Calciphylaxis in a patient with end-stage renal disease secondary to systemic lupus erythematosus associated with acral gangrene and mesenteric ischemia.

A patient with end stage renal disease secondary to systemic lupus erythematosus (SLE) ultimately required amputation of the four extremities and developed mesenteric ischemia. The patient presented with widespread medial calcification involving various small to medium sized arteries, although no noticeable secondary hyperparathyroidism was observed. We speculated that SLE associated with systemic vasculitis and uremic milieu over a number of years may represent the perfect preexisting condition for calcific arteriolopathy to occur following which several factors including chronic administration of corticosteroids, photosensitivity in lupus, and significant weight loss may have contributed to acral gangrene and mesenteric ischemia.

[A case of hepatitis B virus carrier complicated with nephrotic syndrome].

We report a patient, a 23-year-old man, who was a hepatitis B virus(HBV) carrier complicated with nephrotic syndrome. He was admitted to our hospital because of generalized edema and massive ascites. Laboratory data on admission were as follows: proteinuria 9,850 mg/day, Cr 2.7 mg/dl, BUN 73 mg/dl, albumin 1.9 g/dl, cholesterol 501 mg/dl, GOT 23 IU/l, GPT 19 IU/l, HBsAg(+), and HBeAg(222.7). Since his nephrotic symptoms were seriously complicated with renal failure, we selected steroid therapy for nephrosis preference. His renal function was improved and the urinary protein decreased immediately, but his liver function deteriorated. The renal biopsy revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent examination revealed slight deposits of IgG, IgM, and C3 along the glomerular basement membrane and mesangial matrix. He was not compliant and often stopped taking the steroid therapy, thereby causing nephrosis to recur each time. After all, nephrotic symptoms have been well-controlled with cyclosporin and steroid. In spite of the seroconversion of HB virus by formation of HBe antibody, mutant HBV infection continued. The fact that liver biopsy revealed severe lymphoid infiltration at the portal area suggested chronic active hepatitis. His clinicopathologic course suggests that HBV-associated nephropathy does not always remit as there are some cases in whom hepatitis remains in an active state even after seroconversion, due to its mutant status. In these cases, the long-term prognosis of HBV nephropathy has not been defined. Further study is necessary to establish the optimal treatment for HB nephropathy in adults.

[A case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive rapidly progressive glomerulonephritis].

We report a case of hepatitis C virus-associated glomerulonephropathy presenting with MPO-ANCA-positive, rapidly progressive glomerulonephritis(RPGN). A 60-year-old woman was admitted to our hospital for evaluation of RPGN. Laboratory evaluation revealed microhematuria, proteinuria(800 mg/day), anemia, renal failure(blood urea nitrogen 27 mg/dl, serum creatinine 2.2 mg/dl), cryoglobulinemia, hypocomplementemia, positive MPO-ANCA(232 EU), and hepatitis C virus infection(GOT 58 IU/l, GPT 38IU/l, HCV-RNA(PCR) 1,200 kcopy/ml, serotype 1). After admission, the patient's renal function and anemia deteriorated rapidly, then prednisolone(30 mg/day) was started. After treatment her renal function gradually improved, then a renal and liver biopsy was performed. The renal biopsy revealed six sclerosing fibrous crescentic glomeruli in twelve glomeruli. Immunofluorescent examination revealed granular deposits of IgG, C3, and fibrinogen along the glomerular basement membrane and mesangial matrix. The pathogenesis of RPGN in this case may relate to the deposition of immune complexes in the glomeruli because immunofluorescent examination was revealed to be the immune-complex type, but not pauci immune type nephritis. Liver histology revealed chronic active hepatitis with mild piecemeal necrosis and did not reveal vasculitis. Although her renal function was improved after treatment with prednisolone, she suffered from pulmonary manifestations(dry cough etc.) on the 120th hospital day. Suddenly she died because of pulmonary hemorrhage on the 180th hospital day. These findings suggest that various HCV-induced immunological abnormalities, such as positive MPO-ANCA, cryoglobulinemia and hypocomplementemia, play an important role in the pathogenesis of this RPGN, although we could not demonstrate deposition within glomeruli of immune complexes containing HCV. The effect of interferon therapy on such immunological abnormalities remains to be documented. Since interferon is known to have immunomodulatory effects, we selected corticosteroid therapy. Future studies need to focus on the optimal treatment strategy for hepatitis C virus-associated glomerulonephritis.

Two cases of aorto-gastrointestinal fistula.

