The effects of chemical sympathectomy on the differentiation of the generative cells, superficial epithelial cells and gastrin cells of the gastric mucosa of hamster were examined by 3H-thymidine autoradiography. The labeling indices of the generative cell zone in the gastric mucosa and antral gastrin cells showed a transient significant decrease after chemical sympathectomy, and then they were gradually restore with time. After 4 weeks onward, the labeling indices of the generative cells showed a slightly low value compared with those in controls. The renewal of superficial epithelial cells and gastrin cells was examined in the hamster sympathectomized for 4 weeks. The time required for the differentiation to PAS positive superficial epithelial cells or gastrin cells had a tendency to elogate after chemical sympathectomy. These results suggest that chemical sympathectomy played an inhibitive action on the proliferation and the differentiation of gastric mucosa.
While gastric mucosa contains prostaglandins and leukotrienes, the roles of these substances in the gastric mucosal protection and damage are not clarified. Using AA-861, a specific 5-lipoxynenase inhibitor, and indomethacin, a cyclooxygenase inhibitor, we investigated the roles of intrinsic prostaglandins and leukotrienes in the gastric circulatory change and the development of gasstric lesion induced by ethanol. Rats were fasted for 48 hours and allowed free access to water. After light ether anesthesia, rats were orally given AA-861 (gift from Takeda Chem. Industry; 2.5, 10, 40 or 640mg/kg), indomethacin (20mg/kg), and the both or AA-861 (40mg/kg) and indomethacin (20mg/kg). Thirty min after the treatment, 2ml of ethanol (30, 40, 70, 99.5%) was orally administered. Sixty min later, the rats were killed to measure the area of mucosal lesions. The gastric mucosa was damaged by ethanol (≥40%) in a dose-dependent manner. The treatment with AA-861 prohibited the gastric mucosal damage. However, the treatment with indomethacin did not show a significant influence to the mucosal damage. Combined treatment of AA-861 and indomethacin yielded no significant difference from that of single treatment with AA-861 in acute gastric mucosal ulceration. The mucosal blood flow velocity was monitored by laser doppler velocimetry before and after the ethanol administration in the groups treated with vehicle, AA-861 or indomethacin. The blood flow velocity decreased after the administration of 40% ethanol in the group treated with indomethacin, and in a group treated with vehicle. By contrast, in the group treated with AA-861, the velocity did not show a significant decrease after the ethanol administration. The results suggested that the basal level of intrinsic prostaglandins may not affect the mucosal protection against the gastric injury induced by high concentration of ethanol, and that the formation of gastric mucosal lesion induced by ethanol may be due to the increase of leukotrienes in gastric musoca, which caused the decrease of gastric mucosal flow velocity resulting in the mucosal injury.
To elucidate the risk factors of peptic ulcer which require surgical treatments, we examined the influences of following factors such as sex, age, smoking, and alcohol in 308 peptic ulcer patients. In the group with gastric ulcers, high age group was likely to be operated. On the contrary, young patients with duodenal ulcers were likely to be treated surgically. Sex, smoking and alcohol were not regarded as risk factors. The correlations between the degree of neurosis and the amounts of smoking and alcohol were analyzed in the cases with duodenal ulcers. In the cases treated surgically, the degree of neurosis showed no or little correlations. In the cases treated conservatively, however, the degree of neurosis showed positive correlation with the amounts of smoking and alcohol.
Fecal fat excretion rate was determined by the method of Van de Kamer in 31 patients with Crohn's disease and six healthy controls, when fed by the diet containing 50g/day of fat. Patients with jejuno-ileitis and those with partial and extensive resection showed a significantly greater excretion rate compared with patients with ileitis and healthycontrols, however, there was no significant difference between patients with ileitis and helthycontrols. In this study, the fecel excretion rate was less than 10g/day in non-operated cases. Our results seems to be smaller than those in previous studies from the western countries. Fecel fat excretion rate was determined in 12 patients with non-operated Crohn's disease and six healthy controls, when fed by the additional 50g/day butter fat during the elemental diet. With ingestion of the additional 50g/day butter fat during elemental diet, fecal fat excretion rate was significantly increased in the patients with non-operated Crohn's disease than the results of the diet containing 50g/day fat, but not significantly changed in the healthy controls. This result suggest that determination of fecal fat excretion rate with fed by the additional 50 g/day butter fat during elemental diet is a useful test for detecting a mild fat malabsorption in non-operated Crohn's disease.
To depict of porto-systemic collaterals clearly, and to analyze of hemodynamics of liver, we developed new method of per-rectal portal scintigraphy (direct intramural administration of 99mTcO-4 by 23G needle). And we used this method in patient with liver diseases (acute hepatitis: 5, chronic hepatitis: 7, liver cirrhosis: 25 cases). From time activity curve of the liver and the heart, liver/heart ratio; index of porto-systemic shunt via inferior mesenteric vein (IMV) and first flow ratio(k); index of portal blood flow from IMV pathway/index of hepatic total blood flow were calculated. In our method, the images of portal vein, liver, heart, especially porto-systemic collaterals were visualized more clearly than enema methods. The liver/heart ratio was significantly lower in patients with liver cirrhosis than that in non-cirrhotic patients (p<0.01), which indicated that patients with liver cirrhosis had more porto-systemic collaterals than non-cirrhotic diseases. The k was more lower in liver cirrhosis than in acute hepatitis (p<0.01). And the k was also more lower in chronic hepatitis than in acute hepatitis (p<0.1), which indicated that portal blood flow via IMV reduced in early stage of chronic liver diseases. In conclusion, new method of per-rectal portal scintigraphy has more advantage for analysis of hepatic hemodynamics than enema methods.
