Transitional cell carcinoma of the renal pelvis and ureter: Outcome and patterns of relapse in patients treated with postoperative radiation

We assessed the records of 101 patients with locally advanced transitional cell carcinoma (TCC) of the renal pelvis and ureter treated with postoperative radiation therapy to determine outcome and patterns of failure. Locally advanced disease (i.e., T3–4N0 or N+ disease) was identified in 65 patients. Postoperative radiation was used to treat 86 patients, with a median dose of 35 Gy in 20 fractions over 4 weeks to the tumor bed and regional lymph nodes. There were 15 patients with no residual disease who were offered no further therapy. No patient received postoperative chemotherapy. Prognostic factors were examined using univariate and multivariate analysis, and the patterns of failure were identified after postoperative irradiation. Median follow-up was 9.3 years, during which 76 deaths occurred. The 5-year overall survival was 43% and 10-year survival was 23%. A multivariate analysis identified T3 category, lymph node involvement, and age at diagnosis as significant prognostic factors for survival. Tumor grade was a significant prognostic factor on univariate analysis but not on multivariate analysis. Failure analysis showed that only 36% of patients with locally advanced disease remained relapse free. For this group of patients, distant metastases developed in 53%, and locoregional failured occurred in 35% despite postoperative irradiation. Locoregional failure occurred in 95% of patients with nodal involvement who received postoperative radiation, and 77% of those developed distant relapse. This leads us to conclude that patients with resected locally advanced (T3, T4N0, N+) TCC of the upper urinary tracts have a high risk of relapse and death from disease despite postoperative radiotherapy. Because the main feature of the disease is early distant failure, post-operative chemotherapy is required to improve the outcome for this group of patients.     

Retropublic colpourethropexy with transabdominal anterior and/or posterior repair for the treatment of genuine stress urinary incontinence and genital prolapse

A new operative technique combining retropublic colpourethropexy with transabdominal internal anterior and/or internal posterior repair for the treatment of genuine stress incontinence (GSI) and genital prolapse is described in 75 cases. The overall success rate in correcting GSI was 92.0%, with a 94.8% success rate in the primary surgical group (n=58) and an 82.4% in the secondary group (n=17). Average follow-up has been 1.31 years (range 6 weeks–6 years). There was a 3.4% incidence of residual prolapse. Nine patients also underwent concomitant colpourethropexy. Overall surgical complications include febrile morbidity 4/75 (5.3%), wound infection 1/75 (1.3%), deep vein thrombosis 1/75 (1.3%) and partial ureteric obstruction 1/75 (1.3%). There were no statistically significant changes in multichannel urodynamic studies preoperatively and at 1 year following surgery. Onethird (2/6) of the GSI failures had low MUCP (<20 cm H₂O) prior to surgery and continued so at 1 year follow-up.EDITORIAL COMMENT: Genital prolapse is often present in patients who have GSI. If an operation is performed to correct the GSI, and those areas of weakness in the pelvic support system that are contributing to the genital prolapse are not treated, the genital prolapse will become more severe. In the operation which has been described, the colpopexy sutures will correct any cystourethrocele, and the removal of the wedge of tissue from the anterior superior vaginal wall will correct the cystocele. The removal of the wedge of tissue from the posterior superior vaginal wall will reduce the redundancy of the posterior vaginal fornix, but a culdeplasty of the Moschcowitz or Halban type is recommended to treat or prevent an enterocele and to place the vaginal apex in the hollow of the sacrum. Any coexistent rectocele must always be treated vaginally. If it is not treated, it will appear to be more advanced following elevation of the anterior vaginal wall by retropubic urethropexy and the anterior repair which has been recommended.Genital prolapse is best treated by a vaginal approach. When one must une an abdominal approach, ancillary procedures such as the authors have described should be considered. A bulbous upper vagina is ideal for childbearing but if the apical support system and vaginal wall is weakened it is predisposed to prolapse. If the surgeon, in operating for genital prolapse, which involves the upper vagina, will taper the vaginal apex and support it by obliteration of the cul-desac and shortening and reattachment of the uterosacralcardinal complex, postoperative prolapse will be less likely to recur.     

Auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy in genitourinary cancer patients

To determine the auditory toxicity effects of long-term cis-dichlorodiammineplatinum II therapy, pure tone hearing thresholds were measured prior to therapy and repeated before each subsequent treatment. CDDP was given by a slow intravenous drip method at a low dose of 1 mg/kg body weight, with 37.5 gm mannitol, once a week for six treatments and every 3 weeks thereafter. From a group of 173 genitourinary cancer patients treated, 50 male patients were selected who received at least 12 months of CDDP with no active conductive ear pathology, and whose audiograms obtained at baseline, 6th weeks, 26th weeks, and 52nd weeks of treatment were all available for comparison. Pure tone threshold levels deteriorated across time particularly by the 52nd week and at the higher frequencies. Threshold differences across time were statistically significant and within a linear trend. Of the 50 cases, 30% showed suspect or no ototoxicity, 26% mild, 32% moderate, 2% marked, and 4% showed severe ototoxic changes. Of the two cases who developed severe ototoxicity, one showed complete recovery. There was partial recovery in 26% and no recovery in 54%. Individual variability in susceptibility to and recovery from ototoxicity necessitates systematic audiometric monitoring throughout the therapy.     

Influence of age and of desmotropic drugs on the step phenomenon observed in rat skin

Summary Comprehensive analysis of the mechanical properties of rat skin revealed the step phenomenon. This particular observation was made after constant strain rate (analysis of stress strain curves) as well as after constant load (creep experiments). Relative low extensions or low loads were necessary to provoke the steps. In most cases two, sometimes three steps were observed. The step phenomenon was found mainly in skin strips punched out perpendicularly to the body axis. Probably some bonds in the fibrous network are broken giving way to additional elongation whereafter stronger links take over the stress. Since earlier studies demonstrated a pronounced influence of age and of desmotropic drugs on mechanical properties at ultimate load, e.g., tensile strength, ultimate modulus of elasticity, and ultimate strain, also the step phenomenon was studied under these conditions. In stress-strain experiments most of the steps were found at the ages of 2 and 4 months. Total stress loss and total work loss due to the steps were the highest at the age of 4 months. If, however, these values were calculated as percentage of ultimate values, the highest figures were found in young animals. Elongation gain due to the steps also showed a maximum at time of maturation, e.g., 4 months. Similar findings were achieved in creep experiments at medium load (200 g). After treatment with prednisolone acetate more steps and after treatment with d-penicillamine fewer steps were observed. In stress-strain experiments total stress loss and total work loss due to steps were more than twice as high than controls after prednisolone treatment and only one half after d-penicillamine. If calculated as percentage of ultimate stress or percentage of work input, these changes disappeared because of similar changes at ultimate load. However, elongation gain due to steps, which was not significantly influenced by prednisolone acetate but significantly decreased by d-penicillamine, showed the same changes when calculated as percentage of ultimate strain. Under all conditions the step phenomenon mainly influenced the extension parameters. The data presented here confirm earlier observations that mechanical properties at low loads or low and medium extensions show at least to some extent a different pattern under the influence of maturation and age and after treatment with desmotropic drugs compared to the mechanical parameters at ultimate load.     

Analysis of the pharmacokinetics of lithium in man

Summary An analysis of the single and multiple dose pharmacokinetics of lithium in 7 healthy volunteers is presented. A solution of lithium chloride was administered in single dose experiments and the same solution and a sustained release preparation were employed in multiple dose experiments, which were carried out at steady state. A fixed dose of 24 mmol was used in the single dose experiments and in the subsequent multiple dose experiments in the same subjects the same dose was administered once daily for a week. Distinct two-compartment characteristics were found, with a mean disposition rate constant () of 0.035 h^–1±0.010 SD, corresponding to a mean biological half-life of about 19.8 h. The mean half-time of the distributory -phase was about 1.15 h. The absorption of lithium from an orally administered solution took place with a half-time of about 0.15 h in the single dose experiments. The apparent volume of distribution of the central compartment (V_c) was 0.307 1 kg^–1±0.046 SD, less than half that of V_de at equilibrium. V_d (V_darea) was 0.8291 kg^–1±0.184 SD and mean total body clearance was 27.6 ml kg^–1 h^–1±4.7 SD.     

