Secondary arterial hypertension: when, who, and how to screen?

Secondary hypertension refers to arterial hypertension due to an identifiable cause and affects ∼5-10% of the general hypertensive population. Because secondary forms are rare and work up is time-consuming and expensive, only patients with clinical suspicion should be screened. In recent years, some new aspects gained importance regarding this screening. In particular, increasing evidence suggests that 24 h ambulatory blood pressure (BP) monitoring plays a central role in the work up of patients with suspected secondary hypertension. Moreover, obstructive sleep apnoea has been identified as one of the most frequent causes. Finally, the introduction of catheter-based renal denervation for the treatment of patients with resistant hypertension has dramatically increased the interest and the number of patients evaluated for renal artery stenosis. We review the clinical clues of the most common causes of secondary hypertension. Specific recommendations are given as to evaluation and treatment of various forms of secondary hypertension. Despite appropriate therapy or even removal of the secondary cause, BP rarely ever returns to normal with long-term follow-up. Such residue hypertension indicates either that some patients with secondary hypertension also have concomitant essential hypertension or that irreversible vascular remodelling has taken place. Thus, in patients with potentially reversible causes of hypertension, early detection and treatment are important to minimize/prevent irreversible changes in the vasculature and target organs.

Non-invasive and non-occlusive blood pressure estimation via a chest sensor

The clinical demand for a device to monitor Blood Pressure (BP) in ambulatory scenarios with minimal use of inflation cuffs is increasing. Based on the so-called Pulse Wave Velocity (PWV) principle, this paper introduces and evaluates a novel concept of BP monitor that can be fully integrated within a chest sensor. After a preliminary calibration, the sensor provides non-occlusive beat-by-beat estimations of Mean Arterial Pressure (MAP) by measuring the Pulse Transit Time (PTT) of arterial pressure pulses travelling from the ascending aorta towards the subcutaneous vasculature of the chest. In a cohort of 15 healthy male subjects, a total of 462 simultaneous readings consisting of reference MAP and chest PTT were acquired. Each subject was recorded at three different days: D, D+3 and D+14. Overall, the implemented protocol induced MAP values to range from 80 ± 6 mmHg in baseline, to 107 ± 9 mmHg during isometric handgrip maneuvers. Agreement between reference and chest-sensor MAP values was tested by using intraclass correlation coefficient (ICC = 0.78) and Bland-Altman analysis (mean error = 0.7 mmHg, standard deviation = 5.1 mmHg). The cumulative percentage of MAP values provided by the chest sensor falling within a range of ±5 mmHg compared to reference MAP readings was of 70%, within ±10 mmHg was of 91%, and within ±15mmHg was of 98%. These results point at the fact that the chest sensor complies with the British Hypertension Society (BHS) requirements of Grade A BP monitors, when applied to MAP readings. Grade A performance was maintained even two weeks after having performed the initial subject-dependent calibration. In conclusion, this paper introduces a sensor and a calibration strategy to perform MAP measurements at the chest. The encouraging performance of the presented technique paves the way towards an ambulatory-compliant, continuous and non-occlusive BP monitoring system.

Response of day-to-day home blood pressure variability by antihypertensive drug class after transient ischemic attack or nondisabling stroke.

BACKGROUND AND PURPOSE Visit-to-visit variability in systolic blood pressure (SBP) is associated with an increased risk of stroke and was reduced in randomized trials by calcium channel blockers and diuretics but not by renin-angiotensin system inhibitors. However, time of day effects could not be determined. Day-to-day variability on home BP readings predicts stroke risk and potentially offers a practical method of monitoring response to variability-directed treatment. METHODS SBP mean, maximum, and variability (coefficient of variation=SD/mean) were determined in 500 consecutive transient ischemic attack or minor stroke patients on 1-month home BP monitoring (3 BPs, 3× daily). Hypertension was treated to a standard protocol. Differences in SBP variability from 3 to 10 days before to 8 to 15 days after starting or increasing calcium channel blockers/diuretics versus renin-angiotensin system inhibitors versus both were compared by general linear models, adjusted for risk factors and baseline BP. RESULTS Among 288 eligible interventions, variability in SBP was reduced after increased treatment with calcium channel blockers/diuretics versus both versus renin-angiotensin system inhibitors (-4.0 versus 6.9 versus 7.8%; P=0.015), primarily because of effects on maximum SBP (-4.6 versus -1.0 versus -1.0%; P=0.001), with no differences in effect on mean SBP. Class differences were greatest for early-morning SBP variability (3.6 versus 17.0 versus 38.3; P=0.002) and maximum (-4.8 versus -2.0 versus -0.7; P=0.001), with no effect on midmorning (P=0.29), evening (P=0.65), or diurnal variability (P=0.92). CONCLUSIONS After transient ischemic attack or minor stroke, calcium channel blockers and diuretics reduced variability and maximum home SBP, primarily because of effects on morning readings. Home BP readings enable monitoring of response to SBP variability-directed treatment in patients with recent cerebrovascular events.

