Detrusor overactivity is associated with downregulation of large-conductance calcium- and voltage-activated potassium channel protein

Chang S, Gomes CM, Hypolite JA, Marx J, Alanzi J, Zderic SA, Malkowicz B, Wein AJ, Chacko S. Detrusor overactivity is associated with downregulation of large-conductance calcium-and voltage-activated potassium channel protein. Am J Physiol Renal Physiol 298: F1416-F1423, 2010. First published April 14, 2010; doi: 10.1152/ajprenal.00595.2009.-Large-conductance voltage-and calcium-activated potassium (BK) channels have been shown to play a role in detrusor overactivity (DO). The goal of this study was to determine whether bladder outlet obstructioninduced DO is associated with downregulation of BK channels and whether BK channels affect myosin light chain 20 (MLC(20)) phosphorylation in detrusor smooth muscle (DSM). Partial bladder outlet obstruction (PBOO) was surgically induced in male New Zealand White rabbits. The rabbit PBOO model shows decreased voided volumes and increased voiding frequency. DSM from PBOO rabbits also show enhanced spontaneous contractions compared with control. Both BK channel alpha- and beta-subunits were significantly decreased in DSM from PBOO rabbits. Immunostaining shows BK beta mainly expressed in DSM, and its expression is much less in PBOO DSM compared with control DSM. Furthermore, a translational study was performed to see whether the finding discovered in the animal model can be translated to human patients. The urodynamic study demonstrates several overactive DSM contractions during the urine-filling stage in benign prostatic hyperplasia (BPH) patients with DO, while DSM is very quiet in BPH patients without DO. DSM biopsies revealed significantly less BK channel expression at both mRNA and protein levels. The degree of downregulation of the BK beta-subunit was greater than that of the BK alpha-subunit, and the downregulation of BK was only associated with DO, not BPH. Finally, the small interference (si) RNA-mediated downregulation of the BK beta-subunit was employed to study the effect of BK depletion on MLC(20) phosphorylation. siRNA-mediated BK channel reduction was associated with an increased MLC(20) phosphorylation level in cultured DSM cells. In summary, PBOO-induced DO is associated with downregulation of BK channel expression in the rabbit model, and this finding can be translated to human BPH patients with DO. Furthermore, downregulation of the BK channel may contribute to DO by increasing the basal level of MLC(20) phosphorylation.

High Penetrance of Pheochromocytoma Associated with the Novel C634Y/Y791F Double Germline Mutation in the RET Protooncogene

Context: Previous studies have shown that double RET mutations may be associated with unusual multiple endocrine neoplasia type 2 (MEN 2) phenotypes. Objective: Our objective was to report the clinical features of patients harboring a previously unreported double mutation of the RET gene and to characterize this mutation in vitro. Patients: Sixteen patients from four unrelated families and harboring the C634Y/Y791F double RET germline mutation were included in the study. Results: Large pheochromocytomas measuring 6.0-14 cm and weighing upto 640 g were identified in the four index cases. Three of the four tumors were bilateral. High penetrance of pheochromocytoma was also seen in the C634Y/Y791F-mutation-positive relatives (seven of nine, 77.7%). Of these, two cases had bilateral tumors, one presented with multifocal tumors, two cases had large tumors (>5 cm), and one case, which was diagnosed with a large (5.5 x 4.5 x 4.0 cm) pheochromocytoma, reported early onset of symptoms of the disease (14 yr old). The overall penetrance of pheochromocytoma was 84.6% (11 of 13). Development of medullary thyroid carcinoma in our patients seemed similar to that observed in patients with codon 634 mutations. Haplotype analysis demonstrated that the mutation did not arise from a common ancestor. In vitro studies showed the double C634Y/Y791F RET receptor was significantly more phosphorylated than either activated wild-type receptor or single C634Y and Y791F RET mutants. Conclusions: Our data suggest that the natural history of the novel C634Y/Y791F double mutation carries a codon 634-like pattern of medullary thyroid carcinoma development, is associated with increased susceptibility to unusually large bilateral pheochromocytomas, and is likely more biologically active than each individual mutation. (J Clin Endocrinol Metab 95: 1318-1327, 2010)

Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT = 6 ml/kg and positive end-expiratory pressure (PEEP) = 5 cmH(2)O for 1 h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40 s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP = 40 cmH(2)O), with interposed periods of PIP = 10 cmH(2)O above a PEEP = 15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury. (C) 2009 Elsevier BLV. All rights reserved.

