A case of spontaneous myocardial necrosis and cerebral ischemic lesions in a laboratory beagle dog.

A beagle dog treated with saline as a control animal in a preclinical study was euthanized due to sudden systemic deterioration. On histopathological examination, contraction band necrosis of myocardial cells was observed widely in the left ventricular wall, including the papillary muscle and apex, and observed slightly in the ventricular septum and left atrium. In the brain, necrosis was observed in neurons and glia of the cerebral cortex, hippocampal pyramidal cells, glial cells of the rostral commissure and Purkinje cells of the cerebellar vermis. It is highly probable that the marked systemic deterioration was caused by cardiac dysfunction due to the spontaneous contraction band necrosis of the myocardial cells, although the pathogenesis of the myocardial lesions remains unclear. Given the distribution of neuronal necrosis in the brain, it is likely that these lesions resulted from the ischemia responsible for acute cardiac failure.

Spontaneous nephroblastoma with lung metastasis in a rat.

This report describes a spontaneous nephroblastoma with lung metastasis in a 10-week-old male Crl:CD(SD) rat. Macroscopically, a white mass in the kidney and two white masses in the lung were observed. Histopathologically, the renal mass was located in the cortex of a kidney, and it caused pressure on the surrounding renal parenchyma. Three components could be distinguished in the tumor: blastemal, epithelial (primitive glomerular/tubular structures) and mesenchymal (neoplastic connective tissues) elements. Immunohistochemically, the tumor cells were positive for Wilms tumor 1 protein (WT1) and vimentin. Metastasis was found in the lung. Thus, the case was diagnosed as a nephroblastoma with lung metastasis.

Assessment of peripheral arterial disease of lower limbs with ultrasonography and ankle brachial index at the initiation of hemodialysis.

AIM: Peripheral arterial disease (PAD) of the lower limbs carries high risks of leg amputation, quality of life deterioration, and death in hemodialysis (HD) patients. However, the frequency of PAD at the initiation of HD has not been adequately documented. In addition, the applicability of ultrasonography to diagnosing PAD is not yet clear in HD patients. METHODS: Twenty-seven patients within three months after HD initiation were enrolled. Ultrasonography was performed regardless of ischemic symptoms. Significant stenosis or obstruction of lower limb arteries on ultrasonography was diagnosed as PAD. RESULTS: Sixteen of the 27 (59.3%) showed PAD on echography. On the other hand, only six of the 27 (22.2%) had an ABI < 0.9. Sixteen patients had a total of 37 lesions revealed by ultrasonography, and the average number of PAD lesions was 2.3 per patient. The numbers of PAD lesions on ultrasonography were as follows: iliac artery, 7; femoral-popliteal artery, 15; and infra-popliteal artery, 15. The ABI was 0.95 +/- 0.29 in PAD and 1.23 +/- 0.13 in non-PAD patients (p = 0.005). CONCLUSIONS: A high prevalence of PAD at HD initiation was demonstrated. PAD may be missed using only the ABI (ankle brachial index). Ultrasonography is a reliable and non-invasive examination for detecting PAD.

Hypothermia-related testicular toxicity of reserpine in mice.

Local cooling of the testis was reported to cause testicular abnormality, but there is no information regarding the effect of whole body cooling, such as hypothermia on spermatogenesis. We investigated whether hypothermia would cause testicular toxicity in mice. Male mice were administered with a single intraperitoneal dose of 100mg/kg of reserpine. The rectal temperature decreased to 29 degrees C 6h post dosing and thereafter sustained at lower values (24-25 degrees C) until 96 h post dosing. The histopathological examination of the testis showed nuclear vacuolation of round spermatids at stages I-V in mice examined 24, 48, 72 and 96 h post dosing. The lesions were more severe in the groups examined 72 and 96 h post dosing than in the groups examined 24 and 48 h post dosing. These results suggested that hypothermia condition at lower than 30 degrees C and sustained for more than 18 h could induce nuclear vacuolation of round spermatids at stages I-V in the testis. In order to demonstrate that the testicular lesion in the reserpine-treated mice was induced by hypothermia, mice were given a single intraperitoneal dose of 100mg/kg of reserpine, and each dosed group was housed under different environmental conditions for 72 h; one consisted of housing the mice individually at room temperature, and the other consisted of housing the mice individually under heated condition. In the mice administered with reserpine and housed at room temperature, hypothermia below 30 degrees C with a minimal of 26 degrees C was observed for 66 h. In contrast, the mice administered with reserpine and housed under heated condition maintained the rectal temperature of 33-36 degrees C. Nuclear vacuolation of round spermatids at stages I-V in the testis was observed in reserpine-treated mice maintained at room temperature, but not in reserpine-treated mice kept under heated condition. These data strongly indicated that nuclear vacuolation of round spermatids at stages I-V observed in reserpine-treated mice was related to hypothermia.

