These pediatric hypertension guidelines are an update to the 2004 “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents.” Significant changes in these guidelines include (1) the replacement of the term “prehypertension” with the term “elevated blood pressure,” (2) new normative pediatric blood pressure (BP) tables based on normal-weight children, (3) a simplified screening table for identifying BPs needing further evaluation, (4) a simplified BP classification in adolescents ≥13 years of age that aligns with the forthcoming American Heart Association and American College of Cardiology adult BP guidelines, (5) a more limited recommendation to perform screening BP measurements only at preventive care visits, (6) streamlined recommendations on the initial evaluation and management of abnormal BPs, (7) an expanded role for ambulatory BP monitoring in the diagnosis and management of pediatric hypertension, and (8) revised recommendations on when to perform echocardiography in the evaluation of newly diagnosed hypertensive pediatric patients (generally only before medication initiation), along with a revised definition of left ventricular hypertrophy. These guidelines include 30 Key Action Statements and 27 additional recommendations derived from a comprehensive review of almost 15 000 published articles between January 2004 and July 2016. Each Key Action Statement includes level of evidence, benefit-harm relationship, and strength of recommendation. This clinical practice guideline, endorsed by the American Heart Association, is intended to foster a patient- and family-centered approach to care, reduce unnecessary and costly medical interventions, improve patient diagnoses and outcomes, support implementation, and provide direction for future research.

Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents.

Statistical Methods in Medical Research.

ROS are highly reactive molecules which consist of a number of diverse chemical species, including radical and non-radical oxygen species. Oxidative stress occurs as a result of an overproduction of ROS not balanced by an adequate level of antioxidants. The natural antioxidants are: thiol compounds among which GSH is the most representative, and non-thiol compounds such as polyphenols, vitamins and also various enzymes. Many diseases have been linked to oxidative stress including bone diseases among which one of the most important is the osteoporosis. The redox state changes are also related to the bone remodeling process which allows the continuous bone regeneration through the coordinated action of bone cells: osteoclasts, osteoblasts and osteocytes. Changes in ROS and/or antioxidant systems seem to be involved in the pathogenesis of bone loss. ROS induce the apoptosis of osteoblasts and osteocytes, and this favours osteoclastogenesis and inhibits the mineralization and osteogenesis. Excessive osteocyte apoptosis correlates with oxidative stress causing an imbalance in favor of osteoclastogenesis which leads to increased turnover of bone remodeling and bone loss. Antioxidants either directly or by counteracting the action of oxidants contribute to activate the differentiation of osteoblasts, mineralization process and the reduction of osteoclast activity. In fact, a marked decrease in plasma antioxidants was found in aged or osteoporotic women. Some evidence shows a link among nutrients, antioxidant intake and bone health. Recent data demonstrate the antioxidant properties of various nutrients and their influence on bone metabolism. Polyphenols and anthocyanins are the most abundant antioxidants in the diet, and nutritional approaches to antioxidant strategies, in animals or selected groups of patients with osteoporosis or inflammatory bone diseases, suggest the antioxidant use in anti-resorptive therapies for the treatment and prevention of bone loss.

Oxidative stress in bone remodeling: role of antioxidants.

Textbook of biochemistry with clinical correlations , 4th edn TM Devlin, ed pp xvii + 1186, illustrated Wiley-Liss, New York, 1997 £2995, hardback

This beautifully illustrated and well-written book, with an impressive array of authors, is aimed at both undergraduate and postgraduate level As the editor states in the preface, it is not intended to be a compendium of biochemistry but rather emphasises the biochemistry of mammalian cells The first 22 chapters cover …

Textbook of biochemistry with clinical correlations

Mitochondria has an essential role in myocardial tissue homeostasis; thus deterioration in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death and consequent cardiovascular dysfunction. Several chemical compounds and drugs have been known to directly or indirectly modulate cardiac mitochondrial function, which can account both for the toxicological and pharmacological properties of these substances. In many cases, toxicity problems appear only in the presence of additional cardiovascular disease conditions or develop months/years following the exposure, making the diagnosis difficult. Cardiotoxic agents affecting mitochondria include several widely used anticancer drugs [anthracyclines (Doxorubicin/Adriamycin), cisplatin, trastuzumab (Herceptin), arsenic trioxide (Trisenox), mitoxantrone (Novantrone), imatinib (Gleevec), bevacizumab (Avastin), sunitinib (Sutent), and sorafenib (Nevaxar)], antiviral compound azidothymidine (AZT, Zidovudine) and several oral antidiabetics [e.g., rosiglitazone (Avandia)]. Illicit drugs such as alcohol, cocaine, methamphetamine, ecstasy, and synthetic cannabinoids (spice, K2) may also induce mitochondria-related cardiotoxicity. Mitochondrial toxicity develops due to various mechanisms involving interference with the mitochondrial respiratory chain (e.g., uncoupling) or inhibition of the important mitochondrial enzymes (oxidative phosphorylation, Szent-Gyorgyi-Krebs cycle, mitochondrial DNA replication, ADP/ATP translocator). The final phase of mitochondrial dysfunction induces loss of mitochondrial membrane potential and an increase in mitochondrial oxidative/nitrative stress, eventually culminating into cell death. This review aims to discuss the mechanisms of mitochondrion-mediated cardiotoxicity of commonly used drugs and some potential cardioprotective strategies to prevent these toxicities.

Drug-induced mitochondrial dysfunction and cardiotoxicity.