PHRENIC NERVE TRANSFER IN THE RESTORATION OF ELBOW FLEXION IN BRACHIAL PLEXUS AVULSION INJURIES: HOW EFFECTIVE AND SAFE IS IT?

OBJECTIVE: Phrenic nerve transfer has been used for treating lesions of the brachial plexus since 1970. Although, today, surgeons are more experienced with the technique, there are still widespread concerns about its effects on pulmonary function. This study was undertaken to evaluate the effectiveness and safety of this procedure. METHODS: Fourteen patients with complete palsy of the upper limb were submitted to phrenic nerve transfer as part of a strategy for surgical reconstruction of their plexuses. Two patients were lost to follow-up, and 2 patients were followed for less than 2 years. Of the remaining 10 patients, 9 (90%) were male. The lesions affected both sides equally. The mean age of the patients was 24.8 years (range, 14-43 years), and the mean interval from injury to surgery was 6 months (range, 3-9 months). The phrenic nerve was always transferred to the musculocutaneous nerve, and a nerve graft (mean length, 8 cm; range, 4.5-12 cm) was necessary in all cases. RESULTS: There was no major complication related to the surgery. Seven patients (70%) recovered functional level biceps strength (Medical Research Council grade >= 3). All of the patients exhibited a transient decrease in pulmonary function tests, but without clinical respiratory problems. CONCLUSION: On the basis of our small series and data from the literature, we conclude that phrenic nerve transfer in well-selected patients is a safe and effective procedure for recovering biceps function.

CLINICAL TUMOR DIMENSIONS MAY BE USEFUL TO PREVENT GEOGRAPHIC MISS IN CONVENTIONAL RADIOTHERAPY OF UTERINE CERVIX CANCER-A MAGNETIC RESONANCE IMAGING-BASED STUDY

Purpose: To evaluate the risk of geographic miss associated with the classic four-field ""box"" irradiation technique and to define the variables that predict this risk. Materials and Methods: The study population consisted of 80 patients with uterine cervix cancer seen between 2001 and 2006. Median age was 55 years (23-82 years), and 72 (90%) presented with squamous cell carcinoma. Most patients (68.7%) presented with locally advanced disease (IIb or more). Magnetic resonance imaging findings from before treatment were compared with findings from simulation of the conventional four-field ""box"" technique done with rectal contrast. Study variables included tumor volume; involvement of vagina, parametrium, bladder, or rectum; posterior displacement of the anterior rectal wall; and tumor anteroposterior diameter (APD). Margins were considered adequate when the target volume (primary tumor extension, whole uterine body, and parametrium) was included within the field limits and were at least 1 cm in width. Results: Field limits were inadequate in 45 (56%) patients: 29 (36%) patients at the anterior and 28 (35%) at the posterior border of the lateral fields. Of these, 12 patients had both anterior and posterior miss, and this risk was observed in all stages of the disease (p = 0.076). Posterior displacement of the anterior rectal wall beyond S2-S3 was significantly correlated with the risk of geographic miss (p = 0.043). Larger tumors (APD 6 cm or above and volume above 50 cm(3)) were also significantly correlated with this risk (p = 0.004 and p = 0.046, respectively). Conclusions: Posterior displacement of the anterior rectal wall, tumor APD, and volume can be used as guidance in evaluating the risk of geographic miss. (C) 2009 Elsevier Inc.

