Impact of unilateral interposition sural nerve graft on the recovery of sexual function after radical prostatectomy in Japanese men: A preliminary study

PURPOSE: To determine the effect of an interposition nerve graft on sexual function after radical prostatectomy. METHODS: This study includes 64 patients, without hormonal therapy, who underwent a radical prostatectomy and intraoperative electrophysiological confirmation of cavernous nerve preservation. Twelve patients underwent a unilateral interposition sural nerve graft (UNG) for the resected neurovascular bundle. Twenty-one and 31 patients underwent bilateral nerve-sparing (BNS) and unilateral nerve-sparing (UNS) surgery without a nerve graft, respectively. As the age of patients was significantly younger in the UNG group than in the other groups, age-matched analysis also was conducted. Sexual function, evaluated by a self-administered questionnaire using the University of California Los Angeles-Prostate Cancer Index, was compared statistically among the three groups. RESULTS: In the age-matched analysis, the postoperative sexual function (SXF) score of the UNG group showed an intermediate level of recovery between those of the BNS and UNS groups at 12 months and reached the same level as the score at 12 months of the BNS group at 18 months postoperatively. The difference in the SXF score between the UNG and UNS groups began to appear after 6 months postoperatively and increased steadily with time. However, the background factors, such as the baseline SXF score, the usage rate of phosphodiesterase 5 inhibitors, and the rate of comorbidities were different between the UNG and UNS groups. CONCLUSIONS: The difference of the SXF score between the UNG and UNS groups increased with time after 6 months postoperatively. However, it might be difficult at present to attribute a better recovery of the SXF score to the nerve graft because of the difference in the background factors between the groups.     

A female case with Down syndrome and non-neurogenic neurogenic bladder

Although the prevalence of a learned voiding dysfunction and non-neurogenic neurogenic bladder (NNB), which is one type of dysfunctional elimination syndrome, is considered to be relatively rare, the association of NNB with Down syndrome (DS) has been elucidated in male patients. We herein describe the occurrence of NNB in an adult female with DS. The diagnosis was confirmed after completely ruling out any neurological or anatomical anomalies that could be related to a lower urinary tract dysfunction. She had renal dysfunction and multiple obstructive uropathies for which clean intermittent catheterization was successfully introduced.     

A case of leiomyosarcoma of the prostate

A 50-year-old man with the symptom of anal pain was treated by pelvic exenteration, ileal conduit diversion and artificial anus. The pathologic diagnosis was leiomyosarcoma of the prostate. At 5 months post-operatively, the patient had no evidence of metastasis or recurrence.     

The Japan Morning Surge-1 (JMS-1) study: protocol description.

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.     

Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP₂) and Ca²⁺ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ-calpain demonstrated μ-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of μ-calpain, and increased immunostaining for inactivated and activated forms of μ- and m-calpains and for PIP₂. Activated μ-calpain and PIP₂ were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca²⁺ mobilization with increased PIP₂ immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca²⁺ and PIP₂ breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.     

Inhibitory reflex during bronchoconstrictions induced by histamine and Ascaris suum antigen.

We investigated the involvements of sympathetic and nonadrenergic nervous systems in the inhibitory reflex following bronchoconstriction in dogs. Inhalations of a 0.00125% solution of histamine and Ascaris suum antigen (3 mg protein) to the bronchial side induced reflex tracheal constriction following bronchoconstriction. An intra-arterial infusion of 5 micrograms/min of atropine to the tracheal site changed the reflex tracheal constrictions by histamine and antigen inhalations into tracheal dilatations. The reflex tracheal dilatations were abolished by the combination of intra-arterial propranolol (100 micrograms) and transections of both the bilateral superior laryngeal nerves and the spinal cord at the C1 level. The reflex tracheal constrictions induced by histamine and antigen inhalations were increased with 100 micrograms propranolol. Furthermore, the reflex tracheal constrictions were enhanced by the combination of 100 micrograms propranolol and transection of the spinal cord. These findings indicate that during the constriction of the bronchial smooth muscle, not only a reflex tracheal constriction mechanism but also one of reflex dilatation operates and that the latter reflex response may be mainly mediated by the sympathetic nerves, with partial involvement of the nonadrenergic nerves. This inhibitory reflex may attenuate asthmatic bronchoconstriction.     

Association of BRCA2 polymorphism at codon 784 (Met/Val) with breast cancer risk and prognosis.