[A case of localized AL-type amyloidosis of the stomach].

A 78-year-old woman was admitted to our hospital for treatment of liver cirrhosis and an esophageal varix. Endoscopy revealed a protruding nodular lesion with a transparent smooth surface proximal to the pylorus, which was accompanied by a partly yellow-whitish spot. A depressed lesion with an even edge was found. Histologically, the protruding lesion and depressed lesion showed amyloid deposits, mainly in the mucosal layer. The lesions were found to correspond to AL type amyloidosis by immunochemical analysis. General examination showed no other amyloid deposits. Thus, we diagnosed localized amyloidosis of the stomach.

[A case of anti-GBM-antibody positive rapidly progressive glomerulonephritis who was weaned from hemodialysis after combination therapy with steroid and plasmapheresis].

We report an anti-GBM antibody-positive crescentic glomerulonephritis patient who benefitted from maintenance hemodialysis 4 months after the initial treatment, which included steroid pulse therapy and plasma exchange. A-29-year-old male was referred to our hospital because of high fever, abnormal urinary findings (leukocytes 3+, protein 2+, occult blood 3+) and a moderate degree of azotemia(S-Cr 2.9 mg/dl). C-reactive protein (CRP) was 18.9 mg/dl and antibiotics were administered intravenously for 7 days under the diagnosis of pyelonephritis. High fever persisted, however, and S-Cr increased to 9.2 mg/dl even though a sufficient volume of urine was maintained. Blood and urine cultures were negative for bacteria. A kidney biopsy was performed and cellular crescents were observed around the glomeruli. No abnormal finding was observed in the lung and the nasopharyngeal region. To treat the crescentic glomerulonephritis, steroid and cyclophosphamide were administered while hemodialysis was carried out simultaneously. Although P-ANCA and C-ANCA were negative, anti-GBM antibody was proven to be positive thereafter (169 U) and six sessions of plasmapheresis were additionally performed to remove the antibody. Two months after the last plasmapheresis, the reduced urine volume (300 ml/day) gradually returned to normal. Hemodialysis was terminated because the S-Cr concentration reached a plateau at 4 mg/dl. Repeated biopsy revealed marked glomerulosclerosis, hence hypertension treatment and a low protein diet were ordered. In conclusion, residual renal function might improve even after 4 months of hemodialysis in cases of intensively treated anti-GBM-positive crescentic glomerulonephritis, though consecutive renoprotective therapy is required.

Collaborative work on evaluation of ovarian toxicity. 7) Effects of 2- or 4- week repeated dose studies and fertility study of cyclophosphamide in female rats.

The main focus of this study was to determine the optimal administration period concerning the toxic effects on ovarian morphological changes in the repeated dose toxicity study. In order to assess the morphological and functional changes induced in the ovary by cyclophosphamide (CP), the compound was administrated to female rats at dose levels of 0, 5, 10 and 20 mg/kg for the repeated dose toxicity study for 2 or 4 weeks, and at 0, 5, 10, and 20 mg/kg for the female fertility study from 2 weeks prior to mating to Day 7 of pregnancy. In the repeated dose toxicity study, increases in large sized atretic follicles, atrophy of corpora lutea were observed in the 20 mg/kg group in the 4-week study by the histopathological examination of the ovaries. There were no drug-related changes in the ovary in the 2-week study. In the female fertility study, the numbers of implantation were slightly decreased and the corpora lutea of pregnancy was not observed in the 20 mg/kg group. The dose-dependent increase in the incidence of post-implantation loss was observed, and no abnormalities were observed in the estrus cycle and mating in all treated groups. From these findings, the histopathological changes in the ovary are important endpoints for the evaluation of drug-induced ovarian damage as well as caesarean section. In conclusion, a 4-week administration period is sufficient to detect the ovarian toxicity of CP in the repeated dose toxicity study.

Mixed connective tissue disease associated with MPO-ANCA-positive polyangiitis.

The patient was a 42-year-old woman diagnosed as having MCTD and Sjögren's syndrome in 1989, and who was taking oral prednisolone. Proteinuria and microscopic hematuria were pointed out for the first time in December 2004. She was referred to our hospital because of massive hemoptysis. Advanced renal failure, anemia and pulmonary alveolar hemorrhage were diagnosed on admission. She was positive for serum MPO-ANCA. The patient was started on a therapy that included steroids, cyclophosphamide and plasmapheresis. However, her respiratory condition was untreatable and she died on the 16th day of hospitalization. The autopsy revealed alveolar hemorrhage in the lungs and crescentic glomerulonephritis. This patient was considered as a rare case of MCTD associated with MPO-ANCA-positive microscopic polyangiitis.