Possible correlation between polymorphism in the tumor necrosis factor-beta gene and the clinicopathological features of bladder cancer in Japanese patients

OBJECTIVES: In a variety of cancers, several polymorphisms of the tumor necrosis factor (TNF) genes have been reported to result in different clinical outcomes. We investigated whether a polymorphism of the TNF gene is associated with a susceptibility to bladder cancer and its disease status. METHODS: Polymorphisms in the TNF-alpha gene promoter (-308 bp) and the NcoI site in the first intron of the TNF-beta gene were analyzed in 141 Japanese patients with bladder cancer and 173 Japanese controls by polymerase chain reaction-restriction fragment length polymorphism. The correlations between the polymorphisms of the TNF genes and the clinicopathological features were analyzed. RESULTS: The number of cases and controls with TNF-alpha2 was too small to be assessable. In contrast, the TNF-beta1/2 genotype at the NcoI site in the first intron conferred a 1.71-fold increased risk of bladder cancer compared to the TNF-beta2/2 genotype. In the bladder cancer group, patients with the TNF-beta1 allele had a significantly higher risk for a high-grade tumor (grade 3) or carcinoma in situ (CIS) than those without the TNF-beta1 allele. Moreover, in the superficial bladder cancers, patients with the TNF-beta1 allele showed a significantly higher intravesical recurrence rate than those without the TNF-beta1 allele. CONCLUSION: This polymorphism in the TNF-beta gene appears to be associated with tumor occurrence and disease status, such as the tumor grade and the presence of CIS. Further study with an increased sample size is warranted.     

Phenytoin-induced cerebral thrombosis in rats: cerebral ultrastructure, water content and ischaemic volume in the acute phase

A new rat model for multifocal cerebral thrombosis has recently been reported (Tani et al. , 1994; 1995). Ultrastructural changes in the cerebral neocortex in the acute phase were investigated in order to characterize the early pathological events in this model. A bolus injection of alkaline phenytoin solution (pH 10.8) into one internal carotid artery in the rat caused severe endothelial injury accompanied by thrombosis in the cerebral vasculature within 5 minutes, and severe oedema of the ipsilateral hemisphere within an hour. Cerebral water content was measured by the simple dry–wet method, and cerebral surface area and the surface area and volume of the ischaemic zone were measured using computer-aided image analysis. Good correlations were demonstrated between cerebral water content and cerebral surface area, and between the surface area and volume of the ischaemic zone. We report here that quantitative evaluation of acute cerebral damage induced by phenytoin solution is possible with high reliability using simple image analysis.     

Liquid chromatographic determination of magnolol in urine collected from volunteers after a single dose of Saiboku-To,an oriental herbal medicine for bronchial asthma

Abstract— Saiboku-To is an anti-asthmatic herbal remedy which consists of ten herbal extracts. To investigate the clinical relationship between the effects and chemical components of Saiboku-To, a simple and sensitive high-performance liquid chromatographic method (HPLC) for determination of magnolol, one of the major urinary products, was developed. Organic solvent extraction of urinary magnolol was conducted by diatomaceous earth column rapid-flow fractionation using ethanol/dichloromethane (8/92, v/v). Recovery rates of magnolol were more than 99% with coefficient of variations less than 6% in the concentration range 9·7–970 ng mL^?1. Subsequent HPLC determination of magnolol was achieved using a conventional silica-gel column, a mobile phase mixture of acetic acid/diethyl ether/n-hexane (0·2/17·0/82·8, v/v), and a UV-absorption detector set at 290 nm. Calibration was on the basis of peak height ratio between magnolol and flavone as an internal standard. The method was used to demonstrate excretion profiles of magnolol in healthy and asthmatic subjects following single administration of Saiboku-To.     

SUCCESSFUL SURGICAL MANAGEMENT AND LONG-TERM FOLLOW-UP OF EPIDERMOLYSIS BULLOSA

Background. Esophageal stenosis and hand deformity are serious complications of recessive dystrophic epidermolysis bullosa that influence the prognosis of patients. To control such complications we have used surgical treatments with favorable results. Additional objectives were to summarize the results of long-term follow-up. Methods. Six patients with esophageal stenosis and nine patients (13 hands) with hand deformity (contracted fingers, mitten-like deformity) were treated surgically after anemia and malnutrition were corrected by intravenous iron infusion, high-energy diet, and blood transfusion. As intubation was contraindicated, topical anesthesia was used (eg., lidocaine spray to the nasopharyngeal mucosa for esophageal dilatation and brachial block, ketamine drip, and nitrous oxide inhalation for reconstruction of contracted fingers). We established a new method for esophageal dilatation using a microvasive rigiflex balloon catheter. This catheter was advanced to the stenotic area under radiography and then expanded by injecting contrast medium into the balloon. For reconstruction of hand deformities, the epidermal glove was initially peeled off, and then the combined digits separated carefully by hand, if the release of the contracture was not sufficient, a skin incision was made avoiding injury to nerves and blood vessels. Any skin defects that appeared after the release of the contracture were covered with skin grafts taken from the abdominal wall. K-wire fixation was used to maintain the extended position of the fingers. Three weeks after the operation, the K-wires were removed and rehabilitation was commenced. Results. The esophageal stenosis was successfully dilated with the balloon catheter; in all six cases the dysphagia was relieved immediately. There was no recurrence in any of the patients on long-term follow-up. After reconstruction of the hand, daily activity improved in 12 of the 13 hands. The remaining hand was difficult to reconstruct due to severe mutilation and bone deformity. During follow-up, 6 of the 12 hands maintained successful reconstruction, whereas the remaining 6 hands showed slight to moderate recontraction of the fingers. Conclusion. Esophageal dilatation with a balloon catheter is safer and has fewer side effects compared to other surgical procedures. This method can provide favorable results and can be carried out repeatedly in a short time. Daily and social activities of patients can be improved upon reconstruction of hand deformities.     

