Nutrient intakes during diets including unkilned and large amounts of oats in celiac disease.

BACKGROUND/OBJECTIVES: We have shown earlier that consumption of moderate amount of oats improve intakes of vitamin B(1), fiber, magnesium and iron in celiac patients using gluten-free diet (GFD). The objective of this study was to clarify the effect of high amount of both kilned and unkilned oats on food and nutrient intakes in celiac patients in remission. Kilning as an industrial heating process is performed to preserve the main properties of oats and to lengthen its useableness. Kilning may, however, change the protein structure of oats and therefore influence on the intake of nutrients. SUBJECTS/METHODS: The study group consisted of 13 men and 18 women with celiac disease in remission. The patients who were earlier using moderate amount of oats as part of their GFD were randomized to consume kilned or unkilned oats. After 6 months, the patients changed the treatment groups. The goal of daily intake of oats was 100 g. Food records and frequency questionnaire were used to follow nutrient intakes. RESULTS: Type of oats did not affect the amount of oats used. In the group using kilned oats, the intake of vitamin B1 and magnesium and in the group of unkilned oats that of magnesium and zinc increased significantly during the first 6 months (P

Cardiac autonomic regulation during gastroscopy.

BACKGROUND: Gastroscopy is sometimes associated with adverse cardiovascular events. AIMS: We evaluated the effects of sedation and pharyngeal anaesthesia on cardiac autonomic regulation during gastroscopy. PATIENTS: Two hundred thirteen outpatients undergoing gastroscopy. METHODS: The patients were assigned to 4 groups: (1) sedation with intravenous midazolam and placebo throat spray (midazolam group), (2) placebo sedation and pharyngeal anaesthesia with lidocaine (lidocaine group), (3) placebo sedation and placebo throat spray (placebo group), and (4) no intravenous cannula nor throat spray (control group). Continuous electrocardiogram was recorded. Heart rate variability was assessed; the powers of low frequency (0.04-0.15 Hz) and high frequency (0.15-0.40 Hz) components as well as total power (0.0-0.4 Hz) were calculated. RESULTS: Gastroscopy was associated with a decrease in high frequency normalized units, increases in low frequency normalized units and low frequency/high frequency ratio indicating activation of sympathetic and withdrawal of vagal modulation. Sympathetic activation resulted in a decrease in total power and all components of heart rate variability. The decrease was most prominent in the midazolam treated patients (p<0.001 vs the lidocaine group and p<0.01 vs placebo and control groups during the postendoscopy phase). CONCLUSION: Gastroscopy induces a shift towards dominance of the sympathetic modulation of the heart. Premedication with midazolam potentiates this shift.

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.

Elevated expression of hyaluronan and its CD44 receptor in the duodenal mucosa of coeliac patients.

AIMS: Since hyaluronan (HA) metabolism is disturbed in some malignant tumours and in inflammatory diseases, we analysed HA and its receptor CD44 as well as the expression of the Ki67 nuclear protein, a marker of cell proliferation, in histological sections of duodenal biopsies of coeliac disease patients and controls. METHODS AND RESULTS: The study group consisted of 52 patients with coeliac disease in remission, 40 patients with newly diagnosed disease and 10 healthy control subjects. HA was detected with a specific biotinylated probe prepared from cartilage aggrecan and link protein, and CD44 with an antibody recognizing all forms of CD44 and another specific for its v6 variant. For the expression of the nuclear protein, monoclonal antibody MIB-1 was used. The percentage of HA-positive cells in surface epithelium was higher in newly diagnosed patients (13%) compared with patients in remission (11%) and controls (2%). In addition, HA intensity in the lamina propria was decreased in the newly diagnosed patients. In patients with active disease, 22-26% of the surface epithelium was CD44+, whereas the corresponding figure in patients in remission was 5%, and that of controls 1%. The more intensive MIB-1 labelling in the duodenal epithelium of coeliac patients without treatment was normalized after gluten-free diet. CONCLUSIONS: The HA-positive coat on surface epithelium seen even in patients in remission suggests persistent or even permanent changes in the epithelial permeability barrier in coeliac disease.

