Ventilation Patterns Influence Airway Secretion Movement

BACKGROUND: Retention of airway secretions is a common and serious problem in ventilated patients. Treating or avoiding secretion retention with mucus thinning, patient-positioning, airway suctioning, or chest or airway vibration or percussion may provide short-term benefit. METHODS: In a series of laboratory experiments with a test-lung system we examined the role of ventilator settings and lung-impedance on secretion retention and expulsion. Known quantities of a synthetic dye-stained mucus simulant with clinically relevant properties were injected into a transparent tube the diameter of an adult trachea and exposed to various mechanical-ventilation conditions. Mucus-simulant movement was measured with a photodensitometric technique and examined with image-analysis software. We tested 2 mucus-simulant viscosities and various peak flows, inspiratory/ expiratory flow ratios, intrinsic positive end-expiratory pressures, ventilation waveforms, and impedance values. RESULTS: Ventilator settings that produced flow bias had a major effect on mucus movement. Expiratory How bias associated with intrinsic positive end-expiratory pressure generated by elevated minute ventilation moved mucus toward the airway opening, whereas intrinsic positive end-expiratory pressure generated by increased airway resistance moved the mucus toward the lungs. Inter-lung transfer of mucus simulant occurred rapidly across the ""carinal divider"" between interconnected test lungs set to radically different compliances; the mucus moved out of the low-compliance lung and into the high-compliance lung. CONCLUSIONS: The movement of mucus simulant was influenced by the ventilation pattern and lung impedance. Flow bias obtained with ventilator settings may clear or embed mucus during mechanical ventilation.

Is facial pattern a predisposing factor for otitis media with effusion in children?

Abnormalities in craniofacial morphology are associated with Eustachian tube dysfunction and otitis media with effusion (OME). Aim: to evaluate the relationship between facial pattern and craniofacial growth direction, and OME in children with enlarged tonsils and adenoids (ETA). Methods: Clinical prospective survey in 79 children (41 male and 38 female), ranging from 4 to 10 years of age, with tonsil and adenoid enlargement (Brodsky`s grades III and IV). Forty children presented with OME (study group) and 39 did not (control group). Cephalometric analysis was used to determine the facial pattern. Results: There was no correlation observed between facial pattern and OME (c 2 = 0.25 p = 0.88). Facial Axis was larger in the OME group (F(1.75) = 3.68 p = 0.05) and the Lower Anterior Facial height was smaller (F(1. 75) = 3.99 p = 0.05) in children with otitis media with effusion. Conclusions: There was no correlation between OME and facial pattern in children with ETA although a more horizontal facial growth direction, and a smaller lower anterior facial height was observed consistently among subjects in this group. This suggests that abnormal positioning of the eustachian tube influences the development of OME in children with ETA.

Hyrax appliance opening and pattern of skeletal maxillary expansion after surgically assisted rapid palatal expansion: a computed tomography evaluation

Objective. The objective of this study was to evaluate, using computed tomography, correlations between Hyrax appliance opening and post-SARPE skeletal changes. Study design. Fifteen patients underwent SARPE according to a specific protocol and were followed. Linear and angular measurements of the anterior, intermediate, and posterior portions of the maxilla were evaluated. The correlation between maxillary expansion and appliance opening was investigated. Results. Significant overall expansion was observed. In the anterior and intermediate portions of the maxilla, the increase in maxillary width was greater than that observed in the posterior portion. The degree of appliance opening was significantly greater than that of the skeletal expansion. Also, no linear correlation between appliance opening and regional maxillary expansion was established. Conclusion. The transverse expansion of the maxilla was less than uniform. The lack of linear correlation between appliance opening and skeletal expansion is attributable to multiple factors, including those related to the device, the surgical technique, and the craniofacial deformity itself. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008; 106: 812-819)

