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Objective: Apolipoprotein E (apoE) polymorphism affects the risk of advanced coronary artery disease, but its role in early atherosclerosis remains unknown. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to the apoE genotype., Material and Methods: Samples from 44 mildly hypercholesterolaemic men (aged 35 +/- 4 years) of an earlier trial were re-analysed according to apoE genotype. Subjects were randomized to receive either 40 mg/day pravastatin or placebo for 6 months. To assess coronary reactivity, myocardial blood flow was measured by PET at rest and during adenosine infusion. PET studies and lipid analyses were done at baseline and after 6 months of therapy., Results: There were no differences between apoE epsilon3/3 and epsilon4/3 genotypes in basal or adenosine-stimulated flow or in coronary flow reserve (CFR) at baseline. There was a significant apoE genotype-by-treatment group interaction regarding the change in adenosine-stimulated flow (ANCOVA; p = 0.018) and CFR (p = 0.020) at the end of the study. In the pravastatin group, the adenosine-stimulated flow increased by 32.5 % in subjects with epsilon3/3 (n = 9), but decreased non-significantly (-14.4 %) in subjects with epsilon4/3 (n = 9) (p = 0.0009). The corresponding changes in CFR were +17.8 % for epsilon3/3 and (-11.9 % for epsilon4/3 (p = 0.05). There were no significant changes from the baseline values in placebo recipients. After pravastatin treatment, both genotype groups showed a similar decrease in serum total and low-density lipoprotein cholesterol (p<0.0001 for both)., Conclusions: Coronary function improves by 6 months of pravastatin in subjects with the apoE epsilon3/3 genotype, but not in those with the epsilon4/3.

Objective: To assess the mortality and causes of death in a cross-sectional population-based study of 1042 patients with rheumatoid arthritis (RA)., Methods: In 1988, 604 RA patients [470 females (F), 134 males (M)] and 457 age- and sex-matched controls (352 F, 105 M) were examined prospectively (participants) and 438 (183 F, 81 M) non-participant RA patients retrospectively. In 1999, vital status and causes of death were determined. Mortality in the total RA population was compared to that in the general population, and that among participant RA patients to their matched controls., Results: A total of 384 (37%) RA patients and 71 (16%) controls died. RA patients had increased mortality compared to the general population (standardized mortality ratios SMR 2.64) or controls (1.71). This was observed in both sexes. Over 40% of deaths in all groups were due to cardiovascular diseases. RA patients were at increased risk of dying of urogenital, gastrointestinal, respiratory and cardiovascular diseases, infections, and cancers when compared to the general population or controls., Conclusions: Our results show that a cross-sectional cohort of RA patients had an increased risk of death from various causes.

Background: Evidence suggests the acceptability of oats in a gluten-free diet in coeliac disease. We investigated the impact of an oats-containing diet on quality of life and gastrointestinal symptoms., Methods: Thirty-nine coeliac disease patients on a gluten-free diet were randomized to take either 50 g of oats-containing gluten-free products daily or to continue without oats for 1 year. Quality of life was assessed using the Psychological General Well-Being questionnaire and gastrointestinal symptoms using the Gastrointestinal Symptom Rating Scale. Small-bowel mucosal villous architecture, CD3+, alphabeta+, gammadelta+ intraepithelial lymphocytes, serum endomysial and tissue transglutaminase antibodies were investigated., Results: Twenty-three subjects were randomized to the oats-containing diet and 16 to the traditional gluten-free diet. All adhered strictly to their respective diet. Quality of life did not differ between the groups. In general, there were more gastrointestinal symptoms in the oats-consuming group. Patients taking oats suffered significantly more often from diarrhoea, but there was a simultaneous trend towards a more severe average constipation symptom score. The villous structure did not differ between the groups, but the density of intraepithelial lymphocytes was slightly but significantly higher in the oats group. The severity of symptoms was not dependent on the degree of inflammation. Antibody levels did not increase during the study period., Conclusion: The oats-containing gluten-free diet caused more intestinal symptoms than the traditional diet. Mucosal integrity was not disturbed, but more inflammation was evident in the oats group. Oats provide an alternative in the gluten-free diet, but coeliac patients should be aware of the possible increase in intestinal symptoms.

