Effect of profound acid suppression in functional dyspepsia: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. METHODS: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. CONCLUSION: A subset of patients with FD will respond to therapy with omeprazole.

Subsensitive alpha-2-adrenoceptor function in male alcohol-dependent individuals during 6 months of abstinence.

Postsynaptic alpha-2-receptor function, as assessed by growth hormone (GH) response to clonidine (CLON), has been shown to be downregulated in patients investigated in acute but also in late withdrawal after heavy alcohol intake. The results are however sometimes conflicting. The question whether this changed receptor function is a trait or state marker is not fully investigated so far. A total of seven male patients with alcohol dependence according to DSM-IV were assessed for the postsynaptic alpha-2-receptor function with the CLON/GH test (2.0 microg/kg body weight; i.v.) starting immediately after a period of heavy drinking. Neuroendocrine tests were repeated after 7 days, 2 and 6 months. A total of six healthy males were used as controls. The maximum GH responses to CLON were significantly lower on all four test occasions in the patient group as compared to the controls. Furthermore, in the patient group all neuroendocrine test results showed blunted GH responses to CLON. Thus, patients with downregulated alpha-2-receptor function during acute withdrawal after heavy alcohol intake showed similar subsensitive receptor function abnormality after a prolonged period of abstinence. The findings in this study indicate that alcohol dependent individuals have a persistent subsensitive alpha-2-adrenoceptor function which may constitute a trait factor for alcohol dependence.

[Antibiotic resistance among strains of Helicobacter pylori in Gothenburg. Bacteria resistant to metronidazole]. / Antibiotikaresistens hos stammar av Helicobacter pylori i Göteborg. Bakterierna resistenta mot metronidazol.

AIM: Primary resistance of H pylori strains to antimicrobials has direct therapeutical implications. For this reason we studied the prevalence of primary resistance of H pylori of Sweden, in a regional setting. MATERIAL AND METHODS: A total of 244 patients referred to our endoscopy unit have been evaluated prospectively for the occurrence of H pylori. Helicobacter pylori infection was established by a positive rapid urease test on an antral biopsy. If positive the biopsy specimen was transferred to a transportmedium for culture on a Skirrow medium. Antimicrobial resistance was evaluated by the E-test. RESULTS: In 109 patients H pylori infection was seen and in all of them the culture was positive. No resistance was seen for amoxycillin and tetracycline. The resistance against metronidazole was 40.3% and and against clarithromycin it was 2.8%. For metronidazole there was a significantly higher resistance seen in women compared to men (53.3% vs 31.2%; p < 0.001). CONCLUSIONS: Primary resistance to metronidazole was higher than expected and over average in Europe. The resistance for clarithromycin is still rare. Further monitoring is mandatory to detect changes in the community.

Comparison of two low-dose one-week triple therapy regimens with and without metronidazole for cure of H. pylori infection.

BACKGROUND: One-week triple therapy consisting of omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and tinidazole 500 mg b.d. is an effective therapy for H. pylori infection with a cure rate of 93%. We therefore compared two similar 1-week regimens consisting of a lansoprazole, clarithromycin and either metronidazole or tetracycline in a prospective study. METHODS: Two cohorts, each of 60 patients suffering from H. pylori infection associated with peptic ulcer disease or ulcer-like dyspepsia, were treated for 1 week with either lansoprazole 30 mg b.d., clarithromycin 250 mg b.d. and either metronidazole 400 mg b.d. (cohort A, n = 60) or tetracycline 300 mg b.d. (cohort B, n = 60). Four weeks after treatment, cure of H. pylori infection was evaluated by endoscopy using rapid urease testing together with histology. RESULTS: In cohort A, 55 patients out of 60 showed cure of H. pylori infection (92%); the treatment was well tolerated, but three patients suffered from side-effects. In cohort B, which was free of metronidazole, 50 out of 60 patients showed cure of H. pylori infection (83%); two patients reported side-effects. The differences between the two cohorts were not statistically significant. CONCLUSION: Triple therapy for 1 week with lansoprazole as the antisecretory agent seems to be as effective as is reported for omeprazole-based regimens.

Luminometry and PCR-based monitoring of gene-tagged cyanobacteria in Baltic Sea microcosms.

The cyanobacterium Synechocystis 6803 was tagged by chromosomal integration of the firefly luciferase gene, luc, resulting in the modified strain Synechocystis 6803-luc. The tagged cells were monitored in Baltic Sea microcosms both by detection of the luc gene by PCR amplification and by measurement of luc gene expression (bioluminescence) in total protein extracted from sediment and water. A new method was developed for isolation and concentration of total protein from sediment for optimization of luciferase quantitation. The detection limit for Synechocystis with a chromosomal luc insertion by bioluminescence was in the order of 4 x 10(3) cells per g sediment, a considerable improvement in sensitivity over previous methods. Another improvement was to use an internal luciferase standard to correct for quenching of light output by impurities in the samples. Baltic sea microcosms were inoculated with Synechocystis 6803-luc, and the luc DNA and luciferase protein specific to the tagged cells were monitored over time. A decrease in luminescence in the microcosm water was observed, simultaneously with an increase in luminescence in the sediment, suggesting settling of the luc-tagged cells in the sediment layer.

