No Role for Cerebrospinal Fluid Myelin Basic Protein Levels in Patients Treated for Childhood Acute Lymphoblastic Leukemia.

INTRODUCTION: Central nervous system prophylaxis of childhood acute lymphoblastic leukemia has dropped rates of relapses but has been associated with neurotoxicity and imaging abnormalities. Predictors of neurotoxicity are lacking, because of inconsistency between clinical symptoms and imaging. Some have suggested that cerebrospinal fluid myelin basic protein (MBP) levels to be of potential interest. A retrospective analysis of MBP levels in correlation with clinical and radiologic data is presented. MATERIALS AND METHODS: MBP levels obtained at the time of intrathecals, charts, and neuroradiology reports were retrospectively analyzed. Academic achievement data were obtained from phone contacts with patients and families. RESULTS: We retrieved 1248 dosages of MBP in 83 patients, 381 neurologic examinations in 34 patients and 69 neuroradiologic investigations in 27 patients. Fifty-two patients had abnormal MBP levels. Radiologic anomalies were present in 47% of those investigated, 14% of them having school difficulties. Proportions of patients with school difficulties in the groups with abnormal MBP levels but no radiologic anomalies or with no radiologic investigations were 0% and 3%, respectively, which was lower than in the group of patients with normal MBP levels (100%, 22%, and 5%, respectively). DISCUSSION: Notwithstanding the retrospective character of our study, we conclude that there is limited usefulness of systematic dosage of MBP as indicator of treatment-induced neurotoxicity in acute lymphoblastic leukemia patients.

Zeitpunkt der Medikamenten-einnahme bei Hypertonie und Angina pectoris. Eine kontrollierte Uberwachungsstudie. [Time of drug intake in hypertension and angina pectoris. A controlled monitoring study]

A prospective cross-over study was performed in a general practice environment to assess and compare compliance data obtained by electronic monitoring on a BID or QD regimen in 113 patients with hypertension or angina pectoris. All patients were on a BID regimen (nifedipine SR) during the first month and switched to QD regimen (amlodipine) for another month. Taking compliance (i.e. the proportion of days with correct dosing) improved in 30% of patients (95% confidence interval 19 to 41%, p < 0.001), when switching from a BID to a QD regimen, but at the same time there was a 15% increase (95% confidence interval 5 to 25%, p < 0.02) in the number of patients with one or more no-dosing days. About 8% of patients had a low compliance rate, irrespective of the dosage regimen. Actual dosage intervals were used to estimate extent and timing of periods with unsatisfactory drug activity for various hypothetical drug durations of action, and it appears that the apparent advantage of QD regimen in terms of compliance is clinically meaningful only, when the duration of activity extents beyond the dosage interval in all patients.

Preliminary estimates and forecasts of the population prevalence of self reported of hypertension, of ischaemic heart disease and stroke in the Republic of Ireland from 2005 - 2015

Ireland and Northern Ireland’s Population Health Observatory (INIsPHO) recently published estimates of the population prevalence of diabetes in 2005 and forecasts to 2010 and 2015 for the island of Ireland, at the national and sub-national levels. These estimates are based the PBS Model developed by York and Humber Public Health Observatory (YHPHO), Brent NHS Trust and the School of Health and Related Research (ScHARR).The Department of Health and Children (DoHC) has requested additional estimates and forecasts for hypertension.This paper outlines the results from preliminary work from the initial steps towards a more systematic approach to monitoring the prevalence of other chronic diseases on the island.

Making Chronic Conditions Count: 3. Hypertension

Chronic conditions are responsible for a significant proportion of early deaths. They reduce quality of life in many of the adults living with them, represent substantial financial costs to patients and the health and social care system, and cause a significant loss of productivity to the economy. This report contains estimates and forecasts of the population prevalence of hypertension and shows how it varies across the island and what change is expected between 2007, 2015 and 2020.

Hypertension Briefing

Blood pressure is the force exerted on artery walls as the heart pumps blood through the body. Hypertension, or high blood pressure, occurs when blood pressure is constantly higher than the pressure needed to carry blood through the body. The Chronic Conditions Hub is a website that brings together information on chronic health conditions. It allows you to easily access, manage and share relevant information resources. The Chronic Conditions Hub includes the Institute of Public Health in Ireland’s (IPH) estimates and forecasts of the number of people living with chronic conditions. On the Chronic Conditions Hub you will find:- A Briefing for each condition - Detailed technical documentation - Detailed national and sub-national data that can be downloaded or explored using online data tools - A prevalence tool that allows you to calculate prevalence figures for your population data

Hypertension Briefing: Technical documentation

Blood pressure is the force exerted on artery walls as the heart pumps blood through the body. Hypertension, or high blood pressure, occurs when blood pressure is constantly higher than the pressure needed to carry blood through the body. This document details how the IPH uses a systematic and consistent method to produce prevalence data for hypertension on the island of Ireland.

Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

A Tobacco-Free Future - An all-island report on tobacco, inequalities and childhood 2013

A Tobacco-Free Future - An all-island report on tobacco, inequalities and childhood 2013 reveals declines in smoking rates among both children and pregnant women over the past decade, both North and South of the border. This report published by the Institute of Public Health in Ireland (IPH) and the TobaccoFree Research Institute Ireland (TFRI), shows that while tobacco control measures are being successful, disadvantaged children are at particular risk of tobacco-related harms.

Prevalence of chronic conditions – Hypertension

IPH has estimated and forecast clinical diagnosis rates of hypertension among adults for the years 2010, 2015 and 2020. In the Republic of Ireland, the data are based on the Survey of Lifestyle, Attitudes and Nutrition (SLÁN) 2007. The data describe the number of people who report that they have experienced doctor-diagnosed hypertension in the previous 12 months (annual clinical diagnosis). Data are available by age and sex for each Local Health Office of the Health Service Executive (HSE) in the Republic of Ireland. In Northern Ireland, the data is based on the Health and Social Wellbeing Survey 2005/06. The data describe the number of people who report that they have experienced doctor/nurse-diagnosed hypertension at any time in the past (lifetime clinical diagnosis). Data are available by age and sex for each Local Government District in Northern Ireland. Clinical diagnosis rates in the Republic of Ireland relate to the previous 12 months and are not directly comparable with clinical diagnosis rates in Northern Ireland which relate to anytime in the past.   The IPH estimated prevalence per cents may be marginally different to estimated prevalence per cents taken directly from the reference study. There are two reasons for this: 1) The IPH prevalence estimates relate to 2010 while the reference studies relate to earlier years (Northern Ireland Health and Social Wellbeing Survey 2005/06, Survey of Lifestyle, Attitudes and Nutrition 2007, Understanding Society 2009). Although we assume that the risk of the condition in the risk groups do not change over time, the distribution of the number of people in the risk groups in the population changes over time (eg the population ages).  This new distribution of the risk groups in the population means that the risk of the condition is weighted differently to the reference study and this results in a different overall prevalence estimate. 2) The IPH prevalence estimates are based on a statistical model of the reference study. The model includes a number of explanatory variables to predict the risk of the condition. Therefore the model does not include records from the reference study that are missing data on these explanatory variables. A prevalence estimate for a condition taken directly from the reference study would include these records.

Closeness in relationships as a mediator between sexual abuse in childhood or adolescence and psychopathological outcome in adulthood.

The risk of adverse psychological outcomes in adult victims of childhood and adolescent sexual abuse (CSA) has been documented; however, research on possible mediating variables is still required, namely with a clinical perspective. The attachment literature suggests that secure interpersonal relationships may represent such a variable. Twenty-eight women who had experienced episodes of CSA, and 16 control women, were interviewed using Bremner's Early Trauma Inventory and the DSM-IV Global Assessment of Functioning; they also responded to Collins' Relationship Scales Questionnaire, evaluating adult attachment representations in terms of Closeness, Dependence and Anxiety. Subjects with an experience of severe abuse reported significantly more interpersonal distance in relationships (low index of Closeness) than other subjects. The index of psychopathological functioning was correlated with both the severity of abuse and attachment (low index of Closeness). Regression analysis on the sample of abused women revealed that attachment predicted psychopathology when abuse was controlled for, whereas abuse did not predict psychopathology when attachment was controlled for. Therefore, preserving a capacity for closeness with attachment figures in adulthood appears to mediate the consequences of CSA on subsequent psychopathological outcome.

Effect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia.

AIM: Improving cerebral perfusion is an essential component of post-resuscitation care after cardiac arrest (CA), however precise recommendations in this setting are limited. We aimed to examine the effect of moderate hyperventilation (HV) and induced hypertension (IH) on non-invasive cerebral tissue oxygenation (SctO2) in patients with coma after CA monitored with near-infrared spectroscopy (NIRS) during therapeutic hypothermia (TH). METHODS: Prospective pilot study including comatose patients successfully resuscitated from out-of-hospital CA treated with TH, monitored with NIRS. Dynamic changes of SctO2 upon HV and IH were analyzed during the stable TH maintenance phase. HV was induced by decreasing PaCO2 from ∼40 to ∼30 mmHg, at stable mean arterial blood pressure (MAP∼70 mmHg). IH was obtained by increasing MAP from ∼70 to ∼90 mmHg with noradrenaline. RESULTS: Ten patients (mean age 69 years; mean time to ROSC 19 min) were studied. Following HV, a significant reduction of SctO2 was observed (baseline 74.7±4.3% vs. 69.0±4.2% at the end of HV test, p<0.001, paired t-test). In contrast, IH was not associated with changes in SctO2 (baseline 73.6±3.5% vs. 74.1±3.8% at the end of IH test, p=0.24). CONCLUSIONS: Moderate hyperventilation was associated with a significant reduction in SctO2, while increasing MAP to supra-normal levels with vasopressors had no effect on cerebral tissue oxygenation. Our study suggests that maintenance of strictly normal PaCO2 levels and MAP targets of 70mmHg may provide optimal cerebral perfusion during TH in comatose CA patients.