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.

No support for endoscopic surveillance for gastric cancer in hereditary non-polyposis colorectal cancer.

BACKGROUND: The DNA mismatch repair gene mutations underlying hereditary non-polyposis colorectal cancer syndrome (HNPCC) also predispose, besides colorectal and endometrial cancer, to gastric cancer. usually of the intestinal type. The carcinogenetic pathway behind the elevated gastric cancer risk is largely unknown. METHODS: The aim of this study was to determine whether there are any premalignant lesions to search for in gastric surveillance in HNPCC by comparing gastric histopathology between mutation-positive and mutation-negative family members. We searched for differences in occurrence of Helicobacter pylori, inflammation, atrophy, intestinal metaplasia and dysplastic changes. Upper gastrointestinal endoscopy was performed for 73 mutation-positive and 32 mutation-negative family members. RESULTS: One case of duodenal cancer was detected in the mutation-positive group, but no gastric neoplastic lesions were seen in either group. There were no differences in the occurrence of polyps, H. pylori, inflammation, activity, atrophy nor intestinal metaplasia tested with binaric, logistic, regression analysis. CONCLUSIONS: We conclude that surveillance gastroscopy may not be beneficial in HNPCC, since neither cases of early cancer nor premalignant lesions could be detected in our series of 73 mutation-positive subjects.

No harm from five year ingestion of oats in coeliac disease.

BACKGROUND: Six to 12 months of ingestion of moderate amounts of oats does not have a harmful effect in adult patients with coeliac disease. As the safety of long term intake of oats in coeliac patients is not known, we continued our previous 6-12 month study for five years. AIM: To assess the safety of long term ingestion of oats in the diet of coeliac patients. PATIENTS: In our previous study, the effects of a gluten free diet and a gluten free diet including oats were compared in a randomised trial involving 92 adult patients with coeliac disease (45 in the oats group, 47 in the control group). After the initial phase of 6-12 months, patients in the oats group were allowed to eat oats freely in conjunction with an otherwise gluten free diet. After five years, 35 patients in the original oats group (23 still on an oats diet) and 28 in the control group on a conventional gluten free diet were examined. METHODS: Clinical and nutritional assessment, duodenal biopsies for conventional histopathology and histomorphometry, and measurement of antiendomysial, antireticulin, and antigliadin antibodies. RESULTS: There were no significant differences between controls and those patients consuming oats with respect to duodenal villous architecture, inflammatory cell infiltration of the duodenal mucosa, or antibody titres after five years of follow up. In both groups histological and histomorphometric indexes improved equally with time. CONCLUSIONS: This study provides the first evidence of the long term safety of oats as part of a coeliac diet in adult patients with coeliac disease. It also appears that the majority of coeliac patients prefer oats in their diet.

Prevalence of gastric metaplasia in the duodenal bulb is low in Helicobacter pylori positive non-ulcer dyspepsia patients.

BACKGROUND: Gastric metaplasia in duodenum is a common phenomena in duodenal ulcer patients. However, the role of gastric metaplasia in patients with non-ulcer dyspepsia is not clear. It is not known either whether Helicobacter pylori infected non-ulcer patients who are CagA-seropositive have gastric metaplasia in duodenum more often than CagA-negative patients. AIMS: To compare prevalence of gastric metaplasia in duodenum in non-ulcer dyspepsia patients according to Helicobacter pylori status. PATIENTS AND METHODS: A series of 400 unselected dyspeptic patients in primary care were investigated. Patients with no endoscopic evidence of organic disease (n=236) were enrolled in the study. Duodenal bulb and gastric biopsies were collected, as well as blood samples for Helicobacter pylori determination. RESULTS: There were no differences between CagA-seropositive and -seronegative Helicobacter pylori infected patients as far as concerns gastric metaplasia in duodenal bulb (20% vs 25%). Helicobacter pylori negative non-ulcer patients more often had gastric metaplastic changes (46%, p<0.0001) in duodenum. CONCLUSION: Helicobacter pylori infection has no major role in development of gastric metaplasia in duodenal bulb in non-ulcer dyspeptic patients. Furthermore, it does not result in positive CagA-serology, an increased risk for gastric metaplasia compared with CagA-seronegative cases.

