Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function

The level of fractional exhaled nitric oxide (FENO) is significantly elevated in uncontrolled asthma and decreases after anti-inflammatory therapy The aim of this prospective study was to analyze the behavior of FENO in the follow-up and management of the inflammation in asthmatic pediatric patients treated with inhaled corticosteroids (ICS), compared to sputum cellularity, serum interleukins (IL), and pulmonary function. Twenty-six clinically stable asthmatic children aged from 6 to 18 years, previously treated or not with ICS were included. Following an international consensus (GINA), the patients were submitted to standard treatment with inhaled fluticasone for 3 months according to the severity of the disease. During this period, each patient underwent three assessments at intervals of approximately 6 weeks: Each evaluation consisted of the measurement of FENO, determination of serum interleukins IL-5, IL-10, IL-13, and interferon gamma (INF-gamma), spirometry and cytological analysis of spontaneous or induced sputum. A significant reduction in mean FENO and IL-5, without concomitant changes in FEV1, was observed along the study. There was no significant correlation between FeNO and FEV1 in the three assessments. A significant correlation between FeNO and IL-5 levels was only observed in the third assessment (r = 0.499, P=0.025). In most patients, serum IL-10, IL-13, and INF-gamma concentrations were undetectable throughout the study Sputum samples were obtained spontaneously in 11 occasions and in 56 by induction with 3% hypertonic saline solution (success rate: 50.8%), with 39 (69.9%) of them adequate for analysis. Only two of the 26 patients produced adequate samples in the three consecutive evaluations, which impaired the determination of a potential association between sputum cellularity and FeNO levels throughout the study. In conclusion, among the parameters of this study, it was difficult to perform and to interpret the serial analysis of spontaneous or induced sputum. Serum interleukins, which remained at very low or undetectable levels in most patients, were not found to be useful for therapeutic monitoring, except for IL-5 that seems to present some correlation with levels of FeNO exhaled. Monitoring of the mean FEV1 indicated no significant variations during the treatment, demonstrating that functional stability or the absence of obstruction may not reflect the adequate management of asthma. Serial measurement of FeNO seemed to best reflect the progressive anti-inflammatory action of ICS in asthma.

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 +/- A 10, Post 70 +/- A 18 mmol/kg/wt; PL Pre 52 +/- A 13, Post 46 +/- A 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4 +/- A 16.9, Post 96.1 +/- A 15.0 mL/min/1.73 m(2); PL Pre 97.9 +/- A 21.6, Post 96.4 +/- A 26.8 mL/min/1.73 m(2); p = 0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.

Mandibular Function is Severely Impaired in Systemic Sclerosis Patients

Aims: To evaluate the presence of temporomandibular disorders (TMD) in systemic sclerosis (SSc) patients and its possible association with the severity of skin involvement. Methods: The presence of TMD was evaluated in 35 SSc women and 30 age- and sex-matched healthy controls by means of the anamnestic (A(i)) and clinical (D(i)) Helkimo indices; the jaw mobility was further analyzed (M(I)). Skin involvement was scored by the Modified Rodnan Skin Score (MRSS). Results: Signs and symptoms of TMD were more frequent in SSc patients than in controls, the frequency distribution of the different clinical dysfunction indices differing significantly (P < .001) between patients (D(i)0 8.6%, D(i)I 48.6%, D(i)II 22.8%, and D(i)III 20%) and controls (D(i)0 50%, D(i)I 33.3%, and D(i)II 16.7%). Cyclophosphamide for severe and rapidly progressive cutaneous fibrosis was prescribed in six out of seven patients with severe signs (D(i)III), in contrast this treatment was indicated for only two out of 25 patients with mild to moderate signs (D(i)I and D(i)II, P <. 001). Impaired jaw mobility was more frequent in SSc patients than controls (P < .001). It was severe in 77.1% (M(I)II) and mild in 22.9% (M(1)I) of the cases, in contrast to controls (M(I)0 33.4%, M(I)I 53.3%, and M(I)II 13.3%; P < .001). Approximately half of SSc patients with severe (M(I)II) but none of those with mild impairment were on cyclophosphamide treatment for severe cutaneous fibrosis (P = .02). Conclusion: Severe signs of TMD according to the anamnestic and clinical Helkimo indices were very frequent in SSc patients. J OROFAC PAIN 2010;24:197-202

Clinical Approaches to Preserve beta-Cell Function in Diabetes

In type 2 diabetes (DM2) there is progressive deterioration in beta-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in beta-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the beta-cells, those to lead to short-term improvement of beta-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.

