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.     

Reduction of infarct size and infiltration of polymorphonuclear leukocytes by a thromboxane synthetase inhibitor. Studies in a rabbit ischemic heart model.

The effect of sodium 6-(2-(1-(1H)-imidazolyl)methyl-4,5-dihydrobenzo(b) thiophene)carboxylate (RS-5186), a potent and long acting thromboxane synthetase inhibitor in vitro and in vivo, on infarct size and on the infiltration of polymorphonuclear leukocytes (PMNs), was studied in a rabbit coronary artery occlusion (1 h)--reperfusion (0.5 h or 3 h) model. The infarcted region was stained with triphenyltetrazolium, and the ratio of infarcted area/left ventricular area was calculated. The infiltration of PMNs into the infarcted region was determined by measuring the PMNs specific enzyme, myeloperoxidase (MPO) activity. In the vehicle treated group, infarct size and MPO activity were increased with increased reperfusion time from 0.5 h to 3 h (infarct size: 15.3 +/- 2.7 to 25.2 +/- 3.2%; MPO activity: 255 +/- 51 to 825.3 +/- 169.4 units/g wet weight). There was also a significant correlation (r = 0.90, p less than 0.01) between the infarct size and MPO activity. In contrast, in the RS-5186 treated group (2 mg/kg i.v.), both infarct size and MPO activity did not increase with prolongation of the reperfusion period (infarct size: 12.8 +/- 5.5 to 10.3 +/- 3.6%; MPO activity: 318.8 +/- 36.7 to 381.2 +/- 72.6 units/g wet weight). In 0.5 h reperfused samples, there was no significant difference in infarct size or in MPO activity between the vehicle treated group and RS-5186 treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Operative fiberoptic nephroureteroscopy: removal of upper ureteral and renal calculi

We tested 2 prototypes of an operating fiberoptic nephroureteroscope, measuring 3.5 and 4.5 mm. in diameter, that have an adequate working channel for auxiliary instruments and irrigation. Difficulty in passing the fiberscope through the ureteral orifice was overcome by dilation with balloon and polytetrafluoroethylene (Teflon) dilators. Our initial trial for stone retrieval under fiberscopic control was performed on 21 patients with upper ureteral and renal calculi. A stone was removed successfully in 15 of the 21 patients (71 per cent). After electrohydraulic lithotripsy calculi were extracted successfully in 9 of 11 patients (82 per cent). Three patients suffered ureteral perforation. The fiberscope was especially helpful when an upper ureteral stone moved back to the kidney during stone manipulation.     

Treatment with hypotensive agents affects the impaired relaxation of the penile corpus cavernosum in hypertensive rats.

Treatment of erectile dysfunction (ED) in hypertensive subjects remains to be formally established. There is currently no standardized treatment for ED in hypertensive subjects. In this study, we tested our hypothesis that hypotensive drugs would improve impaired relaxation in the corpus cavernosum of spontaneously hypertensive rats (SHR). Ten-week-old SHR was treated with amlodipine, imidapril or hydralazine for 4 weeks. Although all three drugs achieved an equivalent decrease in systolic blood pressure (SBP), only amlodipine and imidapril induced an increase in relaxation in response to electrical field stimulation (EFS) of the corpus cavernosum. In the case of amlodipine, this effect was dose- and SBP-dependent. Nitric oxide (NO)-dependent relaxation was increased by amlodipine over a wide range of EFS frequencies, was increased by imidapril at low EFS frequencies, and was decreased by hydralazine. Carbon monoxide (CO)-dependent relaxation was only increased by hydralazine, and this increase occurred over a wide range of frequencies. The NOx and cGMP levels in the EFS-stimulated corpus cavernosum were increased by amlodipine. Amlodipine did not affect the thiobarbituric acid-reacting substance levels in the serum and the corpus cavernosum, but did decrease superoxide dismutase activity in the tissue. Imidapril and hydralazine inhibited the acetylcholine-induced relaxation in the corpus cavernosum. Sodium nitroprusside-induced relaxation in the tissue was increased by amlodipine. All three agents similarly inhibited the phenylephrine-induced contraction. These results suggest that impaired neurogenic relaxation in the corpus cavernosum of SHR is improved by amlodipine and imidapril through an increase in the synthesis and/or release of neuronal NO, but not CO, and presumably the inhibited detumescence of erection, which is induced by norepinephrine being released from sympathetic neuron. These findings indicate that amlodipine and imidapril may ameliorate the decreased relaxation of cavernous smooth muscle in the setting of hypertension.     