The Effect of Increasing Intracranial Pressure on Ocular Vestibular-Evoked Myogenic Potential Frequency Tuning.

OBJECTIVE Ocular vestibular-evoked myogenic potentials (oVEMPs) represent extraocular muscle activity in response to vestibular stimulation. The authors sought to investigate whether posture-induced increase of the intracranial pressure (ICP) modulated oVEMP frequency tuning, that is, the amplitude ratio between 500-Hz and 1000-Hz stimuli. DESIGN Ten healthy subjects were enrolled in this study. The subjects were positioned in the horizontal plane (0 degree) and in a 30-degree head-downwards position to elevate the ICP. In both positions, oVEMPs were recorded using 500-Hz and 1000-Hz air-conducted tone bursts. RESULTS When tilting the subject from the horizontal plane to the 30-degree head-down position, oVEMP amplitudes in response to 500-Hz tone bursts distinctly decreased (3.40 μV versus 2.06 μV; p < 0.001), whereas amplitudes to 1000 Hz were only slightly diminished (2.74 μV versus 2.48 μV; p = 0.251). Correspondingly, the 500/1000-Hz amplitude ratio significantly decreased when tilting the subjects from 0- to 30-degree inclination (1.59 versus 1.05; p = 0.029). Latencies were not modulated by head-down position. CONCLUSIONS Increasing ICP systematically alters oVEMPs in terms of absolute amplitudes and frequency tuning characteristics. oVEMPs are therefore in principle suited for noninvasive ICP monitoring.

Hipertensão arterial mascarada no idoso

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Seguridad del monitoreo hemodinámico invasivo versus mínimamente invasivo en pacientes con choque cardiogénico en cuidado intensivo adultos. Revisión sistemática

Introducción: El monitoreo hemodinámico es una herramienta para diagnosticar el choque cardiogénico y monitorear la respuesta al tratamiento; puede ser invasivo, mínimamente invasivo o no invasivo. Se realiza rutinariamente con catéter de arteria pulmonar (CAP) o catéter de Swan Ganz; nuevas técnicas de monitoreo hemodinámico mínimamente invasivo tienen menor tasa de complicaciones. Actualmente se desconoce cuál técnica de monitoreo cuenta con mayor seguridad en el paciente con choque cardiogénico. Objetivo: Evaluar la seguridad del monitoreo hemodinámico invasivo comparado con el mínimamente invasivo en pacientes con choque cardiogénico en cuidado intensivo adultos. Diseño: Revisión sistemática de la literatura. Búsqueda en Pubmed, EMBASE, OVID - Cochrane Library, Lilacs, Scielo, registros de ensayos clínicos, actas de conferencias, repositorios, búsqueda de literatura gris en Google Scholar, Teseo y Open Grey hasta agosto de 2016, publicados en inglés y español. Resultados: Se identificó un único estudio con 331 pacientes críticamente enfermos que comparó el monitoreo hemodinámico con CAP versus PiCCO que concluyó que después de la corrección de los factores de confusión, la elección del tipo de monitoreo no influyó en los resultados clínicos más importantes en términos de complicaciones y mortalidad. Dado que se incluyeron otros diagnósticos, no es posible extrapolar los resultados sólo a choque cardiogénico. Conclusión: En la literatura disponible no hay evidencia de que el monitoreo hemodinámico invasivo comparado con el mínimamente invasivo, en pacientes adultos críticamente enfermos con choque cardiogénico, tenga diferencias en cuanto a complicaciones y mortalidad.

