Elevated blood pressure prevalence in children did not follow the increase in overweight: results from a school-based study in a rapidly developing country, 1998-2006

Background: Blood pressure (BP) is strongly associated with body weight and there is concern that the pediatric overweight epidemic could lead to an increase in children's mean BP. Objectives: We analyzed BP trends from 1998 to 2006 among children of the Seychelles, a rapidly developing middle-income country in Africa. Methods: Serial school-based surveys of weight, height and BP were conducted yearly between 1998-2006 among all students of the country in four school grades (kindergarten, 4th, 7th and 10th years of compulsory school). We used the CDC criteria to define "overweight" (BMI _95th sex-, and age-specific percentile) and the NHBPEP criteria for "elevated BP" (BP _95th sex-, age-, and height specific percentile). Methods for height, weight, and BP measurements were identical over the study period. The trends in mean BMI and mean systolic/diastolic BP were assessed with linear regression. Results: 27,703 children aged 4-18 years (participation rate: 79%) contributed 43,927 observations on weight, height, and BP. The prevalence of overweight increased from 5.1% in 1998-2000 to 8.1% in 2004-2006 among boys, and from 6.1% to 9.1% among girls, respectively. The prevalence of elevated BP was 8.4% in 1998-2000 and 6.9% in 2004-2006 among boys; 9.8% and 7.8% among girls, respectively. Over the 9-years study period, age-adjusted body mass index (BMI) increased by 0.078 kg/m2/year in boys and by 0.083 kg/m2/year in girls (both sexes, P_0.001). Age- and height-adjusted systolic BP decreased by -0.37 mmHg/year in boys and by -0.34 mmHg/year in girls (both sexes, P_0.001). Diastolic BP did not change in boys (-0.02 mmHg/year, P: 0.40) and slightly increased in girls (0.07 mmHg/year, P: 0.003). These trend estimates were altered modestly upon further adjustment for BMI or if analyses were based on median rather than mean values. Conclusion: Although body weight increased markedly between 1998 and 2006 in this population, systolic BP decreased and diastolic BP changed only marginally. This suggests that population increases in body weight are not necessarily associated with corresponding rises in BP in children.

Proposal of a new classification for optimising outcome assessment following partial cricotracheal resections in severe pediatric subglottic stenosis.

OBJECTIVE: Creation of a patent subglottic airway after partial cricotracheal resection (PCTR) may not always result in successful decannulation due to associated parameters such as co-morbidity and/or glottic involvement. We classified patients after incorporating these additional parameters into the original Myer-Cotton classification to assess whether this could better predict the outcome measures after PCTR. METHODS: One hundred children with Myer-Cotton grade III or IV subglottic stenosis who underwent PCTR between 1978 and 2008 were identified from a prospectively collected database. The patients were classified into four groups based on the association of co-morbidity and/or glottic involvement. Delay in decannulation, revision open surgery and rates of decannulation were the outcome measures compared between the groups. RESULTS: There were 68 children with Myer-Cotton grade III and 32 children with grade IV stenosis. Based on the new classification, there were 36 children with isolated SGS, 31 with associated co-morbidity, 19 with associated glottic involvement and 14 children with both co-morbidity and glottic involvement. A trend towards less optimal results was noticed with the association of co-morbidity and/or glottic involvement. Statistical significance was reached for maximum decannulation failure in the group with both co-morbidity and glottic involvement. Delayed decannulation significantly correlated in the group with associated glottic involvement. CONCLUSION: This new classification is relatively simple and aimed at providing more accurate and uniform prognostic information to both patients and surgeons when dealing with the whole spectrum of severe SGS.

A 338-bp proximal fragment of the glucose transporter type 2 (GLUT2) promoter drives reporter gene expression in the pancreatic islets of transgenic mice.

The high Km glucose transporter GLUT2 is a membrane protein expressed in tissues involved in maintaining glucose homeostasis, and in cells where glucose-sensing is necessary. In many experimental models of diabetes, GLUT2 gene expression is decreased in pancreatic beta-cells, which could lead to a loss of glucose-induced insulin secretion. In order to identify factors involved in pancreatic beta-cell specific expression of GLUT2, we have recently cloned the murine GLUT2 promoter and identified cis-elements within the 338-bp of the proximal promoter capable of binding islet-specific trans-acting factors. Furthermore, in transient transfection studies, this 338-bp fragment could efficiently drive the expression of the chloramphenicol acetyl transferase (CAT) gene in cell lines derived from the endocrine pancreas, but displayed no promoter activity in non-pancreatic cells. In this report, we tested the cell-specific expression of a CAT reporter gene driven by a short (338 bp) and a larger (1311 bp) fragment of the GLUT2 promoter in transgenic mice. We generated ten transgenic lines that integrated one of the constructs. CAT mRNA expression in transgenic tissues was assessed using the RNAse protection assay and the quantitative reverse transcribed polymerase chain reaction (RT-PCR). Overall CAT mRNA expression for both constructs was low compared to endogenous GLUT2 mRNA levels but the reporter transcript could be detected in all animals in the pancreatic islets and the liver, and in a few transgenic lines in the kidney and the small intestine. The CAT protein was also present in Langerhans islets and in the liver for both constructs by immunocytochemistry. These findings suggest that the proximal 338 bp of the murine GLUT2 promoter contain cis-elements required for the islet-specific expression of GLUT2.

