Adverse drug reactions of intravesical bacillus Calmette–Guérin instillation and risk factors of the development of adverse drug reactions in superficial cancer and carcinoma in situ of the bladder

BACKGROUND: We examined the incidence and severity of adverse drug reactions following intravesical bacillus Calmette-Guerin (BCG) instillation for superficial bladder cancer including carcinoma in situ. We investigated the relationship between adverse drug reactions and patient background to clarify risk factors for the development of adverse drug reactions. METHODS: A total of 123 patients who underwent intravesical BCG instillation for treatment and prophylaxis between April 1997 and June 2000 were included in this study. Adverse drug reactions were divided into local and systemic categories and the severity of reactions was classified according to the presence or absence of postponement or discontinuation of instillation, with or without treatment for the reaction itself. RESULTS: Of 123 patients, 95.9% showed adverse drug effects and 50.4% needed some sort of treatment. Discontinuation of instillation due to adverse drug reactions was observed in nine patients. Regarding the necessity of treatment for adverse drug effects, the purpose of instillation and BCG dose were independent significant factors on multivariate analysis. CONCLUSION: Although there was a high rate of adverse drug reactions after intravesical BCG instillation, the rate of discontinuation of instillation was not high and serious adverse reactions were rare. The scale of the present study was small, but these results suggest that BCG instillation was well tolerated. When instillation is being performed for the purpose of treatment, and the BCG dose is 80 mg, greater attention might be needed to monitor for the development of adverse drug effects.     

Systemic Toxicity of the Heavy Fraction of a Coal Coprocessing Product in Male Rats Following Subchronic Dermal Exposure

The systemic toxicity of a coal coprocessing product [heavygas oil II (HGOII)] following subchronic, dermal exposure inmale Sprague-Dawley rats was investigated. HGOII was appliedto the dorsal skin daily at doses of 8.7, 20.8, 50.0, or 120.0mg/ kg body weight (bw) for 13 weeks. Another group of ratstreated with a medium boiling coal liquefaction product (CLP)served as positive controls. Growth suppression and decreasedfood consumption were noted in the groups exposed to HGOII at20.8 mg/kg and higher, and to CLP starting at the third weekof treatment. Relative liver, kidney, and brain weights in the20.8 mg/kg HGOII group and up were higher than those of thecontrol. Increased spleen weight was observed in all HGOII-treatedgroups. CLP treatment also caused increased relative kidneyand brain weights. Serum cholesterol was elevated in the HGOII-treatedgroups starting at 8.7 mg/kg while increased uric acid and lactatedehydrogenase were observed at 20.8 mg/kg and up. Decreasederythrocyte, hemoglobin, and platelet counts were observed at20.8 mg/kg and higher. All HGOII-treated groups had elevatedreticulocytes. These biochemical and hematological changes werenot observed in the CLP-treated group. Mild to marked histologicalchanges were observed in the thyroid, thymus, liver, spleen,and bone marrow of HGOII groups. In contrast, morphologicalchanges were relatively mild in CLP-treated animals. Data fromthe present study demonstrated that the hematological endpointswere sensitive to the liquid fuels and that HGOII was more toxicthan CLP. Based on the growth rate and biochemical, hematological,and morphological changes, the no observable adverse effectlevel for HGOII is judged to be below 8.7 mg/kg bw in the rat.     

Mechanism for Species-Specific Induction of Leydig Cell Tumors in Rats by Lansoprazole

Lansoprazole is a substituted benzimidazole which inhibits gastricacid secretion by inhibiting the hydrogen-potassium ATPase (protonpump) in the parietal cell. The finding of Leydig cell hyperplasiaand Leydig cell tumors in 2-year oral studies in Sprague-Dawleyrats but not in CD-1 mice prompted investigative studies todetermine the mechanism for the Leydig cell changes. hCG challengestudies in Sprague-Dawley rats revealed decreased testosteroneresponsiveness in rats treated orally for 1 or 2 weeks withlansoprazole. After 4 weeks of daily oral treatment increasesin serum LH and decreases in serum testosterone were detectedwithin a few hours after dosing. In a study where 9-month-oldmale F344 rats were given testosterone supplementation via Silasticimplants and then treated with lansoprazole for 6 months, ahigh incidence of Leydig cell tumors was seen in lansoprazoletreated,unsupplemented rats, whereas no Leydig cell tumors were seenin testosterone supplemented rats. This implied that reductionof the normal feedback inhibition at the level of the hypothalaumsand/or pituitary due to reduced testosterone levels, thus givingrise to elevated levels of LH, was involved in the inductionof Leydig cell tumors by lansoprazole. In vitro studies withLeydig cells from rats using various stimulators and precursorsof testosterone biosynthesis demonstrated that the most sensitivesite for inhibition of testosterone synthesis by lansoprazoleis the transport of cholesterol to the cholesterol side chaincleavage enzyme. The IC50s for inhibition of LH or hCG-stimulatedtestosterone synthesis in Leydig cells from rats, mice, andmonkeys were 11–12, 8, and 27.4 µg/ml, respectively.In vitro studies with metabolites of lansoprazole revealed thatthree metabolites were more potent inhibitors of testosteronesynthesis than the parent drug, two of them being at least 10times more potent. These metabolites are present in rats atsubstantial levels but are undetectable in humans. The lackof induction of Leydig cell tumors in mice, lower sensitivityof primate Leydig cells, and the absence of testosterone synthesisinhibitingmetabolites in man suggest that Leydig cell tumors found inrats represent a species-specific sensitivity and does not implya risk for clinical use in man.     

