Different growth factor activation in the right and left ventricles in experimental volume overload

Mechanical factors play a key role in activation of cardiac growth factor response in hemodynamic overload, and both cooperate in myocardial remodeling. The present study was performed to investigate whether a different growth factor response is activated in the right and left ventricles in aortocaval fistula and its effects on regional myocardial adaptation. Relations between regional growth factor expression (angiotensin II, insulin-like growth factor-I, and endothelin-1), myocyte shape changes, and collagen deposition were investigated at mRNA and peptide levels in adult pigs after the creation of an aortocaval fistula distal to the renal arteries (n=15) and in sham-operated animals (n=15). The role of angiotensin II was investigated by the administration of angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist. In the left ventricle, pure volume overload was accompanied by persistent increase of insulin-like growth factor-I mRNA expression, peptide concentration (2.2-fold versus sham at 3 months, P<0.05), and significant increase of myocyte length (+29% at 3 months, P<0.05). Conversely, the mixed pressure-volume overload faced by the right ventricle resulted in significant regional overexpression of all growth factors investigated (angiotensin II, insulin-like growth factor-I, and endothelin-1), with corresponding increase of myocyte diameter and length and collagen deposition (+117% at 3 months). Collagen accumulation in the right ventricle as well as the increase in right ventricular end-diastolic pressure at the 3-month observation were inhibited by angiotensin II antagonism. The left and right ventricles respond differently to aortocaval fistula, and local growth factor expression is closely related to the regional myocardial adaptation.     

Multidetector computed tomography of the coronary arteries.

Over the past decades, the feasibility of non-invasive coronary imaging has been explored using different modalities, such as magnetic resonance and electron beam computed tomography. Despite encouraging initial results, neither technique is yet considered suitable for routine clinical use. Recent developments in multidetector computed tomography have expanded the potential of contrast-enhanced spiral computed tomography coronary angiography. Promising results have been published with the use of 4-slice spiral computed tomography; however, cardiac motion and calcium deposits in the artery wall rendered a substantial number of scans inadequate for interpretation. Recently, a new generation of scanners, equipped with more and thinner detector rows (8 and 16 detectors) and an increased rotation speed, have been introduced. These technical advances will have a significant impact on cardiac imaging: at an increased gantry rotation rate, up to 32 slices can be acquired in 1 s. The improved spatial and temporal resolutions have led to the opportunity of acquiring high-quality images of the entire heart within a single breath-hold.     

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1‐mg dexamethasone suppression test (1‐mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X‐ray absorptiometry and TBS was assessed in the region of LS‐BMD; BMD and TBS data were reported as Z‐scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS‐BMD (?0.31 ± 1.17), FT‐BMD (?0.29 ± 0.91), and TBS (?3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; ?1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; ?1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1‐mg DST (β = ?0.26, t = ?2.79, p = 0.006) regardless of age, LS‐BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85–12.42, p = 0.001) and with the cluster low TBS plus low LS‐BMD (OR, 4.37; 95% CI, 1.71–11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS‐BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > ?1.5) plus normal LS‐BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71–71.41, p = 0.012) regardless of LS‐BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures. © 2012 American Society for Bone and Mineral Research.     

Early Detection of Left Ventricular Dysfunction in Diabetes Mellitus Patients with Normal Ejection Fraction,Stratified by BMI: A Preliminary Speckle Tracking Echocardiography Study

Background:

Diabetes mellitus (DM) represents by itself a major risk factor for cardiovascular events and the coexistence of obesity with consequent left ventricular volumetric overload could be responsible for further damages on left ventricular function. Aim of this study was to demonstrate the effect of body mass index (BMI) on left ventricular function in diabetes patients with no cardiovascular complications and with normal ejection fraction (EF).

Materials and Methods:

We evaluated 71 stable asymptomatic diabetes patients in optimal medical treatment and 24 healthy controls (C) (45% females; mean age: 58.4 +/− 9.4 years; BMI: 23.5 +/− 1.5). We stratified diabetes patients into two groups according to BMI: BMI <30 kg/m² (A: 44 patients; 47% females; mean age: 60.9 +/− 6.6 years; BMI: 25.7 +/− 1.9; Diabetes duration: 9.1 +/− 9.5 years); BMI >30 kg/m² (B: 27 patients; 37% females; mean age: 56.2 +/− 7.8 years; BMI: 33.0 +/− 2.1; Diabetes duration: 8.5 +/− 5.2 years). The following parameters were evaluated by conventional two dimensional (2D) echocardiography (GE VIVID 7) and tissue Doppler imaging (TDI): left ventricular dimensions (LVIDd; PWTd; IVSd), Left Ventricular Volumes (EDV, ESV), EF (by biplane Simpson’s method), Left Ventricular Mass (by ASE formula), peak mitral annular velocity at septal and lateral levels (Sm and Sl). Global longitudinal strain (GLS) was obtained off line by Speckle tracking imaging method using Echopac 10 software.

Results:

Groups A, B were comparable for diabetes duration and glycated hemoglobin level, history of hypertension, and lipid profile. The EF was similar in the three groups, (A: 64 +/− 6%; B: 63 +/− 4%; C: 61 +/−5%; P= NS). LVMass^2.7 indexed for height was significantly higher in A and B in comparison with C (A: 45.2 +/− 8.1 g/m^2.7; B: 46.1 +/− 9.6 g/m^2.7; C: 39.5 +/− 4.9 g/m^2.7; P < 0.05). The stroke volume index (SVi) was significantly lower in B vs A (B: 35.3 +/− 5.7 ml/m²; A: 39.3 +/7.1 ml/m²; P = 0.033). GLS was significantly lower in group B respect A and C (C: 20.9 +/− 1.3%; A: -20.3+/−2.6%; B: -19 +/− 2; P < 0.05; P < 0.01).