Noninvasive monitoring of activity in Crohn's disease

Background: The fecal neutrophil-derived proteins calprotectin and lactoferrin have proven useful surrogate markers of intestinal inflammation. The aim of this study was to compare fecal calprotectin and lactoferrin concentrations to clinically, endoscopically, and histologically assessed Crohn’s disease (CD) activity, and to explore the suitability of these proteins as surrogate markers of mucosal healing during anti-TNFα therapy. Furthermore, we studied changes in the number and expression of effector and regulatory T cells in bowel biopsy specimens during anti-TNFα therapy. Patients and methods: Adult CD patients referred for ileocolonoscopy (n=106 for 77 patients) for various reasons were recruited (Study I). Clinical disease activity was assessed with the Crohn’s disease activity index (CDAI) and endoscopic activity with both the Crohn’s disease index of severity (CDEIS) and the simple endoscopic score for Crohn’s disease (SES-CD). Stool samples for measurements of calprotectin and lactoferrin, and blood samples for CRP were collected. For Study II, biopsy specimens were obtained from the ileum and the colon for histologic activity scoring. In prospective Study III, after baseline ileocolonoscopy, 15 patients received induction with anti-TNFα blocking agents and endoscopic, histologic, and fecal-marker responses to therapy were evaluated at 12 weeks. For detecting changes in the number and expression of effector and regulatory T cells, biopsy specimens were taken from the most severely diseased lesions in the ileum and the colon (Study IV). Results: Endoscopic scores correlated significantly with fecal calprotectin and lactoferrin (p<0.001). Both fecal markers were significantly lower in patients with endoscopically inactive than with active disease (p<0.001). In detecting endoscopically active disease, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for calprotectin ≥200 μg/g were 70%, 92%, 94%, and 61%; for lactoferrin ≥10 μg/g they were 66%, 92%, 94%, and 59%. Accordingly, the sensitivity, specificity, PPV, and NPV for CRP >5 mg/l were 48%, 91%, 91%, and 48%. Fecal markers were significantly higher in active colonic (both p<0.001) or ileocolonic (calprotectin p=0.028, lactoferrin p=0.004) than in ileal disease. In ileocolonic or colonic disease, colon histology score correlated significantly with fecal calprotectin (r=0.563) and lactoferrin (r=0.543). In patients receiving anti-TNFα therapy, median fecal calprotectin decreased from 1173 μg/g (range 88-15326) to 130 μg/g (13-1419) and lactoferrin from 105.0 μg/g (4.2-1258.9) to 2.7 μg/g (0.0-228.5), both p=0.001. The relation of ileal IL-17+ cells to CD4+ cells decreased significantly during anti-TNF treatment (p=0.047). The relation of IL-17+ cells to Foxp3+ cells was higher in the patients’ baseline specimens than in their post-treatment specimens (p=0.038). Conclusions: For evaluation of CD activity, based on endoscopic findings, more sensitive surrogate markers than CDAI and CRP were fecal calprotectin and lactoferrin. Fecal calprotectin and lactoferrin were significantly higher in endoscopically active disease than in endoscopic remission. In both ileocolonic and colonic disease, fecal markers correlated closely with histologic disease activity. In CD, these neutrophil-derived proteins thus seem to be useful surrogate markers of endoscopic activity. During anti-TNFα therapy, fecal calprotectin and lactoferrin decreased significantly. The anti-TNFα treatment was also reflected in a decreased IL-17/Foxp3 cell ratio, which may indicate improved balance between effector and regulatory T cells with treatment.

Noninvasive monitoring of tissue hemoglobin using UV-VIS diffuse reflectance spectroscopy: a pilot study.

