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P Miettinen

Publications and source records attributed to P Miettinen.

At least 19 recordsLinked to original sources

Changes of gastric mucosal architecture during long-term omeprazole therapy: results of a randomized clinical trial.

BACKGROUND: The impact of long-term acid suppression on the gastric mucosa remains controversial. AIM: To report further observations on an established cohort of patients with gastro-oesophageal reflux disease, after 7 years of follow-up. METHODS: Of the original cohort randomized to either antireflux surgery or omeprazole, 117 and 98 patients remained in the medical and surgical arms, respectively. Gastric biopsies were taken at baseline and throughout the study. RESULTS: Fifty-three antireflux surgery and 39 omeprazole-treated patients had Helicobacter pylori infection at randomization. Eighty-three omeprazole-treated and 60 antireflux surgery patients remained H. pylori negative over the 7 years, and no change was observed in mucosal morphology except for a change in endocrine cell population (linear and diffuse hyperplasia, P = 0.03). During the 7-year study many patients, who were initially H. pylori infected, had the infection eradicated leaving only 13 omeprazole and 12 antireflux surgery patients still infected. In these patients, omeprazole induced a deterioration of the mucosal inflammation scores (P = 0.01) with a numerical increase of glandular atrophy. CONCLUSIONS: Long-term omeprazole therapy does not alter the exocrine oxyntic mucosal morphology in H. pylori-negative patients, but mucosal endocrine cells appear to be under proliferative stimulation; in H. pylori-positive patients there are changes in mucosal inflammation and atrophy.

Aged↗

Minilaparotomy cholecystectomy versus laparoscopic cholecystectomy: a randomized study with special reference to obesity.

BACKGROUND: Minilaparotomy cholecystectomy (MC) has recently challenged the role of the laparoscopic approach (LC) for cholecystectomies. However, the situation is far from clear when operating times and recovery are evaluated. METHODS: Altogether 157 patients with uncomplicated symptomatic gallstones were randomized into MC (n = 85) and LC (n = 72) groups. Both groups were similar in terms of age, body mass index, American Society of Anesthesiology (ASA) physical fitness classification, and operating surgeon. RESULTS: The mean operating time was 55 +/- 19.5 min in the MC group and 79 +/- 27.0 min in the LC group (p < 0.0001). The postoperative hospital stay and length of sick leave did not differ between the two groups. There were no significant differences in postoperative pain, analgesic consumption, or postoperative pulmonary function between the groups. The body mass index did not influence operating time or patient recovery in either group. No major complications occurred in either groups. CONCLUSION: The MC procedure seems to be a faster technique than the LC approach for noncomplicated gallstone disease, with no difference in recovery times. The MC procedure also seems to be suitable for the obese patient.

Adolescent↗

Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric banding.

UNLABELLED: Maintenance of human energy homeostasis is regulated by a complex network. Peptides secreted from the gastrointestinal tract (GI) are signaling to the brain and other organs initiating or terminating food intake and energy expenditure. In the present study we investigated basal plasma levels of apelin, orexin-A, and leptin in morbid obese patients. In addition, we measured in a subgroup of these patients in the same individual orexin-A and leptin plasma levels one year after gastric banding surgery. METHODS: Basal plasma values were determined in obese patients (BMI=48+/-1 kg/m2n=32) after an overnight fast and compared to healthy, normal weighted (BMI=22+/-2 kg/m2n=12) controls. In addition, blood samples were collected in a subgroup of patients (BMI=48+/-1 kg/m2n=8) the day before surgery and 1 year after the operation. Apelin, orexin-A, and leptin levels were analysed using ELISAs. RESULTS: One year after the operation obese patients significantly lost weight (from 48+/-2 kg/m2 to 39+/-2 kg/m2; p<0,001). Apelin, orexin-A and leptin levels in obese patients were significantly higher compared to control individuals (736+/-50 pg/ml vs. 174+/-14 pg/ml, p<0.0001; 75.3+/-24.1 pg/ml vs. 0.8+/-0.4 pg/ml, p<0.0001; 79.0+/-2.4 ng/ml vs. 5.8+/-0.8 ng/ml, p<0.0001, respectively). Apelin and leptin plasma concentrations also correlated significantly with BMI (r=0.769, p<0.0001; r=0.778; p<0.0001, respectively), while orexin-A correlation was rather weak (r=0.335, p<0.03). No difference between pre- and post-operative orexin-A levels was observed, while leptin plasma levels significantly decreased from 45.1+/-5.4 ng/ml to 27.3+/-6.0 ng/ml (p=0.015). CONCLUSIONS: Apelin, orexin-A, and leptin plasma levels correlated positively with the BMI. One year after gastric banding with significant loss in BMI basal plasma levels of leptin decreased, while orexin-A remained unchanged.

