Phosphodiesterase-5 gene (PDE5A) polymorphisms are associated with progression of childhood IgA nephropathy

The phosphodiesterase-5 (PDE-5) gene is highly specific to cyclic GMP (cGMP) and several experimental studies have shown that the nitric oxide/cGMP pathway plays an important role in the pathogenesis of glomerulonephritis, including IgA nephropathy (IgAN). The present study was conducted to investigate the association among 16 single nucleotide polymorphisms (SNPs) of PDE5A and childhood IgAN. The genotyping data from 160 patients with childhood IgAN and 454 controls showed a significant difference in rs13124532 (codominant, P = 0.005; dominant, P = 0.005). Furthermore, patient subgroup analysis revealed an association between the development of proteinuria (>4 and ≤4 mg/m²/h) and rs13124532 (codominant, P = 0.008; dominant, P = 0.011), and between the nephrotic range proteinuria (> 40 mg/m²/h) and rs11734241 (dominant, P = 0.035), rs12510138 (dominant, P = 0.028), rs13134665 (dominant, P = 0.025), rs3822192 (dominant, P = 0.027), rs10013305 (dominant, P = 0.020), rs1480940 (dominant, P = 0.020), rs1480936 (dominant, P = 0.019), rs11947234 (dominant, P = 0.019), and rs2127823 (dominant, P = 0.026). The pathological findings showed that rs13124532 had an association with podocyte foot process effacement (codominant, P = 0.035; dominant, P = 0.044) and with pathological progression (codominant, P = 0.046). Our results suggest that PDE5A is associated with increased disease susceptibility, pathological progression, and development of proteinuria in childhood IgAN.     

Current status of robotic colorectal surgery

To keep pace with the rapidly growing incidence of colorectal cancer, substantial progress has been made in colorectal cancer management in recent decades. Minimally invasive surgery is rapidly gaining acceptance for surgical management of colorectal cancer; however, laparoscopic colorectal surgery is technically demanding and has a steep learning curve. Although many colorectal surgeons have great expectations of the robotic surgical system to overcome the pitfalls of laparoscopic surgery, the application of robots in colorectal cancer surgery seems to be delayed when compared with other surgical fields. However, in recent years, there has been an increasing number of reports on robotic colorectal surgery and much attention is given to it in the colorectal community. Most of the interest has been in robotic total mesorectal excision for rectal cancer. In contrast, the use of robotics for colon resections does not confer significant advantages. We summarize the current evidence on clinical and oncologic outcomes of robotic colorectal surgery.     

In vivo effects of olanzapine on striatal dopamine D(2)/D(3) receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study.

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D(2)/D(3) receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [(123)I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [(123)I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrence of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [(123)I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D(2)/D(3) receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR-BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D(2)/D(3) receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D(2)/D(3) receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D(2)/D(3) availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D(2)/D(3) striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D(2)/D(3) receptor affinity and a similar 5HT(2) receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D(2)/D(3) receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D(2)/D(3) and 5HT(2) receptor antagonism.     

MR lymphangiography using ultrasmall superparamagnetic iron oxide in patients with primary abdominal and pelvic malignancies: radiographic-pathologic correlation

OBJECTIVE: The purpose of this study was to administer ultrasmall superparamagnetic iron oxide (USPIO) and compare changes in signal intensity of lymph nodes in patients with primary abdominal and pelvic malignancies. Also, we correlated radiographic with pathologic findings. SUBJECTS AND METHODS: Nineteen patients with proven primary abdominal or pelvic cancer (prostatic [n = 10]; colonic [n = 5]; endometrial [n = 1]; Merkel cell tumor [n = 1]; lymphoma [n = 1]; seminoma [n = 1]) were enrolled as part of our phase II and phase III clinical trials. In these patients, 49 lymph nodes (mean size, 1.4 cm) revealed on CT or MR imaging were evaluated on T1-weighted spin-echo, T2-weighted fast spin-echo, and T2*-weighted gradient-echo MR imaging at 1.5 T 24-36 hr after IV administration of USPIO. Quantitative analyses used measurements of unenhanced and enhanced region-of-interest values in lymph nodes. Qualitative assessment used subjective evaluation and classification of changes in signal intensity. All patients underwent lymph node biopsy or surgical dissection followed by histopathologic correlation. RESULTS: Of the 49 lymph nodes that were evaluated, 20 were benign and 29 were malignant. A decrease in nodal signal intensity on enhanced T2-weighted and T2*-weighted gradient-echo images was seen in 20 benign lymph nodes and two malignant lymph nodes. No appreciable signal change was noted in 27 of the 29 malignant lymph nodes. The mean signal intensity on fast spin-echo T2-weighted images for benign lymph nodes changed from 186.48 (unenhanced) to 73.66 (enhanced). Conversely, mean signal intensity for malignant lymph nodes was relatively unchanged from 191.17 (unenhanced) to 183.18 (enhanced). CONCLUSION: USPIO appears to be a useful MR contrast agent for characterizing benign and malignant lymph nodes based on the enhancement criteria evaluated in our study.     