We conducted a pilot study on 10 patients undergoing general surgery to test the feasibility of diffuse reflectance spectroscopy in the visible wavelength range as a noninvasive monitoring tool for blood loss during surgery. Ratios of raw diffuse reflectance at wavelength pairs were tested as a first-pass for estimating hemoglobin concentration. Ratios can be calculated easily and rapidly with limited post-processing, and so this can be considered a near real-time monitoring device. We found the best hemoglobin correlations were when ratios at isosbestic points of oxy- and deoxyhemoglobin were used, specifically 529/500 nm. Baseline subtraction improved correlations, specifically at 520/509 nm. These results demonstrate proof-of-concept for the ability of this noninvasive device to monitor hemoglobin concentration changes due to surgical blood loss. The 529/500 nm ratio also appears to account for variations in probe pressure, as determined from measurements on two volunteers.

Monitoring Stormwater Redistribution Into Low Resistivity Soils Using Noninvasive Geophysical Techniques

Water held in the unsaturated zone is important for agriculture and construction and is replenished by infiltrating rainwater. Monitoring the soil water content of clay soils using ground-penetrating radar (GPR) has not been researched, as clay soils cause attenuation of GPR signal. In this study, GPR common-midpoint soundings (CMPs) are used in the clayey soils of the Miller Run floodplain to monitor changes in the soil water content (SWC) before and after rainfall events. GPR accomplishes this task because increases in water content will increase the dielectric constant of the subsurface material, and decrease the velocity of the GPR wave. Using an empirical relationship between dielectric constant and SWC, the Topp relation, we are able to calculate a SWC from these velocity measurements. Non-invasive electromagnetics, resistivity, and seismic were performed, and from these surveys, the layering at the field site was delineated. EM characterized the horizontal variation of the soil, allowing us to target the most clay rich area. At the CMP location, resistivity indicates the vertical structure of the subsurface consists of a 40 cm thick layer with a resistivity of 100 ohm*m. Between 40 cm and 1.5 m is a layer with a resistivity of 40 ohm*m. The thickness estimates were confirmed with invasive auger and trenching methods away from the CMP location. GPR CMPs were collected relative to a July 2013 and September 2013 storm. The velocity observations from the CMPs had a precision of +/- 0.001 m/ns as assessed by repeat analysis. In the case of both storms, the GPR data showed the expected relationship between the rainstorms and calculated SWC, with the SWC increasing sharply after the rainstorm and decreasing as time passed. We compared these data to auger core samples collected at the same time as the CMPs were taken, and the volumetric analysis of the cores confirmed the trend seen in the GPR, with SWC values between 3 and 5 percent lower than the GPR estimates. Our data shows that we can, with good precision, monitor changes in the SWC of conductive soils in response to rainfall events, despite the attenuation induced by the clay.

Noninvasive monitoring of chest wall movement in infants using laser

Traditionally, non-invasive monitoring of tidal volume in infants has been performed using impedance plethysmography analyzed using a one or two compartment model. We developed a new laser system for use in infants, which measures antero-posterior movement of the chest wall during quiet sleep. In 24 unsedated or sedated infants (11 healthy, 13 with respiratory disease), we examined whether the analysis of thoracoabdominal movement based on a three compartment model could more accurately estimate tidal volume in comparison to V(T) measured at the mouth. Using five laser signals, chest wall movements were measured at the right and left, upper and lower ribcage and the abdomen. Within the tidal volume range from 4.6 to 135.7 ml, a three compartment model showed good short term repeatability and the best agreement with tidal volume measured at mouth (r(2) = 0.86) compared to that of a single compartment model (r(2) = 0.62, P < 0.0001) and a two compartment model (r(2) = 0.82, P < 0.01), particularly in the presence of respiratory disease. Three compartment modeling of a 5 laser thoracoabdominal monitoring permits more accurate estimates of tidal volume in infants and potentially of regional differences of chest wall displacement in future studies.

Noninvasive monitoring of serial changes in pulmonary vascular resistance and acute vasodilator testing using cardiac magnetic resonance