Background: In a previous study pulmonary hyperinflation was observed frequently in patients with primary Sjogren's syndrome (pSS) and elevated serum beta-2 microglobulin (beta2m) concentrations were associated with hyperinflation., Objective: To evaluate the significance of baseline serum beta2m concentration and to identify other possible risk factors for pulmonary involvement in long-term follow-up of patients with pSS., Methods: Nineteen pSS patients whose pulmonary function tests (PFTs) had been previously studied were reexamined after a median follow-up of 10 years. Pulmonary symptoms were recorded, chest radiograph, and high-resolution computed tomography (HRCT) were evaluated and methacholine provocation and PFTs including flow-volume spirometry, body plethysmography, and diffusing capacity performed., Results: Baseline serum beta2m concentrations correlated inversely with follow-up total lung capacity (TLC), vital capacity (VC), and diffusing capacity (DL), and positively with residual volume (RV), all expressed as percentage of predicted values. Diminished airways resistance (Raw) and, correspondingly, elevated specific conductance (SGaw) were frequent findings in pSS patients at follow-up, indirectly implying stiffness of the lungs and a restrictive decrease in lung volumes. Baseline serum protein concentration was higher and IgG concentration tended to be higher in pSS patients who at follow-up had elevated SGaw compared with others. Interstitial changes in HRCT were found more frequently in patients with elevated SGaw than in those without., Conclusion: Our results suggest that subtle restrictive changes in pulmonary function are more prone to develop in the long term in pSS patients with elevated serum beta2m concentration and other signs of immunological activity at baseline.

Objectives: Transient loss of consciousness (LOC) is a fairly common phenomenon and frequently carries a risk of injury. The aim was to study the occurrence of injuries and causes of emergency referrals versus later specialist consultation in association with LOC in the primary healthcare setting., Methods: A four-month survey was carried out in the Primary Healthcare Emergency Department of the City of Tampere, Finland (198,000 inhabitants). The subjects comprised consecutive patients aged at least 15 years, attending a primary healthcare emergency department because of LOC. The type of LOC was determined (seizure, syncope and uncertain) and the type and site of all injuries associated with LOC were registered. All referrals to hospital or specialist consultation because of LOC were also registered and the predictors of admission were analysed by logistic regression modelling., Results: Injury was associated with 43 (20%) out of 220 visits because of LOC; in 12/72 (17%) cases with syncope, in 24/118 (20%) with seizures and in 7/30 (23%) with an uncertain cause of LOC. Most of the injuries were minor. Emergency referral was required in 45/220 (20%) cases of LOC. Coronary heart disease and injury were the main predictors of emergency referral to hospital., Conclusions: Injuries are as frequent in patients with syncope as in those suffering seizures. Most patients with LOC in primary healthcare emergency departments do not seem to require emergency admission to hospital.

Background: The consequences of chronic gastroesophageal reflux disease (GERD) starting in childhood have not been widely studied. Our aim was to evaluate the usefulness of endoscopy in the primary diagnosis of GERD and to investigate the long-term course of this disease in children., Methods: Between 1989 and 1999, 136 children had been endoscoped because of persisting symptoms of GER. After exclusions (neurological impairment, infant GER), 96 subjects were included, and files from 76 were available for the final evaluation. Twenty-four hour pH-monitoring had been performed primarily on 67 children and at follow-up on 28, and endoscopy to 69 subjects and at follow-up to 33, respectively. Medical therapy as well as symptoms prior to the therapy were registered. Clinical outcome was assessed at the end of the follow-up period., Results: Presenting symptoms were recurrent abdominal pain, heartburn, regurgitation and vomiting. Twenty-two patients had respiratory symptoms in addition to the gastrointestinal complaints. PH-recording was normal in 17/67 subjects, slightly pathological in 33 and severe reflux was diagnosed in 13 patients. Histologically, minimal changes associated with GER were diagnosed in 22 and mild esophagitis in 7. Thirty-six patients had been treated with prokinetic drugs. H2-blockers had been used in 24 children and proton-pump inhibitors in 4. After a mean follow-up period of 28 months, only 24% of patients had become symptom-free. Control endoscopy showed no progression of the esophageal inflammation in any of the subjects., Conclusions: Pathological reflux in children is associated with no or mild esophageal inflammation, which is unlikely to deteriorate. Therefore endoscopic control could be limited to cases with severe esophagitis.

