Aliment Pharmacol Ther 2011; 33: 679–688
Summary
Background Limited therapeutic options exist for severe gastroparesis, where severe nausea and vomiting can lead to weight loss, dehydration and ...malnutrition due to inadequate caloric and fluid intake. TZP‐101 (ulimorelin) is a ghrelin receptor agonist that accelerates gastric emptying and improves upper gastrointestinal symptoms in diabetic patients with gastroparesis.
Aim To assess effects of TZP‐101 in diabetic gastroparesis patients with severe nausea/vomiting and baseline severity scores of ≥3.5 (range: 0–5) on the Gastroparesis Cardinal Symptom Index (GCSI) Nausea/Vomiting subscale.
Methods Patients were hospitalised and received four single daily 30‐min infusions of one of six TZP‐101 doses (range 20–600 μg/kg) or placebo. Efficacy was assessed by symptom improvement.
Results At baseline, 23 patients had a mean severity score for GCSI Nausea/Vomiting of 4.45 ± 0.44. Statistically significant improvements over placebo occurred in the 80 μg/kg group for end of treatment changes from baseline in GCSI Nausea/Vomiting subscale (reduction in score of −3.82 ± 0.76, P = 0.011) and the GCSI Total score (−3.14 ± 0.78, P = 0.016) and were maintained at the 30‐day follow‐up assessment (−2.02 ± 1.63, P = 0.073 and −1.99 ± 1.33, P = 0.032 respectively). The proportion of days with vomiting was reduced significantly (P = 0.05) in the 80 μg/kg group (mean of 1.2 days of vomiting for four treatment days) compared with placebo (mean of 3.2 days of vomiting across 4 treatment days).
Conclusions TZP‐101 substantially reduced the frequency and severity of nausea and vomiting as well as overall gastroparesis symptoms. The results are consistent with gastrointestinal motility effects of TZP‐101, supporting further investigation of TZP‐101 in the management of severe gastroparesis.
Children with Down Syndrome (DS) suffer from immune deficiency with a severe reduction in switched memory B cells (MBCs) and poor response to vaccination. Chromosome 21 (HSA21) encodes two microRNAs ...(miRs), miR-125b, and miR-155, that regulate B-cell responses. We studied B- and T- cell subpopulations in tonsils of DS and age-matched healthy donors (HD) and found that the germinal center (GC) reaction was impaired in DS. GC size, numbers of GC B cells and Follicular Helper T cells (T
) expressing BCL6 cells were severely reduced. The expression of miR-155 and miR-125b was increased in tonsillar memory B cells and miR-125b was also higher than expected in plasma cells (PCs). Activation-induced cytidine deaminase (AID) protein, a miR-155 target, was significantly reduced in MBCs of DS patients. Increased expression of miR-155 was also observed
. MiR-155 was significantly overexpressed in PBMCs activated with CpG, whereas miR-125b was constitutively higher than normal. The increase of miR-155 and its functional consequences were blocked by antagomiRs
. Our data show that the expression of HSA21-encoded miR-155 and miR-125b is altered in B cells of DS individuals both
and
. Because of HSA21-encoded miRs may play a role also in DS-associated dementia and leukemia, our study suggests that antagomiRs may represent pharmacological tools useful for the treatment of DS.
Objective
To estimate one‐year costs of eating disorders in the United States (U.S.) from a societal perspective, including the costs to the U.S. health system, individual and family productivity ...costs, lost wellbeing, and other societal economic costs, by setting and payer. Findings will inform needed policy action to mitigate the impact of eating disorders in the U.S.
Method
Costs of eating disorders were estimated using a bottom‐up cost‐of‐illness methodology, based on the estimated one‐year prevalence of eating disorders. Intangible costs of reduced wellbeing were also estimated using disability‐adjusted life years.
Results
Total economic costs associated with eating disorders were estimated to be $64.7 billion (95% CI: $63.5–$66.0 billion) in fiscal year 2018–2019, equivalent to $11,808 per affected person (95% CI: $11,754–$11,863 per affected person). Otherwise Specified Feeding or Eating Disorder accounted for 35% of total economic costs, followed by Binge Eating Disorder (30%), Bulimia Nervosa (18%) and Anorexia Nervosa (17%). The substantial reduction in wellbeing associated with eating disorders was further valued at $326.5 billion (95% CI: $316.8–$336.2 billion).
