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Biomedical subjects

H Nuutinen

Publications and source records attributed to H Nuutinen.

At least 19 recordsLinked to original sources
PubMed2002

Ethanol-derived microbial production of carcinogenic acetaldehyde in achlorhydric atrophic gastritis.

BACKGROUND: Acetaldehyde is a local carcinogen in the digestive tract in humans. Atrophic gastritis leads to microbial colonization of the stomach, which could enhance microbial production of acetaldehyde from ethanol. The aim of the study was to study microbial ethanol metabolism and acetaldehyde production in the stomach of achlorhydric atrophic gastritis patients. METHODS: For the in vivo study, glucose or ethanol was infused via a nasogastric tube to the stomach of seven achlorhydric atrophic gastritis patients and five healthy controls. Gastric juice samples for ethanol and acetaldehyde determinations and microbial analysis were obtained at 30 and 60 min after the infusions. For the in vitro study, gastric juice samples from 14 atrophic gastritis patients and 16 controls were obtained during gastroscopy, whereafter the samples were incubated for 2 h with 1% ethanol at 37 degrees C and acetaldehyde was determined. RESULTS: Minor endogenous ethanol and acetaldehyde concentrations were detected after glucose infusion in the gastric juice of four atrophic gastritis patients. After ethanol infusion, the mean intragastric acetaldehyde level of the atrophic gastritis patients was 4.5-fold at 30 min and 6.5-fold at 60 min compared to controls. In vitro, the difference between the study groups was even higher, 7.6-fold. A vast selection of oral bacterial species and some Enterobacteriaceae and yeasts were presented in the gastric juice of atrophic gastritis patients. CONCLUSIONS: Microbial ethanol metabolism leads to high intragastric acetaldehyde levels after ethanol drinking in achlorhydric atrophic gastritis patients. This could be one of the factors responsible for enhanced gastric cancer risk among atrophic gastritis patients.

Acetaldehyde↗
PubMed2001

Factors predicting interferon treatment response in patients with chronic hepatitis c: late viral clearance does not preclude a sustained response.

OBJECTIVES: Because of the suboptimal efficacy, cost, and adverse effects of interferon in chronic hepatitis C (HCV), predictors have been sought to detect patients with a good treatment response. Also, markers for determining a poor response early in the course of therapy, such as the lack of early viral clearance, have been proposed. METHODS: Ninety-seven patients with chronic hepatitis C were enrolled to receive leukocyte alpha-interferon according to a stepped-care management protocol. The final virological treatment response was evaluated in 74 patients after a 6-month post-treatment follow-up. The relationship between pretreatment and during-treatment variables and the long-term response was assessed. RESULTS: Non-1 viral genotype, higher pretreatment ALT levels, and lower gamma-glutamyl transferase (GGT)/ALT ratios and GGT as well as younger age were significantly associated with a sustained response; a trend was also detected for lower serum ferritin levels. Normalization of ALT by 3 months was also a significant predictor of a long-term response. Of the 27 patients carrying the HCV genotype 3a, seven (26%) were still HCV RNA positive at 6 months. Of these patients, however, five (19%) still achieved a sustained virological response after treatment for up to 12 months. CONCLUSIONS: In contrast to some previous reports, our results suggest that a late viral clearance after 6 months of interferon monotherapy may not preclude a favorable long-term response after a 12-month treatment, especially in patients carrying a non-1 HCV genotype. A low pretreatment GGT/ALT ratio is a predictor of a good treatment response.

Adolescent↗
PubMed2001

Long term metabolic consequences of ileal pouch-anal anastomosis for ulcerative colitis.