Objective and Methods: To investigate the significance or mannan-binding lectin (MBL) gene alleles in patients with primary Sjogren's syndrome (pSS). Genotypes were determined in 65 pSS patients and 138 controls., Results: No difference in MBL genotype or allele frequencies was detected between the pSS patients and controls. However, when the effect of MBL genotypes on the diagnostic findings in pSS patients was assessed, none of the eight patients with 52/w genotype fulfilled four (definite) Californian criteria (P = 0.007). Among these eight the Chisholm-Mason histological grade was > or = 3 in only three (P = 0.017). Furthermore, the MBL concentration was lower in patients with 52/w genotype compared to those with wild-type (w/w) genotype (P = 0.035)., Conclusion: Our findings suggest that MBL structural gene polymorphisms do not influence on susceptibility to pSS. However, MBL may be associated with salivary gland destruction in pSS, and its concentration may be comparable with the intensity of inflammatory reaction. Further studies are warranted to clarify the possible mechanisms involved.

Objective: The purpose of this study is psychometric assessment of disease-specific questionnaire, Urinary Incontinence Severity Score (UISS) and Visual Analogue Scale (VAS) in urinary incontinent women. We also investigated functional relationship between UISS, VAS and 15D-valid, generic health-related quality-of-life (HRQoL) instrument., Materials and Methods: Eighty-two incontinent female patients were recruited for the study that included baseline investigation and re-evaluation 13 months (range 6-21 months) after treatment. Twenty-nine control women who had urinary incontinence but were not bothered by it completed the HRQoL measurements., Results: Internal consistency and content validity of UISS was good. Both measures UISS and VAS were reproducible, Spearman's rank correlation between test-retest were 0.88 and 0.85 respectively. The control women's UISS, 15D and VAS scores were significantly lower than the patient's scores (p<0.001, Mann-Whitney U test) which proves to be a good discriminant. The changes in pad test correlated moderately well with those in the VAS and UISS. The UISS, VAS and 15D in the improved group had responsiveness (Guyatt's) statistics: 1.48, 1.74 and -0.80 respectively., Conclusion: The UISS and VAS proved to be valid, reproducible and responsive to treatment for UI women. The functionality of the 15D was good but it demonstrated less sensitivity to changes after treatment.

Objective: Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery, and it may contribute to postoperative complications and even multiple organ dysfunction. We here compared the cytokine responses and the degree of myocardial injury after coronary artery bypass grafting with or without cardiopulmonary bypass., Methods: Nine patients underwent off-pump revascularization and 13 with cardiopulmonary bypass. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-10 were measured before anesthesia induction, and 5 min, 1, 4, and 20 h after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were also measured after the operation., Results: Levels of TNF-alpha were low in both groups. A delayed elevation of IL-6 was noted in the off-pump group. IL-8 and IL-10 levels were significantly higher in the CPB than in the off-pump patients after reperfusion (p=0.006 and 0.001 respectively). Postoperative CK-MB levels were significantly higher in the CPB than in the off-pump group (p=0.001). Cytokine levels correlated with CK-MB values., Conclusion: The results indicated that off-pump revascularization was associated with reduced cytokine responses and less severe myocardial injury. The degree of myocardial injury, as defined by CK-MB release, correlated with cytokine release. Intervention designed to reduce cytokine responses in cardiac surgery may be advantageous for patients with severe comorbidity.