Versagensgründe von Oberflächenersatzimplantaten der Hüfte

Hip resurfacing has been experiencing a revival over the last 5-10 years. Early failure rates are higher than for conventional primary hip arthroplasty. Fractures of the femoral neck or head, cup loosening and persistent pain are the most frequently observed reasons for early revision. In this international retrospective uncontrolled study, 256 revision specimens (219 resurfacing heads, 37 cups) were analysed radiologically, tribologically, morphologically and histologically in order to investigate the failure mechanism. Of the head revisions, 70% were due to neck (median: 67 days after implantation) and head fractures (161 days), 9% were due to cup loosening (350 days) and 21% due to other reasons (602 days). Implants with rim loading (22% of all retrievals, cup inclination 58.0+/-10.9 degrees ) exhibited a head wear rate of 7.1+/-5.2 mm3/year. Non-rim loaded implants exhibited a head wear rate of 0.24+/-0.53 mm3/year (cup inclination 49.0+/-4.0 degrees ). The failure rate was highest during the first 16 weeks after surgery and for the first ten operations performed by a surgeon. Revisions based on problems on the femoral side such as notching and high implantation forces occurred earlier than revisions based on problems on the acetabular side such as cup loosening and high wear due to suboptimal cup position.     

Volume kinetics of Ringer's solution during induction of spinal and general anaesthesia

The kinetics of an i.v. infusion of 20 ml kg^–1 of Ringer’ssolution over 60 min was studied in patients undergoing spinal(n=10) and general (n=10) anaesthesia. The induction resultedin similar changes in volume kinetic parameters in both groups.When a one-volume model was employed (n=8), however, the infusionexpanded a smaller body fluid space in the four patients whohad received preoperative enteric lavage (3.3 vs 8.3 litres),which is consistent with hypovolaemia. When a two-volume modelwas statistically justified (n=12), the induction reduced therate of fluid equilibration between a fairly small central (V₁,mean 1.4 litres) and a peripheral body fluid space by about50% (P<0.01). The kinetic analysis suggested that a rapidfluid load of 350 ml given over 2 min just after the inductioncould possibly prevent arterial hypotension because of centralhypovolaemia. This was confirmed in five additional patients. Br J Anaesth 2001; 87: 406–14     

Toxicity of photodynamic therapy after combined external beam radiotherapy and intraluminal brachytherapy for carcinoma of the upper aerodigestive tract

BACKGROUND AND OBJECTIVE: To describe the toxicity of photodynamic therapy (PDT) in patients with carcinoma of the upper aerodigestive tract who received prior treatment with external beam irradiation and intraluminal brachytherapy (IB). STUDY DESIGN/MATERIALS AND METHODS: Hospital records of PDT patients were reviewed. Three patients who received prior treatment with external beam irradiation and IB were identified. Two patients had esophageal carcinoma treated with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy) followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications: 630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at 1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one light application: 630 nm, 150 J/cm, 200 mW/cm). RESULTS: One patient with esophagus cancer had formation of a tracheoesophageal fistula, which required stent placement. The other esophageal cancer patient developed quadriplegia due to an epidural abscess arising from a fistula with the diseased portion of the esophagus. The lung cancer patient had massive hemoptysis after the procedure and died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary artery. CONCLUSION: Patients with upper aerodigestive tract carcinoma who have received treatment with both external beam irradiation and IB seem to be at higher risk for complications when treated with PDT.     

The Sigma-trial protocol: a prospective double-blind multi-centre comparison of laparoscopic versus open elective sigmoid resection in patients with symptomatic diverticulitis

Backround  

Diverticulosis is a common disease in the western society with an incidence of 33–66%. 10–25% of these patients will develop diverticulitis. In order to prevent a high-risk acute operation it is advised to perform elective sigmoid resection after two episodes of diverticulitis in the elderly patient or after one episode in the younger (< 50 years) patient. Open sigmoid resection is still the gold standard, but laparoscopic colon resections seem to have certain advantages over open procedures. On the other hand, a double blind investigation has never been performed. The Sigma-trial is designed to evaluate the presumed advantages of laparoscopic over open sigmoid resections in patients with symptomatic diverticulitis.     

Plasmacytoid variant urothelial bladder cancer: Is it time to update the treatment paradigm?

ObjectivesPlasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC.Materials and methodsA retrospective analysis of the Indiana University Bladder Cancer Database between January 2008 and June 2013 was performed comparing 30 patients with PCV UC at cystectomy to 278 patients with nonvariant (NV) UC at cystectomy who underwent surgery for muscle-invasive disease. Multivariable logistic regression was used to assess precystectomy variables associated with non–organ-confined disease at cystectomy and Cox regression analysis to assess variables associated with mortality.ResultsPatients with PCV UC who were diagnosed with a higher stage at cystectomy (73% pT3-4 vs. 40%, P = 0.001) were more likely to have lymph node involvement (70% vs. 25%, P<0.001), and positive surgical margins were found in 40% of patients with PCV UC vs. 10% of patients with NV UC (P<0.001). Median overall survival and disease-specific survival were 19 and 22 months for PCV, respectively. Median overall survival and disease-specific survival had not been reached for NV at 68 months (P<0.001). Presence of PCV UC on transurethral resection of bladder tumor was associated with non–organ-confined disease (odds ratio = 4.02; 95% CI: 1.06–15.22; P = 0.040), and PCV at cystectomy was associated with increased adjusted risk of mortality (hazard ratio = 2.1; 95% CI: 1.2–3.8; P = 0.016).ConclusionsPCV is an aggressive UC variant, predicting non–organ-confined disease and poor survival. Differentiating between non–muscle- and muscle-invasive disease in patients with PCV UC seems less important than the aggressive nature of this disease. Instead, any evidence of PCV on transurethral resection of bladder tumor may warrant aggressive therapy.