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E Kivilaakso

Publications and source records attributed to E Kivilaakso.

At least 55 records · Page 3Linked to original sources

Risk of gastric carcinoma in patients with mucosal dysplasia associated with atrophic gastritis: a follow up study.

AIMS: To assess the risk of gastric carcinoma in patients with histologically verified dysplasia and atrophic gastritis of the stomach. METHODS: One hundred and one patients with mild (n = 84), moderate (n = 14), or severe (n = 3) dysplasia among 359 elderly men who smoked underwent gastroscopy because of low serum pepsinogen. Patients with dysplasia were prospectively followed up for an average of four years with repeated gastroscopies and multiple biopsies. RESULTS: Four of the 84 (4.8%) cases of mild dysplasia had progressed to moderate dysplasia during the follow up. Most of the cases of mild dysplasia had resolved spontaneously. No surgical intervention was required. Three of the 14 (21%) cases of moderate dysplasia had progressed to severe dysplasia, but no carcinomas were observed during follow up. Five moderately dysplastic lesions were removed surgically or endoscopically. In two of these five cases, moderate or severe dysplasia recurred. Two of the three severe dysplasias progressed to carcinoma. CONCLUSIONS: In atrophic gastritis progression of mild and moderate dysplastic lesions seems to be a slow process and is rare in mild dysplasia. However, severe dysplasia is highly predictive of subsequent cancer. It is suggested that a five year follow up interval is sufficient in cases with mild dysplasia and two years in those with moderate dysplasia. Local removal of moderate dysplasia is indicated but does not guarantee that the lesion will not progress. Severe dysplasia requires immediate surgical intervention.

Aged↗

Anchoring complex components laminin-5 and type VII collagen in intestine: association with migrating and differentiating enterocytes.

Anchoring complex component laminin-5 and its subunits laminin (Ln)-alpha3 and Ln-beta3 chains, Type VII collagen, and integrin chains alpha3, alpha6, and beta4 were studied in developing and adult human intestine and compared with findings on Ln-alpha1 and Ln-alpha2 chains. In adult human duodenum, jejunum, and ileum, Ln-5 detected with a polyclonal antiserum and Ln-alpha3 and Ln-beta3 chains, detected with monoclonal antibodies (MAbs), were restricted to the epithelial basement membranes (BMs) of villi, whereas Ln-alpha2 chain was seen only focally in crypt bottoms. In double labeling experiments, the stretch of crypt BM corresponding to the proliferative cell compartment was found to be devoid of both Ln-alpha3 and Ln-alpha2 chains. Double labeling for Ln-5 and proliferating cell nuclear antigen also showed an abrupt onset of Ln-5 expression exactly at the upper edge of the proliferative cell compartment. Type VII collagen was negligible in duodenum and showed a rising duodenal-ileal gradient localizing to villar BMs. Double labeling for Ln-5 and Type VII collagen, however, indicated only partial co-distribution in the intestine. Electron microscopy of ileum revealed both anchoring filaments and anchoring fibrils but no hemidesmosomal plaques. Our results demonstrate the expression of Ln-5 in BMs outside of stratified epithelia and indicate that Ln-5 in the intestine is associated with the compartment of migrating and differentiating enterocytes. Absence of hemidesmosomes and the presence of other anchoring complex components, such as Ln-5, Type VII collagen, and integrin chains alpha3, alpha6, and beta4, suggests unique properties for epithelial cell attachment in the intestine.

Adult↗

Helicobacter pylori infection in young patients with gastric carcinoma.

BACKGROUND: Helicobacter pylori infection has been linked with chronic atrophic gastritis and gastric cancer. This case-control study was performed to investigate a possible relationship between H. pylori infection and gastric cancer in young age groups. METHODS: Gastrectomy and/or biopsy samples were collected from 50 consecutive patients 45 years old or younger treated between 1980 and 1994 for noncardiac gastric cancer. The control group consisted of age- and sex-matched dyspeptic patients. The presence of H. pylori infection was assessed by modified Giemsa staining and immunostaining, using antibody against H. pylori. RESULTS: H. pylori was found in 36 (72%; 95% confidence interval 60-84%) cancer patients and in 22 (43%; 30-58%) control patients (p = 0.0023, chi-square test). The odds ratio was 3.27 (1.42-7.52). Nonatrophic (superficial) gastritis was present in 30 (60%) cancer patients and in 19 (38%) (p = 0.028, chi-square test) control cases. CONCLUSIONS: The results of the present study support the hypothesis that H. pylori is a risk factor for gastric cancer also in young age groups and in patients with a diffuse type of gastric cancer.

