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.     

Studies on the synthesis of antiulcer agents. VI. Synthesis and antiulcer activity of dihydrobenzofuranone derivatives

The derivatives (2) of 3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl) acrylic acid (2b) were synthesized. The compounds (3a-g) in which bromo, methoxy, nitro, amino or acetamido group was introduced on the benzene ring of the derivatives (2) and the compounds (3h-k) in which acryloyl moiety was introduced on the 6- or 7-position of the benzofuranone skeleton also synthesized. Furthermore, propionic acid derivatives (4a-c), acetic acid derivatives (4d-g), formic acid derivatives (4h-k) and oxyacetic acid derivatives (5) were prepared by converting the acryloyl moiety of the derivatives (2) into propionyl, acetyl, formyl and oxyacetyl groups. These compounds were tested for antiulcer activities. Among these compounds, 1-[3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl)acryloyl]piperidine (2d) and 4-[3-(2,3-dihydro-2,2-dimethyl-3-oxo-5-benzofuranyl)acryloyl] morpholine (2g) were found to have stronger antiulcer activities.     

The effect of the intraocular pressure reduction on glaucomatous disc changes and visual field defects]

The authors prospectively studied changes in the optic disc and visual field associated with intraocular pressure (IOP) reduction for one year after surgery in 12 primary open-angle glaucoma eyes of 7 patients who underwent trabeculectomy because of elevated IOP despite maximum tolerable medical therapy and whose cup volume was demonstrated to be decreased at 3 or 6 months after surgery. Topographic parameters including C/D ratio, rim area and cup volume were determined by the Optic Nerve Head Analyzer plus (Rodenstock). The 30-2 central threshold field was obtained with a Humphrey Field Analyzer at the same time. Mean deviation (MD), corrected pattern standard deviation (CPSD) and total deviation (TD) were used to evaluate visual field changes. Significant improvement of C/D ratio, rim area and cup volume and significant IOP reduction were noted at 1 year after surgery as compared with preoperative baseline value (p less than 0.01). Also the MD was significantly decreased at 1 year after surgery, compared with the preoperative baseline value (p less than 0.05). There was a significant negative correlation between the preoperative MD and the percent change of the MD at 1 year after surgery (r = -0.80, p less than 0.01). Our results suggest that the decrease of optic disc cupping can persist over one year after surgery and that the early visual field defects in glaucoma eyes can gradually improve in association with the decrease of cupping.     

Different origin of leiomyoblastoma by immunohistochemical study.

Leiomyoblastoma has been regarded as a neoplasm of smooth muscle origin. With recent progress in immunohistostaining techniques, many clinicopathological discrepancies have been pointed out about the origin of leiomyoblastoma. It has been claimed that gastrointestinal non-epithelial tumors should be regarded as stromal tumors in order to study their origin. In the present study, we performed various forms of immunohistostaining in seven cases of leiomyoblastoma to determine their origin. One case expressed desmine and muscle specific actin and was considered to be derived from smooth muscle. Four neoplasms expressed X-100 protein (two cases were also NSE positive) and were thought to be derived from the nerve. Two cases were of unknown derivation. These results suggest that the cells of leiomyoblastoma may arise from a primitive to totipotential cell of neural lineages that may anomalously express smooth muscle filaments.     

Subtle computed tomography abnormalities in cerebral deep sinus thrombosis.

A patient with cerebral deep sinus thrombosis, which was not diagnosed on the first examination, is reported. A 46-year-old woman presented with headache and vomiting. Neurological examination and a brain computed tomography (CT) scan showed no obvious abnormal findings. The patient suffered disturbed consciousness on the day after the examination, and was admitted to our emergency centre. A CT scan and magnetic resonance imaging revealed an ischaemic lesion in the left basal ganglia, suggesting deep sinus occlusion. Anticoagulant therapy was administered. One day after admission, a CT scan showed a haematoma and severe brain swelling in the same region. Cerebral angiography demonstrated a straight sinus occlusion. Intracranial pressure was not controlled with hypothermia, and the patient died 25 days after admission. Review of the initial CT scan revealed subtle, early findings of deep venous thrombosis that were missed on first examination.     