Adult↗

Effect of total colectomy and PYY infusion on food intake and body weight in rats.

PYY (3-36) is postulated to act as a satiety factor in the gut-hypothalamic pathway to inhibit food intake and body weight gain in humans and rodent models. We determined the effect of 14-day continuous intravenous infusion of PYY (3-36) (175 microg/kg/day) on food intake and body weight gain in colectomized male Wistar rats. Colectomy caused an increase in plasma PYY levels at 7 days which was reduced at 14 days but still significantly elevated compared to basal preoperative values. Animals treated with continuous PYY (3-36) infusion had significantly elevated PYY levels compared to the control group throughout the whole experiment, but showed a similar pattern of food intake and body weight gain. In conclusion, although continuous intravenous infusion is the most physiologically relevant method to mimic high postprandial PYY levels, we did not observe any significant effect on food intake and body weight gain in non-food deprived colectomized animals. This suggests that PYY has, if at all, only a minor role in food intake in rats.

Animals↗

Effect of short-term treatment with regular or high doses of omeprazole on the detection of Helicobacter pylori in bleeding peptic ulcer patients.

BACKGROUND: It is unknown whether short-term regular or high-dose omeprazole has any influence on the colonization of Helicobacter pylori in the stomach. We therefore studied the effect of 3-day treatment of 2 different doses of omeprazole. METHODS: H. pylori-positive patients with peptic ulcer bleeding (n = 101) were randomized to receive either a regular dose (20 mg/day for 3 days) (n = 51) or a high dose of omeprazole (80 mg bolus + 8 mg/h infusion/day for 3 days) (n = 50). H. pylori status was assessed by histology and urease testing of gastric biopsies pre-entry and after 3-day therapy. RESULTS: With the high dose of omeprazole, tests for the diagnosis of H. pylori became negative significantly more often than with the regular dose (60% versus 27.5%, P=0.001 (any test), 67.6% versus 31.7%, P=0.003 (histology) and 82.2% versus 43.6%, P=0.001 (urease test)). CONCLUSION: Conversion of the H. pylori tests negative after 3-day treatment of omeprazole is dose-dependent. The diagnosis of H. pylori infection depends on the timing of biopsies in relation to the beginning of proton-pump inhibitor treatment. If samples to find H. pylori are not taken before the treatment, the presence of the bacteria may be overlooked.

Anti-Ulcer Agents↗

Continued (5-year) followup of a randomized clinical study comparing antireflux surgery and omeprazole in gastroesophageal reflux disease.

