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

Prognostic heterogeneity among patients with chronic stable coronary disease: determinants of long-term mortality after treatment with percutaneous intervention

Aims: To evaluate the risk and predictors of death in a large population of patients with stable coronary disease treated with percutaneous intervention. Methods and results: The study population comprised 1,276 patients with chronic angina or silent ischaemia who underwent elective coronary angioplasty. Baseline and in-hospital mortality data were prospectively collected for all patients during the index hospitalisation. Post-discharge outcome was assessed at out-patient clinic, by review of the patients` records, or direct phone contact. Deaths were classified as cardiac and non-cardiac. Age, peripheral arterial disease, congestive heart failure with NYHA class Ill, triple-vessel disease, and procedural success (i.e. angiographic success for all lesions in the absence of pen-procedural infarction) remained as multivariate independent predictors of death. For the entire population 4-year cumulative all-cause and cardiac mortality were respectively 5.4% and 4.1%. Four-year mortality for patients without any multivariate predictor was 2.4%, while for patients with two or more predictors the death rate was 16.3% after four years. Conclusions: Patients with stable coronary disease undergoing percutaneous treatment have an overall low mortality rate after four years. Nevertheless, stable patients comprise a heterogeneous population in terms of risk profile, ranging from patients at very low risk of late death to individuals with a poor long-term prognosis.

Mild chronic kidney dysfunction and treatment strategies for stable coronary artery disease

Objective: Our objective was to evaluate the association of chronic kidney dysfunction in patients with multi-vessel chronic coronary artery disease, preserved left ventricular function, and the possible interaction between received treatment and cardiovascular events. Methods: The glomerular filtration rate was determined at baseline on 611 patients who were randomized into three treatment groups: medical treatment, percutaneous coronary intervention, and coronary artery bypass surgery. Incidence of myocardial infarction, angina requiring a new revascularization procedure, and death were analyzed during 5 years in each group. Results: Of 611 patients, 112 (18%) were classified as having normal renal function, 349 (57%) were classified as having mild dysfunction, and 150 (25%) were classified as having moderate dysfunction. There were significant differences among the cumulative overall mortality curves among the three renal function groups. Death was observed more frequently in the moderate dysfunction group than the other two groups (P < .001). Interestingly, in patients with mild chronic kidney dysfunction, we observed that coronary artery bypass treatment presented a statistically higher percentage of event-free survival and lower percentage of mortality than did percutaneous coronary intervention or medical treatment Conclusions: Our results confirm that coronary artery disease accompanied by chronic kidney dysfunction has a worse prognosis, regardless of the therapeutic strategy for coronary artery disease, when renal function is at least mildly impaired. Additionally, our data suggest that the different treatment strategies available for stable coronary artery disease may have differential beneficial effects according to the range of glomerular filtration rate strata.

Effects of Chronic Exposure to Crack Cocaine on the Respiratory Tract of Mice

Smoked cocaine (crack cocaine) causes several forms of injury to the respiratory tract, including asthma exacerbations, lung edema and hemorrhage, and nasal mucosal alterations. Few studies, however, have assessed respiratory tract pathology in habitual users of crack cocaine. Here, we describe the histological alterations in the respiratory tract of mice caused by chronic inhalation of crack cocaine. Twenty 2-month-old BALB/c mice were exposed to the smoke of 5 g crack cocaine in an inhalation chamber once a day for two months and compared to controls (n = 10). We then morphometrically analyzed nose and bronchiolar epithelial alterations, bronchiolar and alveolar macrophage cell density, alveolar hemosiderin content, and in addition determined the vasoconstriction index and the wall thickness of pulmonary arteries. The serum cocaine level was 212.5 ng/mL after a single inhalation. The mucus content of the nasal epithelium increased in crack-exposed animals, and the nasal and bronchial epithelium thickness decreased significantly. The alveolar hemosiderin content and the alveolar and bronchiolar macrophage cell density increased in animals exposed to crack. The vasoconstriction index increased in the pulmonary arteries of the exposed group. Chronic crack cocaine inhalation causes extensive histological changes along the entire respiratory tract.

