Pharmacological closure of patent ductus arteriosus: effects on pulse pressure and on endothelin-1 and vasopressin excretion

Widened pulse pressure is a classic sign of significant left-to-right shunting patent ductus arteriosus (PDA), but little evidence supports this statement in the early life of premature infants with respiratory distress syndrome (RDS) needing nonsteroidal anti-inflammatory drugs (NSAIDs), the pharmacological treatment for PDA. Pulse pressure and urinary endothelin-1 (ET-1) and arginine vasopressin (AVP) vasoactive factors involved in the transitional circulation were measured before and after the NSAIDs treatment of 46 RDS premature infants receiving either ibuprofen (n = 22) or indomethacin (n = 24), with 28 responders and 18 nonresponders to the first NSAIDs course. We found that following pharmacological PDA closure, systolic and diastolic blood pressure significantly increased, maintaining a stable pulse pressure. However, when pharmacological closure failed, the trend (nonsignificant) was for a more consistent increase in systolic than in diastolic blood pressure, which determined a statistically significant widening pulse pressure. In addition, urinary ET-1 excretion rates decreased significantly after PDA closure, whereas persistent more aggressive pharmacological therapy failed. Urinary AVP excretion rates decreased insignificantly after therapy, uninfluenced by the efficacy of the drugs. We concluded that widened pulse pressure is a clinical sign of failed PDA pharmacological closure in RDS premature infants. ET-1 levels remain elevated when NSAIDs fail to interrupt left-to-right PDA shunting that complicates recovery from RDS.     

Urethral diverticulum as a cause for chronic genitourinary pain: a case report

A 53-year-old woman suffering for 20 years from chronic genitourinary pain was seen in our urogynecological unit. Quality of life assessment by King's Health Questionnaire showed a highly negative impact on quality of life. Clinical examination revealed a painful and swollen distal urethra, and a small fistula was seen located 12 mm proximal to the meatus externus. Perineal ultrasound and magnetic resonance imaging showed multiple cystic formations bilaterally located in the suburethral and paraurethral regions. A diverticulectomy was performed using the vaginal approach. Twelve months after surgery the woman is completely satisfied and only complaining about slight alguria.     

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

A Low-Cost Wireless Bite Force Measurement Device

Assessing maximum voluntary bite force is important to characterize the functional state of the masticatory system. Due to several factors affecting the estimation of the maximum bite force, a unique solution combining desirable features such as reliability, accuracy, precision, usability, and comfort is not available. The aim of the present study was to develop a low-cost bite force measurement device allowing for subject-specific customization, comfortable bite force expression, and reliable force estimation over time. The device was realized using an inexpensive load cell, two 3D printed ergonomic forks hosting reusable subject-specific silicone molds, a read-out system based on a low-cost microcontroller, and a wireless link to a personal computer. A simple model was used to estimate bite force taking into account individual morphology and device placement in the mouth. Measurement reliability, accuracy, and precision were assessed on a calibration dataset. A validation procedure on healthy participants was performed to assess the repeatability of the measurements over multiple repetitions and sessions. A 2% precision and 2% accuracy were achieved on measurements of forces in the physiological range of adult bite forces. Multiple recordings on healthy participants demonstrated good repeatability (coefficient of variation 11%) with no significant effect of repetition and session. The novel device provides an affordable and reliable solution for assessing maximum bite force that can be easily used to perform clinical evaluations in single sessions or in longitudinal studies.     

Two novel loci,COBL and SLC10A2, for Alzheimer's disease in African Americans

Introduction

African Americans' (AAs) late-onset Alzheimer's disease (LOAD) genetic risk profile is incompletely understood. Including clinical covariates in genetic analyses using informed conditioning might improve study power.

Molecular diagnostic tools for the detection of nodal micrometastases in prostate cancer patients undergoing radical prostatectomy with extended pelvic lymph node dissection: a prospective study

Background: Routine pathological examination can miss micro-metastatic tumor foci in the lymph nodes (LN) of patients with prostate cancer (PCa) that undergo radical prostatectomy and pelvic lymph node dissection (PLND). The aim of the present prospective study was to evaluate the impact of micrometastases assessed by serial section (SS), immunohistochemistry (IHC), and Real-time Polymerase Chain Reaction (RT-PCR) in patients undergoing radical prostatectomy with extended PLND. Materials and methods: 32 consecutive patients who underwent radical prostatectomy with extended PLND (obturator, internal/external and distal 2cm common iliac lymph-nodes (LN)) for intermediate (clinical T1c-T2 and PSA:10-20 ng/mL and clinical Gleason Score = 7) or high (clinical stage T3 or PSA>20 or clinical Gleason Score = 8-10) PCa were enrolled. The nodes were processed by the one uropathologist, both according to the routine pathological examination (analysis of the central section for 4 mm nodes or every 2 mm for LN>4 mm), which served as comparative method, both according to SS, IHC with antibodies against PSA and broad-spectrum Cytokeratins (BSCK), and quantitative RT-PCR targeting PSA, PSMA (PS Membrane Antigen), and Glucuronidase-S-Beta (GUSB) mRNA, that are over-expressed in prostatic cancer cells. Results: A total of 628 LN were analyzed, with a mean number of LN removed of 19.6 (SD = 7.2). Applying the routine pathological examination, 10 (31.2%) patients and 23 (3.9%) LN resulted positive for nodal involvement, with mean positive LN of 2.2 (SD = 1.4). After applying the SS and the molecular method of analysis (IHC and RT-PCR), micrometastases were found in 7 LN (SS showed micrometastases in 3 of them, IHC in 6 of them and RT-PCR in 7 of them); a total of 3 (9.3%) node-negative patients showed micrometastases at routine pathological examination (in 2 patients with RT-PCR and in 1 with IHC). Conclusions: The significance of micrometastases in PCa and the potential therapeutic role of PLND is not yet clarified, but the molecular analysis of the LN can detect a significant percentage of patients who harbor micro-metastatic PCa missed at routine pathological examination, and can enhance the accuracy of lymphadenectomy as a staging method.