BACKGROUND: The efficacy of antireflux surgery (ARS) and proton pump inhibitor therapy in the control of gastroesophageal reflux disease is well established. A direct comparison between these therapies is warranted to assess the benefits of respective therapies. STUDY DESIGN: There were 310 patients with erosive esophagitis enrolled in the trial. There were 155 patients randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. Because of various withdrawals during the study course, 122 patients originally having an antireflux operation completed the 5-year followup; the corresponding figure in the omeprazole group was 133. Symptoms, endoscopy, and quality-of-life questionnaires were used to document clinical outcomes. Treatment failure was defined to occur if at least one of the following criteria were fulfilled: Moderate or severe heartburn or acid regurgitation during the last 7 days before the respective visit; Esophagitis of at least grade 2; Moderate or severe dysphagia or odynophagia symptoms reported in combination with mild heartburn or regurgitation; If randomized to surgery and subsequently required omeprazole for more than 8 weeks to control symptoms, or having a reoperation; If randomized to omeprazole and considered by the responsible physician to require antireflux surgery to control symptoms; If randomized to omeprazole and the patient, for any reason, preferred antireflux surgery during the course of the study. Treatment failure was the primary outcomes variable. RESULTS: When the time to treatment failure was analyzed by use of the intention to treat approach, applying the life table analysis technique, a highly significant difference between the two strategies was revealed (p < 0.001), with more treatment failures in patients who originally were randomized to omeprazole treatment. The protocol also allowed dose adjustment in patients allocated to omeprazole therapy to either 40 or 60 mg daily in case of symptom recurrence. The curves subsequently describing the failure rates still remained separated in favor of surgery, although the difference did not reach statistical significance (p = 0.088). Quality of life assessment revealed values within normal ranges in both therapy arms during the 5 years. CONCLUSIONS: In this randomized multicenter trial with a 5-year followup, we found antireflux surgery to be more effective than omeprazole in controlling gastroesophageal reflux disease as measured by the treatment failure rates. But if the dose of omeprazole was adjusted in case of relapse, the two therapeutic strategies reached levels of efficacy that were not statistically different.

Aged↗

Outcome and resource utilization in gastroenterological surgery.

BACKGROUND: A small minority of patients undergoing gastroenterological surgery are at high risk for postoperative complications, which may lead to prolonged hospital stay, disproportionate use of resources and increased mortality. The nature and frequency of, and predictive factors for, postoperative complications were studied and the impact of complications on resource utilization was assessed. METHODS: A prospective observational study was undertaken of 503 patients undergoing gastroenterological surgery in a tertiary care centre. The incidence of cardiorespiratory, infective and surgical complications was assessed. The need for reoperation, intensive care and length of hospital stay, readmission, death at 6 months and costs were evaluated. RESULTS: Some 235 patients (47 per cent) had at least one complication, most commonly delayed oral intake (n = 70). Complications were associated with cardiovascular disease, prolonged operation, high Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity, and increased number of Shoemaker's criteria. The length of hospital stay of patients with complications was longer than that of those without complications (11 versus 6 days). Morbidity resulted in a twofold increase in median costs. CONCLUSION: High-risk patients could be identified by simple clinical criteria, although the commonly used risk criteria were not very sensitive. A reduction in postoperative complication rates would result in marked cost savings.

Adolescent↗

Regular-dose versus high-dose omeprazole in peptic ulcer bleeding: a prospective randomized double-blind study.

BACKGROUND: It has been suggested that profound acid inhibition along with endoscopic therapy might prevent rebleeding and reduce mortality in patients with peptic ulcer bleeding. The aim of the study was to test the possible equivalence of a high dose and the regular dose of omeprazole in peptic ulcer bleeding. METHODS: We performed a prospective randomized double-blind study involving 142 patients with acute peptic ulcer bleeding (Forrest classification I-II: spurting or oozing bleeding, non-bleeding visible vessel, clot and black base). One-hundred-and-two (71.8%) patients received endoscopic treatment (adrenaline injection and/or heater probe) in pre-entry. Patients were randomly assigned to receive the regular dose of omeprazole intravenously (20 mg once a day for 3 days, i.e. 60 mg/72 h) or a high dose of omeprazole (80 mg bolus + 8 mg/h for 3 days, i.e. 652 mg/72 h). Rebleeding, surgery and death were the outcome measures. RESULTS: Six (8.2%) of the 73 patients receiving the regular dose of omeprazole and 8 (11.6%) of the 69 patients receiving the high dose of omeprazole rebled (P = 0.002 for equivalence, equivalence limit 0.15). Three (4.1%) of the former patients and 5 (7.2%) of the latter group underwent surgery. Four (5.5%) patients in the regular-dose and 2 (2.9%) in the high-dose group died within 30 days. CONCLUSION: Under the defined tolerance limits, the regular dose of omeprazole is as successful as a high dose in preventing peptic ulcer rebleeding.

