A prospective randomised double-blind controlled trial evaluating the effect of trans-sacral magnetic stimulation in women with overactive bladder.

Overactive bladder (OAB) is a prevalent condition with 16% of adults having one or more symptoms that significantly affect quality of life. Transcutaneous electrical nerve stimulation and neuromodulators have had success in treating OAB but are expensive, invasive, and sometimes cumbersome. We developed an alternative neuromodulatory technique that involves electromagnetic stimulation of the sacral nerve roots with a portable electromagnetic device to produce trans-sacral stimulation of the S3 and S4 sacral nerve roots. The aim of this study was to evaluate the impact of this device on OAB symptoms in women with a prospectively randomised double-blind controlled study. Following a power analysis, women with symptoms of OAB were prospectively recruited with ethical approval for randomisation to an active treatment (n = 33) or placebo group (n = 30) in a double-blind trial. The patient, at home, used the belt device daily for 20 min over 12 weeks. Outcome measures included a 3-day voiding diary, 1 h pad test, visual analogue score (VAS) for symptom impact (0-100%), Kings Health Questionnaire (KHQ) and Australian Quality of Life questionnaire (AQOL) at baseline, 6 and 12 weeks. Overall, no difference was found between groups for any of the research questions. Specifically, we were unable to demonstrate any difference between the active and sham device groups in frequency, nocturia, urinary leakage, or quality of life, nor was there any evidence of a placebo effect. The quality of the data was high with the number of missing observations (especially for disease specific KHQ and general AQOL) being few. This attempt to promote trans-sacral electromagnetic neuromodulation with a specially created device was ineffective on the symptoms of OAB.

Actions of β2-adrenoceptor agonist drug on human soleus muscle contraction.

PURPOSE: The effects of β(2)-agonists on human skeletal muscle contractile properties, particularly on slow fibers, are unclear. Moreover, it remains to be ascertained whether central motor drive (CMD) during voluntary contractions could counter for eventual contractile alterations induced by β(2)-agonists. This study investigated central and peripheral neuromuscular adjustments induced by β(2)-agonist terbutaline on a predominantly slow human muscle, the soleus. METHODS: Ten recreationally active men ingested either a single dose of 8 mg of terbutaline or placebo in a randomized double-blind order (two experimental sessions). Isometric plantarflexion torque was measured during single and tetanic (10 and 100 Hz) stimulations as well as during submaximal and maximal voluntary contractions (MVC). Twitch peak torque and half-relaxation time were calculated. CMD was estimated via soleus electromyographic recordings obtained during voluntary contractions performed at approximately 50% MVC. RESULTS: MVC and twitch peak torque were not modified by terbutaline. Twitch half-relaxation time was 28% shorter after terbutaline administration compared with placebo (P < 0.001). Tetanic torques at 10 and 100 Hz were significantly lower after terbutaline intake compared with placebo (-40% and -24% respectively, P < 0.001). Despite comparable torque of submaximal voluntary contractions in the two conditions, CMD was 7% higher after terbutaline ingestion compared with placebo (P < 0.01). CONCLUSION: These results provide evidence that terbutaline modulates the contractility of the slow soleus muscle and suggest that the increased CMD during submaximal contractions may be viewed as a compensatory adjustment of the central nervous system to counter the weakening action induced by terbutaline on the contractile function of slow muscle fibers.

Testosterone: a specific competitive antagonist of aldosterone in the toad bladder.

Testosterone (100 nM to 40 microM) antagonized the effect of aldosterone (10 nM) on Na+ transport in the toad bladder measured in vitro as short-circuit current (SCC). Half-maximal inhibition occurred at an antagonist-agonist molar ratio of 150:1. The antagonist action of testosterone was reversed by addition of more aldosterone. The antagonism was specific in the sense that testosterone (20 microM) did not inhibit the response of the SCC to oxytocin (50 mU/ml). By itself, testosterone (up to 20 microM) had no agonist activity on base-line SCC. Finally, testosterone (500 nM to 20 microM) specifically displaced [3H]aldosterone (5 nm) from its cytoplasmic and nuclear binding sites in bladders incubated in vitro at 25 or 0 degrees C and labeled at steady state. There was a significant linear correlation between the effect of testosterone on the aldosterone-dependent SCC and its effect on [3H]aldosterone binding sites in the cytoplasm and in the nucleus. We conclude that 1) testosterone is a specific competitive antagonist of aldosterone, and 2) [3H]aldosterone nuclear and cytoplasmic binding sites could be mineralocorticoid receptors, mediating the action of aldosterone on Na+ transport.

