Multifocal pheochromocytoma-paraganglioma in a 29-year-old woman with cyanotic congenital heart disease

Background

Multifocal pheochromocytoma/paraganglioma presenting at an early age is commonly associated with a hereditary syndrome.

Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation

Recent evidence suggests that binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also beta-arrestin-dependent signaling. One such beta-arrestin-mediated pathway uses the beta(1)-adrenergic receptor (beta(1)AR) to transactivate the EGFR. To determine whether beta-adrenergic ligands that do not activate G protein signaling (i.e., beta-blockers) can stabilize the beta(1)AR in a signaling conformation, we screened 20 beta-blockers for their ability to stimulate beta-arrestin-mediated EGFR transactivation. Here we show that only alprenolol (Alp) and carvedilol (Car) induce beta(1)AR-mediated transactivation of the EGFR and downstream ERK activation. By using mutants of the beta(1)AR lacking G protein-coupled receptor kinase phosphorylation sites and siRNA directed against beta-arrestin, we show that Alp- and Car-stimulated EGFR transactivation requires beta(1)AR phosphorylation at consensus G protein-coupled receptor kinase sites and beta-arrestin recruitment to the ligand-occupied receptor. Moreover, pharmacological inhibition of Src and EGFR blocked Alp- and Car-stimulated EGFR transactivation. Our findings demonstrate that Alp and Car are ligands that not only act as classical receptor antagonists, but can also stimulate signaling pathways in a G protein-independent, beta-arrestin-dependent fashion.     

Acute renal embolism. Forty-four cases of renal infarction in patients with atrial fibrillation

Acute renal embolus is rarely reported in the medical literature; thus, accurate data regarding presentation, laboratory tests, diagnostic techniques, and treatment are lacking. To better define this condition, we examined the medical records of all patients admitted to Kaplan Medical Center and Sheba Medical Center in central Israel from 1984 to 2002 who had a diagnosis of renal infarction and atrial fibrillation. We noted demographic, clinical, and laboratory parameters; method of diagnosis; treatment received; and patient outcome. We identified 44 cases of renal embolus: 23 females and 21 males, with an average age of 69.5 +/- 12.6 years. Thirty (68%) patients had abdominal pain, and 6 (14%) had a previous embolic event. Nine patients were being treated with warfarin on admission, 6 (66%) of whom had an international normalized ratio (INR) < 1.8. Hematuria was present in 21/39 (54%), and 41 (93%) patients had a serum lactate dehydrogenase (LDH) level > 400 U/dL. The mean LDH was 1100 +/- 985 U/dL. Diagnostic techniques included renal isotope scan, which was abnormal in 36/37 cases (97%); contrast-enhanced computed tomography (CT) scan, which was diagnostic in 12/15 cases (80%); and ultrasound, which was positive in only 3/27 cases (11%). Angiography was positive in 10/10 cases (100%). Twenty-three (61%) of 38 patients had normal renal function on follow-up. The 30-day mortality was 11.4%. Renal embolus was diagnosed mainly in patients aged more than 60 years, some of whom had a previous embolic event. Most of those receiving anticoagulant therapy had a subtherapeutic INR. Abdominal pain was common, as well as hematuria and an elevated LDH. These patients are at risk of subsequent embolic events to other organs. The most sensitive diagnostic technique in this population is a renal isotope scan, but contrast-enhanced CT scan requires further assessment.     

Assistive technology and people: a position paper from the first global research,innovation and education on assistive technology (GREAT) summit

Abstract

Assistive technology (AT) is a powerful enabler of participation. The World Health Organization’s Global Collaboration on Assistive Technology (GATE) programme is actively working towards access to assistive technology for all. Developed through collaborative work as a part of the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit, this position paper provides a “state of the science” view of AT users, conceptualized as “People” within the set of GATE strategic “P”s. People are at the core of policy, products, personnel and provision. AT is an interface between the person and the life they would like to lead. People’s preferences, perspectives and goals are fundamental to defining and determining the success of AT. Maximizing the impact of AT in enabling participation requires an individualized and holistic understanding of the value and meaning of AT for the individual, taking a universal model perspective, focusing on the person, in context, and then considering the condition and/or the technology. This paper aims to situate and emphasize people at the centre of AT systems: we highlight personal meanings and perspectives on AT use and consider the role of advocacy, empowerment and co-design in developing and driving AT processes.     

Reserpine-induced altered neuro-behavioral,biochemical and histopathological assessments prevent by enhanced antioxidant defence system of thymoquinone in mice

Metabolic Brain Disease - Thymoquinone (Tq), an active compound of Nigella sativa, has been known for its anti-inflammatory, antioxidant, and neuroprotective characteristics. The present study is...     

Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: lessons from periodic examination screening

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with long-term cardiovascular morbidity. Little is known about these relations at early stages. We conducted a case-control study in which we analyzed the clinical characteristics of young adults who underwent a periodic health examination and were screened for, and eventually found to experience, OSAS. METHODS: We identified 121 subjects newly diagnosed in a sleep study as having OSAS, and 229 matched control subjects in which screening for OSAS was negative. All had a medical interview, physical examination, and routine laboratory tests. RESULTS: Subjects who had OSAS had a higher, body mass index (3-kg/m(2) difference) and a higher diastolic blood pressure (4-mm Hg difference) value, without elevation in systolic blood pressure. There was no metabolic difference (lipids profile and fasting glucose levels) between groups. CONCLUSIONS: Diastolic blood pressure is higher early in the course of OSAS. Long term follow-up may determine effects of prevention and early intervention in OSAS and associated hypertension.     

A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome

OBJECTIVES: Psychological treatments are considered to be useful in the irritable bowel syndrome (IBS), although the evidence is based on small, often flawed trials. Although cognitive behavior therapy (CBT) and relaxation therapy have both been promising, we hypothesized that CBT would be superior to relaxation and standard care alone in IBS patients. The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS. METHODS: Patients (n = 105) with Rome I criteria for IBS were recruited from advertisement (n = 51) and outpatient clinics (n = 54); those patients with resistant IBS were not included. A randomized controlled trial with three arms (standard care for all groups plus either CBT or relaxation) for 8 wk was conducted, which applied blinded outcome assessments using validated measures with 1 yr of follow-up. The primary outcome for this study was bowel symptom severity. RESULTS: Of 105 patients at the commencement of treatment, the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1; this persisted at the 52-wk follow-up, with a significant linear trend for scores to change over time (F = 39.57 p < 0.001). However, there were no significant differences among the three treatment conditions. Significant changes over time were found for physical functioning (F = 4.37, p < 0.001), pain (F = 3.12, p < 0.05), general health (F = 2.71, p < 0.05), vitality (F = 2.94, p < 0.05), and the social functioning scales on the Medical Outcomes Study Short Form 36 (F = 4.08, p < 0.05); however, all three arms showed similar improvement. There were significant reductions in anxiety, depression, and locus of control scales, but no significant differences among the treatment groups were detected. CONCLUSION: Cognitive behavior and relaxation therapy seem not to be superior to standard care alone in IBS.     

Successful use of azithromycin for Escherichia coli–associated renal allograft malakoplakia: a report of two cases

European Journal of Clinical Microbiology & Infectious Diseases - Malakoplakia is a chronic granulomatous disease associated with incomplete clearance of bacterial pathogens. A multimodal...