Behavioral phenotyping of glutathione-deficient mice: Relevance to schizophrenia and bipolar disorder.

Redox-dysregulation represents a common pathogenic mechanism in schizophrenia (SZ) and bipolar disorder (BP). It may in part arise from a genetically compromised synthesis of glutathione (GSH), the major cellular antioxidant and redox-regulator. Allelic variants of the genes coding for the rate-limiting GSH synthesizing enzyme glutamate-cysteine-ligase modifier (GCLM) and/or catalytic (GCLC) subunit have been associated with SZ and BP. Using mice knockout (KO) for GCLM we have previously shown that impaired GSH synthesis is associated with morphological, functional and neurochemical anomalies similar to those in patients. Here we asked whether GSH deficit is also associated with SZ- and BP-relevant behavioral and cognitive anomalies. Accordingly, we subjected young adult GCLM-wildtype (WT), heterozygous and KO males to a battery of standard tests. Compared to WT, GCLM-KO mice displayed hyperlocomotion in the open field and forced swim test but normal activity in the home cage, suggesting that hyperlocomotion was selective to environmental novelty and mildly stressful situations. While spatial working memory and latent inhibition remained unaffected, KO mice showed a potentiated hyperlocomotor response to an acute amphetamine injection, impaired sensorymotor gating in the form of prepulse inhibition and altered social behavior compared to WT. These anomalies resemble important aspects of both SZ and the manic component of BP. As such our data support the notion that redox-dysregulation due to GSH deficit is implicated in both disorders. Moreover, our data propose the GCLM-KO mouse as a valuable model to study the behavioral and cognitive consequences of redox dysregulation in the context of psychiatric disease.

Blood pressure treatment in acute ischemic stroke: a review of studies and recommendations.

PURPOSE OF REVIEW: Elevated blood pressure (BP) is frequent in patients with acute ischemic stroke. Pathophysiological data support its usefulness to maintain adequate perfusion of the ischemic penumba. This review article aims to summarize the available evidence from clinical studies that examined the prognostic role of BP during the acute phase of ischemic stroke and intervention studies that assessed the efficacy of active BP alteration. RECENT FINDINGS: We found 34 observational studies (33,470 patients), with results being inconsistent among the studies; most studies reported a negative association between increased levels of BP and clinical outcome, whereas a few studies showed clinical improvement with higher BP levels, clinical deterioration with decreased BP, or no association at all. Similarly, the conclusions drawn by the 18 intervention studies included in this review (1637 patients) were also heterogeneous. Very recent clinical data suggest a possible beneficial effect of early treatment with some antihypertensives on late clinical outcome. SUMMARY: Observational and interventional studies of management of acute poststroke hypertension yield conflicting results. We discuss different explanations that may account for this and discuss the current guidelines and pathophysiological considerations for the management of acute poststroke hypertension.

Long-term voice outcome following partial cricotracheal resection in children for severe subglottic stenosis.

