Helicobacter pylori infection in combination with the serum pepsinogen I/II ratio and interleukin-1β-511 polymorphisms are independent risk factors for gastric cancer in Thais

Background Thailand has the lowest incidence of gastric cancer in the world. Helicobacter pylori infection, a low serum pepsinogen I/II ratio, and interleukin (IL)-1β-511 polymorphisms are suspected to be risk factors for gastric cancer. Methods A total of 167 Thais, comprising 56 cancer patients and 111 volunteers without cancer, underwent an esophagogastroduodenoscopic examination and three fixed-point biopsies; a cancer tissue biopsy was also done, and blood samples were collected. The subjects without cancer were divided into normal subjects and chronic gastritis patients. IL-1β-511 polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism, and the serum levels of pepsinogen I and II were determined by a radioimmunoassay. Helicobacter pylori IgG antibody and tissue pathology were tested in all groups. Results The pepsinogen I/II ratio was significantly lower in the gastric cancer group than in the normal and chronic gastritis groups [odds ratio (OR), 2.3; 95% confidence interval (CI), 1.10–4.80; P = 0.025]. Gastric cancer patients were positive for the H. pylori IgG antibody more frequently than negative (OR, 2.946; 95% CI, 1.4–6.39; P = 0.005). However, only 15 (27%) cancer patients were both positive for H. pylori IgG antibody and had low serum pepsinogen I/II. The C/C genotype was found more frequently in the gastric cancer group than in the group with a normal gastric mucosa (OR, 0.64; 95% CI, 0.50–0.81; P = 0.014). Conclusions A low serum pepsinogen I/II ratio combined with positivity for H. pylori IgG, and a IL-1β-511 C/C genotype may be independent risk factors for gastric cancer in Thais. Presented at the 19th World Congress of the International Society of Digestive Surgery, Pacifico Yokohama, Japan, December 8–11, 2004 (Helicobacter pylori Symposium)     

Longitudinal study of patients with idiopathic isolated TSH deficiency: possible progression of pituitary dysfunction in lymphocytic adenohypophysitis

The relationship between isolated TSH deficiency and hypophysitis was studied. Six patients (five women and one man) with idiopathic isolated TSH deficiency were longitudinally investigated with an interval of 31 to 60 months. Clinical symptoms, laboratory results and endocrine function were investigated as well as pituitary magnetic resonance imaging (MRI) at the start and the end of the study. Clinically, initial symptoms due to hypothyroidism were ameliorated by the thyroid hormone replacement in all patients. Oligomenorrhea newly appeared during the study in three patients, although no other symptoms appeared. Serum fT3 and fT4 levels were within the reference ranges, and serum TSH level and its response to TRH stimulation remained low in all patients. Peak plasma GH level during GRH stimulation was significantly (p<0.03) decreased, at the end of the study as compared with the start. Peak plasma FSH level to LHRH stimulation was significantly (p<0.03) decreased as well as basal FSH level. In contrast, peak of prolactin during TRH stimulation was significantly (p<0.03) increased at the end of the study as compared with the start as well as basal prolactin level. Endocrine features at the end of the study were compatible with those of lymphocytic adenohypophysitis (LAH). MRI of the pituitary gland showed empty sella in one patient and slight swelling in two patients. These findings remained unchanged during the study period. One patient underwent pituitary biopsy, with histological examination showing atypical form of LAH. LAH can cause idiopathic isolated TSH deficiency and can functionally progress to combine dysfunction of the pituitary gland.     

Opposing effect of p38 MAP kinase and JNK inhibitors on the development of heart failure in the cardiomyopathic hamster