Left Atrial Function After Ablation for Paroxysmal Atrial Fibrillation

Radiofirequency ablation of the pulmonary veins has been used to treat patients with paroxysmal atrial fibrillation (AF), and atrial damage after ablation is an issue of concern. To evaluate left atrial function shortly and midterm after ablation, 33 consecutive patients with paroxysmal AF were studied at baseline, 24 hours, and >= 6 months after ablation. Patients in sinus rhythm with normal ventricular function were included in the study. Echocardiographic measurements of left atrial volumes (Simpson`s rule) and transmitral and tissue Doppler myocardial (A`) velocities at the septal and lateral mitral annulus were undertaken at each time. Left atrial emptying fraction (EF; maximal - minimal left atrial volume/maximal left atrial volume) was used to express left atrial function. After 8 +/- 2 months, 30 of 33 patients returned (23 men, age 53 +/- 13 years), and all except 2 were in sinus rhythm. Shortly after ablation, left atrial minimal volumes increased (from 30 +/- 15 to 35 +/- 15 ml; p = 0.02), with maximal volumes unchanged, resulting in decreased left atrial EF (from 47 +/- 8 to 40 +/- 7 ml; p <0.05). Tissue Doppler septal A` velocities also decreased (from 8.2 +/- 1.8 to 6.9 +/- 2.0 cm/s; p <0.05). However, after midterm follow-up, both left atrial EF and septal A` velocities had slightly increased compared with shortly after ablation, although left atrial volumes remained similar to baseline. Septal A` velocity changes paralleled left atrial EF both shortly (r = 0.46, p = 0.02) and at midterm after ablation (r = 0.47, p = 0.01). In conclusion, after radiofrequency ablation, patients with paroxysmal AF experienced an initial impairment in atrial function, with improvement at longer term follow-up. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;103: 395-398)

Laparoscopic treatment of metabolic syndrome in patients with type 2 diabetes mellitus

Background Metabolic syndrome refers to risk factors for cardiovascular disease. Hyperglycemia is a critical component contributing to the predictive power of the syndrome. This study aimed to evaluate the results from the laparoscopic interposition of an ileum segment into the proximal jejunum for the treatment of metabolic syndrome in patients with type 2 diabetes mellitus and a body mass index (BMI) lower than 35. Methods Laparoscopic procedures were performed for 60 patients (24 women and 36 men) with a mean age of 51.7 +/- 6.4 years (range, 27-66 years) and a mean BMI of 30.1 +/- 2.7 (range, 23.6-34.4). All the patients had a diagnosis of type 2 diabetes mellitus (T2DM) given at least 3 years previously and evidence of stable treatment using oral hypoglycemic agents, insulin, or both for at least 12 months. The mean duration of type 2 diabetes mellitus was 9.6 +/- 4.6 years (range, 3-22 years). Metabolic syndrome was diagnosed for all 60 patients. Arterial hypertension was diagnosed for 70% of the patients (mean number of drugs, 1.6) and hypertriglyceridemia for 70%. High-density lipoprotein was altered in 51.7% of the patients and the abdominal circumference in 68.3%. Two techniques were performed: ileal interposition (II) into the proximal jejunum and sleeve gastrectomy (II-SG) or ileal interposition associated with a diverted sleeve gastrectomy (II-DSG). Results The II-SG procedure was performed for 32 patients and the II-DSG procedure for 28 patients. The mean postoperative follow-up period was 7.4 months (range, 3-19 months). The mean BMI was 23.8 +/- 4.1 kg/m(2), and 52 patients (86.7%) achieved adequate glycemic control. Hypertriglyceridemia was normalized for 81.7% of the patients. An high-density lipoprotein level higher than 40 for the men and higher than 50 for the women was achieved by 90.3% of the patients. The abdominal circumference reached was less than 102 cm for the men and 88 cm for the women. Arterial hypertension was controlled in 90.5% of the patients. For the control of metabolic syndrome, II-DSG was the more effective procedure. Conclusions Laparoscopic II-SG and II-DSG seem to be promising procedures for the control of the metabolic syndrome and type 2 diabetes mellitus. A longer follow-up period is needed.