Adult↗

Serum trypsinogen-2 in the prediction of outcome in acute necrotizing pancreatitis.

BACKGROUND: The accuracy of serum trypsinogen-2 in predicting the severity of acute necrotizing pancreatitis (ANP) was prospectively evaluated in 52 consecutive patients. METHODS: A new sensitive immunofluorometric assay was used for serum trypsinogen-2, RESULTS: Mean values during the first 24 h were 42.1 micrograms/l in control patients, 1435 micrograms/l in uncomplicated cases, and 4090 micrograms/l in complicated or fatal cases. There was a significant difference in serum trypsinogen-2 values between patients with uncomplicated and complicated disease (p = 0.002) already on admission. When a cutoff level of 1000 micrograms/l was used, patients with uncomplicated ANP were differentiated from patients with complicated ANP with a sensitivity of 91% and with a specificity of 71%. CONCLUSIONS: The immunofluorometric assay of serum trypsinogen-2 is a sensitive and specific method for prediction of the severity of the disease in necrotizing pancreatitis.

Adult↗

Urine trypsinogen-2 as marker of acute pancreatitis.

We examined the clinical utility of urine trypsinogen-2 as a marker of acute pancreatitis (AP). Fifty-nine patients with AP, 42 with acute abdominal diseases of extrapancreatic origin, and 63 without evidence of acute abdominal disease were studied. Urine trypsinogen-2 was determined by a time-resolved immunofluorometric assay. As reference methods we used serum trypsinogen-2, urine amylase, and serum amylase. The diagnostic accuracy of the markers was evaluated by receiver-operating characteristic (ROC) analysis. At admission, urine trypsinogen-2 differentiated patients with AP from controls with high accuracy. The area under the ROC curve (AUC) was 0.978, which was equal to that of serum trypsinogen-2 (0.998) and serum amylase (0.969) and significantly larger than that of urine amylase. For differentiation between severe and mild AP, urine trypsinogen-2 (0.730) was equal to serum trypsinogen-2 (0.721), and clearly better than amylase in serum and urine. These results suggest that determination of urine trypsinogen-2 is a useful test to detect AP and to evaluate disease severity.

Acute Disease↗

Alpha 6 beta 4 integrin and newly deposited laminin-1 and laminin-5 form the adhesion mechanism of gastric carcinoma. Continuous expression of laminins but not that of collagen VII is preserved in invasive parts of the carcinomas: implications for acquisition of the invading phenotype.

We studied the expression and distribution of different laminin chains, the alpha 6 beta 4 integrin and type VII collagen, i.e., components of the epithelial adhesion complex, in gastric carcinomas and in suggested preneoplastic stages of this malignancy. Intestinal-type gastric carcinomas showed strong reactivity for laminin alpha 1, alpha 3, beta 1, and beta 3 chains, the components of laminin-1 and -5, at the interface between malignant cells and tumor stroma. The reactivities were continuous throughout the carcinomas, even in structures invading through the smooth muscle layers of the gastric wall. The expression of different laminin chains was accompanied by strong polarized reactivity for the alpha 6 beta 4 integrin, which is a receptor for both laminin-1 and laminin-5. Collagen type VII was only occasionally present at sites showing reactivity for laminin-5 and was totally absent from the cell islands invading through the gastric wall. Intestinalized gastric epithelium showed a similar expression pattern of laminins and the alpha 6 beta 4 integrin as the gastric carcinomas. Our results suggest that gastric carcinomas use the alpha 6 beta 4 integrin and newly deposited laminin-1 and -5, accompanied by the disappearance of type VII collagen, as their mechanism of adhesion during the invasion through surrounding tissues. Unlike in previous studies, the reactivity for the laminin-5 protein was not restricted to the invading cells but surrounded the malignant glandular structures throughout the tumor. Our results also show that both intestinal-type gastric carcinoma, and intestinal metaplasia mimic the gastric surface epithelium in the expression pattern of laminins and the beta 4 integrin subunit. This supports previous studies proposing a pathogenetic sequence from intestinal metaplasia to gastric carcinoma.

Antigens, Surface↗

Laparoscopic cholecystectomy: the Finnish experience.