The thyroid gland plays a major role in the human body; it produces the hormones necessary for appropriate energy levels and an active life. These hormones have a critical impact on early brain development and somatic growth. At the same time, the thyroid is highly vulnerable to autoimmune thyroid diseases (AITDs). They arise due to the complex interplay of genetic, environmental, and endogenous factors, and the specific combination is required to initiate thyroid autoimmunity. When the thyroid cell becomes the target of autoimmunity, it interacts with the immune system and appears to affect disease progression. It can produce different growth factors, adhesion molecules, and a large array of cytokines. Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of AITDs in genetically predisposed individuals. The susceptibility of the thyroid to AITDs may come from the complexity of hormonal synthesis, peculiar oligoelement requirements, and specific capabilities of the thyroid cell's defense system. An improved understanding of this interplay could yield novel treatment pathways, some of which might be as simple as identifying the need to avoid smoking or to control the intake of some nutrients.

/pdf/why-is-the-thyroid-so-prone-to-autoimmune-disease-19qrxpuj4b.pdf

Why is the thyroid so prone to autoimmune disease

Glucocorticoids (GC) are used widely for the treatment of patients with various disorders, including autoimmune diseases, allergies, and lymphoproliferative disorders. Glucocorticoid therapy is often limited by several adverse reactions associated with GC excess. Excess GC can elicit a variety of symptoms and signs, including growth retardation in children; immunosuppression; cardiovascular disorders like hypertension and atherosclerosis; osteoporosis; myopathy; and diabetes mellitus. Currently, attention is focused on oxidative stress as one of the major determinants of endothelial dysfunction and cardiovascular senescence. The main reason for all unwanted effects of GC is that dexamethasone induces the overproduction of reactive oxygen species, causing dysregulation of physiological processes. Humans and animals with GC-induced hypertension exhibit reduced nitric oxide levels; patients with excess GC levels also suffer from depression as a consequence of low levels of serotonin and melatonin. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4), which is required for nitric oxide synthesis.

Glucocorticoids and oxidative stress.

SUMMARY Introduction The manifestations of autonomic nervous system (ANS) dysfunction in autoimmune diseases have been the subject of many studies. However, the published results pertaining to such research are controversial. Sudden cardiac death due to fatal arrhythmias is frequent in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Objective To analyse risk predictors of sudden cardiac death related to the degree of autonomic dysfunction. Methods We performed cardiovascular ANS assessment in 90 patients in this case-controlled study, including 52 (6 male, 46 female) patients with SLE, 38 (6 male, 32 female) with RA and 41 (23 male, 17 female) healthy subjects. The methodology included a comprehensive ECG analysis (with Schiller soft- ware AT-10) of QTc interval, late potentials, short-term heart rate variability (HRV) and nonlinear HRV (Poincare plot) analysis; 24-hour Holter ECG monitoring with ECG QTc interval analysis, HRV analysis; 24-hour blood pressure monitoring with systolic and diastolic blood pressure variability; cardiovas- cular autonomic reflex tests (according to Ewing). Vagal dysfunction was established by performing 3 tests: Valsalva maneuver, deep breathing test and heart rate response to standing test. Dysfunction of the sympathetic nervous system was examined by applying 2 tests: blood pressure response to stand- ing and handgrip test. Results In all cardiovascular reflex tests, the frequencies of abnormal results were significantly higher among the patients than among the healthy subjects. Severe autonomic dysfunction was more common in RA. QTc interval was more prolonged in patients with SLE. Both diseases were associated with depressed heart rate variability compared to controls, the reduction being greater in RA patients. In the patients with SLE, autonomic dysfunction is predominantly with higher sympathetic activity while in RA vagal predominance is evident. Conclusion SLE and RA are associated with severe autonomic dysfunction and the presence of signif- icant risk predictors related to the onset of sudden cardiac death.

http://www.doiserbia.nb.rs/img/doi/0370-8179/2010/0370-81791002026M.pdf

Cardiac autonomic dysfunction in patients with systemic lupus, rheumatoid arthritis and sudden death risk.

Assessment of general movements and heart rate variability in prediction of neurodevelopmental outcome in preterm infants.

Percutaneous balloon aortic valvoplasty (BAV) and surgical aortic valvotomy (SAV) are palliative procedures in patients with non-critical congenital valve stenosis. The aim of the study was to evaluate long-term BAV and SAV results after up to 24 years of follow-up. From 1987 to 2013, 74 consecutive interventions were performed in patients with aortic stenosis, and 62 were included in the study (39 BAVs and 23 SAVs). Age of BAV patients was 1.3 months to 17 years, and of SAV patients 1.2 months to 15 years. Although BAV patients were older, there was no difference between groups according to sex, valve function/morphology, and early/late follow-up results, with exception to hospitalization period. Significant pressure gradient reduction and aortic regurgitation increment were registered after procedures. Three patients did not survive early period after surgery. Follow-up period was 7.0 ± 5.4 and 9.0 ± 8.0 years after BAV and SAV, respectively (p = 0.242). Follow-up pressure gradient rose only in the BAV group, and was emphasized after 10-year-follow-up (p = 0.020). Significant aortic insufficiency progression was registered after 15 years of follow-up in both groups (p = 0.007 and p = 0.009, respectively). Mean reintervention-free survival was 12.0 years in the BAV and 14.5 years in the SAV group (p = 0.733), and mean survival without aortic valve replacement was 15.2 and 17.4 years, respectively (p = 0.877). BAV and SAV in patients with congenital aortic stenosis are very comparable in both early and late follow-up results.

Bojko Bjelakovic

Papers

Why is the thyroid so prone to autoimmune disease

Glucocorticoids and oxidative stress.

Cardiac autonomic dysfunction in patients with systemic lupus, rheumatoid arthritis and sudden death risk.

Assessment of general movements and heart rate variability in prediction of neurodevelopmental outcome in preterm infants.

Balloon dilation and surgical valvotomy comparison in non-critical congenital aortic valve stenosis.