OBJECTIVE: To correlate the postoperative voice outcome to preoperative glottic involvement, following partial cricotracheal resection (PCTR) in children. The glottic involvement was analysed based on the extent of subglottic stenosis (SGS) in the endoscopic image and functional dynamic assessment using flexible endoscopy. METHODS: We conducted an interobserver study in which two ENT surgeons, blinded to one another's interpretation, independently rated the extent of SGS based on the endoscopic image along with the dynamic functional airway assessment, of 108 children who underwent PCTR for grade III or IV stenosis. Based on the observation, the glottic involvement was rated into 4 categories: Evaluation of the voice was based on a parent/patient proxy questionnaire sent in 2008 to assess the current functional status of the patient's voice. RESULTS: Among the 77 patients available for long-term outcome with a minimum 1-year follow-up, 31 patients had isolated SGS free from vocal cords (group A) and 30 had SGS reaching the under surface of vocal cords with partial or no impairment of abduction of vocal cords (group B). Twelve patients belonged to group C with posterior glottic stenosis and/or vocal cord fusion (without cricoarytenoid ankylosis) and 4 patients had transglottic stenosis and or/bilateral cricoarytenoid ankylosis (group D). The long-term voice outcome following PCTR as perceived by the parent or patient was normal in 18% (14 of 77 patients) and the remaining 63 patients demonstrated mild to severe dysphonia. Patients belonging to group A and B exhibited either normal voice or mild dysphonia. Patients in group C demonstrated dysphonia, which was moderate in severity in the majority (83%). All patients in group D with transglottic stenosis and/or CAA showed severe dysphonia. CONCLUSION: Children with associated glottic involvement are at high risk for poor voice outcome following PCTR. The severity of dysphonia was found to be proportional to the preoperative glottic involvement. Preoperative rating of the extent of glottic involvement based on endoscopic image and dynamic assessment was found to be useful in prognosticating the voice outcome.

Local Renal Circadian Clocks Control Fluid-Electrolyte Homeostasis and BP.

The circadian timing system is critically involved in the maintenance of fluid and electrolyte balance and BP control. However, the role of peripheral circadian clocks in these homeostatic mechanisms remains unknown. We addressed this question in a mouse model carrying a conditional allele of the circadian clock gene Bmal1 and expressing Cre recombinase under the endogenous Renin promoter (Bmal1(lox/lox)/Ren1(d)Cre mice). Analysis of Bmal1(lox/lox)/Ren1(d)Cre mice showed that the floxed Bmal1 allele was excised in the kidney. In the kidney, BMAL1 protein expression was absent in the renin-secreting granular cells of the juxtaglomerular apparatus and the collecting duct. A partial reduction of BMAL1 expression was observed in the medullary thick ascending limb. Functional analyses showed that Bmal1(lox/lox)/Ren1(d)Cre mice exhibited multiple abnormalities, including increased urine volume, changes in the circadian rhythm of urinary sodium excretion, increased GFR, and significantly reduced plasma aldosterone levels. These changes were accompanied by a reduction in BP. These results show that local renal circadian clocks control body fluid and BP homeostasis.

Low predictive value of elevated blood pressure during childhood and adolescence

Background: Screening of elevated blood pressure (BP) in children has been advocated to early identify hypertension. However, identification of children with sustained elevated BP is challenging due to the high BP variability. The value of an elevated BP measure during childhood and adolescence for the prediction of future elevated BP is not well described. Objectives: We assessed the positive (PPV) and negative (NPV) predictive value of high BP for sustained elevated BP in cohorts of children of the Seychelles, a rapidly developing island state in the African region. Methods: Serial school-based surveys of weight, height, and BP were conducted yearly between 1998-2006 among all students of the country in four school grades (kindergarten [G0, mean age (SD): 5.5 (0.4) yr], G4 [9.2 (0.4) yr], G7 [12.5 (0.4) yr] and G10 (15.6 (0.5) yr]. We constituted three cohorts of children examined twice at 3-4 years interval: 4,557 children examined at G0 and G4, 6,198 at G4 and G7, and 6,094 at G7 and G10. The same automated BP measurement devices were used throughout the study. BP was measured twice at each exam and averaged. Obesity and elevated BP were defined using the CDC (BMI_95th sex-, and age-specific percentile) and the NHBPEP criteria (BP_95th sex-, age-, and height specific percentile), respectively. Results: Prevalence of obesity was 6.1% at G0, 7.1% at G4, 7.5% at G7, and 6.5% at G10. Prevalence of elevated BP was 10.2% at G0, 9.9% at G4, 7.1% at G7, and 8.7% at G10. Among children with elevated BP at initial exam, the PPV of keeping elevated BP was low but increased with age: 13% between G0 and G4, 19% between G4 and G7, and 27% between G7 and G10. Among obese children with elevated BP, the PPV was higher: 33%, 35% and 39% respectively. Overall, the probability for children with normal BP to remain in that category 3-4 years later (NPV) was 92%, 95%, and 93%, respectively. By comparison, the PPV for children initially obese to remain obese was much higher at 71%, 71%, and 62% (G7-G10), respectively. The NPV (i.e. the probability of remaining at normal weight) was 94%, 96%, and 98%, respectively. Conclusion: During childhood and adolescence, having an elevated BP at one occasion is a weak predictor of sustained elevated BP 3-4 years later. In obese children, it is a better predictor.