Discussion
The impact of eating disorders in the U.S. is substantial when considering both economic costs and reduced wellbeing (nearly $400 billion in fiscal year 2018–2019). Study findings underscore the urgency of identifying effective policy actions to reduce the impact of eating disorders, such as through primary prevention and screening to identify people with emerging or early eating disorders in primary care, schools, and workplaces and ensuring access to early evidence‐based treatment.
Hemangiomas are the most common noncystic benign hepatic tumors and are usually incidentally discovered during routine radiological examinations. The diagnosis of hepatic hemangiomas with a typical ...presentation is generally easy with plain and cross-sectional imaging; however, it can be complicated when hemangiomas undergo histological changes such as fibrosis. Sclerosed hepatic hemangioma (SHH) is the extreme presentation of this fibrotic process. These atypical lesions can be misdiagnosed as primary hepatic malignancies or metastasis. Their diagnosis is established by histological examination. We report the case of a patient with an SHH, which was misdiagnosed as an intrahepatic cholangiocarcinoma. This article's aim is to draw attention to this infrequent pathology and underline the features of this benign tumor that could suggest its diagnosis prior to surgery to avoid unnecessary hepatic resections.
Purpose: To present a comprehensive estimate of the total number of people with visual impairment in the adult Japanese population by age, gender, severity and cause, and to estimate future ...prevalence based on population projections and expected demographic changes.
Methods: Definitions of visual impairment used in this study were based on the United States criteria. Total visual impairment was calculated as the sum of low vision and blindness. The prevalence estimates were based on input from a number of Japanese epidemiological surveys, census material and official population projections.
Results: There were an estimated 1.64 million people with visual impairment in 2007 in Japan. Of these, 187,800 were estimated to be blind. The prevalence of visual impairment in Japan increased with age and half of the people with visual impairment were aged 70 years or older. The leading causes of visual impairment in Japan were glaucoma (24.3%), diabetic retinopathy (20.6%), degenerative myopia (12.2%), age-related macular degeneration (10.9%), and cataract (7.2%). These five major causes comprised three-quarters of all visual impairment. The prevalence of visual impairment was projected to increase from 1.3% of the population in 2007 to 2.0% by 2050.
Conclusions: This comprehensive study presents the prevalence of total visual impairment in the adult Japanese population. The projected increases in the prevalence of visual impairment over time reflect the demographic changes of a declining and aging Japanese population. These projections highlight that the burden of disease due to visual impairment and imposed on society is likely to increase.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purpose/methods
The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis is still ...challenging. The aim of this study was to identify non-invasive circulating biomarkers in MTC. To achieve this goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres and microRNA (miRNA) expression levels were evaluated.
Results
The samples from a discovery cohort of 23 MTC patients were analysed using miRNA arrays. Lasso logistic regression analysis resulted in the identification of a set of circulating miRNAs as diagnostic biomarkers. Among them, miR-26b-5p and miR-451a, were highly expressed and their expression decreased during follow-up in disease-free patients in the discovery cohort. Circulating miR-26b-5p and miR-451a were validated using droplet digital PCR in a second independent cohort of 12 MTC patients.
Conclusion
This study allowed the identification and validation of a signature of two circulating miRNAs, miR-26b-5p and miR-451a, in two independent cohorts reporting a significant diagnostic performance for MTC. The results of this study offer advancements in molecular diagnosis of MTC proposing a novel non-invasive tool to use in precision medicine.