Effect of phototherapy with low intensity laser on local and systemic immunomodulation following focal brain damage in rat

Brain injury is responsible for significant morbidity and mortality in trauma patients, but controversy still exists over therapeutic management for these patients. The objective of this study was to analyze the effect of phototherapy with low intensity lasers on local and systemic immunomodulation following cryogenic brain injury. Laser phototherapy was applied (or not-controls) immediately after cryogenic brain injury performed in 51 adult male Wistar rats. The animals were irradiated twice (3 h interval), with continuous diode laser (gallium-aluminum-arsenide (GaAlAs), 780 nm, or indium-gallium-aluminum-phosphide (InGaAlP), 660 nm) in two points and contact mode, 40 mW, spot size 0.042 cm(2), 3 J/cm(2) and 5 J/cm(2) (3 s and 5 s, respectively). The experimental groups were: Control (non-irradiated), RL3 (visible red laser/ 3 J/cm(2)), RL5 (visible red laser/5 J/cm(2)), IRL3 (infrared laser/ 3 J/cm(2)), IRL5 (infrared laser/5 J/cm(2)). The production of interleukin-1IL-1 beta (IL-1 beta), interleukin6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-alpha) was analyzed by enzyme immunoassay technique (ELISA) test in brain and blood samples. The IL-1 beta concentration in brain of the control group ;was significantly reduced in 24 h (p < 0.01). This reduction was also observed in the RL5 and IRL3 groups. The TNF-alpha and IL-6 concentrations increased significantly (p < 0.01 and p < 0.05, respectively) in the blood of all groups, except by the IRL3 group. The IL-6 levels in RL3 group were significantly smaller than in control group in both experimental times. IL-10 concentration was maintained stable in all groups in brain and blood. Under the conditions of this study, it is possible to conclude that the laser phototherapy can affect TNF-alpha, IL-1 beta and IL-6 levels in the brain and in circulation in the first 24 h following cryogenic brain injury. (C) 2009 Elsevier B.V. All rights reserved.

Reference Values of Tissue Doppler Imaging and Pulsed Doppler Echocardiography for Analysis of Left Ventricular Diastolic Function in Healthy Adults

To determine reference values for tissue Doppler imaging (TDI) and pulsed Doppler echocardiography for left ventricular diastolic function analysis in a healthy Brazilian adult population. Observations were based on a randomly selected healthy population from the city of Vitoria, Espirito Santo, Brazil. Healthy volunteers (n = 275, 61.7% women) without prior histories of cardiovascular disease underwent transthoracic echocardiography. We analyzed 175 individuals by TDI and evaluated mitral annulus E`- and A`-waves from the septum (S) and lateral wall (L) to calculate E`/A` ratios. Using pulsed Doppler echocardiography, we further analyzed the mitral E- and A-waves, E/A ratios, isovolumetric relaxation times (IRTs), and deceleration times (DTs) of 275 individuals. Pulsed Doppler mitral inflow mean values for men were as follows: E-wave: 71 +/- 16 cm/sec, A-wave: 68 +/- 15 cm/sec, IRT: 74.8 +/- 9.2 ms, DT: 206 +/- 32.3 ms, E/A ratio: 1.1 +/- 0.3. Pulsed Doppler mitral inflow mean values for women were as follows: E-wave: 76 +/- 17, A-wave: 69 +/- 14 cm/sec, IRT: 71.2 +/- 10.5 ms, DT: 197 +/- 33.3 ms, E/A ratio: 1.1 +/- 0.3. IRT and DT values were higher in men than in women (P = 0.04 and P = 0.007, respectively). TDI values in men were as follows: E`S: 11 +/- 3 cm/sec, A`S: 13 +/- 2 cm/sec, E`S/A`S: 0.89 +/- 0.2, E`L: 14 +/- 3 cm/sec, A`L: 14 +/- 2 cm/sec, E`L/A`L: 1.1 +/- 0.4. E-wave/ E`S ratio: 6.9 +/- 2.2; E-wave / E`L ratio: 4.9 +/- 1.7. In this study, we determined pulsed Doppler and TDI derived parameters for left ventricular diastolic function in a large sample of healthy Brazilian adults. (Echocardiography 2010;27:777-782).