Infectious Diseases - Childhood Immunisation

Infectious Diseases - Childhood Immunisation

Victimization in Childhood of Male Sex Offenders: Relationship between Violence Experienced and Subsequent Offenses through Discourse Analysis

This study aims at better understanding how the form of childhood violence experienced and the type of offense subsequently committed affect how sex offenders recall punishments and difficult events. Fifty-four male perpetrators convicted of sexual offenses against children (SOCs) or against adults (SOAs) were interviewed in France, Belgium, and Switzerland using the Lausanne Clinical Interview (Entretien Clinique de Lausanne or LCI). Almost three-quarters of the sex offenders reported having been victimized during childhood. The correspondence analysis identified several factors that differentiated them. Their appraisal of the distressing event, method of coping with and distancing themselves from it, and how they dealt with emotions varied markedly depending on whether they recognized having experienced various forms of violence during childhood and on what type of offense they subsequently committed. Victimization can be identified as much by the events experienced as by their effect on the sex offender's discourse. Identification of these discursive indicators may lead to an improved therapeutic approach for potentially traumatic childhood experiences.

Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence.

Long-term implications of the exposure to traumatizing experiences during childhood or adolescence, such as sexual abuse, or cancer, have been documented, namely the subjects' response to an acute stress in adulthood. Several indicators of the stress response have been considered (e.g. cortisol, heart rate). Oxytocin (OT) response to an acute stress of individuals exposed to trauma has not been documented. Eighty subjects (n=26 women who had experienced episodes of child abuse, n=25 men and women healthy survivors of cancer in childhood or adolescence, and 29 controls) have been submitted to a laboratory session involving an experimental stress challenge, the Trier social stress test. Overall, there was a clear OT response to the psychosocial challenge. Subjects having experienced a childhood/adolescence life-threatening illness had higher mean levels of OT than both abused and control subjects. There was a moderate negative relationship between OT and salivary cortisol. It is suggested that an acute stress stimulates OT secretion, and that the exposure to enduring life-threatening experiences in childhood/adolescence has long-lasting consequences regarding the stress system and connected functions, namely the activation of OT secretion. Better knowledge of such long-term implications is important so that to prevent dysregulations of the stress responses, which have been shown to be associated to the individual's mental health.

Efficacy and safety of various combination therapies based on a calcium antagonist in essential hypertension: results of a placebo-controlled randomized trial

We tested the efficacy and safety of different combination therapies in hypertensive patients with uncontrolled blood pressure (BP) on a monotherapy with a calcium antagonist: 1,647 hypertensive patients were enrolled to receive placebo for 4 weeks followed by isradipine (ISR) 2.5 mg twice daily (b.i.d.) for 4 weeks. Nonresponders [diastolic BP (DBP) > 90 mm Hg] were randomly assigned to receive either the beta-blocker bopindolol 0.5 or 1 mg/day, the diuretic metolazone 1.25 or 2.5 mg/day, the angiotensin-converting enzyme (ACE) inhibitor enalapril 10 or 20 mg/day, ISR 5 mg b.i.d., or placebo. One hundred seventy-five receiving placebo dropped out; 93% (n = 1,376) of the 1,472 patients finished 4-week monotherapy with ISR. Sixty percent (n = 826) reached target BP, and 40% (n = 550) remained uncontrolled and were randomized. Regardless of dosage, all drugs led to a comparable reduction in BP except for the lower dosage of bopindolol and ISR 5 mg b.i.d., which were less effective in lowering systolic BP (SBP). The BP decrease achieved by combination therapy ranged from 10 to 15 mm Hg SBP and from 7 to 11 mm Hg DBP but remained unchanged with placebo. Side effects were minor, and only 2.4% of patients discontinued therapy because of side effects. The side-effect score for edema was lower with ISR plus diuretics than with other combinations, whereas the ACE inhibitor was associated with a higher score for cough. Monotherapy with a calcium antagonist normalizes BP in about two-thirds of patients when used in general practice.(ABSTRACT TRUNCATED AT 250 WORDS)