Précipitation et prévention de l'abstinence chez le rat et la souris en état de dépendance aiguë. Comparaison de la naloxone,de la naltrexone et de la diprenorphine

Summary Abstinence signs were precipitated in rats by naloxone (1 mg·kg^-1 s.c.) injected at various times (from 1.5 to 16 h) after a single dose of morphine hydrochloride (15 or 50 mg·kg^-1 s.c.) administered incaqueous solution. Increasing the dose of morphine increased the latency of the phenomena and the duration of the underlying state shifts of signs as described by Bläsig et al. (1974) in chronically morphinized rats also occurred when increasing the dose of morphine and the time interval between the injections of morphine and of naloxone. Naltrexone and diprenorphine were also effective. These three antagonists, given before morphine, were able to prevent precipitated abstinence: however, naloxone was almost ineffective when the higher dose of morphine was used and when the time interval was long. In these latter conditions, naltrexone was definitely more effective and longer acting and diprenorphine still more so. The same characteristics were found for the protective action of the three antagonists in acutely morphinized mice and the same order for their potencies in precipitating abstinence in acutely morphinized mice. Like naloxone, naltrexone and diprenorphine facilitated a nociceptive reaction in normal mice.The abstinence signs precipitated in acutely morphinized rats or mice are probably not unmasked excitatory effects of morphine as such effects should have been increased rather than inhibited by previous administration of specific antagonists; they might correspond to potentiated effects of the antagonists themselves. The prevention by specific antagonists of the abstinence syndrome is most simply interpreted by antagonism (direct or indirect) of dependence induction, but other interpretations are not excluded.

     

Olanzapine optimal dose: results of an open-label multicenter study in schizophrenic patients. Olanzapine Late-Phase II Study Group

This open-label clinical study was conducted for patients with schizophrenia in order to investigate the efficacy, safety and optimal dose of olanzapine. One hundred and fifty-six of the 159 enrolled patients were included in the analysis set. For the primary efficacy measure, the Final Global Improvement Rating (FGIR) score, 15.4% of patients had remarkable improvement, 58.3% of patients had moderate improvement or more, 79.5% of patients had slight improvement or more, and 10.3% of patients had increase in disease symptomatology (worsening). Results from the Brief Psychiatric Rating Scale (BPRS) in all individual items were improved from baseline. Olanzapine was effective not only against positive psychotic symptoms but also against negative symptoms. This was consistent with results from the Positive and Negative Syndrome Scale (PANSS). For the majority of patients, a dose range of 7.5-10.0mg/day, as a lower bound on the minimally effective dose, was suggested by the results of the dose to first response based on improvement in Global Improvement Rating (GIR) analyses. The ratio of olanzapine dose to equivalent haloperidol dose was estimated at 1.2 :1. The most commonly reported treatment-emergent signs and symptoms (TESS) occurring at a frequency of 10% or more were insomnia, weight increase, excitement, sleepiness, anxiety, malaise and dull headaches. There was a low incidence of extrapyramidal treatment-emergent signs and symptoms; the most commonly reported were akathisia (6.4%), tremor (5.8%) and muscle rigidity (2.6%).     

低频超声波透皮给药的强度对皮肤组织的影响

目的　探讨不同强度下低频超声波介导透皮给药对人体皮肤组织的影响。方法　以 2 4例健康青年志愿者的双上臂作为试验区域 ,每个试验者两上臂同时涂抹 1geutecticmixtureoflocalanesthetics,10min后分别采用 0 .5、1W·cm-2 的能量进行低频超声 (2 0kHz )介导 ,介导时间 10min。每 5min测量两组镇痛起始时间 ,试验结束后观察皮肤组织的变化。结果　能量为 1W·cm-2 的低频超声组平均镇痛起始时间为 32 .75± 3.73min ,0 .5W·cm-2 组为 37.6 5± 3.2 4min。低频超声可使角质层间质增宽和疏松 ,0 .5W·cm-2 组未见组织学病理损害 ,1W·cm-2 组可见点状红疹 ,类似二度烫伤。结论　能量高可更快促进药物透过皮肤 ,但高能量可引起皮肤组织病理性损害 ,0 .5W·cm-2 组能量是比较安全的低频给药方式。     

京、沪、穗三城市2001年—2002年抗病毒药物利用分析

目的 :通过京、沪、穗抗病毒用药的药物利用分析 ,为药品研究、生产、流通和宏观控制提供参考。方法 :利用《全国医药信息网》提供的京、沪、穗三地的抗病毒药品 2 0 0 1年和 2 0 0 2年的统计数据 ,通过药品消耗排序、趋势分析、DDDs等指标 ,分析抗病毒药品的利用情况和市场走势。结果 :抗病毒药品的消耗总体呈增长趋势 ,其中专利品种如拉米夫定的优势远远大于仿制品种 ;国产药品目前在抗病毒药品消耗总金额中占绝对优势 ;京、沪、穗抗病毒用药金额差别较大 ,以广州最高。结论 :抗病毒药品具有广阔的市场前景 ,但要重视低水平的重复仿制与科技创新的矛盾。具有自主知识产权的专利品种是保持市场竞争力的关键。