Home and Ambulatory Blood Pressure to Identify White Coat and Masked Hypertension in the Pediatric Patient

OBJECTIVE To evaluate the effect of the environment and the observer on the measurement of blood pressure (BP) as well as to compare home BP (HBP) and ambulatory BP (ABP) measurements in the diagnosis of white coat hypertension (WCH) and masked hypertension (MH) in children and adolescents with hypertension (HT). METHODS BP of 40 patients with HT (75% of which had secondary HT and were on antihypertensive medication), mean age 12.1 years was evaluated through casual measurements at the clinic and at the HT unit, HBP for 14 days with the OMRON HEM 705 CP monitor (Omron, Tokyo, Japan) and ABP performed with SPACELABS 90207 (Spacelabs, Redmond, WA), for 24 h. RESULTS HT was diagnosed at the doctor`s office by ABP and HBP in 30/40, 27/40, and 31/40 patients, respectively. Based on office BP and ABP, 60% of patients were normotensive, 17.5% HT, 7.5% had WCH, and 15% had MH, whereas based on office BP and HBP 65, 12.5, 10, and 12.5% of patients were classified according to these diagnoses, respectively. There was considerable diagnostic agreement of HT by ABP and HBP (McNemar test, P < 0.01) (kappa = 0.56). CONCLUSION In hypertensive children and adolescents, HBP and ABP present comparable results. HBP appears to be a useful diagnostic test for the detection of MH and WCH in pediatric patients.

Characteristics and Predictors of Obstructive Sleep Apnea in Patients With Systemic Hypertension

Obstructive sleep apnea (OSA) is a secondary cause of hypertension and independently associated with target-organ damage in hypertensive patients. However, OSA remains largely underdiagnosed and undertreated. The aim of the present study was to evaluate the characteristics and clinical predictors of OSA in a consecutive series of patients followed up in a hypertension unit. A total of 99 patients (age 46 +/- 11 years, body mass index 28.8 kg/m(2), range 25.1 to 32.9) underwent polysomnography. The clinical parameters included age, gender, obesity, daytime sleepiness, snoring, Berlin Questionnaire, resistant hypertension, and metabolic syndrome. Of the 99 patients, 55 (56%) had OSA (apnea-hypopnea index >5 events/hour). Patients with OSA were older and more obese, had greater levels of blood pressure, and presented with more diabetes, dyslipidemia, resistant hypenension, and metabolic syndrome than the patients without OSA. Of the patients with OSA, 51% had no excessive daytime sleepiness. The Berlin Questionnaire and patient age revealed a high sensitivity (0.93 and 0.91, respectively) but low specificity (0.59 and 0.48, respectively), and obesity and resistant hypertension revealed a low sensitivity (0.58 and 0.44, respectively) but high specificity (0.75 and 0.91, respectively) for OSA. Metabolic syndrome was associated with high sensitivity and specificity for OSA (0.86 and 0.85, respectively). Multiple regression analysis showed that age of 40 to 70 years (odds ratio 1.09, 95% confidence interval 1.03 to 1.16), a high risk of OSA on the Berlin Questionnaire (odds ratio 8.36, 95% confidence interval 1.67 to 41.85), and metabolic syndrome (odds ratio 19.04, 95% confidence interval 5.25 to 69.03) were independent variables associated with OSA. In conclusion, more important than the typical clinical features that characterize OSA, including snoring and excessive daytime sleepiness, the presence of the metabolic syndrome is as an important marker of OSA among patients with hypertension. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;105:1135-1139)

Forefoot Deformity in Diabetic Neuropathic Individuals and its Role in Pressure Distribution and Gait

Background. Foot deformities have been related to diabetic neuropathy progression but their influence on plantar distribution during dynamic tasks is not completely understood. The purpose of the present study was to investigate the influence of metatarsal head prominence and claw toes on regional plantar pressures during gait in patients with diabetic neuropathy Methods Seventy-one adults participated in this study categorized into three groups: a control group (CG, n = 32), patients with diabetic neuropathy without any foot deformities (DG, n = 20), and patients with diabetic neuropathy with metatarsal head prominence and/or claw toes (DMHG, n = 19). Plantar pressure variables (contact area, peak pressure, and maximum mean pressure) were evaluated during gait on rearfoot, midfoot, and forefoot using capacitive insoles (Pedar-X System, Novel Inc., Munich, Germany). A general linear model was applied to repeatedly measure and analyze variance relationships between groups and areas. Results. DMHG. presented larger contact areas at the forefoot and midfoot along with higher peak pressure at the rearfoot compared to the other two groups The DG showed higher mean pressure at the midfoot compared to:the other two groups. Conclusion. The coexistence of diabetic neuropathy and metatarsal head prominence in addition to claw toes, resulted in overloading the rearfoot and enhancing the contact area of forefoot and midfoot while walking. This plantar pressure distribution is a result of a different coordination pattern adopted in order to reduce plantar loads at the anterior parts of the foot that were structurally altered. Patients with diabetic neuropathy without any forefoot deformities presented a different plantar pressure distribution than patients with deformities suggesting that both neuropathy and structural foot alterations can influence foot rollover mechanisms.