Centrilobular Fibrosis: An Underrecognized Pattern in Systemic Sclerosis

Background: The impressive association of lung involvement and gastroesophageal reflux in scleroderma raises the possibility of a cause-effect relationship. Objectives: To determine clinical, radiological and histopathological features of systemic sclerosis (SSc) patients according the presence or absence of centrilobular fibrosis (CLF). Methods: Twenty-eight SSc patients with lung involvement were submitted to open lung biopsy and the specimens classified for the presence of CLF (bronchocentric distribution of the lesions and intraluminal matter according to the classification of idiopathic interstitial pneumonia). HRCT, pulmonary function tests and esophageal analysis were also performed. Subsequently, cyclophosphamide was introduced for the nonspecific interstitial pneumonia subgroup and antireflux treatment was intensified for isolated CLF patients. Results: Isolated CLF was found in 21% of the biopsies and also found associated to nonspecific interstitial pneumonia in 84% of these patients. The other 3 cases had usual interstitial pneumonia, pulmonary hypertension and respiratory bronchiolitis-associated interstitial lung disease. The histopathological analysis revealed that all 6 patients with isolated CLF had the bronchocentric distribution and intraluminal basophilic content, with foreign bodies detected in one third of them. The central distribution of lung involvement on HRCT was found in 67% of these patients with a consistent patchy distribution (100%). Ground glass (67%) and consolidation (33%) were the predominant patterns found. The constant clinical finding in all isolated CLF cases was dyspnea, esophageal abnormalities and a moderate lung impairment (FVC: 63.83 +/- 16.31%; DLCO: 61.66 +/- 18.84%). Lung function parameters in isolated CLF patients remained stable after 1 year of exclusively intensive antireflux treatment (FVC, p = 0.23; DLCO, p = 0.59). Conclusions: The novel description of CLF pattern in SSc lung disease with peculiar histological, tomographic and clinical features will certainly contribute to a more appropriate therapeutic approach. Copyright (C) 2008 S. Karger AG, Basel

Aerobic Exercise Improves Reverse Cholesterol Transport in Cholesteryl Ester Transfer Protein Transgenic Mice

We analyzed the effect of a 6-week aerobic exercise training program on the in vivo macrophage reverse cholesterol transport (RCT) in human cholesteryl ester transfer protein (CETP) transgenic (CETP-tg) mice. Male CETP-tg mice were randomly assigned to a sedentary group or a carefully supervised exercise training group (treadmill 15 m/min, 30 min sessions, five sessions per week). The levels of plasma lipids were determined by enzymatic methods, and the lipoprotein profile was determined by fast protein liquid chromatography (FPLC). CETP activity was determined by measuring the transfer rate of (14)C-cholesterol from HDL to apo-B containing lipoproteins, using plasma from CETP-tg mice as a source of CETP. The reverse cholesterol transport was determined in vivo by measuring the [(3)H]-cholesterol recovery in plasma and feces (24 and 48 h) and in the liver (48 h) following a peritoneal injection of [(3)H]-cholesterol labeled J774-macrophages into both sedentary and exercise trained mice. The protein levels of liver receptors were determined by immunoblot, and the mRNA levels for liver enzymes were measured using RT-PCR. Exercise training did not significantly affect the levels of plasma lipids or CETP activity. The HDL fraction assessed by FPLC was higher in exercise-trained compared to sedentary mice. In comparison to the sedentary group, a greater recovery of [(3)H]-cholesterol from the injected macrophages was found in the plasma, liver and feces of exercise-trained animals. The latter occurred even with a reduction in the liver CYP7A1 mRNA level in exercised trained animals. Exercise training increased the liver LDL receptor and ABCA-1 protein levels, although the SR-BI protein content was unchanged. The RCT benefit in CETP-tg mice elicited by exercise training helps to elucidate the role of exercise in the prevention of atherosclerosis in humans.