Low dose, short-term triple therapy for cure of Helicobacter pylori infection and healing of peptic ulcers.

OBJECTIVES: The aim of this study was to confirm the efficacy and tolerability of a new, low dose, short-term triple therapy for cure of Helicobacter pylori infection, as suggested by Bazzoli, in a larger population. METHODS: On an "intention-to-treat" basis, 116 patients with active (n = 41) or healed (n = 47) peptic ulcer disease or ulcer-like dyspepsia (n = 28) and H. pylori infection received a 1-wk course of omeprazole 20 mg b.i.d., clarythromycin 250 mg b.i.d., and tinidazole 500 mg b.i.d.. Four weeks after treatment withdrawal, cure of H. pylori infection was evaluated by rapid urease test and histology. RESULTS: One hundred and sixteen patients returned for follow-up. In 108 patients, H. pylori could not be identified 4 wk after cessation of therapy. The eradication rate was calculated to 93%. In addition, all patients with active peptic ulcers showed complete healing at follow-up despite no further treatment. Drug acceptance and compliance was excellent. CONCLUSION: Triple therapy as suggested by Bazzoli with omeprazole (in this study given b.i.d. for better compliance), clarythromycin, and tinidazole is indeed highly effective for both cure of H. pylori infection and for healing of peptic ulcers, is easy to perform, is cheap, and is without clinically significant side effects, even in a larger population.

Hormone conference at Sahlgren's University Hospital: polycythemia and inappropriately high serum erythropoietin concentration in a 62-year-old man.

A 62-year-old man with a history of coronary insufficiency complained at his scheduled visit to the outpatient clinic of symptoms suggestive of gastritis. His blood hemoglobin concentration, however, was markedly increased. Results of a hematological work-up suggested an erythropoietin-producing tumor. Signs of increased intracranial pressure then led to the finding of a cerebellar tumor, which could explain his vertigo and abdominal symptoms. This cystic capillary hemangioblastoma probably was responsible for the erythropoietin production and also seemed to produce basic fibroblast growth factor. The clinical evaluation of polycythemia as well as erythropoietin biochemistry and clinical application are reviewed.

Virulence properties of erysipelas-associated group A streptococci.

Group A streptococcal isolates (n = 53) recovered from 38 erysipelas patients in 1988 and 1990 in Sweden were analysed with respect to serotype, erythrogenic toxin production and polymorphism in the emm gene region. Serotype determination showed a dominance of type T1M1 (28.6% of the strains), but T type 8 was also prevalent (14.3%). In the majority of the strains only a low production of erythrogenic toxin A was demonstrated, while both toxin B and C production were high. Polymorphism was detected in the emm gene region of T1M1 strains at a frequency of 64%. These erysipelas associated group A streptococci were more heterogenic with respect to serotype distribution and polymorphism in the emm gene region compared to previously studied group A streptococci isolated during an outbreak of serious streptococcal infections in Sweden in 1988/1989. The material included isolates from two cases of recurrence, and typing of the isolates indicated that the patients had been infected by the same serotype as in the primary infection.

Genetic diversity in T1M1 group A streptococci in relation to clinical outcome of infection.

Genetic diversity was found at high frequency downstream of the emm1 gene among T1M1 group A streptococci (GAS) isolated in Scandinavia during a recent epidemic. Clonal variation was also seen in the speA and speB genes but at much lower frequency; no variation was detected in the speC gene. Erythrogenic toxin A was found to be expressed at low levels in all strains; erythrogenic toxins B and C were produced in high amounts. All strains were found to harbor the speA, speB, and speC genes, regardless of the amount of toxin produced. No correlation was found between one specific T1M1 clone and the more serious infections when isolates from bacteremic patients (fatalities or survivors), those with uncomplicated infections, and healthy carriers were compared. Similar results were obtained in a family study in which 3 family members were found to be asymptomatic carriers of the same GAS T1M1 clone as in the bacteremic patient, defined by genotypic and phenotypic experiments.

Aspects of pathogenesis of serious group A streptococcal infections in Sweden, 1988-1989.

Serotypes of serious, sometimes fatal, streptococcal infections in Sweden during 1988-1989 were analyzed. The T1M1 type totally dominated, representing almost 70% of all group A streptococci from serious and uncomplicated infections at the peak of the outbreak. Immunoblots of isolates from various patient groups showed that all isolates produced high amounts of erythrogenic toxin (ET) B and high amounts of ET-C, whereas ET-A was released only in small amounts and from few isolates. ELISAs showed high antibody levels to these toxins and to the M1 antigen in patients with uncomplicated infections. Low antibody levels against M1 were seen in patients with bacteremia and in fatal cases; the latter also had low antibody levels against ET-B. It seems likely that a combination of production of large amounts of toxin and low antibody titers to it and to the M antigen of the infecting isolate are determining factors for the outcome of the infection. No signs of primary immune deficiency were noted.