Synchronous adenocarcinoma of the major and minor duodenal papilla

A 50-year-old woman presented with pancreatitis, fluctuant jaundice, weight loss, and abdominal pain. Contrast-enhanced computed tomography and abdominal ultrasound showed slight dilatation of the biliary tree and gallbladder without calculi. Endoscopy demonstrated a tumor protruding from the papilla of Vater. First endoscopically biopsy diagnosed no tumor, and a second biopsy diagnosed as papillary adenocarcinoma. The patient underwent duodenopancreatectomy. The specimen was fixed in formalin (10%). The tissue was processed routinely, and paraffin sections were stained with hematoxylin-eosin and periodic acid Schiff. Gross examination showed two tumors seen as prolapsed nodules growing isolated from the minor and major duodenal papillae measuring 1.5 and 1.0 cm, respectively, both covered by duodenal mucosa and the histologic study of both lesions demonstrated a moderately differentiated tubular adenocarcinoma, which invaded duodenal wall. After surgery, she is alive 24 months without evidence of recurrence.

Influence of gender on the clinical and laboratory spectra of patients with primary antiphospholipid syndrome

The objectives of this cross-sectional study were to evaluate the differences between males and females in the clinical and biochemical manifestations of primary antiphospholipid antibody syndrome (PAPS). The method involved 49 patients (38 premenopausal females and 11 males) diagnosed with PAPS (according to the Sapporo criteria) and their demographic data, clinical data, medications used and antiphospholipid antibodies were analyzed. The results of this study are as follows. Both the groups of patients were statistically similar regarding age, race, weight and body mass index. However, males were significantly taller than females (172 +/- A 8.9 vs. 159.2 +/- A 6.2 cm, p < 0.0001). The duration of disease was similar for females and males. The prevalence of pulmonary thromboembolism was higher in females than in males (34.2 vs. 0.0%, p = 0.024). Regarding other PAPS manifestations (arterial events, venous events, deep venous thrombosis, thrombocytopenia, acute myocardial infarction, angina, cerebrovascular accidents and Sneddon syndrome), comorbidities (arterial hypertension and dyslipidemia), lifestyle (physical activity, previous smoking and current smoking) and the use of medications (current and previous use of corticosteroids, as well as the use of statins or chloroquine), both groups were statistically similar (p > 0.05). More females than males tested positive for IgM anticardiolipin antibodies (76.3 vs. 36.4%, p = 0.025) or for at least one of the antiphospholipid antibodies tested (either IgM anticardiolipin or IgG anticardiolipin 84.2 vs. 45.5%, p = 0.016). However, both groups were similar regarding the frequency of positivity for lupus anticoagulant and isolated IgG anticardiolipin, as well as regarding mean levels of IgG and IgM anticardiolipin (p > 0.05). We concluded that, among PAPS patients, the frequency of pulmonary thromboembolism and of positivity for IgM anticardiolipin is higher in females than in males. Our findings show that there are gender differences in PAPS, differences that might be related to alterations in sex hormones.

Trigonal injection of botulinum toxin-A does not cause vesicoureteral reflux in neurogenic patients

Aims: We evaluated the effect of botulinum toxin type A (BTX-A) injections in the trigone on the antireflux mechanism and evaluated its short-term efficacy. Materials and Methods: Between April and December 2006, 21 patients (10 men and 11 women) were prospectively evaluated. All were incontinent due to refractory NDO and underwent detrusor injection of 300 units of BTX-A, including 50 units into the trigone. Baseline and postoperative evaluation after eight weeks included cystogram, urinary tract ultrasound and urodynamics. Results: At baseline, 20 patients had no vesicoureteral (VUR) and one had grade II unilateral VUR. Postoperative evaluation revealed no cases of de novo VUR and the patient with preinjection VUR had complete resolution of the reflux. Ultrasound showed 5 (23.8%) patients with hydronephrosis before BTX-A injection and only one (4.8%) at the followup evaluation (p=0.066). After treatment, 9 (42.8%) patients became dry, 11 (52.4%) were improved and one (4.8%) had no improvement. Improved patients received antimuscarinic treatment and 8 (38.1%) became dry, with a final total continence rate of 80.1%. Cystometric capacity increased from 271 +/- 92 to 390 +/- 1189 ml (p = 0.002), reflex volume varied from 241 +/- 96 to 323 +/- 201 ml (p = 0.020) and maximum detrusor pressure reduced from 66 +/- 39 to 38 +/- 37 cm H2O (p < 0.001). Conclusions: Our results confirm the safety of trigone injections of BTX-A in terms of development of VUR and upper urinary tract damage. Whether they are beneficial for patients with NDO or other causes of voiding dysfunction will need further studies.