The relative value of a subserosal injection of 98% ethanol (0.2ml×4) in controlling acute and chronic bleeding from serosal vessels was assessed in dogs. Blood flow was measured from gastric serosal vessels (average diameter 1.6mm) severed immediately after, 24 hours after, and 48 hours after ethanol injection. Blood flow from severed colonic serosal vessels (averaging diameter 1.0mm) was measured prior to and immediately after ethanol injection. The safety of ethanol injection was tested by endoscopically guided submucosal injection which were sequentially observed endoscopy at one hour, 24 hours, and weekly for weeks after injection. Ethanol injection had no effect on bleeding from larger gastric vessels unless the injection was made 24 or 48 hours peior to vessel severence. Ethanol injection was effective in reducing bleeding from the smaller colonic vessels when done immediately prior to vessel severence. Gastric submucosal injections led to ulcers which extended into the muscle layer at on week and healed completely by three weeks; none perforated or bleed. These data support the potential efficicacy of therapeutic ethanol injection for the control of small vessel (1.0mm diameter) bleeding and the potential prophylactic value against rebleeding from larger vessels. Further studies are needed to determine if these findings are organ related as opposed to being diameter specific.
Serum urea/creatinine (Ur/Cr) ratios were determined in patients showing massive gastrointestinal (GI) bleeding in order to evaluate the bleeding site. In 36 cases of upper GI bleeding, serum Ur/Cr ratios were 119.1±4.0. The ratios were 54.1±12.1 and 58.4±10.3 in 23 cases of lower GI bleeding and 50 control cases without GI bleeding, respectively. The ratio in the upper GI bleeding cases were significantly higher than those in the lower GI bleeding and the control cases. In all cases of upper GI bleeding, except for 6 cases in which blood volume flowed into the GI tract was small, the ratios were beyond 81. On the other hand, in the lower GI bleeding and the control cases, the ratios were all below 81. Values over 81 in serum Ur/Cr ratios in upper GI bleeding cases continued until the 3rd day after bleeding. These results indicate that determination of serum Ur/Cr ratios is a simple and useful procedure for diagnosis of the bleeding site in cases showing massive GI bleeding.
Lymphocyte subsets in the peripheral blood, liver and spleen of patients with idiopathic portal hypertension (IPH) were examined by means of flow cytometry and immunohistochemical analysis using monoclonal antibodies. The patients with IPH showed a slight decrease in the percentage of Leu2a+ cells and a slight increase of the ratio of Leu3a+ to Leu2a+ cells in the peripheral blood compared with the normal subjects. Flow cytometry analysis of the intrasplenic lymphocyte subsets in the patients with IPH revealed a significant elevation in the percentage of Leu2a+ cells (p<0.01) and a reduction of the Leu3a+ to Leu2a+ ratio (p<0.05) compared with the normal subjects, and also showed an increase in the percentage of Leu2a+ cells (p<0.05) in comparison to the patients with cirrhosis of the liver. An immunohistochemical and histometrical study of the spleen in the patients with IPH revealed an elevation of the amount of red pulp area compared to the normal subjects, and also a significantly increased number of Leu2a+ cells in the red pulp (p<0.02) in comparison to the patients with cirrhosis of the liver. Most of the Leu2a+ cells in the spleen were considered to be Leu2a+•15- cells by double immunostaining method. In lymphoid follicles, the IPH cases showed an increase in the size of follicle and germinal center, and an increased number of Leu3a+ cells in the germinal center and the marginal zone compared with the normal subjects. In the liver, the IPH cases showed a similar distribution but fewer lymphocyte subsets in comparison to the patients with cirrhosis of the liver. These reuslts suggested that some immunological disorder is present in patients with IPH.
Twenty patients with HBe antigen positive, chronic active hepatitis receiving interferon-β (HuIFN-β) for 4 weeks were studied. Within the follow-up period (12.3±2.0 months; mean±SD), nine patients were seroconverted to anti-HBe positive and/or HBe antigen negative. In vitro synthesis of interleukin-1 (IL-1), interleukin-2 (IL-2) and interferon-γ (IFN-γ) were determined from supernatants of peripheral blood mononuclear cells (PBMCs) cultured in the presence of lipopolysaccharide or concanavalin-A. PBMCs from patients before IFN-β treatment secreted markedly reduced levels of IL-1 (p<0.01) and IFN-γ (p<0.01) as compared with healthy controls. However, IFN-γ synthesis in the patients was significantly increased (p<0.05) along with the IFN-β treatment. IL-2 synthesis was similar in chronic active hepatitis B patients before and during IFN-β treatment when compared to normal controls, but after the therapy, the elevation of IL-2 synthesis was observed in accordance with the elevation of serum AST in two cases. Nine patients who seroconverted to anti-HBe positive and/or HBe antigen negative showed the significantly lower levels of DNA polymerase berofe IFN-β treatment than non-responder group. There were no other differences in sex, age, serum AST, histologic activities and cytokine production in vitro between two groups. These results indicate the presense of immunologic deficiencies in patients with HBe antigen positive chronic active hepatitis and give the rationales for the use of interferon treatment on immunologic basis.