Rearrangement of chromosome no. 3 in a case of preleukemia with thrombocytosis.

The clinical and cytogenetic findings of a patient with the preleukemic syndrome and a structural rearrangement involving both chromosomes No. 3 are described. The karyotypic abnormality consisted of an insertion of a part of the long arm of one chromosome No. 3 into the other, i.e., ins(3;3)(q27;q21q27). A prominent feature of the bone marrow was a marked megakaryocytic hyperplasia. The platelet count temporarily exceeded 1000 x 10(9)/liter. The findings of the present case, together with similar observations by others, suggest that the long arm of chromosome No. 3 may contain a region involved in the regulation of megakaryopoiesis.

Food iron absorption in iron deficiency.

The absorption of food iron in relation to the diet was studied in 10 phlebotomized normal young male subjects during 3 to 5 months. The iron absorption was calculated from the net increase of the hemoglobin mass. There was pronounced individual variation in the mean dietary absorption ranging between 1.9 and 5.0 mg. There was no correlation between the amount of iron absorbed and the amount of iron ingested. There was no apparent influence of a high or a low intake of animal products, cereals, vegetables, tea, or alcohol on the individual absorption values. A negative correlation between the iron absorption and the total amount of fecal dry substance was observed. This might be ascribed to an influence of dietary fibers on the absorption of food iron.

Haemoglobin synthesis following injection of iron-poly (sorbitol-gluconic acid) complex, Ferastral.

Ferastral, a new iron-poly (sorbitol-gluconic acid) complex for parenteral use has been given to 22 patients with iron deficiency anaemia. The patients were divided in two groups. Group I received a suboptimal dose of Ferastral iron corresponding to 90% of the iron calculated to normalize the haemoglobin value. Increases in total haemoglobin and also blood losses were measured. The availability of the injected iron for haemoglobin synthesis ranged from 63% to 111%. Group II received an amount of Ferastral-iron calculated to be necessary for normalization of the haemoglobin plus an additional 500 mg of Ferastral-iron. In this group the haemoglobin increase was rapid. In 7 weeks 10 out of 14 patients had reached a normal haemoglobin level.

Serum iron increase as a measure of iron absorption - studies on the correlation with total absorption.

The correlation between the magnitude of the increase of serum iron after an oral dose of iron and the total absorption of iron was studied in 51 healthy subjects and 10 patients with iron deficiency anaemia. 59Fe-labelled solutions of ferrous sulphate (25-100 mg iron) were administered to the fasting subjects. The serum iron concentration was followed for 4-6 hours and the absorption was measured in a whole-body counter. Good correlation was found between the maximal increase of serum iron and the total amount of iron absorbed after a dose of iron given as a solution. The serum iron method may be used for comparisons of the absorbability of different doses of iron by performing cross-over studies in groups of subjects. However, it was found that in an individual subject the serum iron method could not be used to determine the amount of iron absorbed from an oral dose of iron.

Absorption of supplemental iron during pregnancy - a longitudinal study with repeated bone-marrow studies and absorption measurements.

Iron absorption, bone-marrow smears and haematological parameters were repeatedly studied during pregnancy in 50 women. The same studies were repeated two months after delivery. The material was randomly divided into two groups. Twenty-four women were treated with 200 mg of ferrous iron daily while 26 were given placebo. The iron absorption was measured from radioiron-labelled test doses of 100 mg ferrous iron in a whole-body counter with high sensitivity. In the placebo group the iron absorption increased throughout pregnancy from an average of 6.5 % at the 12th week to 14.3 % at the 35th week of gestation. Two months after delivery the absorption was higher than initially. In the iron-treated group the absorption increased between the 24th and 35th week of gestation from 6.0 to 8.6 %. After delivery 5.5 % of the test dose was absorbed. The haemosiderin iron in the bone-marrow was mobilized during pregnancy. In the placebo group no woman had more than trace of haemosiderin in the bone-marrow smears at the 35th week of gestation. In the iron-treated group 65 % had the same bone-marrow findings. The amount of bone-marrow haemosiderin at term seems not to have the same significance for the diagnosis of iron deficiency in pregnancy as in non-pregnant subjects. Two months after delivery about 50 % of the women in the placebo group had restored their iron deposits. In the iron-group the haemosiderin content in the bone-marrow smears was enhanced in most women compared to early pregnancy. In the placebo group haematological data indicated a high frequency of iron deficiency in late pregnancy while in the iron-treated group iron deficiency was prevented.