Between January 1992 and December 1994, 5,742 patients were treated by laparoscopic cholecystectomy in 35 Finnish hospitals. The operation was converted to open laparotomy in 360 (6.3%) patients, the most common causes for conversion being technical difficulties in dissection of the gall bladder (2.8%), bleeding (0.9%) and bile duct injury (0.48%). Intraoperative cholangiography was performed selectively in 18%, and common bile duct stones were found in 10.2% of these cases. Postoperative complications occurred in 208 (3.6%) patients, of whom 65 (1.1%) required reoperation. Twenty-eight (0.48%) of these patients had common bile duct injury. In eighteen patients bilio-digestive Roux-en-Y reconstruction was performed, whereas 10 cases could be handled by endoscopic drainage or suturing and T-tube drainage. Thus, the total number of patients with bile duct injury was 56 (0.96%). The reported hospital mortality was 0.08%. The mean hospital stay and the mean sick leave were three days (range 1-41) and 13 days (range 1-60), respectively. These data demonstrate that laparoscopic cholecystectomy can be performed with acceptable morbidity and mortality rates as a routine method in various different hospitals.

Absenteeism↗

Early antibiotic treatment in acute necrotising pancreatitis.

Despite improvements in surgical treatment and intensive care, mortality from severe acute pancreatitis remains high. We have carried out a randomised study of 60 consecutive patients with alcohol-induced necrotising pancreatitis to find out whether early antibiotic treatment can improve outcome. 30 patients were assigned cefuroxime (4.5 g/day intravenously) from admission. In the second group, no antibiotic treatment was given until clinical or microbiologically verified infection or after a secondary rise in C-reactive protein. The inclusion criteria were C-reactive protein concentration above 120 mg/L within 48 h of admission and low enhancement (< 30 Hounsfield units) on contrast-enhanced computed tomography. There were more infectious complications in the non-antibiotic than in the antibiotic group (mean per patient 1.8 vs 1.0, p = 0.01). The most common cause of sepsis was Staphylococcus epidermidis; positive cultures were obtained from pancreatic necrosis or the central venous line in 14 of 18 patients with suspected but blood-culture-negative sepsis. Mortality was higher in the non-antibiotic group (seven vs one in the antibiotic group; p = 0.03). Four of the eight patients who died had cultures from pancreatic necrosis positive for Staph epidermidis. We conclude that cefuroxime given early in necrotising pancreatitis is beneficial and may reduce mortality, probably by decreasing the frequency of sepsis.

Acute Disease↗

Co-localization of NADPH diaphorase reactivity and vasoactive intestinal polypeptide in human colon.

Nitric oxide-containing nervous structures were localized in the human colon using NADPH diaphorase activity and nitric oxide synthase immunoreactivity. We found some, solitary NADPH diaphorase-reactive and nitric oxide synthase-immunoreactive neurons in the submucous plexus, while the myenteric plexus contained several neurons, often arranged in clusters, and nerve fibers showing these markers. The circular muscle layer contained a dense plexus of NADPH diaphorase-reactive nerves, which was greater than that in the longitudinal muscle layer. We report on co-localization of NADPH diaphorase activity and VIP immunoreactivity in several neurons of the myenteric ganglia. Such co-localization has not been reported previously for human colon. Localization of nitric oxide synthase and VIP in the myenteric plexus and in the nerves of circular muscle layer raises the possibility that nitric oxide contributes to the regulation of motility in the human colon.

Colectomy↗

Catecholamine-synthesizing enzymes in the rat stomach.

Local production of catecholamines in the stomach of the rat was studied by immunohistochemical demonstration of tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT), the enzymes catalyzing the formation of dopamine, noradrenaline and adrenaline, respectively. A rich innervation of TH- and DBH-immunoreactive nerve fibers was seen in the muscular layers and the myenteric plexus, in the submucosa and in the walls of submucosal blood vessels and in the lamina propria at the base of the epithelial layer. In addition, TH-, but not DBH-immunoreactive nerve fiber networks surrounding ganglion cells in the myenteric plexus were frequently observed, indicating dopaminergic preganglionic innervation of the myenteric plexus. In the oxyntic epithelium, single TH- and DBH-immunoreactive fibers extended in the strands of lamina propria as far as the middle portion of the gastric glands. A small population of single angulate cells in the oxyntic epithelium showed TH-, but not DBH-immunoreactivity. No specific PNMT immunoreactivity was observed.

Animals↗

Recent trends in mortality from peptic ulcer disease in Finland.

