Effects of selective beta2 and beta3-adrenoceptor agonists on detrusor hyperreflexia in conscious cerebral infarcted rats

PURPOSE: We evaluated the effects of beta-adrenoceptor agonists on detrusor hyperreflexia in cerebral infarcted rats. MATERIALS AND METHODS: To produce cerebral infarction in Sprague-Dawley rats the left middle cerebral artery was occluded by introducing a monofilament nylon thread into the artery. In sham operated rats the same artery was exposed but not occluded. After these operations cystometric and cardiovascular experiments were performed with no anesthesia or restraint. RESULTS: After the operation bladder capacity was significantly decreased and voiding pressure was significantly increased in cerebral infarcted but not in sham operated animals. The difference in cerebral infarcted and sham operated rats was significant for each parameter (p <0.01). Post-void residual urine volume was not affected in either group. In the cerebral infarction group intravenous administration of CL316243 ([R,R]-5-2-[[2-(3-chlorophenyl-2-hydroxyethyl]-amino]propyl] -1,3-benzodioxole-2,2-dicarboxylate) (Kissei Central Laboratories, Hotaka, Japan) a selective beta3-adrenoceptor agonist, significantly increased bladder capacity at 10 and 100 microgram./kg. without affecting voiding pressure or post-void residual urine volume. Procaterol, a selective beta2-adrenoceptor agonist, significantly increased bladder capacity and post-void residual urine volume at 10 microgram/kg. intravenously without affecting voiding pressure. In separate experiments procaterol (1 to 100 microgram./kg. intravenously) decreased mean blood pressure and increased heart rate in a dose dependent manner. In contrast, the effects of CL316243 (0.1 to 100 microgram./kg. intravenously) on mean blood pressure and heart rate were minimal. CONCLUSIONS: These results indicate that in cerebral infarcted rats detrusor hyperreflexia can be suppressed by the selective beta3-adrenoceptor agonist CL316243 without increasing post-void residual volume and without significant cardiovascular side effects. If the current results hold true in humans, selective beta3-adrenoceptor agonists may prove useful for treating detrusor hyperreflexia associated with cerebral infarction.     

In vitro activation of extracellular signal-regulated kinase1/2 in the inner ear of guinea pigs

Growth factors such as vascular endothelial growth factor (VEGF) exert their proliferative properties partly through activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK1/2). Although both VEGF and inactive ERK could be detected in the inner ear of guinea pigs, under normal conditions activated ERK (phospho-ERK) was found only sparely. Cochleae of adult guinea pigs were removed, incubated with VEGF in a carbogen-gased organ-bath for 5, 15, 30 and 60 min (n=6 in each group), fixed with PFA 4%, embedded in paraffin and sectioned, followed by immunohistochemical staining to inactive and active ERK. Whereas inactive ERK was found in all cochleae, in sensory and supporting cells of the apex activated ERK was strongly detected after 5-min VEGF-incubation. After 15 min all Corti-organs showed clear staining corresponding to activated ERK, which decreased again after 30 min. Faint staining in endothelial cells of the spring-coil-vessels and in the spiral ganglion cells was found after 30 min and was increased after 60 min, while the staining in the Corti-organs vanished. Addition of the MEK-inhibitor PD 98059 to the organ-bath led to diminished phospho-ERK1/2 immunostaining. These findings provide evidence for a VEGF-dependent phosphorylation of ERK1/2 in the cochlea. Activated ERK1/2 is thought to support axonal outgrowth, enhancement of cell survival and to regulate the turnover of the NO/cGMP-pathway.     