Oral tolerance attenuates airway inflammation and remodeling in a model of chronic pulmonary allergic inflammation

We investigated the effects of oral tolerance (OT) in controlling inflammatory response, hyperresponsiveness and airway remodeling in guinea pigs (GP) with chronic allergic inflammation. Animals received seven inhalations of ovalbumin (1-5 mg/mL-OVA group) or normal saline (NS group). OT was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st ovalbumin inhalation (OT1 group) or after the 4th (OT2 group). The induction of OT in sensitized animals decreased the elastance of respiratory system (Ers) response after both antigen and methacholine challenges, peribronchial edema formation, eosinophilic airway infiltration, eosinophilopoiesis, and airways collagen and elastic fiber content compared to OVA group (P < 0.05). The number of mononuclear cells and resistance of respiratory system (Rrs) responses after antigen and methacholine challenges were decreased only in OT2 group compared to OVA group (P < 0.05). Concluding, our results show that inducing OT attenuates airway remodeling as well as eosinophilic inflammation and respiratory system mechanics. (C) 2008 Elsevier B.V. All rights reserved.

Influence of Single-Nucleotide Polymorphisms on C-Reactive Protein Levels in Chronic Kidney Disease Before and After Kidney Transplantation

Introduction. We sought to evaluate 2 sing] e-nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene promoter region for their effects on CRP levels in chronic kidney disease (CKD) patients before and after a successful kidney transplantation. Methods. Fifty CKD patients were evaluated before and at the first and second years after the graft. Two SNPs were studied, a bi-allelic (G -> A) at the -409 and a tri-allelic (C -> T -> A) variation at the -390 position in the CRP gene. Results. All patients presented the -409GG genotype. At the -390 position, the ""A"" allele was not found; there were 15 ""CC"" patients, 11 ""TT"" patients, and 24 ""CT"" patients. CRP levels were different among patients with various genotypes (P < .019). Also the presence of the allele ""T"" was sufficient to determine differences in CRP levels both in pretransplantation (P = .045) and at 1 year posttransplantation (P = .011), but not at the second year (P = .448). Conclusion. SNPs at the -390 position of the CRP gene promoter region influence CRP basal levels in such a way that the ""C"" allele correlated with the lowest and the ""T"" with the highest. We did not observe this influence in our patients at the second year posttransplantation.

Impaired IFN-alpha secretion by plasmacytoid dendritic cells induced by TLR9 activation in chronic idiopathic urticaria

P>Background The evolution and therapeutic outcome of American tegumentary leishmaniasis (ATL) depend upon many factors, including the balance between Th1 and Th2 cytokines to control parasite multiplication and lesion extension. Other cytokines known for their role in inflammatory processes such as interleukin IL-17 or IL-18 as well as factors controlling keratinocyte differentiation and the inflammatory process in the skin, like the Notch system, could also be involved in the disease outcome. Notch receptors are a group of transmembrane proteins that regulate cell fate decisions during development and adulthood in many tissues, including keratinocyte differentiation and T-cell lineage commitment, depending on their activation by specific groups of ligands (Delta-like or Jagged). Objectives To compare the in situ expression of Notch system proteins (receptors, ligands and transcriptional factors) and cytokines possibly involved in the disease outcome (IL-17, IL-18, IL-23 and transforming growth factor-beta) in ATL cutaneous and mucosal lesions, according to the response to therapy with N-methyl glucamine. Methods Cutaneous and mucosal biopsies obtained from patients prior to therapy with N-methyl glucamine were analysed by immunohistochemistry and real-time polymerase chain reaction. Results Notch receptors and Delta-like ligands were found increased in patients with ATL, particularly those with poor response to therapy or with mucosal lesions. Conclusions The increase of Notch receptors and Delta-like ligands in patients with a poor response to treatment suggests that these patients would require a more aggressive therapeutic approach or at least a more thorough and rigorous follow-up.

Chemokine Receptors Expression on T Cells and Response to HAART Among Chronic HIV-1-Infected Subjects

Chemokines receptors are used by HIV-1 for entry into CD4(+) T cells. The chemokines are capable of inhibiting HIV replication. This study determined the CCR5 and CXCR4 expression on T cells in HIV-1-infected patients treated with HAART. The successfully treated group ( plasma viral load 400 copies/mL), when compared with the failure group ( plasma viral load >400 copies/mL), had higher median CD4+ T cells count ( 583 and 245 cells/mm(3); respectively, p<0.0001). The failure patients had higher numbers and intensity of CCR5 and CXCR4-expressing T cells. Successfully treated patients were able to normalize the co-receptors expression-over on T cells. The viremic group showed higher CCR5 expression on CD4+ T cells and lower number of cells; CCR5 expression was normalized in the aviremic group; the naive group showed lower CCR5 expression and higher numbers of CD4 T cells; all groups showed normal CXCR4 expression compared to healthy controls. These findings may have clinical implications, since down-regulation of these co-receptors could be an adjuvant strategy for anti-HIV treatment.