Evidence that a substance P-like peptide mediates the non-cholinergic excitatory response of the carp intestinal bulb (Cyprinus carpio)

Summary The participation of substance P in the noncholinergic contraction induced by transmural stimulation (TMS) of the carp intestinal bulb was examined. In the presence of atropine, substance P caused the contraction of carp intestinal bulb smooth muscle in a concentration dependent manner (1 nmol/1 – 1 mol/l). The EC50 value was 28 ± 7 nmol/l (n = 6). Substance P-induced desensitization (1 mol/l for 15 min), decreased the response to substance P and the atropine-resistant contraction induced by TMS (20 Hz) selectively. In contrast, in the absence of atropine, the contraction induced by TMS (20 Hz) was slightly attenuated with the substance P-induced desensitization. The acid extract obtained from the carp intestinal bulb contained a smooth muscle excitatory material whose pharmacological properties were consistent with those of substance P. The present results indicate that a substance P-like peptide is present in the carp intestinal bulb which is involved in the non-cholinergic contraction induced by TMS.Send offprint requests to T. Kitazawa at the above address     

"Spontaneous" pneumocephalus associated with aerobic bacteremia

Three cases of "spontaneous" pneumocephalus suspected to have resulted from aerobic bacteremia caused by Enterobacter cloacae, Escherichia coli, and Klebsiella aerogenes are reported. In two cases, the E. cloacae and K. aerogenes were isolated from the cerebrospinal fluid. These cases were characterized by a rapid accumulation of air, without niveau, in the subarachnoid space and ventricles.     

Possible involvement of arachidonic acid metabolism in phenobarbital promotion of hepatocarcinogenesis

The effects of inhibitors of arachidonic acid metabolism andantioxidants on the rat liver tumor promotion activity of phenobarbital(PB) were assessed using the enzyme-altered focus as the end-pointlesion. Fischer 344 male rats were initiated with N-nitrosodiethylamine(200 mg/kg) and then divided into five groups placed on basaldiet, diet containing 0.05% PB, diet containing 0.05% PB plus0.75%, 1% or 1.5% levels of various inhibitors of arachidonicacid metabolism or antioxidants, or diet containing 1% or 1.5%inhibitors or antioxidants alone for 10 weeks, and then killed.-Bromo phenacyl bromide, an inhibitor of phospholipase A₂ significantly inhibited the promotion activity of PB at dose levelsof 0.75% and 1.5%, reaching plateau at 0.75%. Both quercetin,an inhibitor of lipoxygenase, and morin, a dual inhibitor oflipoxygenase-cyclooxygenase, significantly reduced the promotionactivity of PB at the 1.5% but not 0.75% dose levels. Moreover,acetylsalicylic acid, an inhibitor of cyclooxygenase dose-dependentlyinhibited the promotion activity of PB. Among the antioxidantsinvestigated, vitamin E did not affect, but n-propyl gallateand ethoxyquin exerted a dose-dependent inhibition of PB promotion.These results are strongly suggestive of an involvement of phospholipaseA₂ lipoxygenase and cyclooxygenase arachidonic acid metabolicpathways in the mechanisms underlying PB enhancement of hepatocarcinogenesis.     

Toll-like receptor 9 is expressed on follicle-associated epithelia containing M cells in swine Peyer's patches

The precise distribution and expression of Toll-like receptor (TLR) 9 in gut-associated lymphoid tissues (GALTs) has not been elucidated. In this study, we investigated the expression pattern of TLR9 in adult and neonatal swine GALTs by real-time quantitative PCR, western blot, confocal laser microscopy and flow cytometric analysis. The swine TLR9 gene was preferentially expressed in adult Peyer's patches (Pps) and mesenteric lymph nodes (MLNs), which contained approximately three times higher TLR9 than the spleen. Other tissues exhibited only weak expression of TLR9. In neonatal swine, elevated expression of TLR9 was detected only in MLNs. We firstly showed that highly expressive (TLR9(+)) cells were formed in Pps and MLNs. In addition, TLR9(+) cells were present not only in immune cells such as dendritic cells and B cells but also in follicle-associated epithelia (FAE) including membranous cells (M cells) in Pps. These results suggest that Pps and MLNs provide the host defense with the ability to respond to a variety of bioactive oligonucleotides (ODNs) from bacteria at a conductive site of initial immune responses.