Long-term comparison of antireflux surgery versus conservative therapy for reflux esophagitis.

OBJECTIVE: The purpose of the study was to evaluate the long-term symptomatic and endoscopic outcome in gastroesophageal reflux disease with erosive esophagitis, comparing conservative with operative management. METHODS: The study comprised 105 of 120 patients consecutively referred for severe reflux symptoms to the gastroenterologic outpatient department of a teaching hospital, where erosive esophagitis was confirmed endoscopically. If conservative management (modified lifestyle and medication) failed to relieve symptoms and heal the esophagitis, antireflux surgery (Nissen fundoplication) was undertaken. Follow-up (median, 10.9 years) evaluation of all patients included comprehensive, standardized interviews; self-scoring of symptoms at the time of referral and currently; and observations at endoscopy. RESULTS: Nissen fundoplication was performed on 37 of the 105 patients. At follow-up of these 37 patients, (31) 84% had no or only occasional mild heartburn, (33) 89% were free from erosive esophagitis, and (2) 5% were taking H2 antagonists or omeprazole. The corresponding figures in the 68 patients with only conservative treatment were (36) 53%, (31) 45%, and (14) 21%. The mean change in symptom score between referral time and follow-up was 5.7 in the surgically treated group and 1.7 in the nonsurgically treated group. Fifteen new cases of Barrett's metaplasia were found at follow-up. CONCLUSIONS: In gastroesophageal reflux disease with erosive esophagitis, surgical treatment gave results subjectively and objectively superior to those from conservative management.

Natural course of gastroesophageal reflux disease: 17-22 year follow-up of 60 patients.

OBJECTIVE: To elucidate the long-term course of conservatively managed gastroesophageal reflux disease without H2-antagonists or omeprazole. DESIGN: Clinical trial, uncontrolled. SETTING: Gastroenterological outpatient department of a teaching hospital. PATIENTS: Sixty of 87 patients consecutively referred for severe gastroesophageal reflux symptoms and with objectively proven pathological reflux. MEASUREMENTS: Esophagoscopy, esophagography, cinecardiography of cardiac region, standard reflux test, and confirmatory Bernstein-Baker test. Follow-up included a standardized interview, esophagoscopy with biopsy, and 24-h pH monitoring. RESULTS: At follow-up 17-22 yr after referral, symptoms were less than at the time of referral in 36 of the 50 nonoperated patients (six now symptom-free), were unchanged in five, and were worse in nine patients. Medication for reflux symptoms was no longer used by 34 of the nonoperated patients. The prevalence of erosive esophagitis fell from 40% at referral to 27% at follow-up endoscopy; 42% of the studied patients had pathological 24-h pH, and the endoscopies revealed six new cases of Barrett's metaplasia. Of the 41 nonoperated patients examined with both endoscopy and 24-h pH, 27 (66%) had erosive esophagitis and/or pathological pH values. Of the 10 operated patients, all had fewer symptoms at follow-up than they had at referral (nine were symptom-free). The prevalence of erosive esophagitis fell from 60% at referral to 10% at follow-up. One of the 10 patients had pathological 24-h pH at follow-up. Neither the presence of esophagitis or hiatal hernia nor the severity of symptoms at the time of referral predicted the course of the disease of the conservatively treated patients. CONCLUSIONS: The severity of the symptoms declines in the long term, but pathological reflux persists in most of the conservatively treated patients. Thus, the reflux itself is not self-limiting, and therapy should be designed with this in mind.

Coeliac disease--associated disorders and survival.

The associated diseases in 335 coeliac patients diagnosed 1980-90 were compared with age and sex matched control patients with various gastrointestinal symptoms. Endocrine disorders were found in 11.9% of coeliac and 4.3% of control patients (p = 0.0003). Coeliac patients had insulin dependent diabetes mellitus significantly (p = 0.0094) more often (5.4%) than control patients (1.5%). connective tissue diseases were found in 7.2% of coeliac and in 2.7% of control patients (p = 0.011). Sjögren's syndrome occurred in 3.3% of coeliac patients and in 0.3% of controls (p = 0.0059). Autoimmune thyroid diseases were found in 5.4% and asthma in 3.6% of coeliac patients, but also in 2.7% and 3.6%, respectively, among control patients. The incidences of malignant diseases and the survival rate in coeliac patients were compared with those in the Finnish population. Ten coeliac patients developed a cancer during the follow up (mean 5.3 years, range 1-12) but none had a lymphoma. The risk of malignant diseases in coeliac patients did not differ from that in the Finnish population in general. Eleven coeliac patients died during the follow up. The five year survival rates of coeliac patients did not differ from those in the general population. At least 83% of the coeliac patients adhered strictly to the gluten free diet, which may explain the favourable outcome.