OBJECTIVES: Chronic inflammation in the ileal pouch is the most significant late complication after ileal pouch-anal anastomosis (IPAA). It leads to changes in mucosal morphology, with consequent decreased vitamin B12, bile acid and cholesterol absorption documented. The aims of this study were to evaluate long term metabolic consequences at least 5 yr after IPAA and the influence of pouchitis on pouch histology and on bile acid, lipid, and vitamin B12, A, E, and D metabolism. METHODS: A total of 104 patients with a J-pouch who were operated on between 1985 and 1994, as well as 21 ulcerative colitis patients with a conventional ileostomy were enrolled for the study. Routine blood tests, vitamin status, vitamin B12 levels, and bile acid absorption were determined, as well as endoscopy with biopsies. The pouchitis disease activity index (PDAI) was calculated. On the basis of histology, IPAA patients were divided into three subgroups: 1) those with no villous atrophy, 2) those with partial villous atrophy, and 3) those with subtotal or total villous atrophy. RESULTS: Incidence of pouchitis was 42.3%, and was strongly associated with villous atrophy. In IPAA patients with subtotal or total villous atrophy (32.7%), serum levels of albumin, calcium, total cholesterol, triglycerides, and vitamin E were significantly reduced (p < 0.05). The lowest bile acid and vitamin B12 absorption rates were seen in patients with inflammation in the proximal limb. Vitamin D deficiency was seen in 10.6%, and vitamin A and B12 deficiency in approximately 5% of IPAA patients. CONCLUSIONS: Metabolic consequences after IPAA are associated with pouchitis, grade of villous atrophy, and extent of inflammation in the remaining ileum. Patients with active chronic inflammation need long term follow-up.

Adult↗
PubMed2000

Hypochlorhydria induced by a proton pump inhibitor leads to intragastric microbial production of acetaldehyde from ethanol.

BACKGROUND: Acetaldehyde, produced locally in the digestive tract, has recently been shown to be carcinogenic in humans. AIM: To examine the effect of iatrogenic hypochlorhydria on intragastric acetaldehyde production from ethanol after a moderate dose of alcohol, and to relate the findings to the changes in gastric flora. METHODS: Eight male volunteers ingested ethanol 0.6 g/kg b.w. The pH, acetaldehyde level and microbial counts of the gastric juice were then determined. The experiment was repeated after 7 days of lansoprazole 30 mg b.d. RESULTS: The mean (+/- S.E.M.) pH of the gastric juice was 1.3 +/- 0.06 and 6.1 +/- 0.5 (P < 0.001) before and after lansoprazole, respectively. This was associated with a marked overgrowth of gastric aerobic and anaerobic bacteria (P < 0. 001), by a 2.5-fold (P=0.003) increase in gastric juice acetaldehyde level after ethanol ingestion, and with a positive correlation (r=0. 90, P < 0.001) between gastric juice acetaldehyde concentration and the count of aerobic bacteria. CONCLUSIONS: Treatment with proton pump inhibitors leads to hypochlorhydria, which associates with intragastric overgrowth of aerobic bacteria and microbially-mediated acetaldehyde production from ethanol. Since acetaldehyde is a local carcinogen in the concentrations found in this study, long-term use of gastric acid secretory inhibitors is a potential risk-factor for gastric and cardiac cancers.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Cure of Helicobacter pylori infection after failed primary treatment: one-center results from 120 patients.

BACKGROUND: Treatment with a proton pump inhibitor (PPI) and antimicrobials cures Helicobacter pylori infection in about 90% of patients. This is a retrospective overview of our studies aiming to cure the infection in all compliant patients with failed initial therapy. METHODS: We retreated 120 (19% of 644) H. pylori-infected patients whose initial therapy had failed. The retreatments included (i) triple therapy (TT): colloidal bismuth subcitrate, metronidazole, amoxicillin (or tetracycline); (ii) quadruple therapy (QT): TT and a PPI; or (iii) high doses of both a PPI and clarithromycin combined with a further 1-3 individually selected antimicrobials. The eradication results were determined after 6-12 months. RESULTS: The 1st retreatment was successful in 70 of 120 patients. The 2nd retreatment cured 25 of the remaining 42 patients, the 3rd 13 of 17, and the 4th the last 4 patients. The cumulative eradication rate (ITT) was 93% (95% CI: 88.9%-97.9%; 8 patients withdrew after a failed 1st retreatment) and the rate was 100% in the remaining 112 patients who accepted several retreatments. The 1st retreatment with TT cured 23% (95% CI: 12%-34%) of 57 patients and QT 85% (95% CI: 74%-96%) of 41 patients who had initially undergone a failed metronidazole-based treatment. All retreatments were well tolerated. CONCLUSIONS: In this study, high doses of a PPI and clarithromycin combined with 1-3 antimicrobials according to susceptibility data proved to be the best drug combination in the cure of H. pylori infection after failed primary treatment. Giving imidazole- and bismuth-based QT (without clarithromycin) as the first-line treatment of H. pylori infection ensures that the number of failures remains low.

Anti-Bacterial Agents↗
PubMed2000

Leukocyte interferon-alpha in the treatment of chronic hepatitis C in Finland.