Lack of Smad3 signaling leads to impaired skeletal muscle regeneration.

Smad3 is a key intracellular signaling mediator for both transforming growth factor-β and myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired satellite cell functionality in Smad3-null muscles. In the present study, we have further validated a role for Smad3 signaling in skeletal muscle regeneration. Here, we show that Smad3-null mice had incomplete recovery of muscle weight and myofiber size after muscle injury. Histological/immunohistochemical analysis suggested impaired inflammatory response and reduced number of activated myoblasts during the early stages of muscle regeneration in the tibialis anterior muscle of Smad3-null mice. Nascent myofibers formed after muscle injury were also reduced in number. Moreover, Smad3-null regenerated muscle had decreased oxidative enzyme activity and impaired mitochondrial biogenesis, evident by the downregulation of the gene encoding mitochondrial transcription factor A, a master regulator of mitochondrial biogenesis. Consistent with known Smad3 function, reduced fibrotic tissue formation was also seen in regenerated Smad3-null muscle. In conclusion, Smad3 deficiency leads to impaired muscle regeneration, which underscores an essential role of Smad3 in postnatal myogenesis. Given the negative role of myostatin during muscle regeneration, the increased expression of myostatin observed in Smad3-null muscle may contribute to the regeneration defects.

Avaliacao dos resultados cirurgicos com a tecnica da resseccao do musculo de Muller-conjuntiva no tratamento da blefaroptose. [Evaluation of the surgery results of Muller's muscle-conjunctival resection in the treatment of blepharoptosis]

OBJECTIVE: To evaluate the results of Muller's muscle-conjunctival resection for correction of blepharoptosis and to discuss the advantages of this procedure. METHODS: 38 patients (39 eyelids) were submitted to Muller's muscle-conjunctival resection. Blepharoptosis varied from 1.0 mm to 3.0 mm (mean: 2.0 mm). The amount of eyelid elevation produced by phenylephrine guided the amount of tissue to be resected. RESULT: 33 eyelids (85%) treated with this procedure were cosmetically acceptable. CONCLUSIONS: Muller's muscle-conjunctival resection procedure is a relatively simple technique for blepharoptosis, with good levator function and positive 10% phenylephrine test. The advantages are: preservation of tarsus and predictable results.

Thyroid hormone enhances transected axonal regeneration and muscle reinnervation following rat sciatic nerve injury.

Improvement of nerve regeneration and functional recovery following nerve injury is a challenging problem in clinical research. We have already shown that following rat sciatic nerve transection, the local administration of triiodothyronine (T3) significantly increased the number and the myelination of regenerated axons. Functional recovery is a sum of the number of regenerated axons and reinnervation of denervated peripheral targets. In the present study, we investigated whether the increased number of regenerated axons by T3-treatment is linked to improved reinnervation of hind limb muscles. After transection of rat sciatic nerves, silicone or biodegradable nerve guides were implanted and filled with either T3 or phosphate buffer solution (PBS). Neuromuscular junctions (NMJs) were analyzed on gastrocnemius and plantar muscle sections stained with rhodamine alpha-bungarotoxin and neurofilament antibody. Four weeks after surgery, most end-plates (EPs) of operated limbs were still denervated and no effect of T3 on muscle reinnervation was detected at this stage of nerve repair. In contrast, after 14 weeks of nerve regeneration, T3 clearly enhanced the reinnervation of gastrocnemius and plantar EPs, demonstrated by significantly higher recovery of size and shape complexity of reinnervated EPs and also by increased acetylcholine receptor (AChRs) density on post synaptic membranes compared to PBS-treated EPs. The stimulating effect of T3 on EP reinnervation is confirmed by a higher index of compound muscle action potentials recorded in gastrocnemius muscles. In conclusion, our results provide for the first time strong evidence that T3 enhances the restoration of NMJ structure and improves synaptic transmission.

Connexin26 is regulated in rat urothelium by the scaffold protein IB1/JIP-1.