Selective depletion of neutrophils by a monoclonal antibody, RP-3, suppresses dextran sulphate sodium-induced colitis in rats

Administration of dextran sulphate sodium to animals induces acute colitis characterized by infiltration of large numbers of neutrophils into the colonic mucosa, which histologically resembles human active ulcerative colitis. It has been reported that neutrophils and the reactive oxygen metabolites produced by them are involved in the progress of ulcerative colitis. This study was intended to clarify their roles by using this animal model. First, possible sources and species of reactive oxygen metabolites were determined using luminol-dependent chemiluminescence with addition of enzyme inhibitors and reactive oxygen metabolite scavengers. Next, to examine whether neutrophils and hypochlorous acid derived from them contribute to tissue injury, we administered RP-3, a monoclonal antibody capable of selectively depleting neutrophils, and taurine, a hypochlorous acid scavenger, to rats treated with dextran sulphate sodium. Addition of azide, taurine, catalase, superoxide dismutase and dimethyl sulphoxide into colonic mucosal scrapings significantly inhibited chemiluminescence production, but allopurinol and indomethacin had no effects. These results suggest that excessive hypochlorous acid, hydrogen peroxide, superoxide anion and hydroxyl radical are generated by the inflamed colonic mucosa. Intraperitoneal injections of RP-3 significantly suppressed bleeding, tissue myeloperoxidase activity, chemiluminescence production and erosion formation. On the other hand, administration of taurine tended to inhibit bleeding and erosion formation to some extent, although it could not significantly suppress them. These data suggest that neutrophils play an important role in the development of this colitis and that hypochlorous acid might be one of the causes of tissue injury induced by neutrophils.     

Late relapse of stage I testicular seminoma metastatic to just a para-ureteropelvic region

A follow-up ultrasonography study 43 months after an operation for left stage I testicular seminoma in a 39-year-old man revealed left hydronephrosis. Serum beta-human chorionic gonadotropin (beta-hCG) levels were slightly increased. Computed tomography scans of the abdomen showed a bulky tumor around the ureteropelvic region without para-aortic lymph node enlargement, but did not show a clear distinction between a recurrence of the testicular tumor and an invasive ureteral tumor. After the patient underwent two cycles of chemotherapy with cisplatin and etoposide, the tumor mass decreased by approximately 60% and beta-hCG levels returned to normal. We then performed a resection of the residual tumor involving the upper ureter and left kidney and a retroperitoneal lymph node dissection under a clinical diagnosis of recurrence of the testicular tumor. Histologically, no viable cancer cells remained. The patient has been well with no evidence of recurrence for more than two years.     

A new aspect of tolbutamide metabolism in the rabbit: the role of 1-butyl-3-(p-formylphenyl)sulphonylurea

Abstract— We investigated the metabolism of tolbutamide by using synthetic 1-butyl-3-(p-formylphenyl)sulphonylurea (ATB), an intermediate in the metabolic pathway of tolbutamide. ATB (40 mg kg^?1) administered intravenously to rabbits was oxidized to 1-butyl-3-(p-carboxyphenyl)sulphonylurea (CTB) and also reduced to 1-butyl-3-(p-hydroxymethylphenyl)sulphonylurea (HMTB). Therefore, it is likely that in the metabolism of tolbutamide, the oxidation of HMTB to ATB involved the reverse reaction, suggesting the reduction of ATB to HMTB. The oxidation of ATB to CTB was inhibited by disulfiram pretreatment. ATB was detected in the blood following intravenous administration of HMTB in rabbits pretreated with disulfiram. These results, confirm that ATB is an intermediate in the oxidative metabolism of tolbutamide in the rabbit.     

Case Report: Interferon induced coma in Sheehan's syndrome

A 54-year-old woman who was being treated with 10 million units (mu) of natural interferon (IFN)-α per day for chronic active hepatitis C at a local clinic, developed coma on the fourth day of treatment. On admission to Yamagata University Hospital, she was still in a state of semicoma with severe hyponatraemia (122 mEq/L) and hypochloraemia (89 mEq/L). After the administration of electrolytes, her condition improved remarkably. Endocrinological loading tests showed a hypofunction of the anterior pituitary gland. In consideration of these results, and her past experiences of haemorrhage during childbirth and subsequent amenorrhoea, we diagnosed her illness as a coma as a result of Sheehan's syndrome which had become overt during IFN therapy. She recovered completely after treatment with hydrocortisone and 1-thyroxine.