BACKGROUND: To evaluate the efficacy of leukocyte interferon in previously untreated patients with chronic hepatitis C, 97 patients were enrolled in a prospective study in Finland with a stepped-care management protocol. METHODS: The treatment was initiated with 3 million units of interferon-alpha subcutaneously three times a week. At 3 months, if the serum alanine aminotransferase was still abnormal, the dose was doubled. If serum hepatitis C virus (HCV) RNA had turned negative at 6 months, the treatment was stopped; if it was still positive, treatment was continued for up to 12 months. All patients were followed up after treatment for 6 months. Altogether, 74 patients completed the treatment and follow-up periods. RESULTS: Of all the originally enrolled patients 36% (35 of 97) achieved sustained virologic response, defined as HCV RNA negativity 6 months after the end of treatment. The commonest HCV genotype among these patients was 3a, and as many as 52% of such patients achieved sustained virologic response. Thirty-two per cent of the patients had HCV genotype 1a, 1b, or a mixture of these; a sustained response was achieved in only 6% of such patients but in 50% of patients with a non-1 genotype. Adverse effects caused treatment cessation for 10% of the patients and IFN dose reduction for 20%. CONCLUSIONS: Monotherapy with human leukocyte interferon resulted in sustained virologic response in 36% of patients with chronic hepatitis C. In those infected with a HCV genotype other than 1, the sustained virologic response rate was 50%.

Adult↗
PubMed1999

Endoscopic ultrasonography in the preoperative staging of adenocarcinoma of the distal oesophagus and oesophagogastric junction.

BACKGROUND: Endoscopic ultrasonography is considered to be the most accurate procedure in the preoperative staging of oesophageal carcinoma. Its accuracy was evaluated in the preoperative staging of adenocarcinoma of the distal oesophagus and oesophagogastric junction. METHODS: Thirty-two consecutive patients with adenocarcinoma of the distal oesophagus and oesophagogastric junction were preoperatively examined and staged by means of endoscopic ultrasonography. All patients underwent radical en bloc resection of the oesophagus and proximal stomach (or total gastrectomy) with standard lymphadenectomy including thoracic duct and mediastinal fat tissue. The postoperative histopathologic TNM stage was taken as reference. RESULTS: An endoscopic ultrasonography examination could be completed in 26 of the patients; the other 6 had obstructive tumour. In two patients infiltration of the tumour into the vital organs (in one patient aortic infiltration and in a second patient pericardial infiltration) was incorrectly suspected. The ability to predict T stage was 65.6%. T stage was overstaged in 31.2% and understaged in 3.1% of the cases. The ability to predict N stage was 71.9%. N stage was overstaged in 25.0% and understaged 3.1% of the cases. CONCLUSIONS: In adenocarcinoma of the oesophagus and oesophagogastric junction endoscopic ultrasonography helps in predicting resectability, but the exact TN staging is not accurate. Since early detection of tumour and aggressive surgical intervention constitute the only curative treatment, caution must be exercised when judging a patient to be inoperable solely on the basis of endoscopic ultrasonography findings without proven distant metastases.

Adenocarcinoma↗
PubMed1998

Human gallbladder mucosal function: effects on intraluminal fluid and lipid composition in health and disease.

Gallbladder mucosal absorption of fluid during fasting is a well-known process. Indirect in vivo and recent in vitro evidence for physiologically relevant gallbladder absorption of cholesterol and phospholipids from bile has been observed in humans. The present study explored and compared by indirect means the relative efficiences of human gallbladder mucosal absorption of fluid and lipids in health and disease. Biliary lipids and pigment content were measured in fasting gallbladder bile samples obtained from gallstone-free controls and from four study groups: multiple and solitary cholesterol gallstone patients, and morbidly obese subjects with and without gallstones. Bile salts and pigment content were significantly greater in gallstone-free controls than in all other disease study groups. This was interpreted as evidence of more effective gallbladder mucosal fluid absorption in nonobese gallstone-free controls compared to that in all other groups. Correlation plot analyses of biliary lipids showed lower concentrations of phospholipids than expected from the index bile salt concentrations. The same was found for cholesterol concentrations but only in supersaturated samples. These findings were much more pronounced in gallstone free-controls and were accordingly interpreted as evidence of more efficient gallbladder absorption of both phospholipids and cholesterol in controls compared with that found in each of the disease study groups. Moreover, impaired gallbladder mucosal function, while invariably associated with cholesterol gallstone disease, was not found to be a necessary consequence of the physical presence of stones. It is concluded that efficient gallbladder mucosal absorption of both fluid and apolar lipids from bile is a normal physiological process that is often seriously impaired in the presence of either cholesterol gallstone disease or at least one of its precursor forms.