Proper function of the wall of bladder requires gap junctional communication for coordinating the responses of smooth muscle (SMC) and urothelial cells exposed to urine pressure. In the rat bladder, Cx43 is expressed by SMC and urothelial cells, whereas Cx26 expression is restricted to the epithelium. We used a model of bladder outlet obstruction, in which a ligature is placed around the urethra to increase voiding pressure. Increased fluid pressure was associated with increased Cx43 and Cx26 mRNA expression and with the activation of a signaling cascade including the transcription factor c-Jun, which is a component of the AP-1 complex. The signaling pathway of the c-Jun NH2 terminal kinase (JNK) requires the presence of the scaffold protein Islet-Brain1/c-Jun amino-terminal kinase Interacting Protein-1 (IB1/JIP-1). Under stress conditions resulting from urine retention, we have found a reduced content of IB1/JIP-1 in urothelial cells, which in turn induced a drastic increase of JNK and AP-1 binding activities. The stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1, using a viral gene transfer approach, a condition which also resulted in a decrease in Cx26 mRNA. The data show that: 1) mechanical stress of urothelial cells activates in vivo JNK, as a consequence of a regulated expression of IB1/JIP-1 and 2) that urothelial Cx26 may be directly regulated by the AP-1 complex.

Isolated cerebral metastasis of a triceps muscle leiomyosarcoma: A case report.

Abstract Leiomyosarcomas are rare malignant neoplasms. Intracranial metastases of this tumour are even less frequently observed and have mostly been described from uterine leiomyosarcomas. In this article, we describe the case of a single right frontal subcortical cerebral metastasis in a patient with a right triceps muscle leiomyosarcoma. A right-sided frontal craniotomy with macroscopically complete tumour removal was performed, followed by combined radio-chemotherapy. The patient died 10 months after the initial diagnosis of the intracranial metastasis due to systemic tumour progression, without any evidence of intracranial recurrence.

Transcript profiling suggests that differential metabolic adaptation of mice to a high fat diet is associated with changes in liver to muscle lipid fluxes.

Genetically homogenous C57Bl/6 mice display differential metabolic adaptation when fed a high fat diet for 9 months. Most become obese and diabetic, but a significant fraction remains lean and diabetic or lean and non-diabetic. Here, we performed microarray analysis of "metabolic" transcripts expressed in liver and hindlimb muscles to evaluate: (i) whether expressed transcript patterns could indicate changes in metabolic pathways associated with the different phenotypes, (ii) how these changes differed from the early metabolic adaptation to short term high fat feeding, and (iii) whether gene classifiers could be established that were characteristic of each metabolic phenotype. Our data indicate that obesity/diabetes was associated with preserved hepatic lipogenic gene expression and increased plasma levels of very low density lipoprotein and, in muscle, with an increase in lipoprotein lipase gene expression. This suggests increased muscle fatty acid uptake, which may favor insulin resistance. In contrast, the lean mice showed a strong reduction in the expression of hepatic lipogenic genes, in particular of Scd-1, a gene linked to sensitivity to diet-induced obesity; the lean and non-diabetic mice presented an additional increased expression of eNos in liver. After 1 week of high fat feeding the liver gene expression pattern was distinct from that seen at 9 months in any of the three mouse groups, thus indicating progressive establishment of the different phenotypes. Strikingly, development of the obese phenotype involved re-expression of Scd-1 and other lipogenic genes. Finally, gene classifiers could be established that were characteristic of each metabolic phenotype. Together, these data suggest that epigenetic mechanisms influence gene expression patterns and metabolic fates.

Imaging spectrum of the operated bladder : P41

Multiple complex procedures involving the bladder have been developed by surgeons in both children and adults, with their own advantages and drawbacks. A greater knowledge of the anatomic changes induced by each category of procedure is mandatory in the follow-up of patients and detection of early and late postoperative complications. A retrospective review of 50 pediatric and adult patients referred or treated in our institution is presented. The combined use of plain films, IVP, MCUG, US, Doppler US, CT, 3DCT and MRI is described. The imaging features are compared with surgical and anatomopathological findings. The purpose of this pictorial essay is to present a wide spectrum of diagnostic imaging findings in children and adult patients with operated bladder. The imaging features of surgical procedures with preserved, partially replaced and totally replaced bladder are described, with emphasis on a systematic multimodality approach. Learning objectives: 1) To provide an in-depth review of bladder surgical procedures with their indications, anatomopathological and imaging features. 2) To describe optimal multimodality imaging techniques for evaluating the operated bladder.

Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair.