Accurate measurements of physical processes in high energy frontier experiments demand exceptional spatial, temporal, and energy precision to discern the physics behind high-energy particle jets. ...Calorimeters, like other detection systems, must be able to meet these increasingly challenging performance requirements. In the prospective TeV-scale Muon Collider, the primary hurdle in designing detectors and devising event reconstruction algorithms is the challenge posed by Beam-Induced Background (BIB). Nevertheless, it is conceivable to mitigate the impact of BIB on the Muon Collider's calorimeter by capitalizing on certain characteristics and ensuring key features such as high granularity, precise timing, longitudinal segmentation, and superior energy resolution. This is what the here described Research and Development is trying to achieve with an innovative semi-homogeneous electromagnetic calorimeter constructed from stackable and interchangeable modules composed of lead fluoride crystals (PbF2). These modules are equipped with surface-mount UV-extended Silicon Photomultipliers (SiPMs) and are collectively referred to as the Crilin calorimeter (CRystal calorImeter with Longitudinal INformation). The challenge lies in making sure this calorimeter can operate effectively within an extremely harsh radiation environment, enduring an annual neutron flux of <inline-formula> <tex-math notation="LaTeX">10^{14}~n_{1\text {MeV}}/\text {cm}^{2} </tex-math></inline-formula> and a total ionizing dose (TID) of 10 kGy. In this article, the radiation tolerance measured in several irradiation campaigns is discussed, and the timing performances during a test beam at CERN-H2 with 120-GeV electrons. Additionally, a description of the latest prototype, Proto-1, is provided together with the results of the latest low-energy beam test at the LNF beam test facility (BTF) with 450 MeV electrons.
Salt-sensitive (SS) hypertension affects >30 million Americans and is often associated with low plasma renin activity. We tested the diagnostic validity of several candidate genes for SS and ...low-renin hypertension.
In Japanese patients with newly diagnosed, untreated hypertension (n = 184), we studied polymorphisms in 10 genes, including G protein-coupled receptor kinase type 4 (GRK4), some variations of which are associated with hypertension and impair D1 receptor (D1R)-inhibited renal sodium transport. We used the multifactor dimensionality reduction method to determine the genotype associated with salt sensitivity (> or =10% increase in blood pressure with high sodium intake) or low renin. To determine whether the GRK4 genotype is associated with impaired D1R function, we tested the natriuretic effect of docarpamine, a dopamine prodrug, in normotensive individuals with or without GRK4 polymorphisms (n = 18).
A genetic model based on GRK4 R65L, GRK4 A142V, and GRK4 A486V was 94.4% predictive of SS hypertension, whereas the single-locus model with only GRK4 A142V was 78.4% predictive, and a 2-locus model of GRK4 A142V and CYP11B2 C-344T was 77.8% predictive of low-renin hypertension. Sodium excretion was inversely related to the number of GRK4 variants in hypertensive persons, and the natriuretic response to dopaminergic stimulation was impaired in normotensive persons having > or =3 GRK4 gene variants.
GRK4 gene variants are associated with SS and low-renin hypertension. However, the genetic model predicting SS hypertension is different from the model for low renin, suggesting genetic differences in these 2 phenotypes. Like low-renin testing, screening for GRK4 variants may be a useful diagnostic adjunct for detection of SS hypertension.
Introduction
This study aimed to illustrate the validity of the treatment with vertebroplasty (VP) in patients with aggressive or symptomatic vertebral hemangioma (VH) with or without epidural ...extension.
Methods
From January 2003 to December 2007, 24 consecutive patients have been treated with VP, for a total of 36 vertebral bodies affected by VH: two cervical, ten dorsal, 24 lumbar. All the patients complained of a pain syndrome resistant to continuous medical medication; four of 24 patients also presented aggressive magnetic resonance features of the vertebral lesion and two patients showed also epidural extension. A unipedicular approach has been performed in 16 patients; a bipedicular approach has been performed in six, while for the cervical spine an anterior–lateral approach with manual dislocation of the carotid axis has always been performed. Bone biopsy was never done. All procedures have been carried out with local anesthesia, except for the treatment of the cervical hemangiomas which has always been performed under general anesthesia. Four vertebral bodies in the same session have been treated in one case.
Results
Results have been evaluated with the visual analog scale and the Oswestry Disability Index methods. In all the patients, in the following 24–72 h, a successful outcome has been observed with a complete resolution of pain symptom. Extravertebral vascular or discal cement leakage has been observed in four patients, without any onset of clinical radicular syndrome due to epidural diffusion. Clinical and radiological follow-up until 4 years has been performed in 12 patients and it showed stability of the treatment and absence of pain.
Conclusions
Percutaneous treatment with VP for aggressive and symptomatic vertebral hemangiomas even with epidural extension is a valuable, mini-invasive, and quick method that allows a complete and enduring resolution of the painful vertebral symptoms without findings of fracture of a vertebral body adjacent or distant to the one treated.
PDF
