Influence of ventilatory settings on static and functional haemodynamic parameters during experimental hypovolaemia

Background and objective The influence of ventilatory settings on static and functional haemodynamic parameters during mechanical ventilation is not completely known. The purpose of this study was to evaluate the effect of positive end-expiratory pressure, tidal volume and inspiratory to expiratory time ratio variations on haemodynamic parameters during haemorrhage and after transfusion of shed blood. Methods Ten anaesthetized pigs were instrumented and mechanically ventilated with a tidal volume of 8 ml kg(-1), a positive end-expiratory pressure of 5 cmH(2)O and an inspiratory to expiratory ratio of 1 : 2. Then, they were submitted in a random order to different ventilatory settings (tidal volume 16 ml kg(-1), positive end-expiratory pressure 15 cmH(2)O or inspiratory to expiratory time ratio 2: 1). Functional and static haemodynamic parameters (central venous pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic volume and pulse pressure variation) were evaluated at baseline, during hypovolaemia (withdrawal of 20% of estimated blood volume) and after an infusion of withdrawn blood (posttransfusion). Results During baseline, a positive end-expiratory pressure of 15cmH(2)O significantly increased pulmonary artery occlusion pressure from 14.6 +/- 1.6 mmHg to 17.4 +/- 1.7 mmHg (P<0.001) and pulse pressure variation from 15.8 +/- 8.5% to 25.3 +/- 9.5% (P<0.001). High tidal volume increased pulse pressure variation from 15.8 8.5% to 31.6 +/- 10.4% (P<0.001), and an inspiratory to expiratory time ratio of 2: 1 significantly increased only central venous pressure. During hypovolaemia, high positive end-expiratory pressure influenced all studied variables, and high tidal volume strongly increased pulse pressure variation (40.5 +/- 12.4% pre vs. 84.2 +/- 19.1 % post, P<0.001). The inversion of the inspiratory to expiratory time ratio only slightly increased filling pressures during hypovolaemia, without without affecting pulse pressure variation or right ventricle end-diastolic volume. Conclusion We concluded that pulse pressure variation measurement is influenced by cyclic variations in intrathoracic pressure, such as those caused by augmentations in tidal volume. The increase in mean airway pressure caused by positive end-expiratory pressure affects cardiac filling pressures and also pulse pressure variation, although to a lesser extent. Inversion of the inspiratory to expiratory time ratio does not induce significant changes in static and functional haemodynamic parameters. Eur J Anaesthesiol 26:66-72 (c) 2009 European Society of Anaesthesiology.

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.

Programmed hypertension in rats treated with a NF-kappa B inhibitor during nephrogenesis: renal mechanisms

Suppression of the renin-angiotensin system (RAS) during murine lactation causes progressive renal injury, indicating a physiological action of angiotensin II on nephrogenesis. The nuclear factor NF-kappa B system is one of the main intracellular mediators of angiotensin II. We investigated whether inhibition of this system with pyrrolidine dithiocarbamate (PDTC) during rat nephrogenesis would lead to similar hypertension and renal injury as observed with RAS suppressors. Immediately after delivery, 32 Munich-Wistar dams, each nursing 6 male pups, were divided into 2 groups: C, untreated, and PDTC, receiving PDTC, 280 mg kg(-1) day(-1) orally, during 21 days. After weaning, the offspring were followed until 10 months of age without treatment. Adult rats that received neonatal PDTC exhibited stable hypertension and myocardial injury, without albuminuria. To gain additional insight into this process, the renal expression of RAS components and sodium transporters were determined by quantitative real-time PCR (qRT-PCR) at 3 and 10 months of life. Renal renin and angiotensinogen were upregulated at 3 and downregulated at 10 months of age, suggesting a role for early local RAS activation. Likewise, there was early upregulation of the proximal sodium/glucose and sodium/bicarbonate transporters, which abated later in life, suggesting that additional factors sustained hypertension in the long run. The conclusions drawn from the findings were as follows: (1) an intact NF-jB system during nephrogenesis may be essential to normal renal and cardiovascular function in adult life; (2) neonatal PDTC represents a new model of hypertension, lacking overt structural injury or functional impairment of the kidneys; and (3) hypertension in this model seems associated with early temporary activation of renal RAS and sodium transporters. Hypertension Research (2011) 34, 693-700; doi: 10.1038/hr. 2011.4; published online 17 February 2011

Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo

Pires-Oliveira M, Maragno AL, Parreiras-E-Silva LT, Chiavegatti T, Gomes MD, Godinho RO. Testosterone represses ubiquitin ligases atrogin-1 and Murf-1 expression in an androgen-sensitive rat skeletal muscle in vivo. J Appl Physiol 108: 266-273, 2010. First published November 19, 2009; doi:10.1152/japplphysiol.00490.2009.-Skeletal muscle atrophy induced by denervation and metabolic diseases has been associated with increased ubiquitin ligase expression. In the present study, we evaluate the influence of androgens on muscle ubiquitin ligases atrogin-1/MAFbx/FBXO32 and Murf-1/Trim63 expression and its correlation with maintenance of muscle mass by using the testosterone-dependent fast-twitch levator ani muscle (LA) from normal or castrated adult male Wistar rats. Gene expression was determined by qRT-PCR and/or immunoblotting. Castration induced progressive loss of LA mass (30% of control, 90 days) and an exponential decrease of LA cytoplasm-to-nucleus ratio (nuclear domain; 22% of control after 60 days). Testosterone deprivation induced a 31-fold increase in LA atrogin-1 mRNA and an 18-fold increase in Murf-1 mRNA detected after 2 and 7 days of castration, respectively. Acute (24 h) testosterone administration fully repressed atrogin-1 and Murf-1 mRNA expression to control levels. Atrogin-1 protein was also increased by castration up to 170% after 30 days. Testosterone administration for 7 days restored atrogin-1 protein to control levels. In addition to the well known stimulus of protein synthesis, our results show that testosterone maintains muscle mass by repressing ubiquitin ligases, indicating that inhibition of ubiquitin-proteasome catabolic system is critical for trophic action of androgens in skeletal muscle. Besides, since neither castration nor androgen treatment had any effect on weight or ubiquitin ligases mRNA levels of extensor digitorum longus muscle, a fast-twitch muscle with low androgen sensitivity, our study shows that perineal muscle LA is a suitable in vivo model to evaluate regulation of muscle proteolysis, closely resembling human muscle responsiveness to androgens.

Effects of hyperbaric oxygen treatment on auditory hair cells after acute noise damage

Acute acoustic trauma (AAT) is a sudden sensorineural hearing loss caused by exposure of the hearing organ to acoustic overstimulation, typically an intense sound impulse, hyperbaric oxygen therapy (HOT), which favors repair of the microcirculation, can be potentially used to treat it. Hence, this study aimed to assess the effects of HOT on guinea pigs exposed to acoustic trauma. Fifteen guinea pigs were exposed to noise in the 4-kHz range with intensity of 110 dB sound level pressure for 72 h. They were assessed by brainstem auditory evoked potential (BAEP) and by distortion product otoacoustic emission (DPOAE) before and after exposure and after HOT at 2.0 absolute atmospheres for 1 h. The cochleae were then analyzed using scanning electron microscopy (SEM). There was a statistically significant difference in the signal-to-noise ratio of the DPOAE amplitudes for the 1- to 4-kHz frequencies and the SEM findings revealed damaged outer hair cells (OHC) after exposure to noise, with recovery after HOT (p = 0.0159), which did not occur on thresholds and amplitudes to BAEP (p = 0.1593). The electrophysiological BAEP data did not demonstrate effectiveness of HOT against AAT damage. However, there was improvement of the anatomical pattern of damage detected by SEM, with a significant reduction of the number of injured cochlear OHC and their functionality detected by DPOAE.