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.

Genetic analysis in Finnish families with inflammatory bowel disease supports linkage to chromosome 3p21.

In inflammatory bowel diseases (IBD), certain chromosomal candidate loci have been repeatedly identified by independent studies in different populations. To investigate the contribution of the loci on chromosomes 1, 3, 7, 12, 14, and 16 to the susceptibility of IBD in Finnish population, where the predominant feature is the excess of ulcerative colitis (UC) families compared to Crohn's disease (CD) families, we carried out linkage analyses using 93 Finnish, multiply-affected IBD families. We observed nominal evidence for linkage to chromosome 3p21, consistent with earlier reports. The lod scores peaked at D3S2432, with a maximum two-point lod score of 1.68 (P=0.0027). In addition, we studied whether risk of IBD is associated with functional variants of two positional candidate genes; the chemokine receptor CCR5 gene on chromosome 3p21 and the interleukin-4 receptor alpha-subunit gene (IL4RA) on chromosome 16. We did not find any significant correlation between a 32-bp deletion variant of CCR5 or a single nucleotide change A1902G (Gln576Arg) of IL4RA, and IBD phenotypes, with the exception that in the UC group homozygosity for the G1902 allele of IL4RA was less frequent (0.019 vs 0.049, P=0.038). In conclusion, our study, carried out in a genetically homogenous population, suggests that chromosome 3 may contain a susceptibility gene for IBD.

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.

The effects of gender and age on the colonoscopic examination.

The data concerning the influence of gender and age on a patient's toleration of and the technical difficulty of colonoscopy are conflicting. One hundred eighty patients (108 women and 72 men) undergoing colonoscopy were categorized into three age groups: the young (aged 2040 years), the middle-aged (aged 41-60 years), and the old (aged 61-75 years). The endoscopists assessed the examination immediately after the procedure. The patients completed a questionnaire before leaving the endoscopy unit and again 2 weeks later. The women rated colonoscopy after the procedure more painful (p < 0.01) and in the repeat questionnaire more painful (p < 0.05) and more difficult (p < 0.05) than men. Also, the endoscopists judged colonoscopy to be more difficult (p < 0.001) and the time taken to reach cecum longer (p < 0.01) for women. The young experienced more discomfort than the middle-aged or the old, as evaluated after the procedure (p < 0.05). In the repeat questionnaire, the young reported more discomfort and pain than the middle-aged (p < 0.05). The endoscopists also judged the examination to be more difficult and the time taken to intubate cecum longer for the old than for the middle-aged (p < 0.05) or the young (p < 0.01). Correspondingly, the examination time was shorter among the young when compared with the middle-aged (p < 0.05) or the old (p < 0.001). The young were least willing to repeat the examination (p < 0.05). Colonoscopy is less tolerable and more difficult for women. Although colonoscopy among the old patients was technically more difficult, they tolerated the procedure better than the young.

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.

Effect of conscious sedation on cardiac autonomic regulation during colonoscopy.