Dystrophin negative skeletal and myocardial muscle cells in a carrier of Duchenne's muscular dystrophy

A 47-year-old woman whose elder son had typical Duchenne's musculardystrophy (DMD) was diagnosed as the manifesting carrier ofthe disease. She had developed congestive heart failure buthad no evidence of skeletal muscular atrophy. Histological observationof the cardiac muscle revealed a mosaic pattern of dystrophinnegative fibres detected by immunofluorescence analysis.     

针灸冶疗痹证的临床概况

近年来 ,针灸医学在治疗痹症的临床研究方面 ,取得了满意的成绩。随着研究的深化和提高 ,有必要对痹证的基本病理、临床研究的概况和趋势进行系统性地回顾 ,以其校正科研的方向 ,避免偏差和浪费。本文从痹证的基本概念及病因病机着手 ,就近 5年来中国国内公开发表的有关针灸治疗痹证的临床文献报作一综述报道。择其临床资料相对全面、内容翔实可靠者 6 7篇 ,详细地加以整理和归纳 ,并从治疗的技术方法、取穴的规律以及临床治疗效果等方面进行了分析 ,进而总结提出了目前临床研究中所存在的问题和相应的解决办法设想。     

Clinical Impact of Solifenacin on Generic and Symptom‐Specific Quality of Life for Females with Overactive Bladder: Using the Overactive Bladder Symptom Score and Rand Medical Outcomes Study 36‐Item Health Survey

Objectives: We evaluated the effectiveness of antimuscarinic treatment on disease‐specific and generic quality of life (QoL) in females with clinically diagnosed overactive bladder (OAB) by prospectively analyzing improvements in the overactive bladder symptom score (OABSS) and the Rand Medical Outcomes Study 36‐Item Short Form Health Survey (SF‐36). Methods: We prospectively recruited newly diagnosed female patients with OAB. Pretreatment disease‐specific symptoms were documented, and generic QoL questionnaires were administered. All subjects received solifenacin 5 mg/day for >8 weeks. Symptoms and general health‐related QoL (HRQoL) were assessed using the OABSS and SF‐36, respectively. Other objective variables, such as maximum urinary flow rate and postvoid residual urine volume, were also evaluated. Results: Seventy‐eight subjects met all inclusion criteria and no exclusion criteria. After 8 weeks, the mean OABSS decreased by approximately 50% compared with baseline (from 9.1 ± 2.8 to 4.5 ± 3.6). All individual scores in OABSS improved after administration of solifenacin. Before treatment, the scores of the study subjects in all SF‐36 domains were significantly worse than the age‐ and gender‐adjusted Japanese national norms (P < 0.01), except the vitality (VT) scale. Intra‐group comparisons between age groups showed worse mental health (MH) scores in all age groups. In the OAB group, three mean SF‐36 scales (physical function [PF], VT, and MH) significantly improved after treatment. Conclusion: Treatment of OAB with solifenacin is associated with significant improvement in generic HRQoL and disease‐specific symptoms at 8 weeks after drug administration. Particularly for generic HRQoL as measured by the SF‐36, solifenacin treatment effectively improves three SF‐36 scores: PF, VT, and MH.     

Safety and Validity of Anterior Cervical Disc Replacement for Single-level Cervical Disc Disease: Initial Two-year Follow-up of the Prospective Observational Post-marketing Surveillance Study for Japanese Patients

Anterior cervical disc replacement (ACDR) using cervical artificial disc (CAD) has the advantage of maintaining the range of motion (ROM) at the surgical level, subsequently reducing the postoperative risk of adjacent disc disease. Following the approval for the clinical use in Japan, a post-marketing surveillance (PMS) study was conducted for two different types of CAD, namely, Mobi-C (metal-on-plastic design) and Prestige LP (metal-on-metal design). The objective of this prospective observational multicenter study was to analyze the first 2-year surgical results of the PMS study of 1-level ACDR in Japan. A total of 54 patients were registered (Mobi-C, n = 24, MC group; Prestige LP, n = 30, PLP group). Preoperative neurological assessment revealed radiculopathy in 31 patients (57.4%) and myelopathy in 15 patients (27.8%). Preoperative radiological assessment classified the disease category as disc herniation in 15 patients (27.8%), osteophyte in 6 patients (11.1%), and both in 33 patients (61.1%). The postoperative follow-up rates at 6 weeks, 6 months, 1 year, and 2 years after ACDR were 92.6%, 87.0%, 83.3%, and 79.6%, respectively. In both groups, patients'' neurological condition improved significantly after surgery. Radiographic assessment revealed loss of mobility at the surgical level in 9.5% of patients in the MC group and in 9.1% of patients in the PLP group. No secondary surgeries at the initial surgical level and no serious adverse events were observed in either group. The present results suggest that 1-level ACDR is safe, although medium- to long-term follow-up is mandatory to further verify the validity of ACDR for Japanese patients.