Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.

Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4-21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0-78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-ß, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-ß in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-ß and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-ß production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D.

Methods of emergency surgery in high-risk stigmata peptic ulcer hemorrhage.

AIM: The choice of emergency operative methods in management of peptic ulcer hemorrhage (PUH) is controversial. The aim of this study was to analyze the patient characteristics, surgical methods and treatment outcome of patients with PUH during 10 years. METHODS: Of the 953 admitted PUH patients all 67 (7.0%) operated cases had high-risk stigmata PUH (Forrest classification). These patients were grouped and their data were compared under two 5-year periods: period I - 32 patients (2003-2007) and period II - 35 patients (2008-2012). RESULTS: The majority of the patients had giant ulcer (diameter ≥ 2 cm) hemorrhage at 75.0% (24/32) and 94.3% (33/35) during study periods I and II, respectively (P=0.04). Giant duodenal and gastric ulcers for PUH were operated in 16 and 8 vs 27 and 6 during periods I and II, respectively. Ulcer exclusion or ulcerectomy combined with definitive acid reducing surgery was applied in 68.7% (22/32) and 71.4% (25/35) of the patients, respectively, without early recurrent hemorrhage. Postoperative in hospital mortality in the 10-year study period was 6.0% (4/67); 2.1% (1/48) of the patients died after definitive operations and 15.8% (3/19) (P=0.04) died after non-definitive operations. CONCLUSION: The surgical treatment of high-risk stigmata PUH was mainly associated with giant, particularly giant duodenal ulcer. As a rule, ulcer exclusion or ulcerectomy as hemorrhage control, combined with definitive surgery, was applied in the majority of the cases with an in hospital mortality of 2.1%.

Diversity of Helicobacter pylori genotypes among Estonian and Russian patients with perforated peptic ulcer, living in Southern Estonia.

To compare the genomic variation of Helicobacter pylori in samples obtained from patients with perforated peptic ulcer, living in the same area of Estonia but belonging to different nationalities, 50 non-consecutive patients (32 Estonians and 18 Russians) admitted in the Tartu University Hospital in 1997-1999 were studied. Gastric samples of antral mucosa were obtained during operation and analysed histologically and with PCR for detection of different genotypes of H. pylori (cagA and vacA s and m subtypes). Among the 50 perforated peptic ulcer patients with histologically proven H. pylori colonisation no sample of gastric mucosa showed the s1b subtype of the vacA gene. The perforated peptic ulcer patients were mainly infected with cagA (82%) and s1 (98%) genotypes of H. pylori. The distribution of s1a/m1, s1a/m2 and s2/m2 subtypes of vacA genes was statistically different in Estonian and Russian patients (P<0.05). In conclusion differences in the distribution of vacA s and m subtypes of H. pylori were revealed between Estonian and Russian patients with perforated peptic ulcer from Southern Estonia.

Risk evaluation of postvagotomy ulcer recurrence by using endoscopic Congo red test and gastric secretion tests.

BACKGROUND/AIMS: To evaluate the usefulness of the endoscopic Congo red test (ECRT), and to compare sensitivity and specificity of different tests in the discrimination of cases with high risk for postvagotomy recurrent ulcer (RU). METHODOLOGY: In 271 consecutive postvagotomy duodenal ulcer patients the endoscopic Congo red test (ECRT) was used 5-12 years after vagotomy. Further, 39 patients out of 271 were selected and classified into two groups: A--13 ECRT positive cases with RU, B--26 controls without RU (13 ECRT positive and 13 ECRT negative cases). Basal acid output (BAO), maximal acid output (MAO), and nocturnal acid output (NAO) were determined pre- and postoperatively, the serum pepsinogen I (S-PGI) and insulin test were estimated postoperatively. RESULTS: Positive ECRT had 95% sensitivity and 53% specificity for RU. S-PGI > 150 microg/l had 54% sensitivity and 92% specificity (in ECRT positive cases 100% specificity). The insulin test showed 83% sensitivity and 78% specificity. The respective data for the combination of BAO > 1.5 mmol/h + NAO > 30 mmol/12 h were 80% and 81%. CONCLUSION: ECRT should be a primary step in estimating postvagotomy ulcer risk. In negative ECRT cases, the development of recurrent ulcer is unlikely. Additional gastric secretion studies as S-PGI or BAO+NAO or insulin test are needed only in ECRT positive cases.

