Repeated botulinum toxin A injections in the treatment of spastic equinus foot.

Equinus foot disorder is a common problem for patients with cerebral palsy who are able to ambulate. Botulinum toxin A is a recommended method of treatment for temporary reduction of muscle tone. The efficacy of repeated botulinum toxin A injections in the calf muscles was evaluated in a clinical trial involving 21 children with cerebral palsy and dynamic equinus foot deformity who were able to ambulate. The mean age of the children was 5.7 years. All patients received at least two injections, six patients received at least three injections, and three patients received four injections. The outcome was evaluated using observational and three-dimensional instrumented gait analysis. Significant improvements of the gait parameters were observed at 6 and 18 weeks after the first and second injections. Botulinum toxin A injections in gastrocnemius and soleus muscles may change the natural history of equinus foot deformity in patients with spastic diplegia. Orthopaedic surgery may be postponed or avoided.     

Diagnostic steps in the evaluation of patients with erectile dysfunction

PURPOSE: The necessity for a thorough diagnostic evaluation for erectile dysfunction has been questioned after the availability of effective oral therapies. We determined the impact of the different diagnostic steps on the management strategy for erectile dysfunction. MATERIALS AND METHODS: The study included all patients who presented at an andrology outpatient clinic during a 4-year period. Baseline evaluation included medical and sexual history, blood tests, physical examination and intracavernous injection test. Patients with normal initial screening were evaluated with specific diagnostic procedures. The results were analyzed to identify the diagnostic potential of each screening step separately. RESULTS: Overall 1,644 patients presented at the clinic during the study period, of whom 368 (22.4%) were excluded from study due to severe psychiatric (5.2%) or cardiovascular (2.7%) disease, or to a history of erectile dysfunction less than 3 months in duration (14.5%). In the remaining 1,276 patients with a mean age plus or minus standard deviation of 56 +/- 14 years, and a mean duration of erectile dysfunction of 4.9 +/- 3.4 years medical history revealed erectile dysfunction associated medical conditions in 57%, blood tests identified previously undiagnosed medical conditions in 6.2%, and physical examination and the intracavernous injection test were diagnostic in 13.9% and 2.6%, respectively. Initial screening was negative in 259 cases (20.3%), in which specific diagnostic procedures identified an underlying vascular pathology in 165 (12.9%) and unfavorable penile geometry in 16 (1.3%). The remaining 78 men (6.1%) had no evidence of organic disease. CONCLUSIONS: Baseline diagnostic evaluation for erectile dysfunction can identify the underlying pathological condition or erectile dysfunction associated risk factors in 80% of patients. Such screening may diagnose reversible causes of erectile dysfunction and also unmask medical conditions that manifest with erectile dysfunction as the first symptom. Specific diagnostic procedures may be limited in patients with primary erectile dysfunction or those without risk factors. Such clinical data support previously published guidelines for erectile dysfunction management.     

Intraluminal Intestinal Administration of Oxygenated Perfluorocarbon Improves Acid–Base and Cardiopulmonary Parameters After Acute Mesenteric Ischemia. An Experimental Study in Rabbits

Purpose The aim of this study was to evaluate the effects of the intraluminal intestinal administration of oxygenated perfluorocarbon, during experimental acute intestinal ischemia, on the acid–base blood status and the cardiopulmonary parameters. Methods Thirty-six rabbits were separated into three groups: (a) Control group (ischemia alone), (b) PFC-O₂ group (ischemia plus infusion of oxygenated F-Decalin in intraluminal intestinal administration), and (c) PFC group (ischemia plus infusion of nonoxygenated F-Decalin in intraluminal intestinal administration). An equal number of the animals was then subjected to 8 h of intestinal ischemia by ligation of the superior mesenteric artery (subgroups 1), the mesenteric vein (subgroups 2) or both vessels (subgroups 3). At 0, 2, 4, 6, and 8 h arterial blood samples were taken for acid–base status tests and the vital signs (heart and respiratory rate, pressure of inferior vena cava, and systolic arterial pressure) were noted. The statistical analysis was performed by the nonparametric Kruskal–Wallis test. Results There were no significant differences in any of the studied parameters (pH, base excess, respiratory gases, pressure of inferior vena cava, systolic arterial pressure, heart and respiratory rate) between animals of the same group and subgroup. In addition, the differences among Control and PFC groups and their equal subgroups were not significant. On the other hand, the measurements of the PFC-O₂ animals showed significant differences at 4, 6, and 8 h of ischemia (P < 0.05) in comparison with those from the Control and PFC groups. Conclusion We conclude that the intraluminal intestinal administration of oxygenated perfluorocarbons may thus be a useful adjunctive therapy in the treatment of patients with acute mesenteric ischemia.     

Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use.

OBJECTIVE: Levosimendan is a promising new inotrope. We investigate the proper time for its infusion during or after open-heart surgery to avoid complications related with low-output syndrome and high dosage of inotropes. METHODS: Forty-five consecutive patients were randomised to receive levosimendan in addition to the conventional therapy, its infusion starting in the operating theatre (Group OT) or in the ICU (Group ICU) when low-output syndrome was certified and were consequently dependent on classical inotropic support and IABP. Levosimendan was infused at a rate of 0.1 microg/kg min without loading dose, the infusion being for at least 24h to a maximum 48 h. RESULTS: Levosimendan was well tolerated, with the simultaneous infusion of norepinephrine if required. Its efficacy was identical in both groups with improvement in the haemodynamic and functional status of patients (amelioration of stroke volume, cardiac index and mixed venous blood oxygen saturation, increase of left ventricular ejection fraction by echo study, de-escalation of traditional inotropes, subtraction of IABP and reduction in BNP plasma levels). The ICU stay and hospital stay were significantly decreased in patients of Group OT, compared to patients of Group ICU. Four patients died because of multiple organs dysfunction syndrome (MODS) due to sepsis (all patients of Group ICU). CONCLUSION: Levosimendan is a safe and efficient choice in the management of low-output syndrome during and after open-heart surgery. The shortening of hospitalisation and the trend for better outcome confirm its clear superiority when the infusion starts from the operating theatre.     

Limited feedback and video tutorials optimize learning and resource utilization during laparoscopic simulator training

BACKGROUND: The purpose of this study was to determine the impact of instructor feedback and video tutorials on skill acquisition during proficiency-based laparoscopic suturing training. METHODS: Performance data from a prospectively maintained database were reviewed for three groups of novices (n = 34 medical students) who completed the same proficiency-based laparoscopic suturing curriculum on a Fundamentals of Laparoscopic Surgery-type videotrainer model as part of two separate institutional review board-approved, randomized controlled trials. Group I (n = 9) watched the video tutorial once and received intense feedback during each training session; Group II (n = 13) watched the video tutorial once and received limited feedback (<10 min per session); Group III (n = 12) watched the video tutorial several times and also received limited feedback (<10 min per session). Feedback was given by the same instructor and was quantified on a 0 (none) to 4 (extensive) Likert scale. RESULTS: Baseline characteristics were similar for all groups. All participants achieved the proficiency level (512) on two consecutive attempts. Group III required the shortest training time and number of repetitions to reach proficiency, with statistically significant differences compared with Group I (P < 0.02). This strategy led to a cost savings of $139 per trainee. CONCLUSIONS: Limited instructor feedback appears to be superior to intense feedback during proficiency-based laparoscopic simulator training. Coupled with video tutorials, this type of feedback may accelerate learning and improve resource utilization by minimizing the need for instructor involvement.     

Application of self-expandable metal stents for ureteroileal anastomotic strictures: long-term results

PURPOSE: We report our long-term experience with the management of benign ureteroileal anastomotic strictures using self-expandable metal stents. MATERIALS AND METHODS: A total of 16 male and 2 female patients with a mean+/-SD age of 72+/-7 years (range 66 to 78) with benign fibrotic strictures at the site of ureteroileal anastomosis underwent implantation of self-expandable metal stents with a nominal diameter of 6 to 8 mm. A total of 24 ureteroileal conduits were treated. The external nephrostomy tubes were removed after fluoroscopic validation of ureteral patency. Patients were followed with blood biochemistry, ultrasonography, urography and/or virtual endoscopy. Retrograde external-internal catheter insertion through the cutaneous stoma was performed in cases of recalcitrant stricture. RESULTS: The technical success rate of ureteroileal stricture crossing and stenting was 100% (24 of 24 cases). Mean followup was 21 months (range 7 to 50). The clinical success rate during the immediate post-stenting period was 70.8% (17 of 24 cases). The 1 and 4-year primary patency rates were 37.8% and 22.7%, respectively. Secondary interventions included repeat balloon dilation in 15 ureters, of which 8 also underwent subsequent coaxial stent placement. The 1 and 4-year secondary patency rates were 64.8% and 56.7%, respectively. Except in 2 patients who died external-internal Double-J catheters continued to be inserted retrograde in 6 ureteroileal conduits. They are periodically exchanged to prevent mucous inspissation and stent encrustation. CONCLUSIONS: Metal stents served as the definitive treatment for stricture in more than half of the cases, whereas in the remainder the stents allowed the uncomplicated and regular exchange of Double-J catheters in retrograde fashion. This combined, less invasive treatment for ureteroileal anastomotic strictures may help patients avoid surgical revision and preserve quality of life.     