Discordant secular trends in elevated blood pressure and obesity in children and adolescents in a rapidly developing country

BACKGROUND: The effect of the increasing prevalence of obesity on blood pressure (BP) secular trends is unclear. We analyzed BP and body mass index secular trends between 1998 and 2006 in children and adolescents of the Seychelles, a rapidly developing island state in the African region. METHODS AND RESULTS: School-based surveys were conducted annually between 1998 and 2006 among all students in 4 school grades (kindergarten and 4th, 7th, and 10th years of compulsory school). We used the Centers for Disease Control and Prevention criteria to define obesity and elevated BP. The same methods and instruments were used in all surveys. Some 25 586 children and adolescents 4 to 18 years of age contributed 43 867 observations. Although the prevalence of obesity in boys and girls increased from 5.1% and 6.0%, respectively, in 1998 to 2000 to 8.0% and 8.7% in 2004 to 2006, the prevalence of elevated BP decreased from 8.4% and 9.8% to 6.9% and 7.8%. During the interval, mean age-adjusted body mass index increased by 0.57 kg/m(2) in boys and 0.58 kg/m(2) in girls. Mean age- and height-adjusted systolic BP decreased by -3.0 mm Hg in boys and -2.8 mm Hg in girls, whereas mean diastolic BP did not change substantially in boys (-0.2 mm Hg) and increased slightly in girls (0.4 mm Hg). CONCLUSIONS: At a population level, the marked increase in the prevalence of obesity in children and adolescents in the Seychelles was not associated with a commensurate secular rise in mean BP.

Non-functioning pituitary macro-incidentalomas benefit from early surgery before becoming symptomatic.

OBJECTIVE: Pituitary incidentalomas (PIs) constitute an increasingly clinical problem. While the therapeutic management is well defined for symptomatic non-functioning PIs (NFPIs), a controversy still exists for asymptomatic macro-NFPIs between surgery and a "wait and see" approach. The aim of this study is to compare surgical results between symptomatic and asymptomatic macro-NFPIs. METHODS: We conducted a retrospective study on 76 patients with newly diagnosed symptomatic and asymptomatic macro-NFPIs operated on between 2001 and 2010. We compared age, tumor size and surgical results between these two patient groups. RESULTS: After the initial evaluation, 48 patients were found to be symptomatic. Gross total removal (GTR) rate was significantly higher in asymptomatic (82%) than in symptomatic patients (58%; p=0.03). Gross total removal was strongly associated with Knosp's classification (p=0.01). Postoperative endocrinological impairment was significantly associated with the existence of preoperative symptoms (p=0.03). It was 10 times less frequent in the asymptomatic group. In symptomatic patients, postoperative visual and endocrinological impairment were present in 49% and 78% versus 0% and 14% in asymptomatic patients respectively. CONCLUSIONS: The endocrinological and visual outcome was better in those patients who underwent surgery for asymptomatic tumors. The extent of tumor resection was also significantly greater in smaller tumors. It would therefore be appropriate to offer surgery to patients with asymptomatic macro-NFPIs.

Association between growth and blood pressure during the life course in children and adolescents

Background: Little is known on the relative importance of growth at different periods between birth and adolescence on blood pressure (BP). Objective: To assess the association between birth weight, change in body weight (growth) and BP across the entire span of childhood and adolescence. Methods: School-based surveys were conducted annually between 1998 and 2006 among all children in four school grades (kindergarten, 4th, 7th, and 10th year of compulsory school) in the Seychelles, Indian Ocean. Height and weight and BP were measured. Three cohorts of children examined twice were analyzed: 1606 children surveyed at age 5.5 and 9.1, 2557 at age 9.2 and 12.5, and 2065 at age 12.5 and 15.5, respectively. Weights at birth and at one year were extracted from medical files. Weights were expressed as Z-scores and growth was defined as a change in weight Z-scores (corresponding to weight centile crossing). The association between BP (at age 5.5, 9.2, 12.5, and 15.5) and weight at different times was assessed by linear regression. Using results of regression models of BP on all successive weights, life course plots were drawn by plotting regression coefficients against age at which weight was measured. The figure shows a life course plot of systolic BP in boys aged 15.5. Results: Without adjustment for current weight (at the time of BP measurement), birth weight was not associated with current BP, irrespective of age, excepted for girls at age 15.5 for whom a modest positive association was found. When adjusted for current weight, birth weight was negatively and modestly associated with current BP. BP was strongly associated with current weight, irrespective of age. Life course plots showed that BP was strongly associated with growth during the few preceding years but not with growth during earlier years, except for growth during the first year of life which tended to be associated with systolic BP. Conclusions: Our findings suggest that BP during childhood and adolescence is mainly determined by current body weight and recent growth.