alpha daily for 6 weeks, followed by 6 MU three times a week (tiw) for 18 weeks and then 3 MU tiw until week 48. Group B (n = 77): standard therapy with 6 MU IFN alpha tiw for 24 weeks, followed by 3 MU until week 48. All patients received oral ribavirin (10 mg/kg/day) and amantadine (200 mg/day). The triple therapy was safe and well tolerated. There were no significant differences between the groups with respect to biochemical response rates. Groups A and B did not differ in virological response rates at the end of treatment (33%vs 35%) or at the end of the 6 month follow up period (37%vs 39%). We could not detect favourable effects on sustained virological response rates using induction therapy, in either genotype 1 or non-1 infected patients. In summary, induction therapy with 6 MU IFN alpha daily did not result in increased overall response rates compared with standard IFN alpha dosages of 6 MU tiw.

Adolescent↗
PubMed1999

[The duodenojejunal flexure--a gap in the routine diagnosis of gastrointestinal bleeding].

HISTORY AND ADMISSION FINDINGS: Because of tarry stools a 64-year-old woman had two years previously undergone oesophagogastroduodenoscopy (OGD), coloscopy and examination of the small intestine (according to Sellink) without significant findings. She was again hospitalized because of anemia (6.1 g/dl). Physical examination was unremarkable. INVESTIGATIONS: After unremarkable OGD (as far as the descending part of the duodenum) and coloscopy, hypotonic duodenography revealed a tumor in the region of the duodenojejunal flexure. TREATMENT AND COURSE: The tumor, histologically a leiomyoma, was resected. CONCLUSION: OGD, coloscopy and small intestinal radiography may fall to identify the source of bleeding because of a diagnostic gap in the region of the duodenojejunal flexure. In this case hypotonic duodenography should be performed, if enteroscopy is not available.

Colonoscopy↗
PubMed1999

Analysis of DNA strand breaks, oxidized bases, and glutathione S-transferase P1 in human colon cells from biopsies.

The balance of genetic damage and deactivating enzymes is decisive for cancer risk. To assess these factors in normal human colon cells, we determined background levels of DNA breaks or oxidized bases and of glutathione S-transferases (GSTs) as potential biomarkers of risk and chemoprevention, respectively. Also, genotoxicity by compounds involved in lipid peroxidation was determined to elucidate possible sources of damage. Cells were isolated from sigmoid biopsies of 51 donors and processed with the comet assay to reveal genetic damage. GST proteins were analyzed immunologically. HT29 clone 19A colon tumor cells, resembling primary cells, were treated with 2-trans-hexenal (400 microM) or hydrogen peroxide (75 microM) and processed for damage. Fifteen percent of primary colon cells contained strand breaks; 22% contained additional oxidized bases, with distinct sex differences. Similar damage was found in HT29 clone cells and is induced by both test compounds. GST levels were similar in both cell types. The comet assay is sufficiently sensitive to detect oxidative genetic damage in small amounts of cells from small amounts of biopsies. Lipid peroxidation is a possible risk factor. Together with GST as a potential biomarker of chemoprevention, the technique may serve as a valuable biomarker to assess exposure to risk factors.

Biomarkers, Tumor↗
PubMed1998

[Reflux disease: drug treatment].

Reflux disease of the esophagus is characterized by a high prevalence and by high relapse rates. Upper endoscopy is the key procedure for diagnosis of the disease as well as for follow up, since treatment is determined by disease intensity as judged by endoscopy. High activity of disease is associated with an increased risk of complications, in the worst case development of adenocarcinoma. General recommandations (weight reduction, change of eating habits) constitute the start of each treatment regimen, and may add to improvement of symptoms, sometimes in combination with antacids. Prokinetics and H2-receptor antagonists are effective in mild reflux disease (grade O, I), but even in these situations proton pump inhibitors (PPI) exhibit better relief of symptoms and more rapid healing. PPI are the drugs of first choice for higher disease activity, often in larger than standard daily doses. The treatment period for acute disease may be as long as 12 weeks. Long term prophylaxis is only effective with PPIs, mostly in the standard daily dose. Duration of long term treatment is determined by disease activity and tendency of the lesions to heal. Today, in case of treatment failure and of high grade lesions antireflux surgery is increasingly being reconsidered, particularly since minimally invasive methods are available.

Gastroesophageal Reflux↗
PubMed1996

Lack of pharmacokinetic interaction of pantoprazole with diazepam in man.

Pantoprazole, a substituted benzimidazole, is a potent and well tolerated inhibitor of the gastric H+,K(+)-ATPase with a low potential to inhibit cytochrome P450. In this randomized, placebo-controlled two-period crossover study, 12 healthy volunteers received placebo (reference) and 240 mg of pantoprazole (test) i.v. within 2 min once daily for 7 days each. On day 4 of either period, a 1 min bolus of diazepam (0.1 mg kg-1 body weight) was additionally injected. Pantoprazole was well tolerated and did not cause clinically relevant changes in heart rate, blood pressure, ECG and routine clinical laboratory parameters. There was no effect on diazepam clearance (0.021 1 h-1 kg-1 for test and reference) and elimination half-life (36.8 for test, 40.4 h for reference). Diazepam metabolism to desmethyldiazepam was not affected by pantoprazole. In conclusion, pantoprazole and diazepam may be administered concomitantly without dose adjustment even when high doses of pantoprazole are required.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Superoxide inhibition following different stimuli of respiratory burst and metabolism of aminosalicylates in neutrophils.