PURPOSE: The association of BRCA2 polymorphisms at codon 372 [Asn (N)/His (H)]and codon 784 [Met (M)/Val (V)] with breast cancer risk was evaluated in Japanese women. In addition, the prognostic significance of these polymorphisms was studied in breast cancer patients. EXPERIMENTAL DESIGN: A case-control study was conducted to examine the association of the BRCA2 N/H372 polymorphism and M/V 784 polymorphism with breast cancer risk (cases = 149, controls = 154). The prognostic significance of these polymorphisms was evaluated in 139 patients with primary breast cancer. RESULTS: No significant association was observed between the N/H372 polymorphism and breast cancer risk. In contrast, a significant increase in breast cancer risk (odds ratio, 2.03; 95% confidence interval, 1.07-3.87) was observed in carriers of the variant allele (V784) of the M/V784 polymorphism as compared with noncarriers after adjustment for the classical risk factors, age, family history, parity, body mass index, and so forth. Among breast cancer patients, various clinicopathological parameters including menopausal status, tumor size, lymph node status, histological grade, and estrogen-receptor status were not significantly different between the carriers and noncarriers of the variant allele with regard to both N/H372 and M/V784 polymorphisms. The N/H 372 polymorphism was not significantly associated with patient prognosis. On the other hand, breast cancer patients carrying the variant allele of M/V784 polymorphism showed a significantly (P = 0.014) lower 3-year disease-free survival rate (63%) than noncarriers (92%). Multivariate analysis has revealed that the M/V784 polymorphism is a significant prognostic factor, being independent of the other conventional prognostic factors such as lymph node status and estrogen receptor status. CONCLUSION: These results suggest that the M/V784 polymorphism, but not the N/H372 polymorphism, would be useful in the selection of women at high risk for developing breast cancer and would also serve as a clinically useful prognostic factor in breast cancer patients.     

TNF-alpha augments the expression of RhoA in the rat bronchus.

While nonspecific airway hyperresponsiveness (AHR) is a central feature of allergic bronchial asthma, the mechanism underlying the development of AHR is not clearly understood. We have previously demonstrated in vitro hyperresponsiveness of bronchial smooth muscle to acetylcholine (ACh) in rats that were actively sensitized and repeatedly challenged with aerosolized antigen. It has also been demonstrated that the ACh-induced, RhoA-mediated Ca(2+) sensitization is markedly augmented concomitantly with an increased expression and activation of RhoA protein in the bronchial smooth muscle of the antigen-treated rats. In the present study, we have investigated whether TNF-alpha, a proinflammatory cytokine which is involved in bronchial asthma, causes upregulation of RhoA mRNA and protein in the rat bronchus. Treatment of rat bronchial smooth muscle preparations with TNF-alpha (300 ng/ml for 24 hr) significantly shifted the concentration-response curve to ACh upwards, but did not alter the response to high K(+), when compared to that of control tissues. Levels of RhoA mRNA and protein in the TNF-alpha-treated bronchus were significantly greater than those in the control group. In conclusion, it is suggested that the augmentation of the ACh-induced contractile response evoked by TNF-alpha might be mediated by an upregulation of RhoA in rat bronchial smooth muscle.     

Tissue renin content in superficial, midcortical, and juxtamedullary afferent arterioles in rabbits]

Tissue renin content within the kidney decreases from outer to inner cortex. However, it is not known whether this gradient is due to a decrease in the number of afferent arterioles from the outer to inner cortex or the decrease in renin content per afferent arteriole. Furthermore, it is still controversial whether sodium depletion increases or decreases this gradient. According to Taugner et al., sodium depletion induces the extension of renin positive part of afferent arterioles from vascular pole toward interlobular artery. Since the length of extension may differ among superficial, midcortical, and juxtamedullary afferent arterioles, the observed gradient may vary depending on whether the entire afferent arteriole or only the vascular pole is examined. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined tissue renin content. We studied: 1. whether tissue renin content per afferent arteriole decreases from the outer to inner cortex. 2. whether sodium depletion affects the gradient of tissue renin content within the cortex. In result, we reached the conclusions, as follows: 1. Tissue renin content per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles. 2. The absolute difference in renin content among the three types of afferent arterioles becomes greater during sodium depletion. The internephron heterogeneity of tissue renin content may contribute to functional heterogeneity.