Comparison of reading performance after bilateral implantation of multifocal intraocular lenses with+3.00 or+4.00 diopter addition

PURPOSE To compare reading ability after cataract surgery and bilateral implantation of multifocal intraocular lenses (IOLs) with a +3 00 diopter (D) addition (add) or a +4 00 D add SETTING Department of Ophthalmology, University of Sao Paulo, Sao Paulo, Brazil DESIGN Prospective comparative study METHODS Patients scheduled for cataract surgery were randomly assigned to bilateral implantation of an aspheric AcrySof ReSTOR multifocal IOL with a +3 00 diopter (D) addition (add) or a +4 00 D add The reading speed, critical print size, and reading acuity were measured binocularly with best correction using MNREAD acuity charts 6 months after surgery Patients were tested with the chart at the best patient-preferred reading distance and at 40 cm Binocular uncorrected and best distance-corrected visual acuities at far and near were also measured RESULTS The study enrolled 32 patients At the best reading distance the results were similar between the 2 IOL groups in all reading parameters When tested at 40 cm, reading speed at all print sizes from 03 to 00 (all P< 001), critical print size (P< 001) and reading acuity (P = 014) were statistically significantly better in the +3 00 D IOL group than in the +4 00 DIOL group Uncorrected and corrected visual acuities at far and near were similar between the 2 groups CONCLUSION Although the 2 IOL groups had similar performance in reading parameters, patients had to adjust to their best reading distance The +3 00 D IOL performed better than the +4 00 D IOL at 40 cm

Repetitive Transcranial Magnetic Stimulation Is Efficacious as an Add-On to Pharmacological Therapy in Complex Regional Pain Syndrome (CRPS) Type I

Single session repetitive transcranial magnetic stimulation (rTMS) of the motor cortex (M1) is effective in the treatment of chronic pain patients but the analgesic effect of repeated sessions is still unknown We evaluated the effects of rTMS in patients with refractory pain due to complex regional pain syndrome (CRPS) type I Twenty three patients presenting CRPS type I of 1 upper limb were treated with the best medical treatment (analgesics and adjuvant medications physical therapy) plus 10 daily sessions of either real (r) or sham (s) 10Hz rTMS to the motor cortex (M1) Patients were assessed daily and after 1 week and 3 months after the last session using the Visual Analogical Scale (VAS) the McGill Pain Questionnaire (MPQ) the Health Survey 36 (SF 36) and the Hamilton Depression (HDRS) During treatment there was a significant reduction in the VAS scores favoring the r rTMS group mean reduction of 4 65 cm (50 9%) against 2 18 cm (24 7%) in the s rTMS group The highest reduction occurred at the tenth session and correlated to improvement in the affective and emotional subscores of the MPQ and SF 36 Real rTMS to the M1 produced analgesic effects and positive changes in affective aspects of pain in CRPS patients during the period of stimulation Perspective This study shows an efficacy of repetitive sessions of high frequency rTMS as an add on therapy to refractory CAPS type I patients It had a positive effect in different aspects of pain (sensory discriminative and emotional affective) It opens the perspective for the clinical use of this technique (C) 2010 by the American Pain Society

Thin superior medial pedicle reduction mammaplasty for severe mammary hypertrophy