Completeness of vagotomy, Helicobacter pylori colonization and recurrent ulcer 9 and 14 years after operation in duodenal ulcer patients.

OBJECTIVE: To clarify the relationship between the completeness of vagotomy and Helicobacter pylori colonization in the development of recurrent ulcer (RU) during a long-term follow-up period after the operation in duodenal ulcer (DU) patients. DESIGN: 122 consecutive vagotomized DU patients were studied twice on average 9 and 14 years after vagotomy. METHODS: The presence of RU and completeness of vagotomy were assessed simultaneously endoscopically and by endoscopic Congo Red test (ECRT). The positive ECRT showed incomplete vagotomy. The amount of H. pylori in the biopsy specimens of the gastric antrum and corpus mucosa was detected histologically by microscopic counting. RESULTS: The cumulative increase in RU occurred from 4% (5/122) at 9 years to 18% (22/122) at 14 years (P < 0.001) and the rate of ECRT positive cases rose from 52 to 71%, respectively (P < 0.01). All RU cases were ECRT positive. H. pylori colonization occurred in 92% of cases at 9 years and in 98% of cases at 14 years. Vagotomy increased H. pylori prevalence in the corpus mucosa and the rate of the high intensity grade of H. pylori in the antrum and corpus mucosa. CONCLUSION: The number of RU after vagotomy increases with time and is limited to patients with incomplete vagotomy. H. pylori colonization and the increased rate of its high intensity in the gastric mucosa after vagotomy may promote the development of RU only in incomplete vagotomy cases.

Interpretation of postvagotomy endoscopic Congo red test results in relation to ulcer recurrence 5 to 12 years after operation.

BACKGROUND: The aim of the present study was to estimate, after vagotomy, the location and extension of residual vagal innervation of the gastric corpus mucosa by using the endoscopic Congo red test (ECRT) and its relation to recurrent ulcer (RU), as well as the results of quantitative gastric acid tests: basal acid output (BAO), maximal acid output (MAO), and nocturnal acid output (NAO). METHODS: A total of 271 consecutive vagotomized duodenal ulcer (DU) patients were studied 5 to 12 years (mean 8 years) after the operation. In all cases gastroscopy and ECRT were performed simultaneously. ECRT was considered positive if a red to black-blue (pH <3.0) color change of the gastric corpus mucosa occurred within the first 3 minutes, and the cases were classified as having small extension (SE), ie, one or more areas with a diameter of 1 to 30 mm, or large extension (LE), ie, 20% or more of the gastric corpus showing residual vagal innervation. No red to black-blue changes (pH >3.0) were attributed to negative ECRT. BAO, MAO, and NAO were determined preoperatively and postoperatively in 108 cases out of 271 and correspond with ECRT results. RESULTS: Recurrent ulcer occurred in 18 out of 135 ECRT-positive and in 1 out of 136 ECRT-negative cases. RU occurred 5 times more frequently in LE than SE cases (P <0.05). The postoperative mean values of BAO, MAO, and NAO were significantly higher in ECRT-positive than in ECRT-negative cases (P <0.001), and higher in LE than in SE cases (P <0.01; for NAO, P >0.05). CONCLUSION: ECRT is a practical and reliable method in the evaluation of postvagotomy DU patients: Negative ECRT practically includes recurrent ulcer risk; positive ECRT of large extension is related to fivefold higher recurrent ulcer risk compared with ECRT of small extension; and ECRT reflects BAO, MAO, and NAO results and can be used instead of them as a less time-consuming procedure, which is more convenient for the patient.