Reactive oxygen species such as superoxide radicals have been proposed to play an important role in the pathogenesis of inflammatory bowel disease. Some of the antiinflammatory actions of aminosalicylates have been ascribed to their capability to scavenge superoxide radicals directly or to inhibit its production in stimulated neutrophils. However, as a controversy still exists with regard to the precise mechanisms of inhibition and the metabolism within inflammatory cells, we compared scavenger properties of 5-aminosalicylic acid, 4-aminosalicylic acid, N-acetyl aminosalicylic acid, olsalazine, and benzalazine in systems with defined superoxide radical generation such as the dimethyl sulfoxide-NaOH and the potassium superoxide system. We also studied possible inhibition of the superoxide production following different stimuli of the respiratory burst in neutrophils and investigated the uptake and potential metabolism (N-acetylation) of 5-aminosalicylic acid in lipopolysaccharide-primed and resting neutrophils. We found that 5-aminosalicylic acid and 4-aminosalicylic acid had defined scavenger properties in the dimethyl sulfoxide-NaOH or potassium superoxide systems, respectively, whereas compounds with a modified aminophenolic structure had no effects. At the cellular level, 5-aminosalicylic acid inhibited phorbol myristate acetate (100 ng/ml)-activated superoxide generation to 82.3 +/- 9.3%, the formylmethionyl leucyl peptide (10(-5) M) to 61.0 +/- 6.8%, and the NaF (20 mM)-stimulated production to 32.3 +/- 3.2% (mean +/- SD, P < 0.01). The actions of the other drugs were less pronounced. Almost identical retention times (Rt = 11.2 min) of 3H-labeled phorbol myristate acetate in the presence and absence of 5-aminosalicylic acid revealed no in vitro interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗
PubMed1994

H2-antagonists and alcohol. Do they interact?

There are conflicting data on the existence of significant first-pass metabolism of alcohol (ethanol) in the human stomach and its inhibition by histamine H2-receptor antagonists. Alcohol is predominantly metabolised in the liver by the microsomal alcohol oxidising system, alcohol dehydrogenase (ADH) and a catalase enzyme. Histochemical and kinetic studies have revealed several ADH isoenzymes in the gastric mucosa with different kinetic properties. After small oral doses of alcohol first-pass metabolism in the stomach occurs, as shown by reduced area under the plasma concentration-time curve (AUC) compared with intravenous or intraduodenal administration. The activity of gastric ADH is reduced in women, the elderly, Asian individuals, the fasting state, chronic alcoholism and after gastrectomy. The effect is only present with small (< or = 0.3 g/kg) alcohol doses and with a high alcohol concentration. In a number of studies, cimetidine in therapeutic doses over 7 days produced a significant increase in the AUC and in the peak plasma concentration after administration of alcohol 0.15 and 0.30 g/kg. This was related to an inhibition of gastric ADH activity, as shown by in vitro studies. Ranitidine inhibited gastric ADH to a similar extent on a molar basis, but its effect on alcohol levels in vivo was less constant in various studies. Nizatidine also reduced gastric alcohol first-pass metabolism, but famotidine and roxatidine did not show this effect. In other studies, H2-receptor antagonists did not change AUC and peak alcohol concentration. The controversy is not easy to resolve, since a number of the positive studies did not use a placebo-controlled, randomised, crossover design, while some of the negative studies did not exclude habitual alcohol consumers and included Oriental volunteers, although both groups have been shown to lack significant gastric ADH activity. In this case, when first-pass metabolism of alcohol does not exist, this by definition cannot be abolished by H2-antagonists. The inclusion of oral and intravenous dosage data of alcohol is mandatory to positively identify first-pass metabolism in any individuals. The significance of the effect of H2-antagonists on blood alcohol concentrations is minor. It only occurs in young, male, nonalcoholic, non-Asian individuals, and alcohol must be given in a small (social) dose, in a high concentration, and after meals. An increase in alcohol levels in predisposed patients during treatment with some H2-antagonists cannot be excluded, although the likelihood is small. Furthermore, carefully designed studies are needed to clarify fully the significance of this interaction.

Alcohol Dehydrogenase↗
PubMed1992

Superoxide, hydroxyl and fatty acid radical scavenging by aminosalicylates. Direct evaluation with electron spin resonance spectroscopy.

Reactive oxygen radicals such as superoxide and hydroxyl radicals, as well as intermediate unsaturated fatty acid radicals, have been proposed as playing an important role in various diseases including inflammatory bowel disease (IBD). In this study we evaluated radical scavenger properties of aminosalicylates used in the therapy of IBD using spin trapped electron spin resonance spectroscopy. 5-Aminosalicylic acid (5-ASA), 4-aminosalicylic acid and olsalazine had superoxide radical scavenger properties (IC50 = 0.4, 0.4 and 1.0 mM, respectively). 5-ASA and benzalazine also inhibited hydroxyl radicals (IC50 = 6.5 mM). Fatty acid radicals were not inhibited by aminosalicylates. Our results support the hypothesis that therapeutically active compounds may be oxygen radical scavengers and that fatty acid radical scavenging has to be performed by drugs other than aminosalicylates.

Aminosalicylic Acid↗