Conclusions:

In uncomplicated asymptomatic DM patients, the presence of first degree obesity plays an incremental role in adversely affecting left ventricular function and remodeling. The conventional echocardiographic methods such as the EF and the TDI are not so sensitive to identify the early LV dysfunction such as the evaluation of GLS by Speckle Tracking echocardiography. The longitudinal subendocardial fibers dysfunction in diabetes/obese patients could be derived by the complex interaction between metabolic (diabetes) and hemodynamic/endocrine abnormalities.     

Cardiac Involvement in Fabry Disease: JACC Review Topic of the Week

Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by deficient α-galactosidase A activity that leads to an accumulation of globotriasylceramide (Gb3) in affected tissues, including the heart. Cardiovascular involvement usually manifests as left ventricular hypertrophy, myocardial fibrosis, heart failure, and arrhythmias, which limit quality of life and represent the most common causes of death. Following the introduction of enzyme replacement therapy, early diagnosis and treatment have become essential to slow disease progression and prevent major cardiac complications. Recent advances in the understanding of FD pathophysiology suggest that in addition to Gb3 accumulation, other mechanisms contribute to the development of Fabry cardiomyopathy. Progress in imaging techniques have improved diagnosis and staging of FD-related cardiac disease, suggesting a central role for myocardial inflammation and setting the stage for further research. In addition, with the recent approval of oral chaperone therapy and new treatment developments, the FD-specific treatment landscape is rapidly evolving.     

Treatment options for glucocorticoid-induced osteoporosis

ABSTRACT

Introduction

Glucocorticoid (GC) induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. It develops in a dose and time dependent manner, due to a rapid and transient increase in bone resorption, followed by the inhibition of bone formation.     

Physicochemical and biopharmaceutical characterization of endo-2-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-1H-benz[e]isoindol-1-one (CR3124) a novel potent 5-HT3 receptor antagonist

The physicochemical and biopharmaceutical properties, such as pK(a), crystal habit, water solubility, logD, molecular structure and dynamics, and membrane permeability of CR3124 (endo-2-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-1H-benz[e]isoindol-1-one, a novel potent 5-HT(3) receptor antagonist) have been studied in order to obtain preformulation information. The study showed that CR3124 is a very rigid molecule in which conformational freedom due to the presence of a rotatable bond is restricted by the interaction between an activated hydrogen and the amide oxygen and the conformation of the tropane piperidine ring is regulated by the environment in such a manner as to optimize the intermolecular interactions with the solvent. This chameleon behavior appears to be capable of explaining the biopharmaceutical properties showed by CR3124, such as low wettability, relatively good solubility, and very high membrane permeability.     

Why do we have to review our experience in managing cases with idiopathic fistula-in-ano regularly？

“Why do we have to review our experience in managing idiopathic fistula-in-ano regularly?” In order to answer this apparently simple question, we reviewed our clinical and surgical cases and most important relevant literature to find a rational and scientific answer. It would appear that whatever method you adopt in fistula management, there is a price to pay regarding either rate of recurrence (higher with conservative methods) or impairment of continence (higher with traditional surgery). Since, at the moment, reliable data to identify a treatment as a gold standard in the management of anal fistulas are lacking, the correct approach to this condition must consider all the anatomic and clinicopathological aspects of the disease; this knowledge joined to an eclectic attitude of the surgeon, who should be familiar with different types of treatment, is the only guarantee for a satisfactory treatment. As a conclusion, it is worthwhile to remember that adequate initial treatment significantly reduces recurrence, which, when it occurs, is usually due to failure to recognise the tract and primary opening at the initial operation.     

Implant therapy in irradiated patients

In this multicenter study, submerged implants were prospectively followed to evaluate their long-term prognosis in irradiated patients. In a total of 77 patients treated for oral or neck cancer, 188 implants were consecutively placed. After a healing period, the successfully integrated implants were restored with 69 removable and 38 fixed restorations. The implants cumulative survival and success rates were evaluated over a period of at least 36 months. In addition, cumulative success rates were calculated for implant subgroups divided per implant site (mandible or maxilla), radiation dosage, and the time interval between the last irradiation and implant placement. During the healing period, 20 implants did not successfully integrate, whereas 168 implants were classified as success (including both survival and success rates). The analysis of implant subgroups showed slightly more favorable cumulative success rate for mandibular implants (98.4%) compared with maxillary implants (57.1%) and clearly better success rate for a radiation dosage minor of 50-Gy doses. A time greater than 12 months as interval between last irradiation and implant placement seems not to promote better clinical results.     

Quality of randomised controlled trials in dentistry

Randomised controlled trials (RCTs) are regarded as the best study designs to test the efficacy of medical and dental intervention. Many reports, however, have shown that at the moment the quality of dental RCT reports is still poor, and further efforts to improve it are necessary. It has been suggested that trials that are not well designed provide biased estimates of the treatment effects and that a journal's impact factor is not related to the quality of RCTs published. For these reasons, before trusting RCT reports, a careful assessment of the study selected is needed. Randomisation, blinding, allocation concealment, drop outs analysis are essential quality components of RCTs. Many systems for RCTs quality assessment are available. In this report the concept of quality of RCTs will be critically evaluated and the most commonly used instruments available for quality assessment of RCTs in dental research will be reviewed.