Cardiac disease in diabetic end-stage renal disease

Summary Little is known about the epidemiology of cardiac disease in diabetic end-stage renal disease. We therefore prospectively followed a cohort of 433 patients who survived 6 months after the inception of dialysis therapy for an average of 41 months. Clinical and echocardiographic data were collected yearly. At baseline, diabetic patients (n = 116) had more echocardiographic concentric left ventricular hypertrophy (50 vs 38 %, p = 0.04), clinically diagnosed ischaemic heart disease (32 vs 18 %, p = 0.003) and cardiac failure (48 vs 24 %, p < 0.00 001) than non-diabetic patients (n = 317). After adjusting for age and sex, diabetic patients had similar rates of progression of echocardiographic disorders, and de novo cardiac failure, but higher rates of de novo clinically diagnosed ischaemic heart disease (RR 3.2, p = 0.0002), overall mortality (RR 2.3, p < 0.0001) and cardiovascular mortality (RR 2.6, p < 0.0001) than non-diabetic patients. Mortality was higher in diabetic patients following admission for clinically diagnosed ischaemic heart disease (RR 1.7, p = 0.05) and cardiac failure (RR 2.2, p = 0.0003). Among diabetic patients older age, left ventricular hypertrophy, smoking, clinically diagnosed ischaemic heart disease, cardiac failure and hypoalbuminaemia were independently associated with mortality. The excessive cardiac morbidity and mortality of diabetic patients seem to be mediated via ischaemic disease, rather than progression of cardiomyopathy while on dialysis therapy. Potentially remediable risk factors include smoking, left ventricular hypertrophy, and hypoalbuminaemia. [Diabetologia (1997) 40: 1307–1312] Received: 25 March 1997 and in final revised form: 23 June 1997     

Three-dimensional intravascular ultrasonic volumetric quantification of stent recoil and neointimal formation of two new generation tubular stents

Currently, several different designs of coronary stents are available. However, only a few of the new generation stents have been investigated in large randomized trials. Mechanical behavior of first-generation stents (Palmaz-Schatz, Gianturco-Roubin) may not be applied to the new designs. We investigated the chronic mechanical behavior (recoil) of 2 stents recently approved by the Food and Drug Administration (MULTILINK and NIR). Forty-eight patients with single-stent implantation (23 MULTILINK and 25 NIR) were assessed by means of volumetric 3-dimensional intravascular ultrasound analysis after the procedure and at 6-month follow-up. In addition, volumetric assessment of neointimal formation was performed. No significant chronic stent recoil was detected in both groups (delta MULTILINK stent volume: +5.6+/-41 mm3 [p = NS] and delta NIR stent volume + 2.1+/-26 mm3 [p = NS]). A similar degree of neointimal formation at 6 months was observed between the 2 stents (MULTILINK 46+/-31.9 mm3 vs NIR 39.9+/-27.6 mm3, p = NS). In conclusion, these 2 second-generation tubular stents did not show chronic recoil and appeared to promote similar proliferative response after implantation in human coronary arteries.     

Abnormalities of serotonin metabolism and their relation to symptoms in untreated celiac disease.

BACKGROUND AND AIMS: Serotonin (5-hydroxytryptamine [5-HT]) is a key modulator of gut function that in excess causes nausea, vomiting, and diarrhea. We recently showed that patients with post-infective irritable bowel syndrome have increased postprandial release of 5-HT associated with low-grade T-cell mediated inflammation. Celiac disease is another common disease in which a T-cell enteropathy is associated with increased mucosal 5-HT levels. Our aim was to determine how this inflammatory lesion influenced 5-HT bioavailability and how changes in 5-HT related to the symptoms of nausea, vomiting, and diarrhea seen in untreated celiac patients. METHODS: Fasting plasma and platelet 5-HT and postprandial plasma 5-HT levels were measured after a high-carbohydrate meal in celiac patients (n = 18) and healthy controls (n = 18) using high-pressure liquid chromatography. Dyspepsia was assessed during the postprandial period using a questionnaire. Finally, we compared the histology and mucosal 5-HT levels in duodenal biopsy specimens from celiac patients and controls. RESULTS: Celiac patients had increased 5-HT-containing enterochromaffin cell numbers and significantly higher peak plasma 5-HT levels (P = .0002), postprandial area under the curve (P = .0006), and platelet 5-HT stores (P = .031) than controls. Peak 5-HT levels correlated significantly with postprandial dyspepsia scores (P = .005). Celiac patients had higher duodenal 5-HT levels (P = .007) than controls. CONCLUSIONS: Celiac disease is associated with increased mucosal 5-HT content and enhanced 5-HT release from the upper small bowel, which correlates with postprandial dyspepsia. Serotonin excess may mediate dyspeptic symptoms in untreated celiac disease.     