BACKGROUND: Colonoscopy is associated with cardiovascular events including hypotension, hypertension, and myocardial ischemia. The pathogenetic mechanisms of these cardiovascular events are unknown, but there is evidence that the autonomic nervous system may play a role. Conscious sedation is often used to relieve the inconvenience caused by the procedure. In this study, we evaluated the effects of sedation on cardiac autonomic regulation during colonoscopy. METHODS: One hundred and eighty patients undergoing elective colonoscopy were prospectively randomized into three groups: (i) sedation with intravenous midazolam (midazolam group); (ii) sedation with intravenous saline (placebo group); and (iii) no intravenous cannula (control group). Continuous electrocardiogram was recorded prior to, during, and after the colonoscopic procedure. Heart rate variability (HRV) was assessed by means of the power spectral analysis; the powers of low-frequency (LF 0.04-0.15 Hz) and high-frequency (HF 0.15-0.40 Hz) components were calculated. RESULTS: Intubation of the colonoscope increased the LF component of HRV and decreased HF power in all study groups compared to baseline recording. Furthermore, compared to baseline, the LF/HF ratio--a marker of cardiac sympathetic regulation--increased during intubation in the midazolam (P < 0.001) and placebo (P < 0.05) groups, with no change in the control group. During intubation the midazolam group presented with higher LF and lower HF power than placebo (P < 0.001) and control groups (P < 0.01). Accordingly, the LF/HF ratio was higher in the midazolam group than in the placebo (P < 0.05) or control groups (P < 0.05). CONCLUSIONS: Midazolam potentiates the dominance of the sympathetic nervous system induced by colonoscopy. Therefore, conscious sedation with midazolam may contribute to the occurrence of cardiovascular events during colonoscopy.

GPs' ability to diagnose dyspepsia based only on physical examination and patient history.

OBJECTIVES: To evaluate the diagnostic value of the general practitioner's (GP's) unaided working diagnoses in dyspepsia. To compare the proportions of final diagnoses and the characteristics of patients who would have been referred to gastroscopy or to empirical drug treatment. DESIGN: Clinical study. PATIENTS: 400 consecutive dyspeptic patients consulting their GPs. MAIN OUTCOME MEASURES: Sensitivity, specificity and positive and negative predictive values (PV+ and PV-) were calculated for the GP's working diagnoses in cases of dyspepsia. The outcome of his/her decisions on how to manage dyspeptic patients was also evaluated. RESULTS: Gastroesophageal reflux disease would have been diagnosed accurately, with a sensitivity of 0.59, specificity 0.83, PV+ 0.43 and PV- 0.90. GPs diagnosed functional disorders with a sensitivity of 0.43, specificity 0.69, PV+ 0.56 and PV- 0.54; peptic ulcer with a sensitivity of 0.37, specificity 0.83, PV+ 0.28 and PV- 0.88; and malignancy with a sensitivity of 0.13, specificity 0.97, PV+ 0.08 and PV- 0.98. Patients who would have been referred to gastroscopy had more often lost weight (p = 0.01), suffered from abdominal pain (p=0.03) and from symptoms partly suggesting irritable bowel syndrome (p< or =0.03). CONCLUSIONS: The clinical diagnosis of the causes of dyspepsia is unreliable. In selecting patients for gastroscopy, more attention should be paid to risk factors such as age, use of non-steroidal anti-inflammatory drugs and history of previous peptic ulcer.

Conscious sedation and cardiorespiratory safety during colonoscopy.

BACKGROUND: Cardiorespiratory events during colonoscopy are common. The effect of sedative premedication on cardiorespiratory parameters during colonoscopy has not been studied in controlled, prospective trials. METHODS: One hundred eighty patients undergoing colonoscopy were divided into 3 groups: (1) sedation with intravenous midazolam (midazolam group); (2) sedation with intravenous saline (placebo group); and (3) no intravenous cannula (control group). Arterial oxygen saturation (SaO(2)), systolic and diastolic blood pressure and continuous electrocardiogram were recorded prior to, during and after the endoscopic procedure. RESULTS: Midazolam produced lower SaO(2) values during colonoscopy compared with placebo or control groups (p < 0.001, repeated measures analysis of variance). Systolic and diastolic blood pressure during colonoscopy were lower in the midazolam group than in the placebo group (p < 0.01 and p < 0.05, respectively), but no difference was found between the midazolam and the control groups. Hypotension (systolic blood pressure less than 100 mm Hg) occurred more frequently in the midazolam group (19%) than in the placebo (3%; p < 0.01) or control groups (7%; p < 0.05). ST-segment depression developed in 7% of patients during the recording with no difference between the groups. In 75% of cases ST-depression appeared prior to the endoscopic procedure. CONCLUSIONS: Premedication with midazolam induced a statistically significant decrease in arterial oxygen saturation and increased the risk for hypotension. However, colonoscopy proved to be a safe procedure both with and without sedation.