HUMAN CHOLESTERYL ESTER TRANSFER PROTEIN EXPRESSION ENHANCES THE MOUSE SURVIVAL RATE IN AN EXPERIMENTAL SYSTEMIC INFLAMMATION MODEL: A NOVEL ROLE FOR CETP

Mice expressing human cholesteryl ester transfer protein (huCETP) are more resistant to Escherichia coli bacterial wall LIPS because death rates 5 days after intraperitoneal inoculation of LIPS were higher in wild-type than in huCETP(+/-) mice, whereas all huCETP(+/+) mice remained alive. After LIPS inoculation, plasma concentrations of TNF-alpha and IL-6 increased less in huCETP(+/+) than in wild-type mice. LPS in vitro elicited lower TNF-alpha production by CETP expressing than by wild-type macrophages. In addition, TNF-alpha production by RAW 264.7 murine macrophages increased on incubation with LPS but decreased in a dose-dependent manner when human CETP was added to the medium. Human CETP in vitro enhanced the LIPS binding to plasma high-density lipoprotein/low-density lipoprotein. The liver uptake of intravenous infused C-14-LPS from Salmonella typhimurium was greater in huCETP(+/+) than in wild-type mice. Present data indicate for the first time that CETP is an endogenous component involved in the first line of defense against an exacerbated production of proinflammatory mediators.

Quantifying subclinical central nervous lesions in primary antiphospholipid syndrome: The role of magnetization transfer imaging

Purpose: To define the role of magnetization transfer imaging (MTI) in detecting subclinical central nervous system (CNS) lesions in primary antiphospholipid syndrome (PAPS). Materials and Methods: Ten non-CNS PAPS patients were compared to 10 CNS PAPS patients and 10 age- and sex-matched controls. All PAPS patients met Sapporo criteria. All Subjects underwent conventional MRI and complementary MTI analysis to compose histograms. CNS viability was determined according to the magnetization transfer ratio (MTR) by mean pixel intensity (MPI) and the mean peak height (MPH). Volumetric cerebral measurements were assessed by brain parenchyma factor (BPF) and total/cerebral volume. Results: MTR histograms analysis revealed that MPI was significantly different among groups (P < 0.0001). Non-CNS PAPS had a higher MPI than CNS PAPS, (30.5 +/- 1.01 vs. 25.1 +/- 3.17 percent unit (pu); P < 0.05) although lower than controls (30.5 +/- 1.01 vs. 31.20 < 0.50 pu; P < 0.05). MPH in non-CNS PAPS (5.57 +/- 0.20% (1/pu)} was similar to controls (5.63 +/- 0.20% (1/pu), P > 0.05) and higher than CNS PAPS (4.71 +/- 0.30% (1/pu), P < 0.05). A higher peak location (PL) was also observed in the CNS PAPS group in comparison with the other groups (P < 0.0001). In addition, a lower BPF was found in non-CNS PAPS compared to controls (0.80 +/- 0.03 vs. 0.84 +/- 0.02 units; P < 0.05) but similar to CNS PAPS (0.80 +/- 0.03 vs. 0.79 +/- 0.05 units; P > 0.05). Conclusion: Our findings suggest that non-CNS PAPS patients have subclinical cerebral damage. The long-term-clinical relevance of MTI analysis in these patients needs to be defined by prospective studies.

Volume reduction of the corpus callosum and its relationship with deficits in interhemispheric transfer of information in recent-onset psychosis

The present study aimed to investigate the presence of corpus callosum (CC) volume deficits in a population-based recent-onset psychosis (ROP) sample, and whether CC volume relates to interhemispheric communication deficits. For this purpose, we used voxel-based morphometry comparisons of magnetic resonance imaging data between ROP (n = 122) and healthy control (n = 94) subjects. Subgroups (38 ROP and 39 controls) were investigated for correlations between CC volumes and performance on the Crossed Finger Localization Test (CFLT). Significant CC volume reductions in ROP subjects versus controls emerged after excluding substance misuse and non-right-handedness. CC reductions retained significance in the schizophrenia subgroup but not in affective psychoses subjects. There were significant positive correlations between CC volumes and CFLT scores in ROP subjects, specifically in subtasks involving interhemispheric communication. From these results, we can conclude that CC volume reductions are present in association with ROP. The relationship between such deficits and CFLT performance suggests that interhemispheric communication impairments are directly linked to CC abnormalities in ROP. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

From EEG to BOLD: Brain mapping and estimating transfer functions in simultaneous EEG-fMRI acquisitions