Left ventricular Systolic function and outcome after in-hospital cardiac arrest

Background - The effect of prearrest left ventricular ejection fraction ( LVEF) on outcome after cardiac arrest is unknown. Methods and Results - During a 26-month period, Utstein-style data were prospectively collected on 800 consecutive inpatient adult index cardiac arrests in an observational, single-center study at a tertiary cardiac care hospital. Prearrest echocardiograms were performed on 613 patients ( 77%) at 11 +/- 14 days before the cardiac arrest. Outcomes among patients with normal or nearly normal prearrest LVEF ( >= 45%) were compared with those of patients with moderate or severe dysfunction ( LVEF < 45%) by chi(2) and logistic regression analyses. Survival to discharge was 19% in patients with normal or nearly normal LVEF compared with 8% in those with moderate or severe dysfunction ( adjusted odds ratio, 4.8; 95% confidence interval, 2.3 to 9.9; P < 0.001) but did not differ with regard to sustained return of spontaneous circulation ( 59% versus 56%; P = 0.468) or 24-hour survival ( 39% versus 36%; P = 0.550). Postarrest echocardiograms were performed on 84 patients within 72 hours after the index cardiac arrest; the LVEF decreased 25% in those with normal or nearly normal prearrest LVEF ( 60 +/- 9% to 45 +/- 14%; P < 0.001) and decreased 26% in those with moderate or severe dysfunction ( 31 +/- 7% to 23 +/- 6%, P < 0.001). For all patients, prearrest beta-blocker treatment was associated with higher survival to discharge ( 33% versus 8%; adjusted odds ratio, 3.9; 95% confidence interval, 1.8 to 8.2; P < 0.001). Conclusions - Moderate and severe prearrest left ventricular systolic dysfunction was associated with substantially lower rates of survival to hospital discharge compared with normal or nearly normal function.

Short-term specialized enteral diet fails to attenuate malnutrition impairment of experimental open wound acute healing

Objective: We assessed the effect of enteral refeeding on the morphology, gene expression, and contraction of acute open wounds in previously malnourished rats using two different enteral diets. Methods: Adult male isogenic Lewis rats divided into two groups (eutrophic, n = 30; and previously malnourished, 12-15% body weight loss, n = 27) were subjected to cutaneous dorsal wounds and gastrostomy. Control rats received a standard oral diet (AIN-93M chow) plus enteral saline solution. Subject rats received chow plus a standard enteral diet or an enteral diet enriched with arginine and antioxidants. On post-trauma days 7 and 14, wound granulation tissue samples were collected for morphologic analysis using hematoxylin and eosin and picrosirius stain or immunohistochemistry slides and real-time polymerase chain reaction for collagen I and III gene expression. Wound contraction was also evaluated by comparing wound images from days 0,7, and 14. Results: Malnourished control rats had increased intensity and duration of wound inflammation, impaired increase of fibroblast cells contingent on post-trauma days 7 to 14, decreased expression of collagen III, and less wound contraction compared with eutrophic control rats. A specialized enteral diet did not improve wound healing of malnourished rats but did promote wound contraction at post-trauma day 7 in eutrophic rats. Conclusion: Short-term enteral refeeding, even with a specialized diet, failed to protect previously wounded malnourished rats from a prolonged inflammatory phase and impaired healing. (C) 2010 Elsevier Inc. All rights reserved.