Fate of Nissen fundoplication after 20 years. A clinical, endoscopical, and functional analysis.

Of 46 patients who had Nissen fundoplication for proved gastro-oesophageal reflux, 25 were available for follow up after a median of 20 years, 15 had died of unrelated causes, and six could not be traced. All 25 patients in the follow up study were personally interviewed: 21 consented to an endoscopy, 14 to 24 hour recording of oesophageal pH and manometry, and 15 to radionuclide transit test. Repeat fundoplication for recurrent reflux was performed in two cases during the study. Heartburn and regurgitation were significantly lessened (p < 0.005), but the incidence of dysphagia was slightly increased. Endoscopy showed six of 21 fundic wraps to be defective. Erosive oesophagitis was seen in two patients, and Barrett's oesophagus (histologically confirmed) in one of them and six other patients. Total reflux time was abnormal in four of 14 patients. No patient with an intact fundic wrap seen on endoscopy, only two of seven with Barrett's oesophagus, and one of four with abnormal reflux had oesophagitis. Fundoplication in itself did not affect oesophageal motility or transit, provided that the wrap was intact. It is concluded that Nissen fundoplication gave a reasonably good longterm effect in chronic reflux disease, with the stage of the fundic wrap as the main determinant of outcome.

Selective IgA deficiency and coeliac disease.

Twenty-five children and adults with concomitant coeliac disease and selective IgA deficiency are described. IgG-class reticulin antibodies were positive in 94%. The clinical course of coeliac disease did not differ from that of patients with normal serum IgA level. Patients with IgA deficiency also had other concomitant diseases, especially autoimmune diseases. Patients with selective IgA deficiency have at least a tenfold risk of coeliac disease compared with the population in general.

Rheumatic complaints as a presenting symptom in patients with coeliac disease.

Twenty-three cases of coeliac disease were found after a small bowel biopsy had been carried out on seventy patients with various rheumatic complaints. The prevalence of coeliac disease in patients with rheumatic disorders was estimated to be 1 in 243. The majority (19) of these cases were found by screening patient sera with a reticulin antibody test. Sjögren's syndrome was the most frequent rheumatic diagnosis, with a total of six cases. Coeliac disease may occur concomitantly with various rheumatic complaints, and serological screening is advisable.

Celiac disease, brain atrophy, and dementia.

We report 5 patients who developed dementia before age 60 and were subsequently found to have celiac disease (CD). Intellectual deterioration ranged from moderate to severe, and diffuse cerebral or cerebellar atrophy was found on brain CT. Diagnosis of CD was confirmed by findings of subtotal villous atrophy in jejunal biopsy specimens and positive serum reticulin and gliadin antibodies. Conspicuously, gastrointestinal symptoms were mild. The gluten-free diet failed to improve the neurologic disability except in 1 patient. CD is a multisystem disorder and may play a role in some cases of presenile dementia. Although the pathogenetic mechanisms are obscure, immunologic mechanisms are implicated.

Dental enamel defects in celiac disease.

The teeth of 40 adults aged 19 to 67 yr with celiac disease (CD) were examined for dental enamel defects (ED). A total of 33 of the 40 adults with CD (83%) had systematic ED in contrast to only 5 of the 112 clinical controls (4%). Unspecific enamel lesions were found in both groups, but they were more common in the control group (80% vs. 18%). Altogether 69% of the permanent teeth in adults with CD were found to be defected, in clinical controls only 19%. In adults with CD the ED were in contrast to those in controls symmetrically and chronologically distributed in all four sections of dentition. The present study clearly shows that symmetrically and chronologically distributed enamel defects are strongly associated with CD. Therefore in the absence of symptoms and signs of malabsorption dentists could easily select the right patients possibly suffering from CD for gastroenterologic consultations.

Atypical coeliac disease found with serologic screening.