Relationship Between Blood Pressure and Anthropometry in a Cohort of Brazilian Men: A Cross-Sectional Study

BACKGROUND Hypertension, a risk factor for cardiovascular diseases, and obesity are becoming a health problem in many developed and developing countries, as Brazil. Although hypertension and obesity are both closely associated, there is no universal anthropometric marker of this association. This is probably due to distinct population characteristics, and in the case of Brazil, the highly heterogeneous population. We evaluated which anthropometric measurement closely relates to high blood pressure in a sample of Brazilian factory workers. METHODS A cross-sectional study was designed. In this study, multiple logistic regression and receiver operating characteristics analysis were performed in order to obtain the precise relevance of each anthropometric measurement as a blood pressure marker. Nine hundred and thirteen men, 36 +/- 8 years-old, were submitted to a standardized questionnaire of demographic and risk factors knowledge, anthropometric and conventional blood pressure measurements were taken, and blood sample evaluations of glucose, total cholesterol, LDL-Cholesterol, and triglycerides were performed. RESULTS Overweightness or obesity was identified in 64, 11.1% were smokers and hypertension was detected in 29.2% of the participants. A linear correlation was significant (P < 0.001) between both the systolic and diastolic blood pressure and all anthropometric measurements, except for the systolic blood pressure and waist-to-hip ratio. Waist circumference (WC) was the only independent anthropometric measurement related to hypertension. Hypertensive patients presented all anthropometric measurements larger than normotensives. CONCLUSIONS Age and WC were the only independent predictors of hypertension, indicating that this simple measurement may be useful as a marker of hypertension in the Brazilian male, younger adult population. Am J Hypertens 2009; 22:980-984 (C) 2009 American Journal of Hypertension, Ltd.

Paracoccidioidomycosis Epidemiological Features of a 1,000-Cases Series from a Hyperendemic Area on the Southeast of Brazil

Paracoccidioidomycosis has been known for over 100 years, and until now, there were only few estimates of the disease`s incidence. We aim to analyze 1,000 cases treated between 1960 and 1999 at Ribeirao Preto city, Sao Paulo, Brazil, where the disease`s incidence range detected was 1.6 to 3.7 cases per 100,000 habitants per year (mean = 2.7 cases/year). We observed a male to female ratio of 6:1 and an age distribution from 3 to 85 years. The acute/subacute form of the disease accounted for 25.4% of cases. Most of the patients (93.5%) had lived or worked in rural areas before the disease development. Smoking and alcoholism were reported by 64.7% and 37.2% of patients, respectively. Comorbidities identified included tuberculosis (8.3%), Chagas` disease (8.6%), and human immunodeficiency virus/acquired immunodeficiency syndrome (4.2%). The present study revealed an area in Brazil where paracoccidioidomycosis is hyperendemic (has the highest reported incidence of this disease); this endemic area is probably caused by geological and climatic conditions as well as intensive agriculture.

Detection of Auditory Cortex Activity by fMRI Using a Dependent Component Analysis

Functional MRI (fMRI) data often have low signal-to-noise-ratio (SNR) and are contaminated by strong interference from other physiological sources. A promising tool for extracting signals, even under low SNR conditions, is blind source separation (BSS), or independent component analysis (ICA). BSS is based on the assumption that the detected signals are a mixture of a number of independent source signals that are linearly combined via an unknown mixing matrix. BSS seeks to determine the mixing matrix to recover the source signals based on principles of statistical independence. In most cases, extraction of all sources is unnecessary; instead, a priori information can be applied to extract only the signal of interest. Herein we propose an algorithm based on a variation of ICA, called Dependent Component Analysis (DCA), where the signal of interest is extracted using a time delay obtained from an autocorrelation analysis. We applied such method to inspect functional Magnetic Resonance Imaging (fMRI) data, aiming to find the hemodynamic response that follows neuronal activation from an auditory stimulation, in human subjects. The method localized a significant signal modulation in cortical regions corresponding to the primary auditory cortex. The results obtained by DCA were also compared to those of the General Linear Model (GLM), which is the most widely used method to analyze fMRI datasets.

Evaluation of albuminuria and its relationship with blood pressure in dogs with chronic kidney disease

Background Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD). Objective The objective of this study was to evaluate albuminuria and its association with arterial hypertension in dogs with CKD. Methods Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine (UPC) ratio, and systolic blood pressure were determined in 39 clinically healthy dogs and 40 dogs with CKD. Results UAC in dogs with CKD (range, 0.002-7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005-0.01; median, 0.002). Microalbuminuria (UAC 0.03-0.3) and macroalbuminuria (UAC > 0.3) were detected in 32.5% and 50% of dogs with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic pressure >= 180 mmHg; in these dogs, UAC ratio (range, 0.006-7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure < 180 mmHg (range, 0.002-4.83; median, 0.10). Of hypertensive dogs with CKD, those with UPC > 1.0 usually had macroalbuminuria, those with UPC 0.5-1.0 usually had microalbuminuria, and those with UPC < 0.5 usually lacked albuminuria. Conclusions UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC < 1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.

Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study

Risk factors for melanoma include environmental (particularly ultraviolet exposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, with more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi so that genes controlling nevus phenotype could be such melanoma susceptibility genes. A large Australian study involving twins aged 12 y of predominantly U.K. ancestry showed strong evidence for genetic influence on nevus number and density. We carried out essentially the same study in the U.K. to gain insight into gene-environment interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10-18 y were examined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p = 0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12 y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m(2)) than sun-protected sites (58 per m(2)) (p < 0.0001). Correlations in sex and age adjusted nevus density were higher in MZ pairs (0.94, 95% CI 0.92-0.96) than in DZ pairs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.

Three-dimensional orthotropic viscoelastic finite element model of a human ligament

Ligaments undergo finite strain displaying hyperelastic behaviour as the initially tangled fibrils present straighten out, combined with viscoelastic behaviour (strain rate sensitivity). In the present study the anterior cruciate ligament of the human knee joint is modelled in three dimensions to gain an understanding of the stress distribution over the ligament due to motion imposed on the ends, determined from experimental studies. A three dimensional, finite strain material model of ligaments has recently been proposed by Pioletti in Ref. [2]. It is attractive as it separates out elastic stress from that due to the present strain rate and that due to the past history of deformation. However, it treats the ligament as isotropic and incompressible. While the second assumption is reasonable, the first is clearly untrue. In the present study an alternative model of the elastic behaviour due to Bonet and Burton (Ref. [4]) is generalized. Bonet and Burton consider finite strain with constant modulii for the fibres and for the matrix of a transversely isotropic composite. In the present work, the fibre modulus is first made to increase exponentially from zero with an invariant that provides a measure of the stretch in the fibre direction. At 12% strain in the fibre direction, a new reference state is then adopted, after which the material modulus is made constant, as in Bonet and Burton's model. The strain rate dependence can be added, either using Pioletti's isotropic approximation, or by making the effect depend on the strain rate in the fibre direction only. A solid model of a ligament is constructed, based on experimentally measured sections, and the deformation predicted using explicit integration in time. This approach simplifies the coding of the material model, but has a limitation due to the detrimental effect on stability of integration of the substantial damping implied by the nonlinear dependence of stress on strain rate. At present, an artificially high density is being used to provide stability, while the dynamics are being removed from the solution using artificial viscosity. The result is a quasi-static solution incorporating the effect of strain rate. Alternate approaches to material modelling and integration are discussed, that may result in a better model.

Assessing self- and peer-assessment: The students' views

Self- and peer-assessment are being used increasingly in higher education, to help assign grades to students' work and to help students to learn more effectively. However, in spite of this trend there is little in the published literature on how students view these methods. In this paper we present an analysis of the views of a large number of students (N = 233) who had just experienced self- and peer-feedback as part of one of their subjects. It is a rarely questioned commonplace in the literature that in order to gain benefit from peer and self-assessment schemes students first need training in the specific scheme being used; ideally they will play a role in devising the scheme. The intervention reported here, which involved a large (N = 233) group of students, included no such measures. The results show that students felt, nonetheless, that they benefited from the intervention. The results also present prima facie evidence that training or other measures to further involve the students in the peer and self-assessment scheme might be beneficial. Our analysis of students' views revealed eight general dimensions under which are grouped twenty higher order themes. The results both support and extend previous research and give a more detailed picture than previously available. The general dimensions found were: Difficult; Gained Better Understanding of Marking; Discomfort; Productive (including learning benefits and improved work); Problems with Implementation; Read Others' Work; Develop Empathy (with assessing staff); and, Motivation (especially motivation to impress peers). The practical implications of these findings are discussed.