Chronic exposure to ambient levels of urban particles affects mouse lung development

Rationale- Chronic exposure to air pollution has been associated with adverse effects on children`s lung growth. Objectives: We analyzed the effects of chronic exposure to urban levels of particulate matter (PM) on selected phases of mouse lung development. Methods: The exposure occurred in two open-top chambers (filtered and nonfiltered) placed 20 m from a street with heavy traffic in Sao Paulo, 24 hours/day for 8 months. There was a significant reduction of the levels of PM(2.5) inside the filtered chamber (filtered = 2.9 +/- 3.0 mu g/m(3), nonfiltered = 16.8 +/- 8.3 mu g/m(3); P = 0.001). At this exposure site, vehicular sources are the major components of PM(2.5) (PM <= 2.5 mu m). Exposure of the parental generation in the two chambers occurred from the 10th to the 120th days of life. After mating and birth of offspring, a crossover of mothers and pups occurred within the chambers, resulting in four groups of pups: nonexposed, prenatal, postnatal, and pre+postnatal. Offspring were killed at the age of 15 (n = 42) and 90 (n = 35) days; lungs were analyzed by morphometry for surface to volume ratio (as an estimator of alveolization). Pressure-volume curves were performed in the older groups, using a 20-ml plethysmograph. Measurements and Main Results: Mice exposed to PM(2.5) pre+postnatally presented a smaller surface to volume ratio when compared with nonexposed animals (P = 0.036). The pre+postnatal group presented reduced inspiratory and expiratory volumes at higher levels of transpulmonary pressure (P = 0.001). There were no differences among prenatal and postnatal exposure and nonexposed animals. Conclusions: Our data provide anatomical and functional support to the concept that chronic exposure to urban PM affects lung growth.

Effects of Residual Oil Fly Ash (ROFA) in Mice with Chronic Allergic Pulmonary Inflammation

transition metals, which are involved in the pathological effects of PM. The objective of this study was to investigate the effects of intranasal administration of ROFA on pulmonary inflammation, pulmonary responsiveness, and excess mucus production in a mouse model of chronic pulmonary allergic inflammation. BALB/c mice received intraperitoneal injections of ovalbumin (OVA) solution (days 1 and 14). OVA challenges were performed on days 22, 24, 26, and 28. After the challenge, mice were intranasally instilled with ROFA. After forty-eight hours, pulmonary responsiveness was performed. Mice were sacrificed, and lungs were removed for morphometric analysis. OVA-exposed mice presented eosinophilia in the bronchovascular space (p < .001), increased pulmonary responsiveness (p < .001), and epithelial remodeling (p = .003). ROFA instillation increased pulmonary responsiveness (p = .004) and decreased the area of ciliated cells in the airway epithelium (p = .006). The combined ROFA instillation and OVA exposure induced a further increase in values of pulmonary responsiveness (p = .043) and a decrease in the number of ciliated cells in the airway epithelium (p = .017). PM exposure results in pulmonary effects that are more intense in mice with chronic allergic pulmonary inflammation.

Chronic autoimmune urticaria as the first manifestation of juvenile systemic lupus erythematosus

Chronic urticaria (daily or almost daily symptoms lasting for more than six weeks) is characterized by wheals and erythema, with or without itching. A few case reports have shown chronic autoimmune urticaria at the beginning of systemic lupus erythematosus (SLE), particularly in adults. However, the prevalence of this manifestation in a lupus paediatric population was not studied. During 27 consecutive years, 5419 patients were followed up at our University Hospital and 271 (5%) had juvenile SLE (American College of Rheumatology criteria). Two of them (0.7%) had chronic and painless autoimmune urticaria as the first manifestation of juvenile SLE, and were reported herein. One case was a five-year old female with continuous widespread urticaria (duration 120 days), antinuclear antibodies (ANA) 1:640 (dense fine speckled pattern) and elevated complement levels. The juvenile SLE diagnosis was established after one year. The other case was a 13-year old female who had chronic widespread urticaria (lasting 45 days), ANA 1:160 (fine speckled pattern) and normal complement levels. The juvenile SLE diagnosis was established after three years. In conclusion, chronic autoimmune urticaria is very rare and may be the first lupus manifestation, particularly associated with the presence of autoantibodies. This study reinforces the importance of a rigorous follow-up in children and adolescents suffering from autoimmune urticaria due to the possibility of connective tissue disorders, such as paediatric lupus. Lupus (2011) 20, 763-766.