We report two cases of aorto-gastrointestinal fistula. Case 1, a 60-year-old man, suffered from repeat hematemesis. He was preoperatively diagnosed as aortoesophageal fistula with thoracic aortic aneurysm and was successfully treated by graft replacement of the aneurysm. Case 2, a 73-year-old man, presented with massive gastrointestinal bleeding, yet repeat endoscopical examination did not reveal the origin of the bleeding. He died of catastrophic hematochezia. The pathological findings at autopsy revealed an aortoduodenal fistula. These two cases suggested the importance to consider an aorto-gastrointestinal fistula in the differential diagnosis of patients presenting gastrointestinal hemorrhage.

Quantitative analysis of the gastric ulcer healing process using video endoscopic pseudocolor imaging systems.

We developed an endoscopic pseudocolor imaging system in cooperation with Olympus Optical. This system was used for color processing of ulcer images observed over time using an electronic endoscope with measurement capability. The patients were receiving ranitidine (group R) or lansoprazole (group L) for ulcer treatment. By this method it is possible to differentiate between the types of healing tissue by their color. The total area of regions with a high degree of redness in the pseudocolor processed images was measured with a digitizer, and the hemoglobin-rich area (HA) in the regenerated epithelium was determined for the two groups. In the second week of drug administration, the HA was significantly larger in group L, at 170.70 +/- 64.70 mm2, than in group R, at 22.61 +/- 5.72 mm2 (p < 0.05). The hemoglobin rate was significantly higher in group L, at 0.90 +/- 0.02 (p < 0.01) at 2 weeks and 0.94 +/- 0.02 (p < 0.05) at 4 weeks, than in group R, at 0.72 +/- 0.06 and 0.86 +/- 0.05 at 2 and 4 weeks, respectively.

[Brain injury induced by continuous infusion of endotoxin in rats--protective effects of methylprednisolone on intracerebral blood vessels].

Hemorrhagic intracerebral lesions, analogous to multiple punctate hemorrhagic necrosis seen in the brain of human disseminated intravascular coagulation (DIC), can be induced in rats by continuous intravenous infusion of E. coli endotoxin lipopolysaccharide (ET) at 88.5 micrograms/hour. The occurrence of cerebral lesions increases with time of ET infusion initially, but levels off after 120 hours of the continuous administration. To investigate protective effects of methylprednisolone (MP) against intracerebral vascular injury, 122 male rats were divided into the basic endotoxemic rats without MP medication (Group 1), and MP medication of 0.2mg/kg body weight, 1.0mg/kg, 2.0mg/kg and 20.0mg/kg immediately before induction of endotoxemia (Groups 2-5), one dose of 20.0mg/kg MP at 48 hours and 2 doses at 48 and 72 hours after induction of endotoxemia (Groups 6-7), and 3 doses each of 2.0mg/kg, 20.0mg/kg and 100.0mg/kg MP for 3 days immediately before and at 24 and 48 hours after induction of endotoxemia (Groups 8-10). All surviving rats were autopsied after 120 hours of ET infusion and histologic sections were made. Multiple hemorrhagic intracerebral lesions developed in 83% (10/12) of Group 1 rats, whereas the frequency of brain lesions in Groups 4, 5, 8, 9 and 10 was significantly lower than that in Group 1 (p < 0.05). Electron microscopically, the frontal lobe cortex of Group 1 after 120 hours of ET infusion showed subendothelial dilatation containing macrophages, and perivascular accumulation of erythrocytes (diapedesis). In contrast, the frontal lobe cortex of Group 5 revealed no appreciable electron microscopic changes of intracerebral blood vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Brain injury induced by continuous infusion of endotoxin (ET) in rat--relationship between ET infusion hours and development of cerebral and visceral lesions].

Experimental generalized Shwartzman reaction (GSR) in animals can be induced by systemic injection of bacterial endotoxin lipopolysaccharide (ET) and presents with thrombotic occlusions of small blood vessels in different organs analogous to disseminated intravascular coagulation (DIC) in man. It is known that DIC involvement of the central nervous system (CNS) in man presents with grave prognosis, but there is a paucity of information concerning CNS involvement in animals with ET induced GSR. In order to better understand the pathogenesis of CNS involvement of DIC in man, and to search for better prophylactic and therapeutic measures against DIC, animal model of DIC was induced by continuous intravenous infusion of E coli ET. A total of 56 male Donryu rats were divided into 6 groups and infused with physiologic saline (controls) and ET lipopolysaccharide at 88.5 micrograms/hour. The rats were killed at 6 different intervals from 24 to 160 hours and examined postmortem. Intracerebral hemorrhagic lesions were seen in 2 of 7 rats (29%) as early as 24 hours of ET-infusion and increased to 77% to 87% of rats receiving continuous ET infusion up to 160 hours. Formation of fibrin thrombi was uncommon in intracerebral blood vessels, but it was frequently observed in choroid plexus capillaries. Fibrin thrombi in other viscera (heart, lungs, liver, kidneys, spleen) were common but decreased toward the end of 160-hour infusion period. Results of this study showed that a continuous intravenous infusion of large dose ET lipopolysaccharide in rats produces intracerebral hemorrhagic lesions analogous to DIC changes of brain seen in man.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of bronchogenic cyst of the esophagus].

