Randomised clinical trial: a comparative dose-finding study of three arms of dual release mesalazine for maintaining remission in ulcerative colitis.

BACKGROUND: Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited. AIM: To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis. METHODS: A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline. RESULTS: The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group. CONCLUSION: Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety.

Active motion, communicative aggregations, and the spatial closure of Umwelt.

On the basis of a simple model of movable organisms that are supplied by semiotic force of attraction or repulsion, several general features of spatial behavior are demonstrated: (1) the stochastic spatial distribution of actively moving organisms is unstable; (2) simple or complex aggregations of organisms appear as a result of active motion; and (3) the ability for active motion ties the organisms with place. These results show that models that apply an internalist approach can considerably simplify the theory of spatial behavior of organic systems. Explanations based on the effects of Darwinian fitness may not be necessary for understanding the origin of biological aggregations.

Competition intensity and its importance: results of field experiments with Anthoxanthum odoratum.

The effect of community productivity on competition was studied in 82 permanent plots using two removal experiments with the rhizomatous perennial grass Anthoxanthum odoratum. The removal of neighbouring plants had a positive effect on the number of shoots and total above-ground biomass of Anthoxanthum but no significant effect on mean shoot biomass. The relative competition intensity coefficient (RCI) calculated from these data showed that competition intensity increased with increasing community productivity. Similarly, the importance of competition and the difference between local maximum and local average population density increased with increasing community productivity. We concluded that for Anthoxanthum the impact of competition is greater in high-productivity areas and that competition reduces population density. No evidence was found supporting the importance of positive interactions between plants in tundra areas.

Polymorphisms in tumour necrosis factor and adhesion molecule genes in patients with inflammatory bowel disease: associations with HLA-DR and -DQ alleles and subclinical markers.

BACKGROUND: When investigating susceptibility to inflammatory bowel disease (IBD), a multifactorial disorder with a genetic predisposition, polymorphisms of molecules with immunoregulatory function are of potential interest. This is the first time that the polymorphisms of HLA-DR and -DQ, tumour necrosis factor (TNF), E-selectin (CD62E), L-selectin (CD62L), and intercellular adhesion molecule 1 (ICAM-1, CD54) were determined in Estonians, a population with a low IBD incidence rate, and their occurrence investigated in subgroups of a total of 53 IBD patients. METHODS: The reverse hybridization principle and sequence specific primers were used for HLA genotyping. To analyse the TNF and adhesion molecule polymorphisms, the polymerase chain reaction with subsequent restriction fragment length polymorphism or single-strand conformation polymorphism method was used. RESULTS: In the subgroup of antineutrophil cytoplasmic antibody (ANCA)-positive ulcerative colitis (UC) patients we found a higher frequency of the TNF2 (20.8% versus 0.0% in ANCA-negative UC patients, P = 0.051) and HLA-DRB1*15 allele (35.4% versus 15.7% in controls; P = 0.004). Of ANCA-positive UC patients 87.5% were carriers of one of these alleles (22.2% among ANCA-negative UC patients (P<0.001, Pc = 0.039) and 51.4% among controls (P = 0.002). Specific typing of HLA-DRB1*15 alleles showed that the HLA-DRB1*1501 allele was responsible for the HLA-DRB1*15 association with ANCA-positive UC. Associations of ICAM-1, E-selectin, or L-selectin polymorphisms with IBD were not found. CONCLUSIONS: TNF2 and HLA-DRB1*15 alleles were associated with ANCA-positive UC in the investigated population. ANCA might be a useful marker, at least in some ethnic groups, for dividing IBD patients into genetically more homogeneous subgroups.

High frequency of antigliadin antibodies and absence of antireticulin and antiendomysium antibodies in patients with ulcerative colitis.

Several authors have described an association between celiac disease (CD) and ulcerative colitis (UC), but this has not yet been established. The aim of our study was to examine the frequency of antigliadin antibodies (AGA), antireticulin antibodies (ARA) and antiendomysium (AEM) antibodies in the sera of patients with UC (n = 50), and to evaluate their correlation with clinical variables. Sixteen patients with irritable bowel syndrome (IBS) and 37 healthy individuals served as controls. An enzyme-linked immunosorbent assay was used for the detection of IgA- and IgG-type AGA. IgG-type ARA were determined by an indirect immunofluorescence assay (IIF) using rat kidney, liver, and stomach as antigen substrates. IgA-type AEM antibodies were measured by IIF, using cryostat sections from human umbilical cord. Seventeen of the 50 patients with UC (34%) were positive for IgA- or/and IgG-type AGA. There was no correlation between the presence of AGA and the duration or extent of the disease, or disease activity. However, 5 patients with both IgA- and IgG-types of AGA had extensive colitis. Only 2 controls (4%) were positive for IgG-AGA. ARA and AEM were not detected in any individuals studied. Since the ARA and AEM test results were negative, we conclude that none of the UC patients in this series had CD.

CagA protein seropositivity in a random sample of adult population and gastric cancer patients in Estonia.