SAR imaging of buried objects from MoM modelled scattered field

Synthetic aperture radar (SAR) images of resonant buried objects are modelled in the presence of ground surface clutter. The method of moments (MoM) is used to model scattered fields from a resonant buried conductor and clutter is modelled as a bivariant Gaussian distribution. A diffraction stack SAR imaging technique is applied to the ultra-wideband waveforms to give a bipolar signal image. A number of examples have been computed to illustrate the combined effects of SAR processing with resonant targets and clutter. SAR images of different targets show differences which may facilitate target identification. To maximise the peak signal-to-clutter ratio, an image correlation technique is applied and the results are shown.

The effect of high-pass filtering on TEOAE in 2-month-old infants

The aim of the present study was to investigate the effect of high-pass filtering on TEOAE obtained from 2-month-old infants as a function of filter cut-off frequency, activity states and pass/fail status of infants. Two experiments were performed. In Experiment 1, 100 2-month-old infants (200 ears) in five activity states (asleep, awake but peaceful, sucking a pacifier, feeding, restless) were tested by use of TEOAE technology. Five different filter conditions were applied to the TEOAE responses post hoc. The filter conditions were set at 781 Hz (default setting), 1.0, 1.2, 1.4 and 1.6 kHz. Results from this experiment showed that TEOAE parameters, such as whole-wave reproducibility (WR) and signal-to-noise ratio (SNR) at 0.8 kHz and 1.6 kHz, changed as a function of the cut-off frequency. The findings suggest that the 1.6 kHz and 1.2 kHz filter conditions are optimal for WR and SNR pass/fail criteria, respectively. Although all infant recordings appeared to benefit from the filtering, infants in the noisy states seemed to benefit the most. In Experiment 2, the high-pass filtering technique was applied to 23 infants (35 ears) who apparently failed the TEOAE tests on initial screening but were subsequently awarded a pass status based on the results from a follow-up auditory brainstem response (ABR) assessment. The findings showed a significant decrease in noise contamination of the TEOAE with a corresponding significant increase in WR. With high-pass filtering at 1.6 kHz, 21/35 ears could be reclassified into the pass category.

Outcomes of transient evoked otoacoustic emission testing in 6-year-old school children: A comparison with pure tone screening and tympanometry

Objectives: (1) To establish test performance measures for Transient Evoked Otoacoustic Emission testing of 6-year-old children in a school setting; (2) To investigate whether Transient Evoked Otoacoustic Emission testing provides a more accurate and effective alternative to a pure tone screening plus tympanometry protocol. Methods: Pure tone screening, tympanometry and transient evoked otoacoustic emission data were collected from 940 subjects (1880 ears), with a mean age of 6.2 years. Subjects were tested in non-sound-treated rooms within 22 schools. Receiver operating characteristics curves along with specificity, sensitivity, accuracy and efficiency values were determined for a variety of transient evoked otoacoustic emission/pure tone screening/tympanometry comparisons. Results: The Transient Evoked Otoacoustic Emission failure rate for the group was 20.3%. The failure rate for pure tone screening was found to be 8.9%, whilst 18.6% of subjects failed a protocol consisting of combined pure tone screening and tympanometry results. In essence, findings from the comparison of overall Transient Evoked Otoacoustic Emission pass/fail with overall pure tone screening pass/fail suggested that use of a modified Rhode Island Hearing Assessment Project criterion would result in a very high probability that a child with a pass result has normal hearing (true negative). However, the hit rate was only moderate. Selection of a signal-to-noise ratio (SNR) criterion set at greater than or equal to 1 dB appeared to provide the best test performance measures for the range of SNR values investigated. Test performance measures generally declined when tympanometry results were included, with the exception of lower false alarm rates and higher positive predictive values. The exclusion of low frequency data from the Transient Evoked Otoacoustic Emission SNR versus pure tone screening analysis resulted in improved performance measures. Conclusions: The present study poses several implications for the clinical implementation of Transient Evoked Otoacoustic Emission screening for entry level school children. Transient Evoked Otoacoustic Emission pass/fail criteria will require revision. The findings of the current investigation offer support to the possible replacement of pure tone screening with Transient Evoked Otoacoustic Emission testing for 6-year-old children. However, they do not suggest the replacement of the pure tone screening plus tympanometry battery. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.