A protease inhibitor attenuates gastric erosions and microcirculatory disturbance in the early period after thermal injury in rats

The effects of camostat mesilate, a synthetic serine protease inhibitor on gastric microcirculation and active oxygen species generated by leucocytes from the gastric and jugular veins in the early period after thermal injury were assessed. Male Wistar rats were anaesthetized and a 30% full skin-thickness dorsal burn was inflicted. Camostat mesilate (100 mg/kg) was dissolved in distilled water and administered orally to rats 40 min before thermal injury (the camostat group). The control animals (the vehicle group) were administered distilled water orally. Rolling leucocytes as well as Monastral blue B deposits in venules were observed using in vivo microscopy. Active oxygen species were measured by chemiluminescence. Camostat mesilate decreased the total length of gastric erosion, venular deposits of Monastral blue B, and rolling of leucocytes in venules, and relatively increased luminol-dependent chemiluminescence activity generated by zymosan-stimulated leucocytes 15 min after thermal injury. These results suggest that serine proteases are involved in the formation of gastric erosions and gastric microcirculatory disturbance in the early period after thermal injury.     

Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: Involvement of platelet aggregation

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.     

THE IMPACT OF DIABETES MELLITUS ON THE PROGNOSIS OF ALCOHOLICS

In this study, the mortality of clinically treated Japanesealcoholics with diabetes mellitus was analysed. Fifty-one diabeticalcoholics without liver cirrhosis (DM), 23 diabetic and cirrhoticalcoholics (DM LC), 44 cirrhotic alcoholics without diabetes(LC), and 354 alcoholics without either complication (AL) admittedto the National Institute on Alcoholism in 1985 were studied.Thirty-seven diabetics required insulin treatment, and 12 oralhypoglycemic agents. The 4.4-year survival and drinking statusafter discharge were studied in 1990. Stepwise logistic regressionanalysis showed that the estimated odds for death increased8.10, 4.38, 3.70, and 3.27 times for the subjects with the alcoholmisuse after discharge, DM, DM LC, and LC, respectively. The4.4-year survival rate of alcoholics who continued misusingalcohol was much lower in DM (26%, P < 0.0005) and LC (35%,P < 0.0001) than in AL (73%). The survival rate of thosewho stopped misusing alcohol was significantly higher in DM(90%, P < 0.0001), LC (88%, P < 0.0001) and AL (94%, P< 0.0005) than those who continued misusing alcohol. Therewas no significant difference in the survival rate between thealcoholics with DM LC who continued misusing alcohol (50%) andthose who stopped misusing alcohol (73%). In the dead patients,56% of DM died unexpectedly or suddenly, whereas 71% of LC diedof liver failure after hospitalization. These results suggestthat diabetic alcoholics should be intensively educated forabstinence.     

New Electrophysiologic Features and Catheter Ablation of Atrioventricular and Atriofascicular Accessory Pathways:

Catheter Ablation for Mahaim Pathways. Introduction : Several modalities of catheter ablation have been proposed to eliminate Mahaim pathway conduction. However, limited research has been reported on the electrophysiologic nature of this pathway in its entity.
Methods and Results : In seven patients, electrophysiologic study was performed, and radiofrequency energy was applied to investigate the electrophysiologic clues for successful ablation. In all seven patients, the Mahaim pathway was diagnosed as a right-sided atriofascicular or atrioventricular pathway with decremental properties. In two patients, two different kinds of electrograms were recorded through the ablation catheter positioned at the Mahaim pathway location: one was suggestive of conduction over the decremental portion, demonstrating a dulled potential; and the other of nondecremental conduction, demonstrating a spiked potential. All but one of the Mahaim pathways were eliminated successfully at the atrial origin where the spiked Mahaim potential was recorded. Radiofrequency energy application was performed at the slow potential site resulting in failure to eliminate the conduction over the Mahaim pathway. Conduction block at the site between the slow and fast potential recording sites was provoked by intravenous administration of adenosine, concomitant with a decrease in the amplitude of the Mahaim potential. In one patient, the clinical arrhythmia was a sustained monomorphic ventricular tachycardia originating from the ventricular end of the Mahaim fiber.
Conclusion : The identification of Mahaim spiked potentials may be the optimal method to permit their successful ablation. Detailed electrophysiologic assessment is indispensable for successful ablation of tachycardias associated with Mahaim fibers because tachycardias unassociated with Mahaim fibers can occur despite complete elimination of the Mahaim fiber.     