The inter-physician and inter-patient variability in planning target volume delineation for the radiotherapy of breast cancer after conservative surgery is presented. Eleven experienced radiation oncologists determined the planning target volume (PTV) for four breast cancer patients. Delineation was based on CT slices taken at intervals of 15 mm. The variability in target volume delineation was determined by measuring the volumes in units of cc and the position of the drawn PTVs. Statistical analysis was based on X/R-charts and on Pareto chart and analysis. The maximum range in PTV for one patient was from 670 to 1,200 cc. The observations of three physicians were in excess of the warning limit altogether 18 times. The methods used in this study clearly reveal inter-physician variability in PTV delineation and widest variations found are not acceptable. Training targeted to some physicians and more detailed and unambiguous protocols for PTV delineation are needed.

Background: A wheat starch-based gluten-free diet is widely adopted in the treatment of coeliac disease, even though the products contain trace amounts of gluten. The aim here was to establish whether such a diet sustains abdominal symptoms., Methods: The Gastrointestinal Symptom Rating Scale (GSRS) was applied to 58 coeliac disease patients on gluten-free diets and 110 non-coeliac controls. An estimate was made of daily dietary fibre and wheat starch-derived gluten. Psychological well-being was evaluated by a structured interview. Twenty-three coeliac patients consented to small-bowel biopsy., Results: The mean GSRS score in coeliac disease patients did not differ from that in control subjects. Poorer psychological well-being was associated with abdominal symptoms in coeliac patients, whereas the daily amount of wheat starch had no effect on GSRS score. Overall dietary compliance was good, and villous atrophy was found in only 2 out of 23 patients. The average fibre consumption, 13 g per day, was lower than recommended., Conclusions: Wheat starch-based gluten-free products are well-tolerated in coeliac disease patients, provided that their diets are otherwise strict.

Background: Owing to the current lack of long-term follow-up data on the recurrence of alcohol-induced acute pancreatitis (AP), we studied the pattern of recurrence and determined the characteristics of the disease to predict the recurrence., Methods: Between 1972 and 1991, 2678 AP episodes were detected; 1555 were induced by alcohol, and 591 of them were the first episode. During the first alcohol-induced AP 29 patients died and were excluded from further analysis. Of the 562 included, 503 were men, and 59 women. Admission serum tests, severity index, development of complications, intensive care unit and hospital stay, and need for surgery were assessed. Case records were studied. The national database was used to detect admissions to other hospitals., Results: Overall, 260 (46%) developed recurrent disease. Of the first relapses, 80% developed during 4 years. The recurrence rate has not changed with time. Age less than 45 years increased the risk (odds ratio (OR) = 2.42; 95% confidence interval (CI), 1.30-4.50). The risk factors of the first alcohol-induced AP associated with the development of multi-recurring pancreatitis are age <45 years (OR, 2.42; 95% CI, 1.59-13.0), 0-2 positive Glasgow criteria (OR, 2.45; 95% CI, 1.16-5.19), and arterial oxygen tension >60 mmHg (OR, 9.90; 95% CI, 1.32-74.3)., Conclusions: Fewer than half of the patients develop recurrent alcohol-induced AP. Younger patients are at the highest risk of recurrence. Those whose first alcohol-induced pancreatitis episode was not severe are at a higher risk of developing multi-recurring pancreatitis.

Analytical quality specifications for ordinal scale measurements have not been presented so far. Criteria are suggested for multiproperty (multiple) urine test strips based on upper limits of healthy reference intervals, analytical performance and statistical tests applicable to ordinal scales. Trueness (accuracy) can be evaluated against an acceptable comparison method by applying sensitivity and specificity concepts, and defining a grey zone with a lower detection limit and an upper confirmation limit. Concordance (agreement) of two or more ordinal scale categories should be evaluated by subtracting random agreement, using Kappa statistics. Repeatability (precision) can be calculated for categorized results using binomial statistics.