A comparison of treatment planning techniques for low-dose-rate (LDR) prostate brachytherapy

PurposeThe purpose of this study was to compare low-dose-rate prostate brachytherapy treatment plans created using three retrospectively applied planning techniques with plans delivered to patients.Methods and MaterialsTreatment plans were created retrospectively on transrectal ultrasound (TRUS) scans for 26 patients. The technique dubbed 4D Brachytherapy was applied, using TRUS and MRI to obtain prostatic measurements required for the associated webBXT online nomogram. Using a patient's MRI scan to create a treatment plan involving loose seeds was also explored. Plans delivered to patients were made using an intraoperative loose seed TRUS-based planning technique. Prostate V₁₀₀ (%), prostate V₁₅₀ (%), prostate D₉₀ (Gy), rectum D_0.1cc (Gy), rectum D_2cc (Gy), urethra D₁₀ (%), urethra D₃₀ (%), and prostate volumes were measured for each patient. Statistical analysis was used to assess and compare plans.ResultsProstate volumes measured by TRUS and MRI were significantly different. Prostate volumes calculated by the webBXT online nomogram using TRUS- and MRI-based measurements were not significantly different. Compared with delivered plans, TRUS-based 4D Brachytherapy plans showed significantly lower rectum D_0.1cc (Gy) values, MRI-based 4D Brachytherapy plans showed significantly higher prostate V₁₀₀ (%) values and significantly lower rectum D_0.1cc (Gy), urethra D₁₀ (%), and urethra D₃₀ (%) values, and loose seed MRI-based plans showed significantly lower prostate V₁₀₀ (%), prostate D₉₀ (Gy), rectum D_0.1cc (Gy), rectum D_2cc (Gy), urethra D₁₀ (%), and urethra D₃₀ (%) values.ConclusionsTRUS-based 4D Brachytherapy plans showed similar dosimetry to delivered plans; rectal dosimetry was superior. MRI can be integrated into the 4D Brachytherapy workflow. The webBXT online nomogram overestimates the required number of seeds.     

Correction to: Prenatal attachment: Using measurement invariance to test the validity of comparisons across eight culturally diverse countries

Archives of Women's Mental Health - A Correction to this paper has been published: https://doi.org/10.1007/s00737-021-01122-7     

Position of Glycine Substitutions in the Triple Helix of COL6A1, COL6A2, and COL6A3 is Correlated with Severity and Mode of Inheritance in Collagen VI Myopathies

Glycine substitutions in the conserved Gly‐X‐Y motif in the triple helical (TH) domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate (INT) phenotypes. We describe clinical and genetic characteristics of 97 individuals with glycine substitutions in the TH domain of COL6A1, COL6A2, or COL6A3 and add a review of 97 published cases, for a total of 194 cases. Clinical findings include severe, INT, and mild phenotypes even from patients with identical mutations. INT phenotypes were most common, accounting for almost half of patients, emphasizing the importance of INT phenotypes to the overall phenotypic spectrum. Glycine substitutions in the TH domain are heavily clustered in a short segment N‐terminal to the 17th Gly‐X‐Y triplet, where they are acting as dominants. The most severe cases are clustered in an even smaller region including Gly‐X‐Y triplets 10–15, accounting for only 5% of the TH domain. Our findings suggest that clustering of glycine substitutions in the N‐terminal region of collagen VI is not based on features of the primary sequence. We hypothesize that this region may represent a functional domain within the triple helix.     

A review of cross-sectional imaging,ultrasound and nuclear medicine utilization patterns in paediatric patients in Ireland, 2003–12

Objective:

Recent trends in paediatric imaging have been examined in Australia and the USA. Such literature in Europe is sparse, incomprehensive and outdated. This research investigated (1) population-based trends in the use of advanced medical imaging in children in Ireland from 2003 to 2012; (2) its use across age and gender; and (3) the most commonly performed examinations within each modality.

Methods:

A retrospective cohort analysis study was carried out within Irish paediatric hospitals. All CT, MRI, ultrasound and nuclear medicine (NM) annual examination data from 2003 to 2012 was obtained from radiology information systems.