Estrogen receptor-positive breast carcinomas in younger women are different from those of older women: A pathological and immunohistochemical study

The higher frequency of triple-negative and HER-2-positive tumors detected in younger patients has been suggested as an explanation for the more aggressive tumor types observed in this age group. However, estrogen receptor (ER)-positive tumors are the most frequent subtype of breast carcinomas identified, even in younger patients. In this retrospective study, the morphological and immunohistochemical profiles of ER-positive breast carcinomas from women 35 yrs and younger that were diagnosed between 1997 and 2007 were evaluated. From these cases, 213 were selected based on the availability of pathology reports and paraffin blocks. For comparison, 117 consecutive cases of breast carcinomas diagnosed in patients >60 yrs from 2006 were included. Paraffin-embedded tumors were stained for expression of ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2). Ki-67 antigen, epidermal growth factor receptor (EGFR), cytokeratin 5/6, p53, vimentin, CD117, and p63 using tissue microarrays. ER-positive carcinomas were diagnosed in 120 (56.1%) samples of the younger patient group and in 92 (78.6%) samples of the older patient group. Of these ER-positive carcinomas, 48 (40%) from the younger patient group presented the subtype luminal A, compared with 53 (57.6%) from the older patient group (p=0.01). Tumors from the younger patient group were also associated with increased vascular involvement, co-expression of HER-2, and decreased expression of CD117. These results highlight differences in expression markers and the pathology of ER-positive tumors detected in younger women, with a notable characteristic being co-expression of HER-2. (C) 2010 Elsevier Ltd. All rights reserved.

Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis

Purpose of review The aim of this review is to summarize current evidence about the impact of obstructive sleep apnea (OSA) and intermittent hypoxia on dyslipidemia and provide future perspectives in this area. Recent findings Intermittent hypoxia, a hallmark of OSA, induces hyperlipidemia in lean mice. Hyperlipidemia of intermittent hypoxia occurs, at least in part, due to activation of the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) and an important downstream enzyme of triglyceride and phospholipid biosynthesis, stearoyl-CoA desaturase-1. Furthermore, intermittent hypoxia may regulate SREBP-1 and stearoyl-CoA desaturase-1 via the transcription factor hypoxia-inducible factor 1. In contrast, key genes involved in cholesterol biosynthesis, SREBP-2 and 3-hydroxy-3-methylglutaryl- CoA (HMG-CoA) reductase, are unaffected by intermittent hypoxia. In humans, there is no definitive evidence regarding the effect of OSA on dyslipidemia. Several cross-sectional studies suggest that OSA is independently associated with increased levels of total cholesterol, low-density lipoprotein and triglycerides, whereas others report no such relationship. Some nonrandomized and randomized studies show that OSA treatment with continuous positive airway pressure may have a beneficial effect on lipid profile. Summary There is increasing evidence that intermittent hypoxia is independently associated with dyslipidemia. However, the role of OSA in causality of dyslipidemia remains to be established.

Exercise training associated with estrogen therapy induced cardiovascular benefits after ovarian hormones deprivation

Menopause is recognized as a period of increased risk for coronary heart disease. Although the benefits of exercise training in lowering cardiovascular risk factors are well established, the risks and benefits of hormone therapy have been questioned. The purpose of the present study was to investigate the effects of estrogen therapy (HT) associated or not with exercise training (ET) in autonomic cardiovascular control in ovariectomized (OVX) rats. Female rats were divided into: control, OVX, OVX+HT, OVX+ET and OVX+HT+ET. HT was performed using a 0.25 mg 8-weeks sustained release pellet. Trained groups were submitted to an 8-week exercise training protocol on treadmill. Baroreflex sensitivity (BRS) was evaluated by heart rate responses to arterial pressure (AP) changes, and vagal and sympathetic tonus by pharmacological blockade. Ovariectomy induced an AP increase (123 +/- 2 mmHg vs. 108 +/- 2 mmHg), BRS impairment (similar to 69%), sympathetic activation (similar to 100%) and vagal tonus reduction (similar to 77%) compared to controls. HT or ET normalized the changes in parasympathetic tonus. However, only the association HT + ET was able to promote normalization of AP, BRS and sympathetic tonus, as compared to controls. These results indicate that ET induces cardiovascular and autonomic benefits in OVX rats under HT, suggesting a positive role of this association in the management of cardiovascular risk factor in postmenopausal women. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Agreement for Detecting Glaucoma Progression with the GDx Guided Progression Analysis, Automated Perimetry, and Optic Disc Photography