Population-based molecular detection of hereditary nonpolyposis colorectal cancer.

PURPOSE: Cancer morbidity and mortality can be dramatically reduced by colonoscopic screening of individuals with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, creating a need to identify HNPCC. We studied how HNPCC identification should be carried out on a large scale in a sensitive and efficient manner. PATIENTS AND METHODS: Colorectal cancer specimens from consecutive newly diagnosed patients were studied for microsatellite instability (MSI). Germline mutations in the MLH1 and MSH2 genes were searched for in MSI(+) individuals. RESULTS: Among 535 colorectal cancer patients, 66 (12%) were MSI(+). Among these, 18 (3.4% of the total) had disease-causing germline mutations in MLH1 or MSH2. Among these 18 patients, five were less than 50 years old, seven had a previous or synchronous colorectal or endometrial cancer, and 15 had at least one first-degree relative with colorectal or endometrial cancer. Notably, 17 (94%) of 18 patients had at least one of these three features, which were present in 22% of all 535 patients. Combining these data with a previous study of 509 patients, mutation-positive HNPCC accounts for 28 (2.7%) of 1,044 cases of colorectal cancer, predicting a greater than one in 740 incidence of mutation-positive individuals in this population. CONCLUSION: Large-scale molecular screening for HNPCC can be done by the described two-stage procedure of MSI determination followed by mutation analysis. Efficiency can be greatly improved by using three high-risk features to select 22% of all patients for MSI analysis, whereby only 6% need to have mutation analysis. Sensitivity is only slightly impaired by this procedure.

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%.

Lack of cellular and humoral immunological responses to oats in adults with coeliac disease.

OBJECTIVE: Recent research suggests that oats do not harm intestinal villi in adults with coeliac disease. As the immunological effects of oats have not been examined in detail, it was decided to compare the immunological responses of a gluten free diet including oats with those of a conventional gluten free diet. DESIGN: A randomised controlled intervention study over 6-12 months. SUBJECTS: Forty adults with newly diagnosed coeliac disease and 52 with coeliac disease in remission were examined. INTERVENTION: The effects of a gluten free diet including oats and a conventional gluten free diet were compared. MAIN OUTCOME MEASURES: Serum levels of gliadin and reticulin antibodies as well as numbers of intraepithelial lymphocytes (IELs) in intestinal mucosa were examined before and after the intervention. RESULTS: The rate of disappearance of gliadin and reticulin antibodies did not differ between the diet groups in patients with newly diagnosed coeliac disease. Oats also had no effect on gliadin or reticulin antibody levels in the patients with remission. The number of IELs decreased similarly regardless of the diet of newly diagnosed patients, and no increase in the number of IELs was found in the patients in remission with or without oats. CONCLUSIONS: These results strengthen the view that adult patients with coeliac disease can consume moderate amounts of oats without adverse immunological effects.

Microsatellite instability in adenomas as a marker for hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common of the well-defined colorectal cancer syndromes, accounting for at least 2% of the total colorectal cancer burden and carrying a greater than 80% lifetime risk of cancer. Significant reduction in cancer morbidity and mortality can be accomplished by appropriate clinical cancer screening of HNPCC patients with mutations in mismatch repair (MMR) genes. Thus, it is desirable to identify individuals who are mutation-positive. In individuals with cancer, mutation detection can be accomplished relatively efficiently by germline mutation analysis of individuals whose cancers show microsatellite instability (MSI). This study was designed to assess the feasibility of screening colorectal adenoma patients for HNPCC in the same manner. Among 378 adenoma patients, six (1.6%) had at least one MSI adenoma. Five out of the six patients (83%) had a germline MMR gene mutation. We conclude that MSI analysis is a useful method of prescreening colorectal adenoma patients for HNPCC.