The enormous change of medical therapy of peptic ulcer disease in the 1970s has resulted in a significant decrease of elective ulcer surgery. It has been speculated whether this might be reflected in the mortality of the disease. Therefore, in the present study, the mortality rate of the disease was evaluated in Finland during the past 17 years covering the dramatic change in the medical therapy: the introduction of H2-receptor antagonists. This was done with a population-based epidemiological study by analyzing 1262 death certificates of people dying from peptic ulcer disease in Finland between 1972 and 1989. The study showed that there has been almost twofold increase in the mortality of the disease between 1972 and 1989 in Finland. This was mainly due to the significantly increased number of fatal ulcer hemorrhages in older people, but also mortality from ulcer perforations increased. This unfavorable epidemiological progress was most striking among elderly women and became manifest during the 1980s. We conclude that mortality from peptic ulcer disease has significantly increased in Finland due to fatal ulcer hemorrhages and perforations. This epidemiological change became manifest in the 1980s, concurrently with the dramatic change in the medical therapy of peptic ulcer disease.

Adult↗

Changes in substance P-immunoreactive innervation of human colon associated with ulcerative colitis.

The amount of colonic substance P and substance P-receptors is increased in ulcerative colitis, which may denote that substance-P is involved as a neurogenic mediator in the inflammatory process of ulcerative colitis. We studied the anatomical distribution of elevated colonic substance P in ulcerative colitis and assessed morphometrically whether the changes in substance P correlate with alterations in colonic innervation. Full-thickness specimens of colonic wall were obtained from normal human colons (N = 9) and the most and least affected regions of ulcerative colitis colons (N = 10) and immunostained for substance P. Substance P immunoreactivity index was calculated by multiplying each intensity value by the number of pixels exhibiting this intensity value. The numbers of substance P-immunoreactive nerve fibers in the lamina propria were markedly increased, and their fluorescence intensity was enhanced in ulcerative colitis. The longitudinal muscle layer contained substance P-immunoreactive nerve fibers in ulcerative colitis, but not in the controls. The substance P-immunoreactive index (= number x intensity of nerve fibers) was 3.42 +/- 1.49 in controls, 21.19 +/- 7.79 in mild ulcerative colitis regions (P < 0.05), and 29.68 +/- 9.81 in severe ulcerative colitis regions (P < 0.01). Increase in the number of substance P nerve fibers is in accordance with the hypothesis that substance P contributes to neurogenic mediation of inflammation in ulcerative colitis.

Aged↗

Regulation of intracellular pH in isolated Necturus gastric mucosa during short-term exposure to luminal acid.

BACKGROUND/AIMS: Continuous exposure to gastric acid implies efficient control mechanisms of intracellular pH (pHi) in the gastric epithelium. This study assessed the roles of Na+, H+, and HCO3- transport mechanisms in controlling pHi during short-term exposure of the gastric epithelium to luminal acid. METHODS: pHi and Na+ activity (aiNa) were measured with liquid sensor microelectrodes in isolated Necturus antral mucosa, modulating ion transport mechanisms by ion removal and pharmacological inhibition. RESULTS: Short-term exposure to luminal acid (pH 2.3) acidified pHi by 0.3 pH units, whereafter pHi stabilized. This was associated with transient increase in aiNa. Blocking of Na+/H+ exchange (in the presence of HCO3-/CO2) by removal of Na+ or addition of amiloride eliminated the increase in aiNa and resulted in uncontrolled acidification of pHi. Similarly, blocking of HCO3- transport (in the presence of Na+) by removal of HCO3-/CO2 or addition of 4-acetamido-4-isothiocyanatostilbene-2,2-disulfonic acid resulted in uncontrolled acidification of pHi despite increase in aiNa. Blocking of Na+/K+ exchange with ouabain eliminated the recovery of aiNa and also resulted in uncontrolled acidification of pHi. CONCLUSIONS: The data indicate that during short-term exposure of the gastric mucosa to luminal acid, both Na+/H+ antiport and HCO3- transport are needed to control pHi and maintain it within physiological ranges.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

Milk and egg phospholipids act as protective surfactants against luminal acid in Necturus gastric mucosa.

BACKGROUND: Our previous studies indicate that milk phospholipids have anti-ulcer properties in rats and humans, possibly by forming a hydrophobic surfactant layer at the epithelial surface. In the present study we measured intracellular pH and parameters of membrane resistances in gastric epithelium exposed to luminal acid using a microelectrode technique. METHODS: Chambered isolated Necturus maculosus antral mucosa was exposed to pH 2.3, with or without 20-25 min pre-treatment with milk or egg phospholipids. The pH in surface epithelial cells was measured with double-barrelled liquid sensor pH/PD-microelectrodes. RESULTS: Pre-treatment with phospholipids (2500-5000 micrograms P/mL) significantly (P < 0.01, n = 14) opposed intracellular acidification. Phospholipids significantly (P < 0.05, n = 14) increased the ratio of apical and basal membrane resistances, suggesting that they primarily affect the apical cell membrane. In contrast, there was no significant change in transmucosal resistance suggesting lack of effect on paracellular shunts in the 'leaky' epithelium. CONCLUSIONS: Exogenous phospholipids of dietary origin may be used to form a protective layer in the gastric mucosa against irritants.