Aged↗

Health-related quality of life before and after gastrointestinal surgery.

OBJECTIVE: To assess the impact of surgical treatment on health-related quality of life (QoL) and its various dimensions in four common gastrointestinal diseases, to compare it with that of the general population, and to assess the relationship between the patient's and the surgeon's satisfaction. DESIGN: Prospective, observational study. SETTING: Tertiary care centre, Finland. PATIENTS: 131 patients, of whom 77 had cholecystectomy, 20 fundoplication, 20 incisional herniorrhaphy, 12 large bowel resection, and 2 construction of a stoma only because of unresectable colorectal cancer. INTERVENTIONS: Routine operative treatment of four gastrointestinal diseases. MAIN OUTCOME MEASURES: QoL measured by a generic 15-dimensional instrument. RESULTS: The health-related QoL improved postoperatively in the entire group. Discomfort, symptoms, and vitality were all reduced at 2 months, whereas bowel movements, eating, and usual activities had been restored at 12 months. The health related QoL was comparable with that of the general population at 12 months except for breathing and sleeping. The pattern of recovery varied among diagnostic subgroups, being most improved in patients operated on for biliary disease, those aged 60 years or younger, women and otherwise previously healthy patients. There was a close agreement between the patient's and the surgeon's opinion of outcome. CONCLUSIONS: Gastrointestinal surgery improves quality of life. Separating a generic health-related QoL measure into dimensions allows a more appropriate estimation of quality of life than a single index score. Because some dimensions were made worse soon after operation and some were restored slowly, a minimum 12-month follow-up may be needed to assess the effect of gastrointestinal surgery on health- related QoL.

Aged↗

The cost of long term therapy for gastro-oesophageal reflux disease: a randomised trial comparing omeprazole and open antireflux surgery.

BACKGROUND AND AIM: To comprehensively assess the relative merits of medical and surgical therapy for gastro-oesophageal reflux disease (GORD), health economic aspects have to be incorporated. We have studied the direct and indirect costs of medical and surgical therapy within the framework of a prospective randomised multicentre trial. METHODS: After initial treatment of reflux oesophagitis with omeprazole to control symptoms and to heal oesophagitis, 154 patients were randomised to continue treatment with omeprazole (20 or 40 mg daily) and 144 patients to have an open antireflux operation (ARS). In case of GORD relapse, patients allocated to omeprazole were offered ARS and those initially operated on had either a reoperation or were treated with omeprazole. The costs were assessed over five years from randomisation. RESULTS: Differences in cumulative direct medical costs per patient between the two therapeutic strategies diminished with time. However, five year direct medical costs per patient when given omeprazole were still significantly lower than for those having ARS in Denmark, Norway, and Sweden (differences were DKK 8703 (US$1475), NOK 32 992 (US$ 5155), and SEK 13 036 (US$ 1946), respectively). However, in Finland the reverse was true (the difference in favour of ARS amounted to FMK 7354 (US$ 1599)). When indirect costs (loss of production due to GORD related sick leave) were also included, the cost of surgical treatment increased substantially and exceeded the cost of medical treatment in all countries. CONCLUSIONS: The total costs of medical therapy for chronic GORD were lower than those of open ARS when prospectively assessed over a five year period, although significant differences in cost estimates were revealed between countries.

Aged↗

Long-term management of gastro-oesophageal reflux disease with omeprazole or open antireflux surgery: results of a prospective, randomized clinical trial. The Nordic GORD Study Group.