Absorption↗
PubMed1997

Culture of Helicobacter pylori from gastric biopsies transported in biopsy urease test tubes.

Gastric biopsy specimens of 57 consecutively observed dyspeptic patients were studied for the presence of Helicobacter pylori by histological examination, biopsy urease test (BUT) and culture. For culture, biopsy samples were transported in both Stuart media and BUT tubes. All 15 isolates could be cultured from both Stuart and BUT tubes. Thus, if the main reason for culture of Helicobacter pylori is for antimicrobial susceptibility testing, only positive BUT tubes need to be submitted. This would reduce both the expense and the number of biopsies needed.

Adult↗
PubMed1997

Variations in pigment and carbohydrate content of gallbladder bile affect accurate quantitation of total protein when using the fluorescamine method.

BACKGROUND: Despite solute dilution and reduced total lipid concentrations, an unexplained increase in protein concentration has been reported to occur in the gallbladder bile of cholesterol gallstone patients. METHODS: Solutes in gallbladder bile from gallstone-free controls and from four study groups were measured using standard methods. Total proteins were measured using amino acid analysis and a conventional fluorescamine method. RESULTS: Bile salts and pigment content were greater in gallstone-free controls than in all other study groups, including morbidly obese gallstone-free subjects. Total biliary protein concentration, as determined by amino acid analysis in the gallstone-free control group was higher than in non-obese gallstone patients with multiple stones and in morbidly obese gallstone-free subjects. Total biliary proteins as measured with fluorescamine, however, did not show intergroup differences. A major problem of the conventional fluorescamine assay is shown to be an artefact arising from the high pigment content of the more concentrated samples. CONCLUSIONS: Very dilute gallbladder bile samples are often found in the presence of gallstone disease. This also occurs in morbidly obese subjects, even in the absence of gallstones. Although the contribution of protein secretion/absorption by the gallbladder can also be relevant, especially in the presence of morbid obesity, the protein concentration in gallbladder bile, when accurately measured, generally parallels the concentrations of non-absorbed biliary solutes, reflecting the efficiency of fluid absorption. Measurement of biliary proteins by the conventional fluorescamine method is unreliable in clinical studies in which intergroup differences in pigment content are commonly present.

Adult↗
PubMed1995

Correlation between biliary alpha 1-acid glycoprotein concentration and cholesterol crystal nucleation time in gallstone disease.

A biliary form of the alpha 1-acid glycoprotein (AAG) promotes cholesterol crystallization in the lower-molecular-weight, concanavalin A-bound fraction of gallbladder bile. In addition, bile AAG concentration is higher in cholesterol gallstone patients with multiple stones than in control patients without gallstone disease. In this study we sought to determine whether the increased biliary concentration of AAG in cholesterol gallstone patients is accompanied by a more rapid nucleation time in patients with multiple stones. AAG concentration in native biles was measured by ELISA. Nucleation time was measured using a standard microscopy method. The concentration of biliary AAG was then related to nucleation time in biles from the same patients. Nucleation times were significantly shorter (< or = 5 days) in cholesterol gallstone patients with raised AAG concentrations (P < 0.03). There was a significant (P = 0.004) negative correlation (r = -0.53) between nucleation time and the AAG concentration in cholesterol gallstone patients with multiple stones. The concentration of biliary AAG appears to exert an important influence on the speed of cholesterol nucleation in bile in many patients with cholesterol gallstone disease.

Bile↗
PubMed1995

Biliary alpha 1-acid glycoprotein concentrations in gallstone-free controls and in patients with multiple or solitary cholesterol gallstones.