Primary Adrenocortical Carcinoma and Ganglioneuroblastoma Followed by Rhabdomyosarcoma in a Child: A Case Report

We report a case of a young child affected by triple cancerswho developed a pleomorphic rhabdomyosarcoma of the retroperitoneumfollowing prophylactic chemotherapy after surgery for doubleprimary adrenocortical carcinoma and ganglioneuroblastoma. It is suggested that genetic susceptibility and chemotherapymight be responsible for the development of rhabdomyosarcomaas the second malignant neoplasm.     

Four Cases of T-Cell Malignancy in Childhood

Four cases of T-cell malignancy in childhood are reported. Inthe two older boys (seven [Case 1] and eight [Case 2] yearsold) the disease began as leukemia without a clinically detectablemediastinal mass. However, thymic involvement was found at autopsyin Case 1. Tumor cells of both patients had a rosetteformingcapacity with sheep erythrocytes (ERFC), high terminal deoxynucleotidyltransferase (TdT) activity and a positive acid phosphatase (AcPase)reaction. These findings suggest that the tumor cells of Cases1 and 2 originated from thymic T lymphocytes. The two younger patients (two [Case 3] and three [Case 4] yearsold) had cervical lymphadenopathy with mediastinal mass at onset,followed by leukemic change. The youngest patient (Case 3) lackedERFC and the AcPase reaction, but had C3 Receptor (C3-R), humanT-lymphocyte antigen (HLTA) and TdT activity. These findingsindicate that the tumor cells of Case 3 are compatible withearly thymic T lymphocytes. Tumor cells of Case 4 had ERFC,C3-R, HTLA, and slightly increased TdT activity. These findingssuggest that the tumor cells of Case 4 originated from thymicT lymphocytes. Only one patient has maintained an initial complete remissionfor more than one year. The three others relapsed or had a leukemicconversion within 12 months of the initial remission and twodied within 13 months. This indicates that childhood T-cellmalignancies have a poor prognosis.     

Modulation of intestinal immune system by dietary fat intake: Relevance to Crohn's disease

Gut-associated lymphoid tissue is the major inductive site of the mucosal immune system, which is functionally independent of the systemic immune system. Both the amount and type of dietary fat modulate intestinal immune function. Absorption of long-chain fatty acids stimulates lymphocyte flux and lymphocyte blastogenesis in intestinal lymphatics. Long-chain fatty acid absorption also significantly enhances migration of T lymphocytes to Peyer's patches, possibly due to up-regulation of adhesion molecules, such as α4-integrin and L-selectin. Lipoproteins are involved in stimulation of lymphocyte function by both receptor-dependent and independent mechanisms. However, unsaturated fatty acids at higher concentrations have a suppressive effect on cell-mediated immunity via eicosanoid release, receptor affinity changes or interactions with intracellular signal transduction. Fat absorption also influences various other cells in the intestinal mucosa: increased cytokine release from intestinal epithelial cells follows long-chain fatty acid absorption. In Crohn's disease, elemental diets and total parenteral nutrition often induce remission, possibly by reducing antigenic load on activated immune cells in the intestine and, thus, down-regulating hyperreactive CD4 cells. Dietary oleic acid supplements caused an immunological reversal effect in the intestinal immune system of animals fed an elemental diet. An excess of long-chain fatty acids in an elemental diet, therefore, may negate its beneficial effect on gut-associated lymphoid tissues in Crohn's disease. In contrast, supplemental dietary fish oil apparently tends to prevent relapse of Crohn's disease. Because dietary fat intake is closely associated with immunological function of the intestinal mucosa, careful manipulation of dietary fat can be important in management of this disease.