Simultaneous acquisition of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) aims to disentangle the description of brain processes by exploiting the advantages of each technique. Most studies in this field focus on exploring the relationships between fMRI signals and the power spectrum at some specific frequency bands (alpha, beta, etc.). On the other hand, brain mapping of EEG signals (e.g., interictal spikes in epileptic patients) usually assumes an haemodynamic response function for a parametric analysis applying the GLM, as a rough approximation. The integration of the information provided by the high spatial resolution of MR images and the high temporal resolution of EEG may be improved by referencing them by transfer functions, which allows the identification of neural driven areas without strong assumptions about haemodynamic response shapes or brain haemodynamic`s homogeneity. The difference on sampling rate is the first obstacle for a full integration of EEG and fMRI information. Moreover, a parametric specification of a function representing the commonalities of both signals is not established. In this study, we introduce a new data-driven method for estimating the transfer function from EEG signal to fMRI signal at EEG sampling rate. This approach avoids EEG subsampling to fMRI time resolution and naturally provides a test for EEG predictive power over BOLD signal fluctuations, in a well-established statistical framework. We illustrate this concept in resting state (eyes closed) and visual simultaneous fMRI-EEG experiments. The results point out that it is possible to predict the BOLD fluctuations in occipital cortex by using EEG measurements. (C) 2010 Elsevier Inc. All rights reserved.

Erythema elevatum diutinum presenting with a giant annular pattern

A 45-year-old woman presented with a 3-year history of cutaneous lesions. Clinical examination revealed red-yellow to brownish infiltrated papules coalescing into annular-shaped plaques of several sizes with a hyperpigmented center affecting the abdomen and lower limbs, as well as multiple firm nodules on the right palm, elbows, and knees (Fig. 1a-c). The patient also reported sporadic arthralgia and low fever. She had been treated for leprosy for 2 years with multidrug therapy (clofazimine, dapsone, and rifampicin), with complete remission of the lesions during treatment, but recurrence after discontinuation. Histologic examination of a biopsy specimen taken from the cutaneous lesions showed an interstitial inflammatory infiltrate with the presence of many neutrophils and occasional foamy histiocytes (Fig. 2a). A pattern of perivascular eosinophilic fibrosis was observed in a biopsy specimen from a nodule (Fig. 2b). Special stains for acid-fast bacilli and fungi were negative. Laboratory findings included elevated immunoglobulin A (IgA) serum levels (1016 mg/dL; normal range, 69-382 mg/dL), elevated beta-globulin, and strong tuberculin reactivity. Normal or negative tests included direct immunofluorescence, serum immunofixation, anti-streptolysin O, and chest radiography. Autoimmune disorders and inflammatory intestinal diseases were excluded. The patient was treated with dapsone, 100 mg/day, with great improvement of the clinical picture. Hyperpigmented residual macules and some fibrotic nodules remained after 3 months.

Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease

Background and Aims: Although the metabolic risk factors for non-alcoholic fatty liver disease (NAFLD) progression have been recognized, the role of genetic susceptibility remains a field to be explored. The aim of this study was to examine the frequency of two polymorphisms in Brazilian patients with biopsy-proven simple steatosis or non-alcoholic steatohepatitis (NASH): -493 G/T in the MTP gene, which codes the protein responsible for transferring triglycerides to nascent apolipoprotein B, and -129 C/T in the GCLC gene, which codes the catalytic subunit of glutamate-cystein ligase in the formation of glutathione. Methods: One hundred and thirty-one biopsy-proven NAFLD patients (n = 45, simple steatosis; n = 86, NASH) and 141 unrelated healthy volunteers were evaluated. Genomic DNA was extracted from peripheral blood cells, and the -129 C/T polymorphism of the GCLC gene was determined by restriction fragment length polymorphism (RFLP). The -493 G/T polymorphism of the MTP gene was determined by direct sequencing of the polymerase chain reaction products. Results: The presence of at least one T allele in the -129 C/T polymorphism of the GCLC gene was independently associated with NASH (odds ratio 12.14, 95% confidence interval 2.01-73.35; P = 0.007), whereas, the presence of at least one G allele in the -493 G/T polymorphism of the MTP gene differed slightly between biopsy-proven NASH and simple steatosis. Conclusion: This difference clearly warrants further investigation in larger samples. These two polymorphisms could represent an additional factor for consideration in evaluating the risk of NAFLD progression. Further studies involving a larger population are necessary to confirm this notion.