The characteristic feature of Chlamydia is its tendency to cause chronic infections. It has been hypothesized that prior exposure to C. pneumoniae may lead to chronic infection and the development of associated chronic cardiopulmonary disease. Few studies have so far addressed the occurrence of chlamydial antibodies in an elderly, unselected population. This information is important for the development of possible treatment strategies. Chlamydial antibodies were analysed from 1179 serum samples obtained from 481 men and 698 women, aged 64 y and over, who participated in an epidemiological survey carried out in a Finnish rural district. Specific IgG and IgA antibodies were measured by the microimmunofluorescence (micro-IF) test. The criterion for seropositivity was defined as a titre of > or =32 for both IgG and IgA, independently of each other. C. pneumoniae IgG antibodies occurred in 91% of the men and 75% of the women. The respective figures for C. pneumoniae IgA antibodies were 57% and 28%. The geometric mean titres (GMT) rose with increasing age and were higher in men than in women. The prevalences of C. trachomatis IgG antibodies were 13% in men and 18% in women, and for IgA antibodies, 2% and 1%, respectively. C. psittaci antibodies were rare. Only 3% of the men and women were IgG seropositive, whereas the respective figures for IgA seropositivity were 0.4% and 0.1%. C. pneumoniae antibodies indicative of recurrent or chronic infection were common in the elderly. The geometric mean titres correlated positively with age and were higher in men than in women. Other chlamydial antibodies occurred in low titres.

Oxidation of low-density lipoprotein (LDL) may be an important factor in the development of diabetic macrovascular and renal complications. The level of autoantibodies against oxidized LDL (oxLDL-Ab) can be used as an index of LDL oxidation in vivo. The purpose of this study was to investigate the association between the level of oxLDL-Ab and the presence of coronary heart disease and renal dysfunction in patients with non-insulin-dependent diabetes mellitus (NIDDM). We determined the plasma levels of oxLDL-Ab in 46 NIDDM patients and 48 well matched nondiabetic control subjects. NIDDM patients had a moderately higher level of oxLDL-Ab than control subjects (0.083 +/- 0.051 vs. 0.062 +/- 0.045, p = 0.04). However, there was no difference in the level of oxLDL-Ab between subjects with and without coronary heart disease, and the level of oxLDL-Ab was not associated with indices of glomerular filtration rate or urinary albumin excretion.

Background: The diagnosis of coeliac disease is easily overlooked as patients can present with mild or atypical symptoms, or the condition can even be clinically silent. Our aim was to detect coeliac disease patients with such atypical or no symptoms as well as those with typical features., Methods: The incidence of adult coeliac disease in Tampere was calculated from 1975 to 1994 and the prevalence as of 31 December 1994. Open-access endoscopy was available for general practitioners, and small-bowel biopsy was done routinely. Serologic screening was applied to patients with an increased risk of coeliac disease., Results: The incidence of coeliac disease increased tenfold, and the prevalence was 270 per 100,000 inhabitants in 1994. Twenty per cent were found by serologic screening and 10% as a result of routine biopsy; 24% had dermatitis herpetiformis., Conclusions: Our diagnostic approach gave a coeliac prevalence similar to that found in population screening studies. One-third had silent coeliac disease.

Background: According to some earlier reports, chronic atrophic gastritis is a common finding in Sjögren's syndrome. However, the findings are controversial. The aim of this study was to investigate the occurrence of gastritis classified in accordance with the Sydney System in patients with primary Sjögren's syndrome., Methods: Thirty-two consecutive patients (27 women, 5 men) with primary Sjögren's syndrome, and 64 age- and sex-matched control subjects with dyspepsia underwent gastroscopic examination. Mucosal biopsy specimens were taken from the gastric antrum and corpus., Results: Eight (25%) patients with Sjögren's syndrome and three (4.1%) control subjects had atrophic antral gastritis (P = 0.01). Atrophic corpus gastritis was more frequently found in control subjects, but the difference was not statistically significant. None of the subjects had severe (grade 3) atrophy. Gastric inflammation, in either the corpus or antrum, was found in 85% of patients with Sjögren's syndrome and in 61% of control subjects (P = 0.02). Helicobacter pylori was present in 31% of Sjögren's syndrome patients and in 39% of controls (NS)., Conclusions: In patients with primary Sjögren's syndrome mild atrophic changes in the antrum were common, but severe mucosal atrophy was rare. Compared with control subjects, gastric inflammation was seen more often in patients with Sjögren's syndrome.

