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.     

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.     

A study of five cases of traumatic diaphragmatic rupture

During the last 5 years, 5 cases of traumatic diaphragmatic rupture were surgically treated. These cases were reported and the literature concerning traumatic diaphragmatic hernia in the last one decade in Japan, including 80 cases was studied. The purpose of this study is to discuss the most important early diagnostic tools and to consider the choice of incision and approach. The following two results were gotten. (1) Plain chest X-ray, computed tomography and ultrasonography were the most valuable diagnostic tools. (2) The choice of incision and approach depends on the stage at which the rupture is recognized (early or late), the site of rupture and associate injuries.     

Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.

Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. Introduction: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa.     

A case of hypertrophic pachymeningitis, resolved by antimicrobial therapy]

A 65-year-old woman with diabetes mellitus and chronic otitis media developed headache, fever, and hoarseness, all of which did not responded to the oral antibiotics. As stiff neck and lower cranial nerve palsies appeared, bacterial meningitis was suspected. Neurological examination revealed the right hearing disturbance, right recurrent laryngeal nerve palsy, left sternocleidomastoid muscle atrophy and bilateral tongue atrophy. The CSF examination revealed mild pleocytosis and elevated protein, but no bacterial organism was cultured from the CSF. CT scans showed bilateral mastoiditis, and the right mastoid process and a posterior part of the petrous bone were eroded, indicating the exposed bony structures to the posterior fossa. MRI scans demonstrated the thickening of the dura mater of the posterior fossa and the right cerebellar tentorium. This is a rare example of bacterial pachymeningitis of the posterior fossa, the clinical symptoms and MRI findings of which resolved solely by antimicrobial agents without corticosteroid.     

Approved indications of lipo-PGE1 in Japan

For its peripheral vascular dilating effect and platelet agglutination inhibitory activity, prostaglandin E₁ is used in the treatment of diseases which are likely to cause peripheral circulatory failure or thrombus. In Japan, lipo-PGE₁, which was developed to give it a target-directed nature by modifying the conventional PGE₁, has been used and found to be useful in clinical practice. In this report, we attempt to describe the clinical benefits of lipo-PGE₁ focusing on the diseases which have been approved for its indications.     

Properties of active magnesium flux across the small intestine of the guinea pig.

Steady-state net flux of Mg2+ was measured in everted preparations of guinea pig jejunum and ileum, and effects of anoxia, Na+ and Ca2+ concentration, ouabain, and Ca2+ channel blockers were examined. Uphill Mg2+ flux in the mucosal-to-serosal direction was seen in both intestinal segments, with the flux value being 1.5 times greater in the ileum than in the jejenum. The Mg2+ flux was 1.7 times greater than the net Ca2+ flux under the same experimental conditions. The Mg2+ flux was strongly dependent on oxygen and the presence of Na+ in the medium; both anoxia and total replacement of Na+ inhibited the flux by 90-100%. Also, ouabain added to the serosal side, and verapamil or D600 added to the mucosal side, inhibited the flux by about 90%. Inhibitory effects of both ouabain and Na(+)-free conditions were much greater for the Mg2+ flux than for the Ca2+ flux. A stepwise increase in Mg2+ concentration in a Na(+)-free mucosal solution caused a stepwise elevation of the mucosal negativity. The relative elevation of the evoked potential in response to Mg2+ concentration possessed saturable and linearly increasing components. Only the saturable component was found to be dependent on oxygen and sensitive to ouabain. Under the influence of ouabain and verapamil, the generation of the Mg(2+)-evoked potential was greatly inhibited. These findings suggest that Mg2+ is actively absorbed by the jejunum and ileum of the guinea pig, and that active transcellular transport involves a verapamil-sensitive entry step and Na(+)-dependent or ouabain-sensitive exit process which differs from Ca2+ extrusion mechanisms.     

Primary malignant lymphoma of the rectum with distant metastasis to the stomach: Report of a case

Primary extranodal malignant lymphoma frequently occurs in the gastrointestinal tract; however, it is rarely encountered in the rectum. We report herein the case of an 85-year-old man who underwent abdominoperineal resection for primary malignant lymphoma of the rectum, and 1 year later, developed hematemesis caused by gastric metastasis. To our knowledge this is the first case report of such distant metastasis developing from malignant lymphoma of the rectum.     

Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum.

Wilms tumor gene (WT-1) expression has been reported in many human cancers, including most ovarian and peritoneal serous carcinomas, but has not been studied in carcinomas of the fallopian tube. In this study, the authors evaluated the immunohistochemical expression of WT-1 in serous carcinomas of the fallopian tube and compared their reactivity with that of ovarian, peritoneal, and endometrial serous carcinomas. All primary serous carcinomas of the fallopian tube (13 cases), ovaries (25 cases), and peritoneum (3 cases) were reactive with the WT-1 antibody, whereas all five primary endometrial serous carcinomas were nonreactive. WT-1 reactivity in an unknown primary serous carcinoma is therefore suggestive of an extrauterine site. The marked difference in WT-1 staining raises the possibility of genetic differences between serous carcinomas arising in the endometrium compared with those arising in the ovaries, fallopian tubes, and peritoneum.     

Experimental study on the role of prostaglandin D2 in the pathogenesis of bronchial asthma]

Various kinds of chemical mediators have been implicated in the pathogenesis of bronchial asthma. PGD2 is a cyclooxygenase product which has various physiological effects. In this experimental study, we investigated the role of PGD2 in the pathogenesis of bronchial asthma. In a bioassay system, PGD2 caused dose-dependent contractile responses in non-sensitized guinea pig trachea and lung tissue strips. The subthreshold concentration of PGD2 in both strips was 25 ng/ml. Acetylcholine-induced contractile responses in both strips were significantly increased by continuous infusion of PGD2. In the experimental model of bronchial asthma, the levels of PGD2 were significantly increased in serum, bronchoalveolar lavage fluid (BALF) and lung tissue of sensitized guinea pigs after antigen challenge. We have also reported that the levels of PGD2 in BALF were elevated in patients with stable state bronchial asthma. These results suggest that PGD2 may be a key substance that increases airway responsiveness and induces asthmatic attacks.