Background/Aims: Endogenous Cushing's syndrome is associated with a higher risk of cardiovascular morbidity and mortality. Previous literature suggested multiple possible links by which hypercortisolism may alter the autonomic control of cardiovascular functions. We investigated the impact of chronic endogenous hypercortisolism on the autonomic regulation of cardiac functions by short-term heart rate variability analysis. Methods: Eighteen patients with endogenous Cushing's syndrome and 20 age-, gender- and BMI-matched controls participated in the study. ECG signal was acquired in lead II configuration for 5 min and heart rate variability assessment was made in both time and frequency domain using the extracted RR interval data. Results: All time and frequency domain measures of heart rate variability were significantly (p < 0.05) lower in the patient group compared to the control group. The patient group had an altered sympathovagal balance with low frequency/high frequency band ratio significantly higher than the control group [1.857 (0.6747-2.610) vs. 0.8581 (0.4779-1.352); p = 0.0253]. A significant negative correlation was obtained between normalized high frequency power of heart rate variability and basal cortisol levels (r = -0.6594; p = 0.0029). Multiple linear regression analysis identified age, disease duration (in months), basal cortisol levels and systolic blood pressure as independent predictors of normalized high frequency power. Conclusion: Findings of the study clearly portrayed the diminished autonomic modulation of heart rate in endogenous Cushing's syndrome and its possible relationship with hypercortisolism as the main causative factor. Diminished heart rate variability may be an indicator of the increased risk of cardiac mortality in these patients.
An eight-year old South Asian boy presenting with progressive hyperpigmentation was found to have primary adrenal insufficiency (PAI) in the form of isolated glucocorticoid deficiency. Follow up of this boy for nine years, until the age of 17 years showed normal pubertal onset and progression. Molecular evaluation, by targeted next generation sequencing of candidate genes linked to PAI revealed changes in two genes that are intricately linked in the early stages of steroid biosynthesis: compound heterozygous variants in STAR, c.465+1G>A and p.(E99K), plus a heterozygous rs6161 change in CYP11A1. No variants in other known causal genes were detected. The proband’s mother was heterozygous for the c.465+1G>A STAR and rs6161 CYP11A1 variants, while the father was homozygous for the p.(E99K) alteration in STAR but wild-type for CYP11A1. Both parents had normal adrenal cortical function as revealed by short Synacthen tests. The STAR variant c.465+1G>A will lead to abnormal splicing of exon 4 in mRNA and the addition of the p.(E99K) variant, predicted damaging by SIFT and CADD, may be sufficient to cause PAI but this is by no means certain given that the unaffected father is homozygous for the latter change. The rs6161 CYP11A1 variant [c.940G>A, p.(E314K)] has recently been demonstrated to cause PAI in conjunction with a severe rare disruptive change on the other allele, however sequencing of the coding region of CYP11A1 revealed no further changes in this subject. We wondered whether the phenotype of isolated glucocorticoid deficiency had arisen in this child due to tri-allelic inheritance of a heterozygous CYP11A1 change along with the two STAR variants each of which contribute a partial loss-of-function burden that, when combined, is sufficient to cause PAI or if the loss-of-function c.465+1G>A combined with the presumed partial loss-of-function p.(E99K) in STAR could be causative.
Objective:The present study aimed to evaluate the current trends of drug resistance patterns of Acinetobacter baumannii infection in blood transfusion-dependent thalassemia patients.Study Design:This study was a cross sectional study, conducted at the Liaquat University of Medical and Health Sciences, Jamshoro/Hyderabad, Sindh, Pakistan from October 2014 to January 2016.Subjects and Methods:Of 921 blood samples, A. baumannii strains were isolated from 100 blood samples. Blood samples were processed for the isolation, identification, and drugs sensitivity as per the Clinical and Laboratory Standards Institute. A. baumannii strains were identified by microbiological methods and Gram's staining. API 20 E kit (Biomeriuex, USA) was also used for identification. Data were analyzed on Statisti × 8.1 (USA).Results:Mean ± standard deviation age was 11.5 ± 2.8 years. Nearly 70% were male and 30% were female (P = 0.0001). Of 921 blood transfusion-dependent thalassemia patients, 100 (10.8%) patients showed growth of A. baumannii. Drug resistance was observed against the ceftazidime, cefixime, cefepime, imipenem, meropenem, amikacin, minocycline, tigecycline, and tazocin except for the colistin.Conclusion:The present study reports drug-resistant A. baumannii in blood transfusion-dependent thalassemia patients. National multicenter studies are recommended to estimate the size of the problem.
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