INTENSITY-MODULATED AND 3D-CONFORMAL RADIOTHERAPY FOR WHOLE-VENTRICULAR IRRADIATION AS COMPARED WITH CONVENTIONAL WHOLE-BRAIN IRRADIATION IN THE MANAGEMENT OF LOCALIZED CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a ""boost"" to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels., compared with 3D-CRT. Intensity-modulated radiotherapy provided of 20, 30, and 40 Gy, respectively statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment. (C) 2010 Elsevier Inc.

Renal Cell Carcinoma: T1 and T2 Signal Intensity Characteristics of Papillary and Clear Cell Types Correlated with Pathology

OBJECTIVE. The objective of our study was to describe the T1 and T2 signal intensity characteristics of papillary renal cell carcinoma (RCC) and clear cell RCC with pathologic correlation. MATERIALS AND METHODS. Of 539 RCCs, 49 tumors (21 papillary RCCs and 28 clear cell RCCs) in 45 patients were examined with MRI. Two radiologists retrospectively and independently assessed each tumor`s T1 and T2 signal intensity qualitatively and quantitatively (i.e., the signal intensity [SI] ratio [tumor SI/renal cortex SI]). Of the 49 tumors, 37 (76%) were assessed for pathology features including tumor architecture and the presence of hemosiderin, ferritin, necrosis, and fibrosis. MRI findings and pathology features were correlated. Statistical methods included summary statistics and Wilcoxon`s rank sum test for signal intensity, contingency tables for assessing reader agreement, concordance rate between the two readers with 95% CIs, and Fisher`s exact test for independence, all stratified by RCC type. RESULTS. Papillary RCCs and clear cell RCCs had a similar appearance and signal intensity ratio on T1-weighted images. On T2-weighted images, most papillary RCCs were hypointense (reader 1, 13/21; reader 2, 14/21), with an average mean signal intensity ratio for both readers of 0.67 +/- 0.2, and none was hyperintense, whereas most clear cell RCCs were hyperintense (reader 1, 21/28; reader 2, 17/28), with an average mean signal intensity ratio for both readers of 1.41 +/- 0.4 (p < 0.05). A tumor T2 signal intensity ratio of <= 0.66 had a specificity of 100% and sensitivity of 54% for papillary RCC. Most T2 hypointense tumors exhibited predominant papillary architecture; most T2 hyperintense tumors had a predominant nested architecture (p < 0.05). CONCLUSION. On T2-weighted images, most papillary RCCs are hypointense and clear cell RCCs, hyperintense. The T2 hypointense appearance of papillary RCCs correlated with a predominant papillary architecture at pathology.

Influence of Cochlear Function on Auditory Temporal Resolution in Tinnitus Patients

Our aim was to analyze the influence of subtle cochlear damage on temporal auditory resolution in tinnitus patients. Forty-eight subjects (hearing threshold <= 25 dB HL) were assigned to one of two experimental groups: 28 without auditory complaints (mean age, 28.8 years) and 20 with tinnitus (mean age, 33.5 years). We analyzed distortion product otoacoustic emission growth functions (by threshold, slope, and estimated amplitude), extended high-frequency thresholds, and the Gaps-in-Noise test. There were differences between the groups, principally in the extended high-frequency thresholds and the Gaps-in-Noise test results. Our findings suggest that subtle peripheral hearing impairment affects temporal resolution in tinnitus, even when pure-tone thresholds as conventionally measured appear normal. Copyright (C) 2010 S. Karger AG, Basel

Oral sensorimotor function for feeding in patients with tetanus

Tetanus still remains a significant health problem in developing countries; it is a serious disease with a high mortality rate. The purpose of this study was to characterize the oral sensorimotor function for feeding in patients with tetanus. Thirteen patients clinically diagnosed with tetanus and admitted to an intensive care unit between December of 2005 and May of 2007 underwent a screening too) for dysphagia, involving the assessment of clinical features and 2 swallowing tests. Results indicate that the oral sensorimotor function for feeding in these patients is severely compromised, with the exception for the clinical feature of palate elevation and performance in the saliva swallowing test. The factor analysis indicated that the evaluation of tongue movement change in the oromotor examination is important in predicting alterations of cough/voice in the water swallowing test, thus suggesting that oral feeding might be unsafe. When looking at developing countries, the prolonged intensive medical and nursing care required by many patients with tetanus places extra demands on an already stretched healthcare budget. Intervention by a speech pathologist could mean that time in the ICU would be reduced as well as the number of re-admissions due to complications. (C) 2009 Elsevier B.V. All rights reserved.