Background There are multitudes of procedures in plastic surgery used to correct hypertrophic and pendulous breasts in patients with heavy and ptotic breasts who need great resections of breast tissue, where the suprasternal notch-to-nipple distance is long and the use of nipple-areola transposition techniques is a challenge for the plastic surgeon. The purpose of this study is to present a technique of reduction mammaplasty that could solve these problems based on the following principles: mammary reduction utilizing a thin superior medial pedicle (0.8-1.5 cm thick) and the resection performed in two steps: (1) the base excess at a plane perpendicular to the breast (this determines the cone`s height) and (2) central half keel (this determines the breast diameter reduction). Methods Ninety patients with mammary hypertrophy were operated on at the ""Hospital das Clinicas,"" Sao Paulo University Medical School, between January 2000 and November 2005. Inclusion in this study required a minimum of 12-cm change in nipple position and a 750-g breast resection. Results The mean change in nipple position was 16 cm (range = 12-21 cm). The mean weight of each breast was 1400 (range = 750-3000 g).Considering the great amount of volume removed and the size of the operated breasts, few complications were observed and were similar to those reported following other techniques described in the literature. Patient satisfaction following this procedure was high. Conclusion The results of this study clearly demonstrate that thin superior medial pedicle reduction mammaplasty is a safe and reliable technique in cases of severe mammary hypertrophy.

Relationship between the appearance of tongue carcinoma on intraoral ultrasonography and neck metastasis

To evaluate the usefulness of intraoral ultrasonography (IOUS) as a tool for predicting neck metastasis. Squamous cell carcinoma (SCC) of the tongue is aggressive and has a great propensity to metastasize to cervical lymph nodes. SCC of the oral cavity has a worse prognosis when associated with metastatic cervical nodes. Therefore, the metastatic potential of tongue carcinoma should be graded preoperatively to help determine the requirement for neck dissection. Nineteen patients (11 men, 8 women) between 36 and 79 years of age (mean age 60) with T1 to T4a TNM-stage tongue carcinomas were evaluated preoperatively with IOUS. Clinical and pathological TNM classifications were performed. The average tumor thicknesses measured using histological sections were significantly (p < 0.01) lower than those with IOUS (1.3 vs. 1.6 cm, respectively). A significant correlation was observed between the tumor thickness measured using ultrasonography and that measured using histological sections (pathology). Based on this greater accuracy, the cutoff point of tumor thickness based on IOUS evaluation for predicting neck metastasis was determined to be 1.8 cm. Some factors may influence neck metastasis. A knowledge of these would help to avoid unnecessary surgical intervention for N0 patients. The results of this study indicates that there is a significant correlation between neck metastasis and tumor thickness. Intraoral ultrasonography is useful tool for identifying tongue tumors and measuring their thickness, with the thickness measured by IOUS showing a very good correlation with histological measurements. Moreover, IOUS provides prognostic information prior to surgical treatment since tumor thickness can predict the chance of recognizing metastatic cervical nodes.

Use of an Inflatable Silicone Balloon Improves the Success Rate of Bladder Autoaugmentation at Long-Term Followup

Purpose: Most groups have reported disappointing results with autoaugmentation or detrusor myectomy for low capacity/compliance neuropathic bladders. Failure may be due to an ischemic diverticulum or mucosal shrinkage. We investigated whether a Silimed (R) silicone balloon placed in the bladder after autoaugmentation could prevent these problems, improving surgical results. Materials and Methods: We compared the results of standard bladder autoaugmentation in 12 children (group 1) with those in 10 (group 2) who underwent the same surgery using a bladder conformer. The conformer was a silicone balloon filled with saline that remained in the bladder for 2 weeks. All patients had a neuropathic bladder with poor capacity and compliance, resulting in urinary leakage between catheterizations. Preoperative and postoperative evaluation included a voiding diary, ultrasound, voiding cystourethrogram and urodynamics. Results: In group 1 only 1 patient became dry, 4 had little improvement in continence, 4 remained unchanged and 3 became worse. In group 2, 6 patients (60%) become continent without medication, 2 (20%) become continent with oxybutynin and 2 remained unchanged. Bladder capacity and compliance did not change significantly in group 1. However, in group 2 capacity changed from a mean of 140 to 240 ml and mean +/- SD compliance increased from 15.6 +/- 16.8 to 34.3 +/- 22.8 ml/cm H(2)O (p = 0.02). Conclusions: The inflatable balloon improved our long-term results of bladder auto-augmentation. A larger series may be necessary to confirm procedure efficacy and safety.