Peptic ulcer haemorrhage in Tartu County, Estonia: epidemiology and mortality risk factors.

BACKGROUND: The aim of the study was to assess the epidemiology and mortality risk factors of peptic ulcer haemorrhage (PUH) in Tartu County, Estonia. METHODS: In a prospective unselected defined area study, data for 144 patients aged > or = 15 years with new cases of PUH were analysed during a 2-year period. RESULTS: The incidence of PUH was 57 per 100,000 adult population per year, increasing from 12 in patients aged 20-29 years to more than 135 in those > or = 70 years. The incidence was 2.3-fold higher for men. The incidence of gastric ulcer haemorrhage was 26 (men, 33; women, 20) and that of duodenal ulcer 22 (men, 39; women, 9). Of the women 72% and of the men 37% were > or = 60 years. Nonsteroidal anti-inflammatory drugs (NSAIDs) were used by 45% of the patients (64% of women, 36% of men). Helicobacter pylori infection was present in 93% of the duodenal ulcer patients and in 81% of the gastric ulcer patients. Mortality (8%) was related to age, shock, haemoglobin < 80 g/l, cardiac comorbidity, and recurrence of haemorrhage. CONCLUSIONS: The incidence of PUH is relatively high owing to a high incidence among the younger population in Tartu County. Women with PUH are older, have consumed more NSAIDs, and have mainly gastric ulcer; men are younger, have consumed less NSAIDs, and are prone to duodenal ulcer haemorrhage. H. pylori infection is common in PUH patients. Mortality risk factors coincide with those reported by other researchers.

Long-term effect of vagotomy on gastric mucosa and Helicobacter pylori in duodenal ulcer patients.

The purpose of the study was to evaluate the long-term effects of vagotomy on the morphological status and Helicobacter pylori infestation of the gastric mucosa. Endoscopy with biopsies (2 from antrum and 2 from corpus) was performed in 317 patients on whom vagotomy had been performed on an average 8 years earlier. The success of the vagotomy was estimated by the endoscopic Congo Red technique in 270 cases. Non-operated 187 duodenal ulcer patients were examined endoscopically and bioptically in a similar way and used as a reference series. Helicobacter pylori (HP) was determined by Giemsa staining of biopsy specimens in both series. In non-operated dudoenal ulcer patients, gastritis and HP behaved as expected from the data in literature: antral gastritis was present in nearly all cases (96%), while the corpus mucosa was normal or the process was retarded at the stage of superficial gastritis (76%) and atrophic changes were virtually lacking (1%). On the basis of the Congo Red test the vagotomized patients were separated into two groups: successfully operated, i.e., complete vagotomy, and incomplete vagotomy groups. The results of the examinations were independent of the kind of vagotomy performed, but related significantly to its completeness. The incomplete and complete groups differed significantly. The prevalence of atrophic changes (29%) in the corpus was significantly higher and that of superficial gastritis (69%) lower in the complete than in the incomplete vagotomy group, in which the prevalences were 12% and 85%, respectively. Likewise the prevalence and density of HP was lower in the complete vagotomy group but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Helicobacter (Campylobacter) pylori infestation and the development and progression of chronic gastritis: results of long-term follow-up examinations of a random sample.

One hundred and thirty-nine subjects representing a randomly selected sample of an Estonian urban population examined endoscopically, bioptically and bacteriologically in 1979 was re-examined in 1985. In the antrum the development of superficial gastritis was clearly associated with the appearance or persistence of Helicobacter pylori (HP) infestation. The further progression of superficial gastritis could less clearly be related to HP infestation, although regression and progression of antral superficial gastritis was significantly associated with the disappearance or presence of the bacteria. The progression of atrophic antral gastritis as well as the development and progression of all body gastritis seemed unrelated to the HP infestation. It is concluded, that HP infestation is in some way involved in the appearance of the first stages of chronic gastritis, but is less related or unrelated to its further progression, which is probably determined mainly by factors other than HP.