Purpose: To evaluate the ability of the GDx Variable Corneal Compensation (VCC) Guided Progression Analysis (GPA) software for detecting glaucomatous progression. Design: Observational cohort study. Participants: The study included 453 eyes from 252 individuals followed for an average of 46 +/- 14 months as part of the Diagnostic Innovations in Glaucoma Study. At baseline, 29% of the eyes were classified as glaucomatous, 67% of the eyes were classified as suspects, and 5% of the eyes were classified as healthy. Methods: Images were obtained annually with the GDx VCC and analyzed for progression using the Fast Mode of the GDx GPA software. Progression using conventional methods was determined by the GPA software for standard automated achromatic perimetry (SAP) and by masked assessment of optic disc stereophotographs by expert graders. Main Outcome Measures: Sensitivity, specificity, and likelihood ratios (LRs) for detection of glaucoma progression using the GDx GPA were calculated with SAP and optic disc stereophotographs used as reference standards. Agreement among the different methods was reported using the AC(1) coefficient. Results: Thirty-four of the 431 glaucoma and glaucoma suspect eyes (8%) showed progression by SAP or optic disc stereophotographs. The GDx GPA detected 17 of these eyes for a sensitivity of 50%. Fourteen eyes showed progression only by the GDx GPA with a specificity of 96%. Positive and negative LRs were 12.5 and 0.5, respectively. None of the healthy eyes showed progression by the GDx GPA, with a specificity of 100% in this group. Inter-method agreement (AC1 coefficient and 95% confidence intervals) for non-progressing and progressing eyes was 0.96 (0.94-0.97) and 0.44 (0.28-0.61), respectively. Conclusions: The GDx GPA detected glaucoma progression in a significant number of cases showing progression by conventional methods, with high specificity and high positive LRs. Estimates of the accuracy for detecting progression suggest that the GDx GPA could be used to complement clinical evaluation in the detection of longitudinal change in glaucoma. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2010; 117: 462-470 (C) 2010 by the American Academy of Ophthalmology.

The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome

Objective: Metabolic syndrome (MS) is associated with subclinical atherosclerosis, but the relative role of obstructive sleep apnoea (OSA) is largely unknown. The main objective of this study is to determine the impact of OSA on markers of atherosclerosis in patients with MS. Methods: Eighty-one consecutive patients with MS according to the Adult Treatment Panel III underwent a clinical evaluation, polysomnography, laboratory and vascular measurements of carotid intima media thickness (IMT), carotid-femoral pulse wave velocity (PWV) and carotid diameter (CD) in a blind fashion. OSA was defined as an apnoea-hypopnoea index (AHI) >= 15 events/hour. Multiple linear regression was performed to determine the variables that were independently associated with the vascular parameters. Results: Fifty-one patients (63%) had OSA. No significant differences existed in age, sex, MS criteria, and cholesterol levels between patients with (MS+OSA) and without OSA (MS-OSA). Compared with MS-OSA patients, MS+OSA patients had higher levels of IMT (661 +/- 117 vs. 767 +/- 140 mu m), PWV (9.6 +/- 1.0 vs. 10.6 +/- 1.6 m/s), and CD (6705 +/- 744 vs. 7811 +/- 862 mu m) (P < 0.001 for each comparison). Among patients with MS+OSA, all vascular parameters were similar in patients with and without daytime sleepiness. The independent parameters associated with IMT, PWV, and CD were AHI, abdominal circumference, and systolic blood pressure (R(2) = 0.42); AHI and systolic blood pressure (R(2) = 0.38); and AHI, age, abdominal circumference and systolic blood pressure (R(2) = 0.45), respectively. The R(2) of AHI for IMT, PWV and CD was 0.12, 0.10 and 0.20, respectively. Conclusions: OSA is very common and has an incremental role in atherosclerotic burden in consecutive patients with MS. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

CPAP and survival in moderate-to-severe obstructive sleep apnoea syndrome and hypoxaemic COPD

