Role of prostaglandins and histamine in hyperemic response to superficial and deep gastric mucosal injury and H+ back-diffusion in cats

This study was undertaken to examine the role of prostaglandins and histamine in the hyperemic response to gastric mucosal damage followed by H⁺ back-diffusion. Cat stomachs were exposed to 2 mol/liter NaCl for 10 min followed by luminal perfusion at pH 1. Hypertonic saline caused extensive (microscopic) damage to the surface epithelium, increased gastric mucosal blood flow, and increased release of histamine, PGE₂, and 6-keto PGF_1α (prostacyclin) into portal venous blood. The effect of indomethacin and histamine blockers (H₁+H₂) on the hyperemic response to acid back-diffusion was related to the depth of the mucosal injury and the region of the stomach. In the corpus, indomethacin enhanced mucosal injury. In areas with superficial damage, the hyperemia was inhibited by indomethacin and antihistamines and eliminated by the combination of both. In corpus areas with indomethacin-induced deep lesions, the blood flow was very high, and this hyperemia was partly inhibited by antihistamines. In the antrum the hyperemic response was reduced by antihistamines. Indomethacin increased the release of histamine into the portal venous blood (baseline recordings) and reduced basal gastric mucosal blood flow.     

Gastric carcinogenesis in rats given hypertonic salt at different times before a single dose ofN-methyl-N′-nitro-N-nitrosoguanidine

A 1-ml dose of 4.5 M NaCl was given intragastrically to male Wistar rats at 10 min, 1 h, 4 h, 12 h, 24 h or 48 h before a single intragastric dose of 250 mg/kgN-methyl-N-nitro-N-nitrosoguanidine (MNNG). After 52 weeks the incidence of forestomach squamous cell carcinoma was 21% in control animals receiving MNNG alone. The cancer incidence in the forestomach varied with the time elapsed between application of NaCl and MNNG, and was significantly increased in animals pretreated with NaCl 4 h (43%), 12 h (54%) and 24 h (41%) before MNNG. These results show that salt has a cocarcinogenic effect on initiation of forestomach carcinogenesis in rats, and that this effect depends on the time interval between pretreatment with NaCl and application of MNNG. Gastric adenocarcinomas occurred more frequently in the antrum (78%) than in the corpus (22%). The incidence of gastric adenocarcinoma in animals pretreated with salt before application of MNNG (11%–22%) was not significantly influenced by the time elapsed between pretreatment with salt and application of MNNG, and did not differ from animals receiving MNNG alone (18%). The lack of a cocarcinogenic effect of NaCl on glandular gastric carcinogenesis might be due to the use of dimethyl/sulfoxide as solvent for MNNG.Abbreviations MNNG N-methyl-N-nitro-N-nitrosoguanidine - DMSO dimethylsulfoxide This work was supported by grants from the Norwegian Cancer Society. Dr Sørbye is a Research Fellow of the Norwegian Cancer Society     

Radiofrequency Catheter Ablation of Two Right Mahaïm-like Accessory Pathways in a Patient with Ebstein's Anomaly

A 17-year-old woman with Ebstein's anomaly and recurrent episodes of antidromic tachycardia with two distinct morphologies is described. The tachycardias were produced by two separate Mahaïm-like accessory pathways. These were localized by their activation potentials at the anterolateral ventricular margin of the tricuspid annulus and ablated in a single session using radiofrequency current.     

Duodenogastric reflux increases the penetration of N-3H-methyl-N-nitro-N-nitrosoguanidine into the antral mucosa of rats: a possible role for mucosal erosions and increased cell proliferation in gastric carcinogenesis.

Duodenogastric reflux is a risk factor for gastric carcinogenesis, but the pathogenesis is not fully understood. We studied the risk of N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis in the antrum of rats with duodenogastric reflux. Duodenal fluid was directed into the stomach through the pylorus (pyloric reflux group) or through a gastrojejunostomy (jejunal reflux group). After twenty-four weeks, 5-bromo-2-deoxyuridine (BrdU) was injected intravenously and the stomach was exposed to N-(3)H-methyl-N-nitro-N-nitrosoguanidine ((3)H-MNNG). The antral mucosa was examined with immunohistochemistry and autoradiography for identification of proliferating cells (BrdU labelled) and cells at risk of MNNG-induced carcinogenesis ((3)H-MNNG and BrdU-labelled cells). Duodenogastric reflux increased the number of double-labelled cells in the antral mucosa from 4.8 +/- 0.6 per mm in the control group to 11.3 +/- 1.9 in the jejunal reflux group (P < 0.05) and 12.7 +/- 0.9 in the pyloric reflux group (P < 0.05). Mucosal erosions were observed in 15 of 28 animals with pyloric reflux and the number of double-labelled cells in the erosion area (4.3 +/- 0.7) was higher than in the same area of animals without erosion (1.4 +/- 0.5) (P < 0.05). Duodeno-gastric reflux increased the cell proliferation and significantly changed the distance between the surface epithelial lining and the proliferating cells when compared to the controls. These results indicate that duodenogastric reflux increases the penetration of (3)H-MNNG into the antrum mucosa of rats. Increased cell proliferation and erosions increase the number of cells at risk of an initiation process from a penetrating gastric carcinogen.     

Implantable cardioverter defibrillator dysfunction during and after magnetic resonance imaging

This report describes a patient in whom a MRI of the brain was performed without realizing that an ICD had been implanted 8 days previously. Electromagnetic noise induced during the MRI was detected as ventricular fibrillation and nearly caused inappropriate shocks. Charge time during MRI was prolonged. The battery indicator switched to "end of life," but this was reversed by capacitor reformation. These problems could have been avoided by inactivating the ICD prior to MRI. Three months later, the pacing threshold increased from 0.4 V per 0.5 ms at implantation to 2.8 V per 0.5. It is still uncertain whether radiofrequency current heating at the electrode tip caused the increased pacing threshold or if this would have occurred independently of the MRI. MRI of patients with an active ICD may cause life-threatening complications, and it is unknown if MRI may be safely performed if the ICD is inactivated. Therefore, MRI of patients with an ICD remains contraindicated.     

Univariate and bivariate variance component linkage analysis of a whole-genome scan for loci contributing to bone mineral density

Osteoporosis is a common condition characterized by reduced skeletal strength and increased susceptibility to fracture. The single major risk factor for osteoporosis is low bone mineral density (BMD) and strong evidence exists that genetic factors are in part responsible for an individual's BMD. A cohort of 40 multiplex Caucasian families selected through a proband with osteoporosis was genotyped for microsatellite markers spaced at an average of 10 cM, and linkage to femoral neck (FN), lumbar spine (LS) and trochanter (TR) BMD was analyzed using univariate and bivariate variance component linkage analysis. Maximum univariate multipoint lod-scores were 2.87 on chromosome 1p36 for FN BMD, 1.89 on 6q27 for TR BMD, and 2.15 on 7p15 for LS BMD. Results of bivariate linkage analysis were highly correlated with those of the univariate analysis, although generally less significant, suggesting the possibility that some of these susceptibility loci may exert pleiotropic effects on multiple skeletal sites.