Animals↗

Cure of peptic gastric ulcer associated with eradication of Helicobacter pylori. Finnish Gastric Ulcer Study Group.

The effect of Helicobacter pylori eradication on ulcer healing and the relapse rate were investigated in a multicentre trial of 239 gastric ulcer patients. Patients with H pylori positive gastric ulcer were randomly assigned to one of three groups: (A) 10 days' treatment with metronidazole and eight weeks' treatment with colloidal bismuth subcitrate (CBS) (84 patients); (B) 10 days' treatment with metronidazole placebo and eight weeks with CBS (73 patients); or (C) ranitidine (82 patients). At 12 weeks in 210 patients, gastric ulcer was present in three (9%) of 35 H pylori negative patients, and in 45 (26%) of 175 H pylori positive patients (p < 0.05). Results after one year of follow up were available for 205 patients. Between 12 and 52 weeks, two (7%) ulcer relapses occurred in 29 H pylori negative patients and in 60 (47%) of 128 H pylori positive patients (p < 0.001). After two weeks of open triple therapy (CBS 120 mg four times daily, amoxicillin 500 mg four times daily, and metronidazole 400 mg three times daily), given to the patients with ulcer relapse, only one (an NSAID user) of 55 successfully treated patients had an ulcer relapse during the one year follow up. Healing of gastric ulcer is rapid and recurrence is infrequent after successful H pylori eradication. H pylori eradication changes the natural history of the gastric ulcer disease.

Adult↗

Differential expression of laminin chains and their integrin receptors in human gastric mucosa.

The proliferating cells of the gastric mucosa are found among the pit and mucous neck cells. These cells migrate upward to renew the surface epithelium and downward to restitute the glandular cells. As the epithelial basement membranes (BMs) function as substrate for cell adhesion and migration as well as signals for their differentiation, we studied, by indirect immunofluorescence microscopy, the distribution of different laminin chains and their integrin receptors in adult human stomach. The immunoreactivity for laminin alpha 2 chain localized to the BMs of glands and the lower parts of the gastric pits whereas the laminin alpha 3 chain (laminin-5/kalinin) immunoreactivity was strictly confined to BMs underneath the surface epithelium and the upper parts of the pits. Proliferating mucosal epithelial cells, identified by Ki-67 antibodies, were confined to the areas containing both alpha 2 and alpha 3 laminin chains. The alpha 1, beta 1, and gamma 1 laminin chains were found in all BMs of the mucosa whereas the beta 2 chain was prominent in mucosal blood vessels and also detectable in some glands. Among the laminin integrin receptors, the alpha 3 and beta 4 subunits were seen to be expressed in cells along the BMs with the alpha 3 laminin chain. The alpha 6 integrin, on the other hand, was seen in all gastric epithelia. The present results demonstrate that in the adult human stomach laminin alpha 2 and alpha 3 chains show zonal distribution in BM underlying gastric mucosal epithelium whereas other laminin chains show a more general distribution.

Adult↗

Effect of vagotomy on expression of neuropeptides and histamine in rat oxyntic mucosa.

The effect of vagotomy and pyloroplasty on the density of nerve fibers containing bombesin/gastrin-releasing peptide (GRP), calcitonin gene-related peptide (CGRP), and galanin as well as histamine-, 5-hydroxytryptamine (5-HT)-, and somatostatin-containing cells in the oxyntic mucosa of the rat stomach was studied. Ten days after vagotomy and pyloroplasty the density of histamine-containing cells in the oxyntic mucosa was increased by 70% (P < 0.05), and these cells were larger and showed more extensive cell processes than in control animals. The density of 5-HT-immunoreactive (IR) cells and somatostatin-IR cells were not affected. A marked decrease in the density of CGRP-IR nerve fibers and a slighter decrease in the density of GRP-IR nerve fibers was observed in the mucosal layer, while only a minor reduction of CGRP-IR fibers, and no reduction of GRP-IR fibers was seen in the muscular layer. The density of galanin-IR nerve fibers was not affected. The height of the oxyntic mucosa was reduced by about 25% (P < 0.05). Thus, a striking effect on the histamine-IR cells was seen, supporting the view that these cells are regulated by the vagus nerve. The study also indicates that a major portion of the CGRP-IR nerve fibers, and part of the GRP-IR nerve fibers, in the mucosal layer of the fundic region are of vagal origin or regulated by normal vagus nerve activity.

Animals↗