We recently identified a promoting glycoprotein in the concanavalin A-bound fraction of gallbladder bile as a biliary form of alpha 1-glycoprotein (AAG). The concentration of biliary AAG appears to exert an important promoting effect on the speed of cholesterol nucleation in many patients with cholesterol gallstone disease. In the current study, we provide information about the biliary concentration of AAG as well as the amount and comparative potency of its subfractions in patients with and without cholesterol gallstone disease. The amount of total biliary AAG and the amounts of its different isoforms separated by concanavalin A affinity chromatography were measured by ELISA. Estimates of absolute concentrations of AAG for each sample were normalized to the sample total protein content to give relative AAG values. The promoting activity (potency) of immunopurified biliary AAG from gallstone patients and gallstone-free controls on cholesterol crystallization was compared by a crystal growth assay. The mean absolute concentration of AAG in gallstone-free controls was not significantly different from multiple stone patients. The relative concentration of AAG (micrograms per milligram total protein) was significantly increased in patients with multiple stones when compared to controls (P < 0.05), and both the absolute and relative concentrations of AAG (micrograms per milligram bile), were three- and to five fold higher in a number of these patients. The functional activity and distribution of AAG in different subfractions was similar in gallstone patients and gallstone-free controls. The relative concentration of biliary AAG is significantly greater in cholesterol gallstone patients with multiple stones than in gallstone-free controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed1995

New options in eradication of Helicobacter pylori.

Better treatment options to eradicate Helicobacter pylori are needed, while we await a possible effective vaccine against the world's most common infection. The goals of therapy for H. pylori infection should be an effective and low-cost therapy with a low frequency of side-effects. The currently available eradication regimens are cumbersome, which can lead to a reduction of compliance and a lower efficacy. More recent studies have shown, however, that the duration of antimicrobial treatment may be shortened, which also makes the treatment more cost-effective and more tolerable. At this point it seems relevant to treat H. pylori infection first with some antisecretory modification of triple therapy, while the therapeutic failures can be treated with other more relevant and suitable alternatives. Metronidazole is still a cornerstone of triple therapy and the more expensive clarithromycin is an alternative second-line treatment. Time will show the effectiveness and suitability of the latest topical 1-day treatments.

Helicobacter Infections↗
PubMed1994

Identification of human biliary alpha 1-acid glycoprotein as a cholesterol crystallization promoter.

BACKGROUND/AIMS: We have recently outlined the biochemical features of a human 42-kilodalton biliary glycoprotein that shows concentration-dependent cholesterol crystallization-promoting activity. The goal in this work was to establish its identity and to examine some aspects of its biochemical properties relative to its activity. METHODS: Internal amino acid sequencing following tryptic digestion was performed. Based upon this result, immunoreactivity against the 42-kilodalton glycoprotein was examined using a relevant antibody. With the same antibody, the 42-kilodalton glycoprotein was isolated from bile and assayed for activity. Sequential enzymatic deglycosylation of successive terminal glycans of the purified glycoprotein was performed, and the effects on both reductions in molecular radius (M(r)) and on comparative promoter activities were examined. RESULTS: Both amino acid sequence and immunochemical data identify the 42-kilodalton glycoprotein as a biliary form of alpha 1-acid glycoprotein. When purified by immunoaffinity chromatography, potent promoting activity shown was proportionately reduced by successive removal of terminal glycans that also reduced the M(r)s. CONCLUSIONS: The 42-kilodalton cholesterol crystallization-promoting glycoprotein is now identified as a biliary form of alpha 1-acid glycoprotein. Further, some aspects of the important role of glycans in this extensively glycosylated protein have been explored.

Bile↗
PubMed1993

Isolation and characterization of a cholesterol crystallization promoter from human bile.

BACKGROUND: Recent studies on the pathogenesis of cholesterol gallstone disease have focused on the potential importance of an imbalance between biliary proteins having either inhibitory or promoting activities on nucleation and/or growth of cholesterol crystals as the initial stage in stone formation. The current study describes the purification and partial characterization of a 42-kilodalton biliary glycoprotein that shows concentration-dependent cholesterol crystallization-promoting activity. METHODS: Chromatographic methods were used for separation and purification. Characterization steps included electrophoresis, deglycosylation, amino acid and carbohydrate analysis, and activity analysis by crystal growth assay. RESULTS: The 42-kilodalton purified glycoprotein is an extensively glycosylated (37%) monomer with an acidic isoelectric point (pl < 4.1) that is probably based on the sialic acid content of the carbohydrate moiety. Enzymatic N-deglycosylation removes the carbohydrate moiety and inactivates the promoting activity. Furthermore, enzymatic proteolysis results in both its complete structural degradation and functional inactivation. Although the glycoprotein was isolated from normal human gallbladder biles, its presence in gallstone-associated samples is clearly shown. CONCLUSIONS: This report outlines biochemical features of a human biliary glycoprotein that may be of major pathophysiological significance in gallstone disease.

Amino Acids↗