Endothelial nitric oxide synthase uncoupling impairs endothelial progenitor cell mobilization and function in diabetes

Uncoupling of the endothelial nitric oxide synthase (eNOS) resulting in superoxide anion (O(2)(-)) formation instead of nitric oxide (NO) causes diabetic endothelial dysfunction. eNOS regulates mobilization and function of endothelial progenitor cells (EPCs), key regulators of vascular repair. We postulate a role of eNOS uncoupling for reduced number and function of EPC in diabetes. EPC levels in diabetic patients were significantly reduced compared with those of control subjects. EPCs from diabetic patients produced excessive O(2)(-) and showed impaired migratory capacity compared with nondiabetic control subjects. NOS inhibition with N(G)-nitro-l-arginine attenuated O(2)(-) production and normalized functional capacity of EPCs from diabetic patients. Glucose-mediated EPC dysfunction was protein kinase C dependent, associated with reduced intracellular BH(4) (tetrahydrobiopterin) concentrations, and reversible after exogenous BH(4) treatment. Activation of NADPH oxidases played an additional but minor role in glucose-mediated EPC dysfunction. In rats with streptozotocin-induced diabetes, circulating EPCs were reduced to 39 +/- 5% of controls and associated with uncoupled eNOS in bone marrow. Our results identify uncoupling of eNOS in diabetic bone marrow, glucose-treated EPCs, and EPCs from diabetic patients resulting in eNOS-mediated O(2)(-) production. Subsequent reduction of EPC levels and impairment of EPC function likely contributes to the pathogenesis of vascular disease in diabetes.     

Pediatric scaphoid nonunion

PURPOSE: To report the outcome of pediatric scaphoid nonunions treated with a Herbert screw and bone graft. METHODS: This is a retrospective review of 12 cases of scaphoid nonunion in 12 skeletally immature patients treated with a uniform approach consisting of open reduction, iliac crest bone grafting and Herbert screw fixation. All patients were boys and presented with nonunions of the scaphoid waist. The final follow-up evaluation was at a mean of 32 months, ranging from 22 to 45 months, and consisted of assessing anatomic snuffbox tenderness, wrist arc of motion, grip strength, calculation of the Modified Mayo Wrist score, and assessment of union based on plain radiographs. RESULTS: At the latest follow-up evaluation, all patients were pain free (including absence of snuffbox tenderness) except one who experienced slight discomfort during extreme activities. There was no statistically significant difference in the arc of motion between the surgically treated and healthy sides, and the average grip strength was 96% that of the contralateral extremity. Clinical and radiographic union was present in all cases at a mean of 3.4 months after surgery. The Modified Mayo Wrist score was excellent in 11 patients and good in 1. There were no complications. CONCLUSIONS: Open reduction and internal fixation with a Herbert screw reliably obtained union in all patients. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.     

Inhaled iloprost controls pulmonary hypertension after cardiopulmonary bypass

PURPOSE: Severe pulmonary hypertension (PH) is a major cause of right ventricular (RV) dysfunction. Various iv vasodilator modalities have been used with limited results because of lack of pulmonary selectivity. The aim of the present controlled study was to evaluate the efficacy of inhaled iloprost, a synthetic prostacyclin analogue, in patients with elevated pulmonary vascular resistance (PVR) immediately after separation from cardiopulmonary bypass (CPB). METHODS: Twelve patients with persistent PH after discontinuation of CPB were included in the study. In all patients standard hemodynamic monitoring was used. Inhaled iloprost was administered via nebulized aerosol at a cumulative dose of 0.2 micro g*kg(-1) for a total duration of 20 min. Complete sets of hemodynamic measurements were performed before inhalation (baseline), during and after cessation of the inhalation period. Echocardiographic monitoring of RV function was also used. RESULTS: Inhaled iloprost induced a reduction in the transpulmonary gradient at the end of the inhalation period in comparison to baseline (9.33 +/- 3.83 mmHg vs 17.09 +/- 6.41 mmHg, P < 0.05). The mean pulmonary artery pressure to systemic artery pressure ratio decreased over this period (0.28 +/- 0.08 vs 0.45 +/- 0.17, P < 0.05). A statistically significant decrease of the PVR to systemic vascular resistance ratio was also observed (0.15 +/- 0.05 vs 0.21 +/- 0.05, P < 0.05). Improved indices of RV function were observed in echocardiographic monitoring. CONCLUSION: Inhaled iloprost appears to be a selective pulmonary vasodilator and may be effective in the initial treatment of PH and the improvement of RV performance in the perioperative setting.     

Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.

BACKGROUND: Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1). METHODS: Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion. RESULTS: The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated. CONCLUSIONS: The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.