Cutaneuos cryoglobulinemic vasculitis induced by chronic hepatitis C virus infection

Cutaneous vasculitis may represent a great clinical challenge, even after careful dermatological examination and laboratory assessment. The authors present a case of cutaneous cryoglobulinemic vasculitis associated to chronic hepatitis C virus infection, pointing out the importance of the dermatological examination for diagnostic investigation. They discuss about the importance of defining the etiology and making correct classification for appropriate prognosis and treatment of cutaneous vasculitis.

Variants in the promoter region of IKBL/NFKBIL1 gene may mark susceptibility to the development of chronic Chagas` cardiomyopathy among Trypanosoma cruzi-infected individuals

Chagas` disease, caused by Trypanosoma cruzi, is an inflammatory disorder leading to chronic Chagas cardiomyopathy (CCC). Only one third of T cruzi-infected individuals progress to CCC while the others are considered asymptomatic (ASY). The human inhibitory kappa B-like gene (KBLINFKBIL1), homologous to the I kappa B family of proteins that regulate the NF kappa B family of transcription factors, is suggested as a putative inhibitor of NFKB. We investigated two functional polymorphisms, -62A/T and -262A/G, in the promoter of IKBL by PCR-RFLP analysis in 169 patients with CCC and 76 ASY. Genotype distributions for both -62A/T and -262A/G differed between the CCC and ASY (X-2 = 7.3; P = 0.025 and X-2 = 6.8; P = 0.03, respectively). Subjects, homozygous for the -62A allele, had three-fold risk of developing CCC compared with those carrying the TT genotype (P = 0.0095; Odds Ratio [OR] = 2.9; [95% CI 1.2-7.3]). Similar trend was observed for the -262A homozygotes (P = 0.005; OR = 2.7 [95% CI 1.3-6.0]. The haplotype -262A -62A was prevalent in patients with CCC (40% versus 24%; OR 2.1 [95% C1 1.4-3.3j; Pc = 0.00 14). The I kappa BL locus itself or another critical gene in this region may confer susceptibility to the development of CCC. (C) 2007 Elsevier Ltd. All rights reserved.

Effects of losartan, in monotherapy or in association with hydrochlorothiazide, in chronic nephropathy resulting from losartan treatment during lactation

Fanelli C, Fernandes BH, Machado FG, Okabe C, Malheiros DM, Fujihara CK, Zatz R. Effects of losartan, in monotherapy or in association with hydrochlorothiazide, in chronic nephropathy resulting from losartan treatment during lactation. Am J Physiol Renal Physiol 301: F580-F587, 2011. First published June 8, 2011; doi:10.1152/ajprenal.00042.2011.-We recently standardized a model (L(Lact)) of severe chronic kidney disease based on impaired nephrogenesis by suppression of angiotensin II activity during lactation (Machado FG, Poppi EP, Fanelli C, Malheiros DM, Zatz R, Fujihara CK. Am J Physiol Renal Physiol 294: F1345-F1353, 2008). In this new study of the L(Lact) model, we sought to gain further insight into renal injury mechanisms associated with this model and to verify whether the renoprotection obtained with the association of the angiotensin II receptor blocker losartan (L) and hydrochlorothiazide (H), which arrested renal injury in the remnant kidney model, would provide similar renoprotection. Twenty Munich-Wistar dams, each nursing six pups, were divided into control, untreated, and L(Lact) groups, given losartan (L; 250 mg.kg(-1).day(-1)) until weaning. The male LLact offspring remained untreated until 7 mo of age, when renal functional and structural parameters were studied in 17 of them, used as pretreatment control (L(Lact)Pre), and followed no further. The remaining rats were then divided among groups L(Lact) + V, untreated; L(Lact) + L, given L (50 mg.kg(-1).day(-1)) now as a therapy; L(Lact) + H, given H (6 mg.kg(-1).day(-1)); and L(Lact) + LH, given L and H. All parameters were reassessed 3 mo later in these groups and in age-matched controls. At this time, L(Lact) rats exhibited hypertension, severe albuminuria, glomerular damage, marked interstitial expansion/inflammation, enhanced cell proliferation, myofibroblast infiltration, and creatinine retention. L monotherapy normalized albuminuria and prevented hypertension and the progression of renal injury, inflammation, and myofibroblast infiltration. In contrast to the remnant model, the LH combination promoted only slight additional renoprotection, perhaps because of a limited tendency to retain sodium in L(Lact) rats.