Fatal necrotic enteritis associated with Clostridium perfringens in wild crows (Corvus macrorhynchos)

Sporadic outbreaks of fatal enteritis occurred among free-living wild crows (‘large billed’ or ‘wok’ crow; Corvus macrorhynchos) in an open-air park in Japan in 2002. Eight crows were found dead during February, followed by two more in September, and five of the eight were examined histopathologically. At necropsy, all cases showed a markedly dilated small intestine, especially the jejunum and ileum, with large amounts of gas, and dark red to greenish–brown soft content. The necrotic intestinal wall was markedly thickened with multifocal haemorrhages. All cases had multifocal white foci in the liver, and four cases showed marked splenomegaly. Histologically, there was severe necrotic enteritis characterized by extensive mucosal necrosis and multifocal haemorrhages, as well as inflammatory cell infiltrations. A prominent pseudo-membrane formation was noted in the affected intestine. Severe adhesive peritonitis was also observed in three cases. Gram-positive bacilli were present in large numbers in the lumen, and in and around necrotic lesions in the affected intestine. The bacilli were positive for Clostridium perfringens enterotoxin type A by immunohistochemistry, and were also positive for C. perfringens type A using the immunofluorescence method. C. perfringens was isolated by anaerobic culture from the intestinal contents. The present enteritis was thought to be induced by proliferated C. perfringens in the intestine, and to be the cause of death.     

Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation

Accumulation of unfolded and malfolded proteins causes endoplasmic reticulum (ER) stress, stimulating unfolded protein response (UPR) and c-Jun N-terminal kinase (JNK) activation and activating caspase-12 located on the ER. Little is known about the relationship between the ER stress and polyglutamine [poly(Q)] aggregates. Poly(Q)72 repeats [poly(Q)(72)] induced the stimulation of ER stress signals such as JNK activation, upregulation of Grp78/Bip and caspase-12 activation in C2C5 cells. We prepared antiserum against the cleavage site of mouse caspase-12 at D(318) (anti-m12D318), and showed that poly(Q)(72) with perinuclear aggregates, cytoplasmic inclusions and nuclear inclusions stimulated JNK activation and anti-m12D318 immunoreactivity, but poly(Q)(72) with dispersed aggregates and small nuclear aggregates showed a significantly less effect. Poly(Q)(72) and poly(Q)(11) dispersed in cytoplasm did not. Anti-m12D318-positive cells showed apoptotic features. Unlike anti-m8D387 immunoreactivity, the anti-m12D318 immunoreactivity was not coaggregated with poly(Q). Ac-IETD-fmk (caspase-8 inhibitor) and Ac-DEVD-CHO (caspase-3 inhibitor) did not prevent the anti-m12D318 immunoreactivity induced by poly(Q)(72) aggregates. Anti-m12D318 immunoreactivity was detected in caspase-8(-/-) and caspase-3(-/-) mouse embryonic fibroblasts expressing poly(Q)(72) aggregates. Thus, caspase-12 was activated by poly(Q)(72) aggregates via a pathway independent of caspase-8 and caspase-3 activation, and caspase-12 activation was closely associated with poly(Q) aggregate-mediated cell death. Stimulation of ER stress signals may be involved in the pathogenesis of neurodegenerative disorders with poly(Q) expansion.     

Gastric motility in patients with recurrent gastric ulcers.

The existence of abnormal gastric motility in gastric ulcer disease remains controversial. The aim of this study was to characterize gastric motility in patients with recurrent gastric ulcers. Studies were performed in 10 control subjects and in 24 patients with recurrent active gastric ulcer disease as diagnosed by gastrointestinal endoscopy. Gastric motility was evaluated by cutaneous electrogastrography (EGG) and by gastric semi-liquid meal emptying. The EGG was recorded before and after ingestion of a test meal containing 20 mg/kg of acetaminophen. Patients with a dominant EGG frequency of greater than 0.06 Hz were defined as tachygastria, while those with a frequency of less than 0.04 Hz were defined as bradygastria. A transient frequency decrease, called postprandial dip (PD), was identified visually. The degree of gastric emptying was determined from the serum acetaminophen concentration 45 minutes after the meal. Control subjects showed no irregularity in their dominant EGG frequency in tither fasting or postprandial states. PD was observed in 8 control subjects. In patients presenting with active gastric ulcers, abnormal patterns in the dominant EGG frequency (either as tachygastria or bradygastria) were observed in 14 of the 24 patients when fasting and in 15 of them in the postprandial state. After successful treatment, the number of patients with abnormal patterns in their dominant EGG frequency remained unchanged, while PD was observed in 11 patients. No significant difference was observed in the EGG power ratio as a result of successful treatment. Gastric emptying was significantly delayed compared with controls in both the active and healed stages. These findings suggest that abnormal gastric motility, including gastric electrical abnormalities and delayed gastric emptying, plays an important role in the pathophysiology of recurrent gastric ulcers.     

Expression of CD80 and CD86 on Peripheral Blood T Lymphocytes in Patients with Systemic Lupus Erythematosus

CD80 and CD86 were detected in high amounts on circulating T cells in the peripheral blood of some patients with systemic lupus erythematosus (SLE), using flow cytometry and monoclonal antibodies. Patients with other connective tissue diseases did not have a high percentage of T cells expressing CD80 or CD86 in their peripheral blood. CD80 was expressed mainly on CD4 T cells, whereas CD86 was expressed on CD8 T cells, and these two populations were associated with paticular clinical features. These two molecules were expressed on different T-cell populations and might have different roles in the generation and regulation of immune responses. Since high expression of CD86 on T cells was detected much earlier than the appearance of clinical features and a high titer of anti-DNA antibody, it may be a useful parameter for predicting the flare of SLE.