Results:

224,173 imaging procedures were carried out on 84,511 patients, 68% of which were ultrasound, 15% were MRI, 11% were CT and 6% were NM. Between 2003 and 2012, MRI (+280%) and CT (+80%) saw the largest increases in use, followed by ultrasound (+67%) and NM (+10%). Almost half of the study population were less than 3 years old. CT imaging was more frequent than MR in 2005. By 2012, MR rates were twice that of CT. CT imaging rates were the lowest in the youngest age categories.

Conclusion:

Advanced imaging use, particularly MRI, has risen substantially over the past 10 years. The utilization of non-ionizing modalities increased between 2003 and 2012, especially in brain, spinal and abdominal imaging. MR is now used at twice the frequency of CT.

Advances in knowledge:

Longitudinal advanced imaging utilization trends, including CT trends, have been established in the Irish paediatric population.The use of advanced diagnostic imaging has increased considerably over the past two decades, particularly amongst the paediatric population.^1–3 Advanced imaging modalities used in paediatric radiology include ultrasound, CT, MRI and nuclear medicine (NM).⁴ The quest for safer, more accurate and interpretive-efficient diagnoses has driven technological advances in imaging.⁴ As a result, the quality of information that imaging can provide has significantly improved; this has led to a higher quality of care and reduced patient morbidity and mortality.⁴While there are many benefits to diagnostic imaging, there are also some risks worth considering. Some advanced imaging modalities such as CT and NM involve ionizing radiation and radioactive material that can be detrimental to patient''s health. CT represents just 10% of all imaging modalities that use ionizing radiation; yet, it delivers >50% of the total collective dose in diagnostic imaging.^5,6 The radiation burden of CT and NM is a major concern, particularly when imaging children.^6,7 Children are at higher risk of developing radiation-induced cancers than are adults because their developing tissues are more sensitive to radiation.⁸ Their likelihood of repeat examinations and longer life expectancy allows additional time for the emergence of detrimental effects.^9–11To date, initiatives such as the Image Gently campaign by the Alliance for Radiation Safety in Paediatric Imaging have been established to increase awareness of the opportunities to promote radiation protection when imaging children.¹² The European Society of Radiology recently launched a similar campaign, the EuroSafe Imaging Campaign 2014, to further promote quality and radiation safety in medical imaging. To successfully develop further initiatives and to monitor the success of existing initiatives, it is necessary to analyse the trends in diagnostic imaging over time.Longitudinal studies on the use of paediatric imaging involving radiation have been examined in Australia² and the USA.^3,13 Such literature in Europe is sparse and outdated. The Irish healthcare system currently consists of three tertiary referral paediatric hospitals, located in county Dublin. While paediatric imaging does take place infrequently in regional hospitals, these three specialist centres perform the vast majority, owing to the expertise available therein. This study aimed to investigate the trends in advanced paediatric imaging in Ireland from 2003 to 2012, its use across paediatric age groups and genders, and the most commonly performed procedures in each specialist modality.     

Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo

To evaluate the direct effect of adenosine on cytokine-polarized effector T cells, murine type 1 helper T cells (Th1) and type 1 cytotoxic T lymphocytes (Tc1) and Th2/Tc2 cells were generated using an antigen-presenting cell (APC)-free method. Tc1 and Tc2 cells had similar adenosine signaling, as measured by intracellular cyclic AMP (cAMP) increase upon adenosine A(2A) receptor agonism by CGS21680 (CGS). CGS greatly reduced Tc1 and Tc2 cell interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) secretion, with nominal effect on interferon gamma (IFN-gamma) secretion. Tc2 cell IL-4 and IL-5 secretion was not reduced by CGS, and IL-10 secretion was moderately reduced. Agonist-mediated inhibition of IL-2 and TNF-alpha secretion occurred via A(2A) receptors, with no involvement of A(1), A(2B), or A(3) receptors. Adenosine agonist concentrations that abrogated cytokine secretion did not inhibit Tc1 or Tc2 cell cytolytic function. Adenosine modulated effector T cells in vivo, as CGS administration reduced CD4(+)Th1 and CD8(+)Tc1 cell expansion to alloantigen and, in a separate model, reduced antigen-specific CD4(+) Th1 cell numbers. Remarkably, agonist-mediated T-cell inhibition was abrogated by in vivo IL-2 therapy. Adenosine receptor activation therefore preferentially inhibits type I cytokine secretion, most notably IL-2. Modulation of adenosine receptors may thus represent a suitable target primarily for inflammatory conditions mediated by Th1 and Tc1 cells.