BACKGROUND AND AIM: The efficacy of antireflux surgery (ARS) and omeprazole treatment in the control of gastrooesophageal reflux disease (GORD) are well established. We have compared these two therapeutic options in a randomized, clinical trial. PATIENTS AND METHODS: Three hundred and ten patients with erosive oesophagitis were enrolled into the trial. After a run-in period when all patients had < or = 40 mg of omeprazole daily to heal the oesophagitis and relieve symptoms, 155 patients were randomized to continuous omeprazole therapy and 155 to open antireflux surgery, of whom 144 later had an operation. One hundred and thirty-nine and 129 in the omeprazole and antireflux surgery groups, respectively, completed the 3-year follow-up. Symptoms, 24-h pH monitoring and endoscopy were used to document the outcome. Quality of life was evaluated by the psychological general well-being (PGWB) index and the gastrointestinal symptom rating scale (GSRS). RESULTS: Analysis of time to treatment failure (defined as moderate to severe GORD symptoms for > or = 3 days during the last 7 days, oesophagitis or changed therapy) revealed a significant difference in favour of antireflux surgery (P = 0.0016). Seventeen patients originally submitted to antireflux surgery experienced symptom relapse alone, 14 had oesophagitis at endoscopy and another six had omeprazole for different reasons, leaving 97 patients in clinical remission after 3 years. The corresponding figures in the omeprazole arm were 50 relapses, 18 with oesophagitis, two had surgery, leaving 77 patients in remission. Allowing a dose adjustment in the case of relapse in those on omeprazole therapy to either 40 or 60 mg, the curves describing the failure rates were not significantly different from each other. Quality of life assessment showed a comparable outcome in the two study groups. CONCLUSION: In this randomized multicentre trial we found antireflux surgery to be very efficacious in controlling GORD, a level of control which could also be achieved by omeprazole provided that advantage was taken of the opportunity of adjusting the dose.

Adult↗

Lack of effect of acid suppression therapy on gastric atrophy. Nordic Gerd Study Group.

BACKGROUND & AIMS: A hypothesis suggesting that profound acid inhibition therapy facilitates and hastens the development of gastric glandular atrophy in patients infected with Helicobacter pylori was investigated in this randomized study comparing omeprazole therapy with antireflux surgery (ARS) for chronic gastroesophageal reflux disease (GERD). METHODS: Patients with esophagitis and/or chronic GERD were enrolled; 155 patients were randomized to ARS and 155 to long-term omeprazole therapy. Baseline data were obtained and repeated after 3 years in 131 ARS patients and in 139 omeprazole-treated patients. Histopathologic status of the oxyntic mucosa was assessed according to the Sydney system. RESULTS: Forty omeprazole-treated patients were infected with H. pylori compared with 53 in the ARS group. Basal gastrin levels were significantly higher in H. pylori-infected patients, particularly in the omeprazole group. No further increases in serum gastrin levels were observed during 3 years. Despite 3 years of therapy, only slight changes were found in the prevalence of inflammation in the corpus mucosa of H. pylori-infected subjects. A slow progression of gastric glandular atrophy was observed in these patients irrespective of therapy with no obvious difference between treatment regimens. Intestinal metaplasia (all of type I) was only exceptionally observed with no difference between the treatment arms. CONCLUSIONS: Acid-suppressive therapy in the form of omeprazole maintained for 3 years facilitates neither the development of gastric glandular atrophy of the corpus mucosa nor the occurrence of intestinal metaplasia in H. pylori-infected GERD patients.

Adolescent↗

Site-specific changes in transforming growth factor-alpha and -beta1 expression in colonic mucosa of adolescents with inflammatory bowel disease.

BACKGROUND: Transforming growth factors (TGF-alpha and -beta1) play important roles in intestinal growth and repair. To further understand their roles in the pathophysiology of inflammatory bowel disease (IBD), this study examined changes in their expression in colonic mucosa of adolescents with IBD. METHODS: TGF-alpha and -beta1 expression was examined by immunohistochemistry and in situ hybridization. RESULTS: TGF-gamma immunostaining and mRNA labelling appeared unchanged in the epithelium of specimens with active IBD. Similarly, expression of epithelial TGF-beta1 remained unaltered in IBD. However, the numbers of TGF-beta1-positive cells, including T cells, neutrophils, and monocytes/macrophages, in the lamina propria increased during disease activity. CONCLUSIONS: Adolescent IBD is characterized by a normal expression of TGF-alpha and -beta1 peptide and mRNA in the colonic epithelium but by an increased density of TGF-beta1-positive immune cells in the lamina propria during disease activity, suggesting a role in inflammatory modulation in IBD.