Objectives The study sought to evaluate the ability of cardiac magnetic resonance (CMR) to monitor acute and long-term changes in pulmonary vascular resistance (PVR) noninvasively. Background PVR monitoring during the follow-up of patients with pulmonary hypertension (PH) and the response to vasodilator testing require invasive right heart catheterization. Methods An experimental study in pigs was designed to evaluate the ability of CMR to monitor: 1) an acute increase in PVR generated by acute pulmonary embolization (n = 10); 2) serial changes in PVR in chronic PH (n = 22); and 3) changes in PVR during vasodilator testing in chronic PH (n = 10). CMR studies were performed with simultaneous hemodynamic assessment using a CMR-compatible Swan-Ganz catheter. Average flow velocity in the main pulmonary artery (PA) was quantified with phase contrast imaging. Pearson correlation and mixed model analysis were used to correlate changes in PVR with changes in CMR-quantified PA velocity. Additionally, PVR was estimated from CMR data (PA velocity and right ventricular ejection fraction) using a formula previously validated. Results Changes in PA velocity strongly and inversely correlated with acute increases in PVR induced by pulmonary embolization (r = –0.92), serial PVR fluctuations in chronic PH (r = –0.89), and acute reductions during vasodilator testing (r = –0.89, p ≤ 0.01 for all). CMR-estimated PVR showed adequate agreement with invasive PVR (mean bias –1.1 Wood units,; 95% confidence interval: –5.9 to 3.7) and changes in both indices correlated strongly (r = 0.86, p < 0.01). Conclusions CMR allows for noninvasive monitoring of acute and chronic changes in PVR in PH. This capability may be valuable in the evaluation and follow-up of patients with PH.

Fibre optic distributed sensor system for condition monitoring of synthetic ropes

Reliability of the measuring devices is very important problem. Optical fibre sensors are very efficient. The use of optical fibre sensors for monitoring the physical and chemical parameters has been expanding over resent years. These sensors are applied for monitoring the structural integrity of long, parallel lay synthetic ropes. Such ropes are corrosion free, however, their operational lifetime under cyclic load is not well understood and premature failure can occur due to slippage and breakage of yarns within the rope. The monitoring system has been proposed which is based on acoustic detection of yarn breakage. Monitoring the strain and temperature is performed using the array of fibre gratings distributed along the rope length.

The Acquisition of an Inheritable 50-bp Deletion in the Human mtDNA Control Region Does Not Affect the mtDNA Copy Number in Peripheral Blood Cells

The mitochondrial DNA (mtDNA) control region is believed to play an important biological role in mtDNA replication. Large deletions in this region are rarely found, but when they do occur they might be expected to interfere with the replication of the molecule, thus leading to a reduction of mtDNA copy number. During a survey for mtDNA sequence variations in 5,559 individuals from the general Chinese population and 2,538 individuals with medical disorders, we identified a 50-bp deletion (m.298_347del50) in the mtDNA control region in a member of a healthy Han Chinese family belonging to haplogroup B4c1b2, as suggested by complete mtDNA genome sequencing. This deletion removes the conserved sequence block II (CSBII; region 299-315) and the replication primer location (region 317-321). However, quantification of the mtDNA copy number in this subject showed a value within a range that was observed in 20 healthy subjects without the deletion. The deletion was detected in the hair samples of the maternal relatives of the subject and exhibited variable heteroplasmy. Our current observation, together with a recent report for a benign 154-bp deletion in the mtDNA control region, suggests that the control of mtDNA replication may be more complex than we had thought. Hum Mutat 31:538-543, 2010. (C) 2010 Wiley-Liss, Inc.

Simultaneous monitoring of drug and solvent diffusion across a model membrane using ATR-FTIR spectroscopy

Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to simultaneously follow the diffusion of model drugs and solvent across polydimethylsiloxane (silicone) membrane. Three model drugs, cyanophenol (CNP), methyl nicotinate (MN) and butyl paraben (BP) were selected to cover a range of lipophilicities. Isostearyl isostearate (ISIS) was chosen as the solvent because its large molecular weight should facilitate observation of whether the drug molecules are able to diffuse through the membrane independently of the solvent. The diffusion of the three drugs and the solvent was successfully described by a Fickian model. The effects of parameters such as the absorption wavelength used to follow diffusion on the calculated diffusion coefficient were investigated. Absorption wavelength which affects the depth of penetration of the infrared radiation into the membrane did not significantly affect the calculated diffusion coefficient over the wavelength range tested. Each of the model drugs was observed to diffuse independently of the solvent across the membrane. The diffusion of a CNP-ISIS hydrogen bonded complex across the membrane was also monitored. The relative diffusion rates of the solute and solvent across the membrane can largely be accounted for by the molecular size of the permeant.