It is thought that the platelet activating factor (PAF) enhances the immune response and inflammatory reaction. We studied the production of PAF from liver adherent cells. As a result, liver adherent cells produced PAF, when they were stimulated with calcium ionophore. In addition, when mice were treated with heat-killed Propionibacterium acnes and the mononuclear cells were infiltrated into the liver, a significantly larger amount of PAF was produced compared to normal mice.
A study was conducted to elucidate characteristics of circulatory parameters in patients with acute hepatic failure (AHF) employing Swan-Ganz catheter method and, in particular, ultrasonic quantitative flow measurement (QFM) system. The following results were obtained: 1) In five AHF patients who received Swan-Ganz catheter examinations, significant increases of cardiac index as well as decreased systemic vessel resistance were observed. 2) QFM in 11 patients with AHF revealed a significant increase of brachial artery blood flow (Br.F.), whereas common carotid blood flow (Ca.F.) was found to be significantly decreased. Thus, ratio of Ca.F./Br.F. showed a marked reduction as compared with that of control patients. 3) Vessel resistances measured by QFM were found to be significantly reduced in brachial artery, whereas markedly elevated in common carotid artery. 4) Those changes of circulatory parameters as described above were found to restore toward normal in parallel with the improvement of clinical features. 5) Vessel resistances of common carotid artery (Ca.R.) of AHF patients showed a significant negative correlation with CT values in the white matter of the brain, being regarded to well represent the degree of brain edema. In addition, in a case of AHF in whom intracranial pressure (ICP) was directly measured, time course of changes in Ca.F. was found to be in"mirror image"with that of ICP. Thus, it is strongly suggested that the increase of Ca.R. may well be induced, at least in part, by the elevated ICP in AHF patients.
The common hepatic arterial (CHA), portal venous (PV) and liver tissue (LT) blood flows were measured during continuous infusion of vasoactive agents to the celiac axis under the observation of systemic circulation. The infusions of Angiotensin II (AT) (0.05μg/kg/min) and Prostaglandin F2 alpha (PGF) (0.025-0.05μg/kg/min) reduced CHA and LT blood flow, but caused no remarkable change of PV blood flow. The infusions of AT (0.5μg/kg/min) and PGF (0.5μg/kg/min) caused a biphasic response in CHA blood flow: an initial decrease in CHA blood flow was followed by a marked increase in this parameter (p<0.05), while PV blood flow decreased, but LT blood flow remained unchanged. The infusion of PGF (1.0μg/kg/min) reduced all parameters of CHA, PV and LT blood flows. The infusion of Dibutyryl cyclic AMP (DBcAMP)(2.0mg/kg/hr) increased all parameters of CHA, PV and LT blood flows. Preinfusion of DBcAMP weakened the primary effects of PGF (1.0μg/kg/min) infusion.
Influence of extracorporeal shock wave lithotripsy (ESWL) on human gallstones placed in dog gallbladders was investigated. After irradiation of shock wave more than 600 times, maximal diameter of residual stones of 10mm before irradiation was destroyed to 2mm or less. Levels of serum transaminase (GOT•GPT) were elevated, in parallel with times of shock waves. These results suggested that 600 times of shock waves were enough to destroy one cholesterol stone, diameter of which was about 1cm. Data of elevation of serum transaminase showed that more than 600 times of shock waves were possible to induce the damage of liver.
It has been reported that patients with pancreatic diabetes (PD) show nocturnal hypoglycemia frequently when compared to patients with diabetes mellitus (DM). Present study was carried out to compare patterns of insulin infusion and nocturnal glucose infusion under normoglycemic control in between PD and DM. Eleven PD patients whose onset of diabetes mellitus appeared after the onset of chronic pancreatitis (PD group), and 10 patients with insulin-dependent diabetes mellitus without pancreatic disease (DM group) were studied. To control the blood glucose level, a closed loop insulin delivery system (Biostator GCIIS, Miles Laboratories) was used. 24 hours infused amount of insulin in PD group was not different from that in DM group, while patterns of insulin infusion in both groups were different. Thus, most of 24 h-infused insulin were given during 2 hours postprandial period in PD group, while in DM group, insulin was given mostly as a basal infusion. In this study glucose infusion occurres in a state of hypoglycemia (less than 90mg/dl). 7 of 11 in PD group and 2 of 10 in DM group had glucose infusion which mostly occurred at a night time.