Eighteen patients with coeliac disease were found by screening for reticulin antibodies of unselected sera at the time when determination of various tissue antibodies was requested. Joint disease, allergic and pulmonary disorders, and diabetes were particularly observed. IgA class reticulin antibody, in particular, proved to be specific for coeliac disease. Most patients with coeliac disease also had positive serum gliadin antibodies. Abdominal symptoms and signs of malabsorption were slight and infrequent. In most patients a gluten-free diet resulted in the improvement of jejunal mucosal histology, and serum reticulum and gliadin antibody titres decreased simultaneously, reflecting the appropriateness of the diet. Coeliac disease often has mild and atypical symptoms, and, particularly in certain disease groups, screening with reticulin antibody test seems to be appropriate.

Abrupt withdrawal of isosorbide-5-mononitrate in Durules (Imdur) after long term treatment in patients with stable angina pectoris.

In a single-blind study of 6 weeks' duration, 32 patients with stable angina pectoris, who had been receiving controlled-release, Durules, isosorbide-5-mononitrate (Imdur) 60 to 180 mg daily for at least 1 year, were assessed after abrupt withdrawal of the nitrate. After 2 weeks of placebo treatment nitrate therapy was re-instituted, and the patients followed for another 2 weeks. The possibility of development of tolerance and rebound phenomena was also investigated. Three patients experienced severe anginal symptoms necessitating hospitalization when controlled-release isosorbide-5-mononitrate was withdrawn abruptly. Patients complained of more severe anginal symptoms during the placebo period, experienced more frequent anginal attacks and used more glyceryl trinitrate tablets than during active treatment. ST segment changes during exercise were more pronounced with placebo. After controlled-release isosorbide-5-mononitrate was re-introduced, these variables indicated significant improvement. On the other hand, no deterioration occurred in exercise performance during the placebo phase. Responsiveness to glyceryl trinitrate was maintained, as shown by comparisons of exercise tests performed after the long term treatment and during the placebo phase. Controlled-release isosorbide-5-mononitrate retains a beneficial effect in patients with angina pectoris during prolonged use, although some attenuation of the effect is seen. Abrupt withdrawal of the drug is not recommended because of the possibility of severe exacerbation of anginal symptoms, although no clearcut rebound phenomena were seen.

Comparison of indirect diagnostic methods for hypolactasia.

The aim of this study was to continue our previously published work and to compare the different indirect diagnostic methods for hypolactasia with the lactase to sucrase ratio obtained by jejunal biopsy. The following tests were performed in 63 adult patients: the breath hydrogen test, the lactose tolerance test with ethanol (serum galactose measurement after oral lactose load with ethanol), the urinary lactose tolerance test (urinary galactose measurement after oral lactose load with ethanol), and the strip test (like the former but using a special test strip for urinary galactose). Specificities of all these tests were good (96-98%). The 3-h breath hydrogen test was less sensitive (69%) than the other methods (81-94%). The strip test is recommended for the general practitioner for the diagnosis of this common cause of abdominal complaints.

Anti-anginal efficacy of a controlled-release formulation of isosorbide-5-mononitrate once daily in angina patients on chronic beta-blockade.

The anti-anginal effect of a controlled-release (Durules) formulation of isosorbide-5-mononitrate (5-ISMN) 60 mg, Imdur, once daily was evaluated in a randomised double-blind, placebo-controlled, crossover study with a placebo run-in period. Each period lasted for 2 weeks. A total of 70 patients (58 men and 12 women) with stable exertional angina pectoris on beta-blockade, mean age 59 years (range 39-71), were included. Exercise testing was performed on a bicycle ergometer 3 hours after the dose at the end of each period. Anginal attacks and intake of sublingual nitroglycerin tablets were noted. Imdur in combination with a beta-blocker significantly increased the total exercise capacity, the time and total work until the onset of chest pain and at 1 mm ST-depression compared with beta-blockade alone. The attack rate and the nitroglycerin consumption were significantly decreased. Headache was the only significant side-effect. In conclusion, the addition of Imdur once daily to beta-blockade significantly increased the anti-anginal effect.

Sensitivity of gastric acid secretion in patients with chronic renal failure.