A case of bronchogenic cyst in the lower end of the mediastinal esophagus was reported. A 46 years old man had an abnormal mass shadow at the right cardiophrenic angle revealed by the annual X-ray examination. A 5.5 X 4.5 X 5 cm sized intramurally located tumor was successfully removed. As it was a monolocular cyst that microscopically lined with ciliated columnar epithelium and contained cartilage in the wall, but that was not covered by two muscle layers, the cyst was diagnosed as bronchogenic. The post-operative course was uneventful. The authors discussed the differential diagnosis of this lesion, especially about cysts which were situated in the esophagus. To avoid confusion, a certain diagnostic criteria based on the histological findings was suggested.

Effect of histamine H2-receptor antagonists on DNA synthesis in adult rat hepatocytes in primary culture. Cimetidine enhanced hepatocytes proliferation stimulated with insulin and epidermal growth factor.

The effects of three of the most widely used histamine H2-receptor antagonists, cimetidine, ranitidine and famotidine, on liver cell growth were studied in vitro using adult rat hepatocytes in primary culture, because these antagonists are commonly given to patients with hepatic cirrhosis or fulminant hepatic failure for protection against peptic ulcers and gastrointestinal hemorrhage. At their clinically effective concentrations in the blood (0.5-5 micrograms/ml cimetidine, 0.25-2.5 micrograms/ml ranitidine and 0.05-0.5 microgram/ml famotidine), these three antagonists did not have any effect on replicative DNA synthesis either in the presence or absence of insulin plus epidermal growth factor (EGF). However, unexpectedly DNA synthesis stimulated by insulin and EGF was found to be enhanced by 0.05-0.5 mg/ml cimetidine, although it was unaffected or inhibited by ranitidine and famotidine at the concentrations tested. Cimetidine caused maximal enhancement of 1.5-2 times the control level of DNA synthesis at a concentration of 0.25 mg/ml. Cimetidine also had an enhancing effect at submaximal concentrations of insulin and EGF, but neither cimetidine nor the other antagonists had any stimulatory effect on DNA synthesis in the absence of insulin plus EGF. This enhancement of DNA synthesis by cimetidine resulted in significant increase in the total DNA content of the hepatocytes in culture. Under the conditions used, cimetidine had the lowest toxicity of these three antagonists and ranitidine the highest, as judged from data on DNA synthesis and the total protein content of cultured hepatocytes, leakage of aminotransferases from the cells and morphological observations.

Changes in polyamine metabolism of rat liver after administration of D-galactosamine. Favorable effects of putrescine administration on galactosamine-induced hepatic injury.

There are many reports showing a close relation between polyamine metabolism and tissue growth or recovery of damaged tissues, such as regenerating liver. Thus, changes in polyamine metabolism in the livers from rats treated with D-galactosamine, an inducer of experimental hepatitis, were studied. The activity of ornithine decarboxylase started to increase 14 hr after administration of galactosamine and reached 30 times the normal activity at about 25 hr, the time of maximum severity of hepatitis. The content of putrescine increased to about 10 times the control value. After increases in the putrescine content and ornithine decarboxylase activity, the hepatitis started to diminish. Increases in the activity of S-adenosylmethionine decarboxylase and the content of spermidine were observed 33-37 hr after administration of galactosamine. The maximum values of these parameters, which were significantly higher than the control values, were observed after the healing process had started.

Effect of DL-alpha-hydrazino-delta-aminovaleric acid, an inhibitor of ornithine decarboxylase, on polyamine metabolism and growth of mouse sarcoma-180.

DL-alpha-Hydrazino-delta-aminovaleric acid (DL-HAVA) is a potent and fairly specific inhibitor of ornithine decarboxylase (EC 4.1.1.17). Its effect on polyamine metabolism and cell proliferation was investigated in sarcoma-180, inoculated into the axillary region of mice. In the tumor tissues, the activities of ornithine and S-adenosyl-L-methionine decarboxylases and the putrescine level were much higher in the early stage of growth than those in normal mouse liver. Administration of DL-HAVA greatly depressed the putrescine level and putrescine formation from L-ornithine. It also suppressed DNA synthesis and increase in weight of the tumor tissue. However, it had little effect on RNA synthesis or the tissue concentration of spermidine and spermine. The inhibition of DNA synthesis and subsequent tumor development by DL-HAVA was effectively prevented by putrescine, but not by cadaverine or 1,7-diaminoheptane. From these results it is concluded that the suppression of DNA synthesis and neoplastic growth by DL-HAVA is due to decrease in the putrescine level by inhibition of ornithine decarboxylase.