Previous uncontrolled studies have suggested that patients with Barrett's oesophagus have an increased risk of colonic neoplasia. The present study was undertaken to clarify the occurrence of colorectal neoplasms in patients with Barrett's oesophagus and asymptomatic controls. Colonoscopy in 72 consecutive patients with Barrett's oesophagus and in 27 controls, none with symptoms of colonic neoplasm, revealed colorectal adenoma(s) in 17 cases (24%) in patients with Barrett's oesophagus and in eight (30%) controls. All 34 adenomas were less than 2 cm in diameter, with 30 less than 1 cm. None was malignant. Using logistic regression model with occurrence of colonic adenoma as dependent and sex, age and occurrence of Barrett's oesophagus as explanatory variables, none of these was found to be a significant risk factor for the appearance of colonic adenoma. The study thus suggests that Barrett's oesophagus is not associated with increased risk of colorectal neoplasm. Colonoscopic surveillance of patients with Barrett's oesophagus is not justified.

Symptoms suggestive of gastro-oesophageal reflux disease are very common. The aim of the study was to assess the prevalence of these symptoms and factors influencing them in an unselected adult population. A questionnaire was mailed to a random sample of 2500 people aged > or = 20 years. The questions concerned heartburn, regurgitation, dysphagia, chest and upper abdominal pain, as well as medication and medical consultations for these symptoms. Of the 1700 (68%) responders, 9% had experienced heartburn on the day of response and 15%, 21% and 27% during the preceding week, month and year, respectively. The corresponding figures for regurgitation were 5, 15, 29 and 45%. During the past year 43% of the study group had had no such symptoms. Age, overweight, pregnancy and cigarette smoking significantly influenced the prevalence of symptoms. Using daily heartburn and/or regurgitation as dominant indicators 10.3% (95% CI 12-11.7) of the responders had gastro-oesophageal reflux disease. Medication (most commonly antacids) was used by only 16% of the symptomatic people, and only 5.5% had sought medical advice for symptoms during the past year. Thus, despite commonness of symptoms suggestive of gastro-oesophageal reflux disease only a minority of the individuals suffering from such symptoms use medication or have medical consultation.

The treatment results of all the 95 primary tracheal carcinomas recorded by the Finnish Cancer Registry in 1967-1985 are evaluated. Six of the 95 patients were treated by surgery, 60 received radiotherapy and 29 were left untreated or received only palliative endoscopic or cytostatic therapy. The prognosis of the disease was poor. Among the 44 squamous cell carcinoma patients treated by radiotherapy, the median survival time after the diagnosis was 8 months (range 1-81 months). Complete response to radiotherapy was a favourable prognostic sign; after complete response the survival rates at 1, 2 and 5 years were 45%, 18% and 9% respectively. Patients with adenocystic carcinoma had the best prognosis.

The hypothesis that apolipoprotein E (apoE) polymorphism modulates an individual's response to cholesterol-rich diet was tested in 36 healthy normolipidaemic students with apoE phenotypes E3/2 (n = 9), E3/3 (n = 11), E4/3 (n = 13) and E4/4 (n = 3). The subjects were instructed to eat their usual diets, omitting eggs, for three weeks (baseline). This was followed by a diet high in cholesterol (750 mg/day, from egg yolks) for three weeks (intervention) after which they returned to their normal diet (without eggs for three weeks). Concentrations of plasma lipids and apolipoprotein B, and the composition of total fatty acids were monitored. At baseline, there were no statistically significant differences in lipid concentrations between the phenotype groups. The cholesterol-rich diet induced significant increases in total cholesterol, LDL cholesterol, and apoB in all apoE groups (P less than 0.001). The magnitudes of these increases were similar in groups E3/2, E3/3, and E4/3, in which total cholesterol concentration rose by 13%, 18%, and 12%, respectively. Stronger responses were observed in the small group of E4/4 subjects, in whom the increases in total cholesterol, LDL cholesterol, and apoB were 2.3-fold (P = 0.054), 2.25-fold (P = 0.02) and 2.3-fold (P = 0.004), respectively, compared with all the other phenotypes studied.