A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient]

A 23-year-old man was admitted for treatment of acute exacerbation of ileitis and perianal abscess caused by Crohn's disease. After incision and drainage of the abscess, coupled with antibiotic therapy, 6-mercaptopurine (6-MP) was commenced. His white blood cell (WBC) count on day 12 after initiation of 6-MP was not decreased. However, on day 24 he was re-admitted because of severe myelosuppression (WBC: 300/microl), which was complicated by the recurrence of the perianal abscess. Myelosuppression was prolonged and required the administration of granulocyte colony stimulating factor (G-CSF). G-CSF was continued for 17 days to achieve recovery of his WBC count to a normal level.     

Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

A clinical and pathological study of diffuse axonal injury

There is increasing evidence from human and experimental studies that the most important factor governing the outcome in head injury is the severity of diffuse axonal injuries. The authors have experienced 18 cases of severe diffuse axonal injury which showed post-traumatic coma for more than 24 hours and CT findings resembling those of shearing injuries of the cerebral white matter such as have been presented by Zimmerman et al. (1978). The consciousness levels on admission were 6 or less on the Glasgow Coma Scale and all cases were shown clinically to have primary brain stem injury. The main type of head trauma resulted from road traffic accidents (83%). Skull fractures were found in only 5 cases (28%). These findings suggested that acceleration/deceleration injury produce in the patients severe diffuse axonal injury. Initial ICP was below 20 mmHg in 11 cases out of 13 (85%). Parenchymal small hemorrhagic lesions of initial CT were basal ganglia (7 cases), corpus callosum (4 cases), pons (4 cases), midbrain (3 cases) and thalamus (2 cases). Extraparenchymal hemorrhagic lesions included intraventricular hemorrhage (6 cases) and subarachnoid hemorrhage (6 cases). Two autopsied cases of severe diffuse axonal injury (acute case and chronic case) showed remarkable congestion and edema in the deep part of the frontal white matter. Microscopic examination revealed marked axonal degeneration including axonal retraction ball in the corpus callosum, in the internal capsule and in the white matter of the brain stem. Glasgow Outcome Scale of the 18 patients at 3 months after the trauma made us concerned that no patients indicated good recovery or even only moderate disability.(ABSTRACT TRUNCATED AT 250 WORDS)     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

Epinephrine is an enhancer of rat intestinal absorption.

Some physiological substances, including acetylcholine and nitric oxide, are useful candidates for stimulation of intestinal absorption of drugs. In the present study, we elucidated the ability of epinephrine (Epi) to stimulate the intestinal absorption of drugs. We evaluated the ability of Epi to enhance absorption of macromolecules using dextran (Mw 4000 Da), which is poorly absorbed from the intestine, as a model compound in situ in a closed loop of the rat jejunum. Treatment of the jejunum with Epi resulted in significant increase in absorption of dextran in a dose-dependent fashion. The area under the curve (AUC) from 0 to 4 h in the Epi-treated jejunum was 13-fold higher than that in the vehicle-treated jejunum. The absorption-enhancing activity of Epi was 40-fold higher than that of caprate, a clinically used absorption-enhancer of drugs. In the experimental conditions used in this study, histological injury of the mucosa and perturbation of the mucosal membrane were not observed in the Epi-treated jejunum. Treatment with an antagonist of alpha-adrenergic receptors attenuated the stimulation of intestinal absorption by Epi, and treatment with an agonist of alpha-adrenergic receptors resulted in enhancement of intestinal absorption. While an antagonist of beta-adrenergic receptors enhanced the absorption-enhancing effect of Epi, an agonist of beta-adrenergic receptors stimulated intestinal absorption. These results indicate that stimulation of adrenergic receptors may be a novel strategy for intestinal absorption of drugs.     

Role of Ca2+ on Endotoxin-Sensitivity by Galactosamine Challenge: Lipid Peroxide Formation and Hepatotoxicity in Zymosan-Primed Mice

Abstract: This study was investigated to clarify the role of intracellular Ca²⁺ following endotoxin treatment (1 mg/kg, intraperitoneally) to D-galactosamine-sensitized mice (400 mg/kg, intraperitoneally), and to observe lipid peroxide levels, an index of hepatotoxicity, in endotoxin/galactosamine (Ga1N)-challenged mice under activation of macrophages, especially Kupffer cells, by zymosan. The liver lipid peroxide level and serum glutamic pyruvic transminase activity in mice 18 hr after administration of endotoxin/Ga1N were markedly higher than those in mice treated only with endotoxin. In spite of an increase in lipid peroxide formation, there was little or no effect of Ga1N administration on xanthine oxidase and superoxide dismutase activities in mice given endotoxin. However, the injection of verapamil (10 mg/kg, subcutaneously) markedly decreased lipid peroxide levels in liver of endotoxin/Ga1N-injected mice. In the mice given a Ca²⁺-deficient diet, lipid peroxide level in liver after endotoxin/Ga1N injection was markedly decreased compared to that in mice fed a normal diet. Administration of dexamethasone (200 μg/kg, intraperitoneally) in mice 1 hr before treatment with endotoxin/Ga1N did not induce lipid peroxide formation. Administration of endotoxin to Ga1N-treated mice resulted in a higher level of liver cytosolic free Ca²⁺ ([Ca²⁺]_i) than that in endotoxin-treated mice. On the other hand, Ca²⁺-ATPase activity in liver plasma membrane in the endotoxin/Ga1N-treated mice was markedly decreased as compared with endotoxin alone. On the contrary, the Ca²⁺-ATPase activity in liver mitochondria was higher in endotoxaemic mice treated with Ga1N than in mice given endotoxin alone. State 3 respiration and respiratory control index, which are parameters of mitochondrial function, were decreased more in the liver of mice treated with endotoxin/Ga1N than in the endotoxin-treated group. These findings suggest that [Ca²⁺]_i may participate in the lipid peroxide formation which results from endotoxin/Ga1N-induced hepatotoxicity under conditions of zymosan-activated macrophages, and that the increases of endotoxin-sensitivity caused by Ga1N challenge may greatly contribute to Ca²⁺-mobilization in the hepatocyte.     

Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.