Postischemic administration of basic fibroblast growth factor improves sensorimotor function and reduces infarct size following permanent focal cerebral ischemia in the rat

Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic and protective effects on the brain. bFGF has been reported to exert neuroprotection against a wide variety of insults, including ischemic neuronal injury. To date, animal models of focal ischemia have not been translated to efficacy in stroke clinically with respect to testing of neuroprotective agents. Because functional outcome is the measurement of efficacy for putative neuroprotective agents in the clinic, we sought to evaluate the functional consequences of bFGF administration in rats subjected to focal ischemia. In this study, we assessed the effects of bFGF on functional outcome as well as infarct size in rats subjected to severe cerebral ischemia by permanent occlusion of the middle cerebral artery (MCAO). Male Sprague-Dawley rats were subjected to permanent MCAO by the intraluminal filament technique. Two hours following occlusion, rats were infused intravenously with either bFGF, at a dose of 150 microg/kg, or vehicle alone. Functional sensorimotor impairment, which was assessed by the accelerating rotarod test, was recorded at baseline and compared to performance assessed at 24 h after MCAO. Permanent occlusion of the MCA caused marked impairment in rotarod performance in both groups. Treatment of rats with bFGF showed a significant 46% improvement in rotarod fall latency when compared with that from the animals treated with vehicle alone. The volume of cortical infarction was significantly reduced by 32% as a function of bFGF treatment. These results suggest that the delayed intravenous administration of bFGF improves sensorimotor function as well as reduces infarct size following permanent focal ischemia in rat.     

Elongation of hair cell stereocilia is defective in the mouse mutant whirler

The recessive mouse mutant whirler (wi) shows no response to sound and exhibits circling and head-tossing behaviour, indicative of both auditory and vestibular dysfunction. The wi mutation maps genetically to mouse chromosome 4. We examined the organ of Corti of whirler mutants to explore the possibility that the wi mutation affects sensory hair cells. Scanning electron microscopy (SEM) reveals that the specialised microvilli (stereocilia) that are projected by the sensory hair cells and are vital for sound transduction are abnormal in wi homozygotes. Specifically, wi homozygous inner hair cell (IHC) stereocilia are approximately half the length of equivalent stereocilia in heterozygous littermates. They are arranged normally into ranks, but the gradation in height and width of stereocilia in adjacent ranks is less prominent in wi homozygotes. Analysis of IHC stereocilia during the course of their development shows that, by embryonic day 18.5, mutant stereocilia are already significantly shorter than those in controls. Mutant stereocilia elongate at a normal rate, at least until postnatal day 1, but prematurely stop elongating between postnatal days 1 and 4. Stereocilia length then decreases. At postnatal day 15, outer hair cell (OHC) stereocilia in wi homozygotes appear short and are arranged in a rounded, "U" shape rather than the normal "W" or "V" shape. Eventually, both IHCs and OHCs degenerate. We show that the whirler locus encodes a protein(s) required for the elongation and maintenance of IHC and OHC stereocilia.     

Pancreatico-mediastinal fistula with a mediastinal mass lesion demonstrated by MR imaging

Internal pancreatic fistulas are uncommon but well-recognized complications of inflammatory pancreatic disease. A case of a pancreatico-mediastinal fistula with a mediastinal mass lesion in a patient with a documented history of chronic alcohol consumption and previous episodes of acute pancreatitis is described. Since the clinical symptomatology was dominated by pulmonary complaints, magnetic resonance (MR) imaging using a breathhold coronal T2-weighted sequence with spectral fat saturation was essential in clarifying this difficult and rare pathology. Furthermore, the depiction of a fistulous tract between a mediastinal mass lesion and the retroperitoneum posterior to the pancreas, i.e., a pancreatico-mediastinal fistula by MR imaging has not been previously reported, to the best of our knowledge.     

Transanal endoscopic microsurgery: the first 50 cases

Background: Transanal endoscopic microsurgery is a form of minimally invasive rectal surgery first used at Cabrini Hospital in April 1997. This paper presents a prospective analysis of the first 50 cases with a median follow up of 33 months (range 20?48 months). Methods: Prospective data was obtained from all cases between April 1997 and June 2000. Results: Forty‐nine patients (30 men and 19 women) underwent 50 procedures. Thirty‐six had benign lesions and 14 malignant. The mean distance of the lower edge of the lesion from the anal verge was 8.7 cm. Three cases were converted to traditional transanal or transabdominal operations. Full‐thickness excision was performed on 26 patients and the rectal wound was closed in 13 cases. The mean duration of transanal endoscopic microsurgery was 67 min (range 20?175), with a mean blood loss of 24 mL (0?300). The mean diameter and area of the fixed specimen was 3.7 cm (1.5?9.8) and 11.4 cm² (0.8?18.9), respectively. Complications included postoperative fever (3), urinary retention (1) and per rectum bleeding (1). There was one death. The mean length of stay was 4 days. Histology confirmed complete excision in 39 (78%) cases and there have been two instances of local recurrence of adenoma (5%). Conclusions: Transanal endoscopic microsurgery is an effective, safe and cost‐beneficial procedure for local excision of selected lesions in the middle and upper thirds of the rectum.     