OBJECTIVE: p38 MAP kinase (p38 MAPK) and c-Jun NH2-terminal kinase (JNK) have been implicated in the pathophysiology of heart failure. We investigated the effects of chronic treatment with p38 MAPK and JNK inhibitors on the development of heart failure in dilated cardiomyopathy (DCM) hamster heart. METHODS AND RESULTS: BIO14.6 hamster hearts showed markedly increased p38 MAPK and JNK activities at 6 weeks of age when there was no significant increase in the area of fibrosis, heart weight/body weight, left ventricular (LV) chamber dilation and LV dysfunction. p38 MAPK and JNK activities were attenuated at 26 weeks of age and abolished at 40 weeks of age in BIO14.6 hamster hearts. BIO14.6 hamsters and the control BIOF1B hamsters were chronically treated (i.p.) with the p38 MAPK inhibitors, SB203580 (1 mg/kg/day) and FR167653 (3 mg/kg/day), or the JNK inhibitor, SP600125 (1 mg/kg/day) or vehicle for 20 weeks starting from 6 weeks of age. Treatment of BIO14.6 hamster hearts with SB203580 and FR167653 reduced the number of TUNEL-positive myocytes, the area of fibrosis and heart weight/body weight associated with a significant decrease of LV dimension and an increase in LV ejection fraction and LV contractility compared to the vehicle-treated counterpart. In contrast, treatment with SP600125 increased the number of TUNEL-positive myocytes and the area of interstitial fibrosis associated with aggravation of LV chamber dilation and LV dysfunction. CONCLUSIONS: These results suggest that chronic treatment with p38 MAPK and JNK inhibitors produces opposing effects on the development of heart failure in the DCM hamster heart.     

Phase II study of the combination of gemcitabine and nedaplatin for advanced non-small-cell lung cancer

We examined the efficacy and safety of the combination of gemcitabine and nedaplatin in patients with untreated advanced non-small-cell lung cancer. Thirty-four patients (24 men and 10 women) with a mean age of 69 years (range, 39-75 years) were treated every 3 weeks with gemcitabine (1,000 mg/m(2) on days 1 and 8) and nedaplatin (100 mg/m(2) on day 1). Four patients had stage IIIB disease and 30 patients had stage IV disease. None of the 33 patients achieved a complete response, but 10 achieved a partial response, for a response rate of 30.3% (95% confidence interval, 15.6-48.7%). One patient could not be evaluated for response because only one course of chemotherapy had been administered due to grade 3 eruption. The median survival time was 9.0 months (range, 1-17 months). Grades 3-4 hematological toxicities included leukopenia in 47% of patients, neutropenia in 62%, thrombocytopenia in 56%, and anemia in 44%. Grades 3-4 nonhematological toxicities included nausea and vomiting in 6% of patients, diarrhea in 3%, and hepatic dysfunction in 9%. There were no treatment-related deaths. The dose intensities were 89.6% and 86.7%, respectively, of the planned doses of gemcitabine and nedaplatin. Our results suggest that the combination of gemcitabine and nedaplatin is an acceptable treatment for patients with previously untreated advanced non-small-cell lung cancer.     

Morphological changes ofHelicobacter pylori after antibacterial therapy: an electron microscope study

To investigate the effect of morphological change ofHelicobacter pylori on gastric mucosal inflammation,H. pylori was examined by means of an electron microscope and computer-assisted three-dimensional reconstruction before and after antibacterial therapy. The results showed that the bacterium was usually present in different forms and sizes. Most of these variations are helicobacter shaped, 3–5 m long (43%), or campylobacter shaped, 1–3 m long (38%); fewer are round or coccoid (19%), and only 0.5–1 m long. Active inflammation and an abnormal amount of mucus in the epithelial cells are the main changes seen in gastric mucosa withH. pylori infection. In some cases, 6 weeks after antibacterial therapy,H. pylori could still be observed by toludine blue, with slight positive results withH. pylori-antibody-labeled immunostaining. In contrast to the bacteria before antibacterial therapy, in mostH. pylori-positive cases usually only a minute number of bacteria were seen in coccoid form. These surviving coccoid-form bacteria showed thickened walls, and the surrounding periplasmic space was reduced or nonexistent. The epithelial cells were almost normal and¹³C-text negative. Although neutrophil infiltration was seldom seen, there were still some surviving bulblike cells with excess amounts of mucus in the gastric pits. It is suggested that the coccoid form ofH. pylori may be a static bacterium without urease production. For therapeutic decisions, it may be more important to identify whether there is an active inflammation in the gastric mucosa than to detectH. pylori.This study was presented at the 27th Annual Meeting of the Clinical Electron Microscopy Society of Japan. Kurashiki, September 28–30, 1995.     