By means of a dose-response secretion test the sensitivity of gastric acid secretion was investigated in 85 patients with chronic renal failure and in 85 age- and sex-matched controls. The renal patients were also gastroscoped, with biopsy specimens taken from the gastric body. The examinations were repeated on 18 patients undergoing regular dialysis and 8 patients after successful transplantation. The acid secretion sensitivity of the stomach among the non-dialyzed patients was decreased when compared with the controls (p less than 0.01) but tended to normalize during the intermittent dialysis treatment (p less than 0.05) and particularly after transplantation (p less than 0.01). The low secretion responses were independent of gastric body histology and were also seen in patients with normal body mucosa. The maximum theoretic acid output did not differ significantly from that of the controls. It is concluded that there is an inhibition of gastric acid secretion in chronic renal failure. This inhibition depends on the decreased sensitivity to stimulation and is diminished by treatment of renal failure by dialysis or transplantation.

Strip test is reliable in common prevalences of hypolactasia.

The object of this study was to compare the indirect diagnostic methods on the basis of urinary galactose determination in the diagnosis of lactose malabsorption with the actual lactase activities. One hundred and seven patients were studied. The specificity and sensitivity of the strip test were 97%. With 30% actual prevalence the positive predictive value was 94%, and the negative predictive value was 99%. In common prevalences of hypolactasia the strip test was reliable.

Abrupt withdrawal of isosorbide 5-mononitrate (Imdur) after long term treatment in stable angina pectoris. A preliminary report.

32 patients with stable angina pectoris who had been receiving a controlled-release formulation Durules of isosorbide 5-mononitrate (Imdur) 60 to 120 mg daily with concomitant beta-blocker therapy for at least 1 year were entered into a study to evaluate possible rebound phenomena from the abrupt withdrawal of isosorbide 5-mononitrate and to determine whether nitrate tolerance had developed. Isosorbide 5-mononitrate was abruptly withdrawn and substituted with placebo for 2 weeks, after which the active drug was reintroduced. No deterioration of exercise performance could be detected during withdrawal of therapy, but an increase was seen after reinstitution. No tolerance was found for systolic blood pressure and ST segment changes or for the number of anginal attacks and short-acting glyceryl trinitrate tablets consumed. Three patients had to be hospitalised because of a sudden deterioration of symptoms on withdrawal of isosorbide 5-mononitrate. It was concluded that isosorbide 5-mononitrate in Durules has a beneficial effect and that tolerance does not appear to be clinically relevant.

Effects of omeprazole in duodenal ulcer patients.

The efficacy of and tolerance to omeprazole, 40 mg/day, was studied in an open-label study in 18 patients with endoscopically verified duodenal ulcers. The effects of the drug on the oxyntic mucosa and pentagastrin-stimulated acid secretion during and after treatment were also studied. Fifteen patients completed the final endoscopy. The ulcers were healed in all after 4 weeks' treatment. Both basal and peak acid output were significantly reduced during omeprazole treatment, whereas 4 weeks after the cessation of treatment neither basal nor peak acid output differed from the pretreatment levels. Fasting serum gastrin levels rose by 56% during treatment but had returned to pretreatment values when tested again 4 weeks after the end of the treatment period. Histological examination of the biopsy specimens taken before and after treatment showed that omeprazole had no significant effect on the volume densities of either parietal or endocrine cells. We conclude that omeprazole is of value in the treatment of duodenal ulcer and that the effects of the drug on acid output and serum gastrin levels are fully reversible.

Metoprolol, nifedipine, and the combination in stable effort angina pectoris.

Treatment with metoprolol (100 mg twice daily), nifedipine (10 mg 3 times daily) and both drugs combined were compared for effect on clinical variables, bicycle ergometer exercise tolerance and adverse effects in a randomized double-blind, crossover study in patients with stable effort angina (n = 62). Nitroglycerin consumption and anginal attack rate as recorded in patient diaries indicated a higher antianginal efficacy (p less than or equal to 0.001) with metoprolol and combination therapy than with nifedipine monotherapy. All exercise test variables showed a significantly higher antianginal efficacy with combination therapy than with nifedipine monotherapy (15 to 26%). The combination therapy was also better than metoprolol in all exercise variables (9 to 14%), except for onset and duration of chest pain. Furthermore, metoprolol showed a higher efficacy than nifedipine in all exercise variables (7 to 23%) except total exercise time. More adverse symptoms of peripheral vasodilation were reported for nifedipine than for metoprolol (tachycardia, flushing, headache, p less than or equal to 0.05). It is concluded that combined treatment with metoprolol and nifedipine increased antianginal efficacy compared with the monotherapies, without increasing adverse effects. In effort angina, metoprolol in these doses was more effective and better tolerated than nifedipine.