中晚期癌症患者生命质量调查及思考

目的：了解中晚期癌症患者的生存状况，探讨提高患者带瘤生存质量的方法。方法：对35例中晚期食管癌患者及40例中晚期肝癌患者进行问卷调查和访问，并对所调查的生命质量各项指标进行客观分析。结果：中晚期食管癌组患者的生理状况较中晚期肝癌组差（P〈0．001）；但社会／家庭情况、与医生关系、情感状况、功能状况均优于中晚期肝癌组（P〈0．001）。结论：应对中晚期肝癌患者的生存状况给于关注。     

沙培林联合顺铂腔内给药治疗恶性胸腔积液

目的观察沙培林(OK-432)联合顺铂(DDP)腔内给药治疗恶性胸腔积液的近期疗效和不良反应。方法对42例恶性胸腔积液患者先采用美国Arrow公司生产的一次性单腔中心静脉导管进行胸腔穿刺置管闭式引流胸水,再给予胸腔内注药。将42例随机分成两组,治疗组(n=20)采用沙培林加顺铂,对照组(n=22)单用顺铂。顺铂每次注入60~80 mg,每周注射1次,沙培林每周连续3 d分别注入5KE、10KE、10KE,2周为1周期。结果治疗组有效率90%(18/20),对照组有效率59.1%(13/22),两组间有显著性差异(P<0.05)。结论胸腔闭式引流后联合注入沙培林加顺铂治疗恶性胸腔积液优于单用顺铂治疗,疗效肯定,是控制恶性胸腔积液的有效方法。     

胸水C-反应蛋白在鉴别结核性及癌性胸腔积液中的价值

目的探讨胸水C-反应蛋白(C-reactive protein,CRP)在鉴别诊断结核性胸腔积液及癌性胸腔积液中的价值。方法同时测定30例结核性胸水患者(结核组)和30例癌性胸水患者(肿瘤组)的胸水CRP水平,比较两组之间CRP水平的差别。结果结核组胸水CRP水平明显高于肿瘤组(P<0.05)。结论胸腔积液CRP水平的检测,是鉴别诊断结核性胸腔积液及癌性胸腔积液的重要检测指标之一。     

循环热低渗化疗治疗恶性胸腔积液的临床研究

目的探讨循环热低渗化疗治疗恶性胸腔积液的临床疗效和不良反应。方法将18例恶性胸腔积液病人随机分为两组,治疗组7例,对照组11例。经胸腔闭式引流术排尽胸腔积液后,两组均行40mg/m2的顺铂胸腔内灌注化疗,治疗组予以循环热低渗化疗,对照组予以单次性注射化疗,必要时1个月内重复治疗。比较两组病人的呼吸困难状况、Karnofsky评分、胸腔积液吸收情况及不良反应。结果治疗组均治疗了1次,对照组11例中有6例进行了2次治疗。治疗组病人呼吸困难状况和Karnofsky评分均显著好于对照组。胸腔内化疗后1个月,治疗组胸腔积液的治疗有效率85.71%,对照组66.64%,两组比较无显著性差异(P>0.05);胸腔内化疗后2个月,治疗组胸腔积液的治疗有效率保持在85.71%,对照组下降至12.50%,两组比较有显著性差异(P<0.05)。对照组和治疗组病人均出现较明显的恶心和呕吐反应。结论循环热低渗化疗治疗恶性胸腔积液的临床疗效优于单次性胸腔内化疗,疗效持久,无严重不良反应。