Presumed endocarditis caused by BRO beta-lactamase-producing Moraxella lacunata in an infant with Fallot's tetrad

A case of presumed endocarditis caused by Moraxella lacunata in a 15-month-old male infant with Fallot's tetrad is described. This infection may have occurred as the result of transmission of this organism between the father and his son. This is the first report of BRO beta-lactamase-producing M. lacunata causing presumed endocarditis.     

Gastrospirillum hominis and Helicobacter pylori infection in Thai individuals: Comparison of histopathological changes of gastric mucosa

The presence of Helicobacter pylori (H. pylori ) in the stomach is closely associated with histological signs of chronic active gastritis and peptic ulcer. Another spiral organism named Gastrospirillum hominis (G. hominis ) has led to further interest in the bacterial pathogenesis of gastritis. Due to the low prevalence of G. hominis , it is difficult to evaluate its biological behavior. Recently 16 cases of G. h ominis-associated gastritis were found in 257 Thai individuals, which made it possible to study the biological characteristics of G. hominis and its relationship with gastric mucosal inflammation. The results showed that H. pylori and G. hominis could be easily observed in the lower third of the mucous layer and in the mucosa of the gastric pits by means of toluidlne blue staining. Both bacteria immunostained positive. Helicobacter pylori were usually in the shape of curved bacillary while G. hominis often appeared in spiral configuration. In 257 cases of Thai subjects, 169 cases were found to be H. pylori positive, the detection rate was 65.7%, and 16 cases were G. hominis positive, with a 6.2% detection rate. In G. hominis infection, 43.6% of cases had normal gastric mucosa. Superficial, erosive and atrophlc gastritis cases were 13.2, 10.9 and 12.5%, respectively. Mucosal inflammation was usually severe in H. pylori , but neutrophil polymorph infiltration was often mild and focal in G. hominis Infection. Although no G. hominis infection with carcinoma was shown in our cases, the occurrence of mucosal atrophy, metaplasia and dysplasia was higher in both bacterial infections compared with H. pylori- and G. hominis -negative cases. It is suggested that G. hominis may be partly responsible for the mucosal inflammation and some malignant-associated lesions.     

alpha-Glucosidase inhibitor reduces the progression of carotid intima-media thickness

OBJECTIVE: An open randomized prospective study was performed to elucidate the effect of an alpha-glucosidase inhibitor, voglibose, on the progression of atherosclerosis in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: Voglibose at a dose of 0.4-0.6 mg/day was added on 51 subjects out of 101 type 2 diabetic patients being treated with diet, sulphonylurea (SU) or insulin injections, and the average (AveIMT) and maximum intima-media thickness (MaxIMT) of their carotid arteries were examined for 3 years. RESULTS: Irrespective of the differences in treatments, addition of voglibose reduced the progression of AveIMT and MaxIMT to -0.024 +/- 0.047 (+/-S.D.) and -0.021 +/- 0.144 mm/year, respectively. Without voglibose, diabetic patients showed significant (P < 0.0001) progression of AveIMT and MaxIMT (0.056 +/- 0.046 and 0.098 +/- 0.122 mm/year, respectively). The administration of voglibose resulted in a significant reduction of hemoglobin A1c (HbA1c), total cholesterol and triglyceride concentrations, as well as an increase in HDL cholesterol concentration. Multivariate regression analysis showed that administration of voglibose independently reduced the progression of AveIMT by 0.069 mm/year (P < 0.0001). CONCLUSIONS: These results suggest that voglibose reduces the progression of IMT and may be a candidate for an anti-atherosclerotic drug for type 2 diabetic patients.     

Gene mutations responsible for overexpression of AmpC beta-lactamase in some clinical isolates of Enterobacter cloacae

AmpC regulatory genes in 21 ceftazidime-resistant clinical isolates of Enterobacter cloacae (MICs of > or = 16 microg/ml) were characterized. All isolates exhibited AmpC overproduction due to AmpD mutation. Additionally, we found two AmpR mutants among the isolates. This is the first report of chromosomal ampR mutation in clinical isolates of E. cloacae.