Adolescent↗

Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor.

Stimulation of the epidermal growth factor receptor (EGF-R) produces numerous effects on central nervous system (CNS) cells in vitro including neuronal survival and differentiation, astrocyte proliferation and the proliferation of multipotent progenitors. However, the in vivo role of EGF-R is less well understood. In the present study, we demonstrate that EGF-R null mice generated on a 129Sv/J Swiss Black background undergo focal but massive degeneration the olfactory bulb, piriform cortex, neocortex, and thalamus between postnatal days 5 and 8 which is due, at least in part, to apoptosis. Some of the neuronal populations that degenerate do not normally express EGF-R, indicating an indirect mechanism of neuronal death. There were also delays in GFAP expression within the glia limitans and within structures outside the germinal zones in early postnatal ages. At or just prior to the onset of the degeneration, however, there was an increase in GFAP expression in these areas. The brains of EGF-R (-/-) animals were smaller but cytoarchitecturally normal at birth and neuronal populations appeared to be intact, including striatal GABAergic and midbrain dopaminergic neurons which have previously been shown to express EGF-R. Multipotent progenitors and astrocytes derived from EGF-R (-/-) mice were capable of proliferating in response to FGF-2. These data demonstrate that EGF-R expression is critical for the maintenance of large portions of the postnatal mouse forebrain as well as the normal development of astrocytes.

Animals↗

Comprehensive 1-year cost analysis of open antireflux surgery in Nordic countries. Nordic GORD Study Group. Gastro-oesophageal reflux disease.

BACKGROUND: Antireflux surgery is a highly effective treatment option in patients with severe gastro-oesophageal reflux disease. However, because of the increasing pressure of cost containment within health care, cost aspects must also be added to the decision-making process. METHODS: The aim of this analysis was to assess the total cost of open antireflux surgery during the first year after operation in 178 patients with chronic reflux, who were recruited into a controlled, prospective clinical trial. The study was carried out in 17 hospitals in the Nordic countries. RESULTS: The cost of the operation represented more than 90 per cent of the direct medical costs which amounted to approximately US $5700. For a patient in the work force the indirect cost, i.e. loss of production, represented 47 per cent of the total cost, which was about US $10800. CONCLUSION: The total cost profile of open antireflux surgery has now been established prospectively and can form a basis for future comparisons.

Adolescent↗

Outcome of open antireflux surgery as assessed in a Nordic multicentre prospective clinical trial. Nordic GORD-Study Group.

OBJECTIVE: To evaluate the outcome of antireflux surgery in various hospitals in Scandinavian countries. DESIGN: Partly randomised controlled study, and partly open study. SETTING: Hospitals throughout Norway, Sweden, Denmark and Finland. SUBJECTS: 310 patients with chronic reflux disease and oesophagitis who were initially entered into a randomised controlled study of omeprazole and antireflux surgery. INTERVENTIONS: Total fundic wrap, partial fundoplication, or omeprazole. MAIN OUTCOME MEASURES: Control of symptoms at one year. RESULTS: 154 patients who had their symptoms of reflux completely controlled with omeprazole were initially randomised to have an open operation but 10 refused, leaving 144 for analysis. 34 patients who had only a partial response were also offered operation; 120/178 (68%) had a total fundic wrap, and 53 (30%) partial fundoplication. 6 patients had postoperative complications that required reoperation and 123 made a completely uneventful recovery. Reflux was controlled in most patients, and only 10 (6%) required further treatment with omeprazole. The outcome in those patients who only responded partially to omeprazole was similar to that in patients who had a complete response. CONCLUSION: The outcome of antireflux surgery throughout Norway, Sweden, Denmark, and Finland is good.

Adolescent↗