Tone-evoked ABR in full-term and preterm neonates with normal hearing

This study was designed to investigate the feasibility of applying tone-ABRs in the nursery and neonatal intensive care unit (NICU), and to provide normative tone-ABR data from neonates. Normative tone-ABR latency data were determined. The study obtained intensity series of tone-ABRs from thirty preterm neonates and twenty fullterm neonates who had confirmed normal peripheral auditory function after passing both an OAE and ABR screening examination. ABRs were collected in response to 500, 1500, and 4000 Hz tone bursts at 70, 50, 30, and 20 dB nHL. Mean wave V latencies were compared between groups, ears, and by gender. Responses to tone bursts of 20 and 30 dB nHL were detected in 97% and 100% of all ears respectively, in addition to responses to the higher-intensity stimuli. Preterm neonates` ABRs showed significantly longer latencies than those of the full-term infants. Tone-ABR evaluation was found to be both feasible and reliable as a measure of auditory function in neonates.

Spirometric Function Improves in the Morbidly Obese After 1-Year Post-surgery

Obesity can negatively affect pulmonary function tests, with or without clinical symptoms, but the impact of bariatric weight loss is still debated. Aiming to document such profile in a consecutive homogeneous population, a prospective cohort study was undertaken. Sixty-one patients (100% females, age 40 +/- 8 years, BMI 49 +/- 5 kg/m(2) and without respiratory disease) were enrolled. Spirometric analysis was carried out to compare preoperative respiratory pattern with outcome after 6 and 12 months. Variables included vital capacity (VC), expiratory reserve volume (ERV), forced expiratory volume (1 s) (FEV1), FEV1/FVC ratio and maximum voluntary ventilation (MVV). Correlation of results with weight loss was examined. The following initial variables exhibited significant difference when compared to the 12-month postoperative control: FVC (P = 0.0308), FEV1/FVC (P = 0.1998), MVV (P = 0.0004) and ERV (P = 0.2124). Recovery of FVC and FEV1/FVC occurred earlier by 6 months. The most seriously depressed preoperative finding was ERV, which even after 1 year still remained inadequate. (1) Pulmonary limitations were diagnosed in approximately one third of the population. (2) Changes were demonstrated for FVC, FEV1/FVC, ERV and MVV. (3) FEV1 and FEV1/FVC were acceptable due to the absence of an obstructive pattern. (4) Two variables increased by 6 months (FEV1/FVC and ERV), whereas recovery for others was confirmed after 1 year. (5) The only exception was ERV which continued below the acceptable range.

Pharmacodynamics of PEG-IFN-alpha-2a and HCV Response as a Function of IL28B Polymorphism in HIV/HCV-Coinfected Patients

We examined the association between IL28B single-nucleotide polymorphism rs12979860, hepatitis C virus (HCV) kinetic, and pegylated interferon alpha-2a pharmacodynamic parameters in HIV/HCV-coinfected patients from South America. Twenty-six subjects received pegylated interferon alpha-2a + ribavirin. Serum HCV-RNA and interferon concentrations were measured frequently during the first 12 weeks of therapy and analyzed using mathematical models. African Americans and whites had a similar distribution of IL28B genotypes (P = 0.5). The IL28B CC genotype was overrepresented (P = 0.015) in patients infected with HCV genotype-3 compared with genotype-1. In both genotype-1 and genotype-3, the first-phase viral decline and the average pegylated interferon-alpha-2a effectiveness during the first week of therapy were larger (trend P <= 0.12) in genotype-CC compared with genotypes-TC/TT. In genotype-1 patients, the second slower phase of viral decline (days 2-29) and infected cells loss rate, delta, were larger (P = 0.02 and 0.11, respectively) in genotype-CC than in genotypes-TC/TT. These associations were not observed in genotype-3 patients.