Obstructive sleep apnoea syndrome (OSAS) often coexists in patients with chronic obstructive pulmonary disease (COPD). The present prospective cohort study tested the effect of OSAS treatment with continuous positive airway pressure (CPAP) on the survival of hypoxaemic COPD patients. It was hypothesised that CPAP treatment would be associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving long-term oxygen therapy (LTOT). Prospective study participants attended two outpatient advanced lung disease LTOT clinics in Sao Paulo, Brazil, between January 1996 and July 2006. Of 603 hypoxaemic COPD patients receiving LTOT, 95 were diagnosed with moderate-to-severe OSAS. Of this OSAS group, 61 (64%) patients accepted and were adherent to CPAP treatment, and 34 did not accept or were not adherent and were considered not treated. The 5-yr survival estimate was 71% (95% confidence interval 53-83%) and 26% (12-43%) in the CPAP-treated and nontreated groups, respectively (p<0.01). After adjusting for several confounders, patients treated with CPAP showed a significantly lower risk of death (hazard ratio of death versus nontreated 0.19 (0.08-0.48)). The present study found that CPAP treatment was associated with higher survival in patients with moderate-to-severe OSAS and hypoxaemic COPD receiving LTOT.

Combination of Multiple Molecular Markers Can Improve Prognostication in Patients With Locally Advanced and Lymph Node Positive Bladder Cancer

Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker. Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy. Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly 1 higher predictive accuracy than any single biomarker (p < 0.001.). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p < 0.001) and cancer specific mortality (4.3%, p < 0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p < 0.001). Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.

Home blood pressure monitoring in paediatric chronic hypertension

Blood pressure (BP) measurement is the basis for the diagnosis and management of arterial hypertension. The aim of this study was to compare BP measurements performed in the office and at home (home blood pressure monitoring, HBPM) in children and adolescents with chronic arterial hypertension. HBPM was performed by the patient or by his/her legal guardian. During a 14-day period, three BP measurements were performed in the morning or in the afternoon (daytime measurement) and in the evening (night-time measurement), with 1-min intervals between measurements, totalling six measurements per day. HBPM was defined for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values. HBPM was evaluated in 40 patients (26 boys), mean age of 12.1 years (4-18 years). SBP and DBP records were analysed. The mean differences between average HBP and doctor`s office BP were 0.6 +/- 14 and 4 +/- 13 mm Hg for SBP and DBP, respectively. Average systolic HBPM (daytime and night-time) did not differ from average office BP, and diastolic HBPM (daytime and night-time) was statistically lower than office BP. The comparison of individual BP measurements along the study period (13 days) by s.d. of differences shows a significant decline only for DBP values from day 5, on which difference tends to disappear towards the end of the study. Mean daytime and night-time SBP and DBP values remained stable throughout the study period, confirming HBPM as an acceptable methodology for BP evaluation in hypertensive children and adolescents. Journal of Human Hypertension (2009) 23, 464-469; doi:10.1038/jhh.2008.167; published online 12 March 2009

Effects of Oropharyngeal Exercises on Patients with Moderate Obstructive Sleep Apnea Syndrome

Rationale: Upper airway muscle function plays a major role in maintenance of the upper airway patency and contributes to the genesis of obstructive sleep apnea syndrome (OSAS). Preliminary results suggested that oropharyngeal exercises derived from speech therapy may be an effective treatment option for patients with moderate OSAS. Objectives: To determine the impact of oropharyngeal exercises in patients with moderate OSAS. Methods: Thirty-one patients with moderate OSAS were randomized to 3 months of daily (similar to 30 min) sham therapy (n = 15, control) or a set of oropharyngeal exercises (n = 16), consisting of exercises involving the tongue, soft palate, and lateral pharyngeal wall. Measurements and Main Results: Anthropometric measurements, snoring frequency (range 0-4), intensity (1-3), Epworth daytime sleepiness (0-24) and Pittsburgh sleep quality (0-21) questionnaires, and full polysomnography were performed at baseline and at study conclusion. Body mass index and abdominal circumference of the entire group were 30.3 +/- 3.4 kg/m(2) and 101.4 +/- 9.0 cm, respectively, and did not change significantly over the study period. No significant change occurred in the control group in all variables. In contrast, patients randomized to oropharyngeal exercises had a significant decrease (P < 0.05) in neck circumference (39.6 +/- 3.6 vs. 38.5 +/- 4.0 cm), snoring frequency (4 [4-4] vs. 3 [1.5-3.5]), snoring intensity (3 [3-4] vs. 1 [1-2]), daytime sleepiness (14 +/- 5 vs. 8 +/- 6), sleep quality score (10.2 +/- 3.7vs. 6.9 +/- 2.5), and OSAS severity (apnea-hypopnea index, 22.4 +/- 4.8 vs. 13.7 +/- 8.5 events/h). Changes in neck circumference correlated inversely with changes in apnea-hypopnea index (r = 0.59; P < 0.001). Conclusions: Oropharyngeal exercises significantly reduce OSAS severity and symptoms and represent a promising treatment for moderate OSAS. Clinical trial registered with www.clinicaltrials.gov (NCT 00660777).