INTRODUCTION: Functional muscle recovery after peripheral nerve injury is far from optimal, partly due to atrophy of the muscle arising from prolonged denervation. We hypothesized that injecting regenerative cells into denervated muscle would reduce this atrophy. METHODS: A rat sciatic nerve lesion was performed, and Schwann cells or adipose-derived stem cells, untreated or induced to a "Schwann-cell-like" phenotype (dASC), were injected into the gastrocnemius muscle. Nerves were either repaired immediately or capped to prevent muscle reinnervation. One month later, functionality was measured using a walking track test, and muscle atrophy was assessed by examining muscle weight and histology. RESULTS: Schwann cells and dASC groups showed significantly better scores on functional tests when compared with injections of growth medium alone. Muscle weight and histology were also significantly improved in these groups. CONCLUSION: Cell injections may reduce muscle atrophy and could benefit nerve injury patients.

Effects of epidural analgesia on pelvic floor function after spontaneous delivery : a longitudinal retrospective study

Abstract: The aim of the study was to assess the effects of epidural analgesia on pelvic floor function. Eighty- two primiparous women (group 1, consisting of 41 given an epidural, and group 2 of 41 not given an epidural) were investigated during pregnancy and at 2 and 10 months after delivery by a questionnaire, clinical examination, and assessment of bladder neck behavior, urethral sphincter function and intravaginal/intra-anal pressures. The prevalence of stress urinary incontinence was similar in both groups at 2 months (24% vs. 17%, P = 0.6) and 10 months (22% vs. 7%, P = 0.1), as was the prevalence of decreased sexual vaginal response at 10 months (27% vs. 10%, P= 0.08). Bladder neck behavior, urethral sphincter function and intravaginal and intra-anal pressures showed no significant differences between the two groups. Ten months after spontaneous delivery, there were no significant differences in the prevalence of stress urinary incontinence and decreased sexual vaginal response, or in bladder neck behavior, urethral sphincter function and pelvic floor muscle strength between women who had or had not had epidural analgesia.

Effects of the transition time between muscle-tendon stretch and shortening on mechanical efficiency.

The net mechanical efficiency of positive work (eta(pos)) has been shown to increase if it is immediately preceded by negative work. This phenomenon is explained by the storage of elastic energy during the negative phase and its release during the subsequent positive phase. If a transition time (T) takes place, the elastic energy is dissipated into heat. The aim of the present study was to investigate the relationship between eta(pos) and T, and to determine the minimal T required so that eta(pos) reached its minimal value. Seven healthy male subjects were tested during four series of lowering-raising of the body mass. In the first series (S (0)), the negative and positive phases were executed without any transition time. In the three other series, T was varied by a timer (0.12, 0.24 and 0.56 s for series S (1), S (2) and S (3), respectively). These exercises were performed on a force platform sensitive to vertical forces to measure the mechanical work and a gas analyser was used to determine the energy expenditure. The results indicated that eta(pos) was the highest (31.1%) for the series without any transition time (S (0)). The efficiencies observed with transition times (S (1), S (2) and S (3)) were 27.7, 26.0 and 23.8%, respectively, demonstrating that T plays an important role for mechanical efficiency. The investigation of the relationship between eta(pos) and T revealed that the minimal T required so that eta(pos) reached its minimal value is 0.59 s.

Role of Na+-K+-ATPase in insulin-induced lactate release by skeletal muscle.

Hyperinsulinemia increases lactate release by various organs and tissues. Whereas it has been shown that aerobic glycolysis is linked to Na+-K+-ATPase activity, we hypothesized that stimulation by insulin of skeletal muscle Na+-K+-ATPase is responsible for increased muscle lactate production. To test this hypothesis, we assessed muscle lactate release in healthy volunteers from the [13C]lactate concentration in the effluent dialysates of microdialysis probes inserted into the tibialis anterior muscles on both sides and infused with solutions containing 5 mmol/l [U-13C]glucose. On one side, the microdialysis probe was intermittently infused with the same solution additioned with 2.10(-5) M ouabain. In the basal state, [13C]lactate concentration in the dialysate was not affected by ouabain. During a euglycemic-hyperinsulinemic clamp, [13C]lactate concentration increased by 135% in the dialysate without ouabain, and this stimulation was nearly entirely reversed by ouabain (56% inhibition compared with values in the dialysate collected from the contralateral probe). These data indicate that insulin stimulates muscle lactate release by activating Na+-K+-ATPase in healthy humans.