OBJECTIVE: The prevalence of antibodies to CagA protein, associated with the risk of developing gastric cancer (GC), was studied in an Estonian adult population with a high prevalence of Helicobacter pylori (HP) infection and in a group of GC patients. DESIGN: In a representative sample of a random adult population from the South Estonian town of Karksi-Nuia, containing 199 subjects (86 M, 113 F, mean age 42.4) and in 45 (22 M, 23 F, mean age 64.5) consecutive patients with gastric adenocarcinoma, recruited during the periods 1986-87 and 1995-96 in the Hospital of Oncology, University of Tartu, anti-CagA IgG antibodies were determined by enzyme-linked immunosorbent assay (ELISA) using a recombinant fragment of CagA protein. The occurrence of anti-CagA IgG in ELISA was compared with immunoblot results for 141 subjects. RESULTS: Seropositivity to acid glycine extracted cell surface proteins of HP was 85% in the population and 91% in GC patients (p = 0.39). Anti-CagA IgG antibodies were present in 63% of the population and in 87% of GC patients (p = 0.004). The highest prevalence of anti-CagA IgG in the population sample occurred in the age group 20-29 (76%). A comparison of anti-CagA positivity evaluated by using ELISA and immunoblot showed an agreement of results in 80% of cases. CONCLUSION: HP seropositivity was similarly high in the Estonian random adult population sample and in GC patients, however, the prevalence of anti-CagA IgG was significantly higher in GC patients. Moreover, persons aged 20-29 years in the population possess the highest prevalence of anti-CagA IgG and should be given further attention with respect to the development of GC later in life.

Antineutrophil cytoplasmic antibodies in Estonian patients with inflammatory bowel disease. Prevalence and diagnostic role.

BACKGROUND/AIMS: In Estonia, the incidence of ulcerative colitis and especially Crohn's disease appears to be rare. Antineutrophil cytoplasmic antibodies (ANCA) are frequently found in ulcerative colitis but less frequently in Crohn's disease, their pathophysiological significance is still unclear. METHODOLOGY: Fifty-nine serum samples from patients with ulcerative colitis, 17 with Crohn's disease, 25 with irritable bowel syndrome, and 86 healthy persons were studied. Sera were analyzed for the presence of ANCA by indirect immunofluorescence, and enzyme-linked immunosorbent assay for specific ANCA using different antigens was performed. RESULTS: ANCA were detected in 29 of 59 (49%) patients with ulcerative colitis, 4 of 17 (24%) patients with Crohn's disease, and in 4 of 111 (4%) controls. The immunofluorescence staining was mostly perinuclear (pANCA). There was no correlation between ANCA and the duration or extent of the inflammatory bowel disease. In specific enzyme-linked immunosorbent assays, only 14 sera elicited binding above the normal range. CONCLUSIONS: Although the prevalence of ulcerative colitis and Crohn's disease in Estonia is much lower than in European countries, there seem to be no differences in the presence of ANCA.

Distribution of local anesthetic solution in retromediastinal block. Preliminary experimental results.

BACKGROUND AND OBJECTIVES: Interpleural anesthesia blocks pain perception from the thoracoabdominal wall without impairment of leg function. Bilateral interpleural anesthesia is not recommended because of possible bilateral impairment of respiratory function. Infiltration of the retromediastinum with local anesthetic might cause bilateral thoracoabdominal somatic block and block of sympathetic afferents from the abdominal cavity without impairing respiration. METHOD: Distribution of stained fluid was studied after injection into the retromediastinum through a catheter placed about 10 cm cephalad to the diaphragm via the esophageal hiatus in three human cadavers of normal size and in six anesthetized pigs of 20-30 kg. In the pigs serum levels of bupivacaine were measured after injection of 10 mL of 0.5% bupivacaine stained with 1 mL of methylene blue. RESULTS: The injected Dye stained intercostal nerves 6-11 in cadavers and 5-12 in pigs symmetrically on both sides, along with the adjacent parts of the sympathetic chain and both vagal nerves but not the phrenic nerves. During the sampling period of 50-60 minutes, bupivacaine serum concentrations rose slowly to a maximum of 4.2 micrograms/mL. CONCLUSIONS: Block of pain perception from the abdominal wall and cavity is possible by injection of local anesthetic into the retromediastinum via a catheter introduced through the esophageal diaphragm hiatus. The block would not be expected to impair respiratory or leg function. Its efficacy and safety have yet to be established.

Factors influencing survival of patients after radical surgery for gastric cancer. A regional study of 406 patients over a 10-year period.

The present retrospective report presents a review of prognostic factors influencing the survival of 406 gastric cancer patients radically operated on in the Tartu Oncology Hospital, Estonia in 1978-1987. All patients underwent total (n = 170) or subtotal (n = 236) gastrectomies with extensive lymphadenectomy (260 R2- and 146 R3-resections) according to the General Rules for the Gastric Cancer Study in Surgery and Pathology established by the Japanese Research Society for Gastric Cancer, introduced in our hospital at the end of the 1970s and now used as the unavoidable procedure for curative gastric cancer surgery. The 30-day postoperative mortality was 5.9% and the overall 5-year survival 46.1%. The male:female ratio was 0.95 and the mean age 62.4 years. Only 7.6% of all our patients operated on had early gastric cancer with a 5-year survival of 80.7% whereas 76.8% had T3-T4 tumours with a 5-year survival of 41.0%. Lymph node involvement was found in 44.6% of the patients. Independent favourable prognostic factors were (the 5-year survivals are presented within parentheses): limited (N0-N1) lymph node involvement (56.4 vs. 22.6%), pT 1-2 stage (62.8 vs. 41.0%), papillary, tubular or poorly differentiated histological pattern (51.9 vs. 33.1%), subtotal gastrectomy (55.9 vs. 32.4%) and age below 70 years (51.9 vs. 35.2%). Sex of patients, Borrmann type, size and site of tumour were not statistically associated with prognosis at multivariate analysis. Our results also suggested that besides predetermined prognostic factors, the surgical policy had a great impact on the prognosis of gastric cancer patients. We conclude that gastrectomy with combined resections of neighbouring organs directly invaded and with extensive lymphadenectomy at least up to the second node group might be the procedure of choice for advanced gastric cancer.