Adrenalectomy counteracts the local modulation of astroglial fibroblast growth factor system without interfering with the pattern of 6-OHDA-induced dopamine degeneration in regions of the ventral midbrain

The present study investigated the effects of bilateral adrenalectomy (ADX) on the synthesis of basic fibroblast growth factor (bFGF, FGF-2) mRNA and on the expression of its FGF receptor subtype-2 (FGFR2) mRNA after a 6-hydroxydopamine (6-OHDA)-induced lesion of nigrostriatal dopamine system. In previous papers we have demonstrated that corticosterone increases FGF-2 immunoreactivity mainly in the astrocytes of the substantia nigra [Chadi, G., Rosen, L., Cintra, A., Tinner, B., Zoli, M., Pettersson, R.F., Fuxe, K., 1993b. Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat. Neuroreport 4, 783-786.] and that 6-OHDA injected in the ventral midbrain upregulates FGF-2 synthesis in reactive astrocytes in the ascending dopamine pathways [Chadi, G., Cao, Y., Pettersson, R.F., Fuxe, K., 1994. Temporal and spatial increase of astroglial basic fibroblast growth factor synthesis after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine neurons. Neuroscience 61, 891-910.]. Rats were adrenalectomized and received a 6-OHDA stereotaxical injection in the ventral midbrain 2 days later. Seven days after the dopamine lesion, Western blot analysis showed a decreased level of tyrosine hydroxylase in the lesioned side of the midbrain, an event that was not altered by ADX or corticosterone replacement. Moreover, the degeneration of nigral dopamine neurons, which was confirmed by the disappearance of acidic FGF (FGF-1) mRNA and the decrement of tyrosine hydroxylase mRNA labeled nigral neurons, was not altered by ADX. The FGF-2 protein (23 kDa isoform but not 21 kDa fraction) levels increased in the lesioned side of the ventral midbrain. This elevation was counteracted by ADX, an effect that was fully reversed by corticosterone replacement. In situ hybridization revealed that ADX counteracted the elevated FGF-2 mRNA levels in putative glial cells of the ipsilateral pars compacta of the substantia nigra and in the ventral tegmental area. The ADX also counteracted the increased density and intensity of the astroglial FGF-2 immunoreactive profiles within the lesioned pars compacta of the substantia nigra and the ventral tegmental area as determined by stereology. The stereotaxical mechanical needle insertion triggered the expression of FGFR2 mRNA in putative glial cells, spreading to the entire ipsilateral ventral midbrain from the region of needle track, an occurrence that was partially reversed by ADX. In conclusion, bilateral ADX counteracted the increased astroglial FGF-2 synthesis in the dopamine regions of the ventral midbrain following a 6-OHDA-induced local lesion and interfered with FGF receptor regulation around injury. These findings give further evidence that adrenocortical hormones may regulate the astroglial FGF-2-mediated trophic mechanisms and wound repair events in the lesioned central nervous system. (c) 2007 Elsevier B.V. All rights reserved.

Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern and predictors

One hundred forty-two women with polycystic ovary syndrome (PCOS) with an average body mass index (BMI) of 29.1 kg/m(2) and average age of 25.12 years were studied. By BMI, 30.2% were normal, 38.0% were overweight and 31.6% were obese. Thirty-one eumenorrheic women matched for BMI and age, with no evidence of hyperandrogenism, were recruited as controls. The incidence of dyslipidemia in the PCOS group was twice that of the Control group (76.1% versus 32.25%). The most frequent abnormalities were low high-density lipoprotein cholesterol (HDL-C; 57.6%) and high triglyceride (TG) (28.3%). HDL-C was significantly lower in all subgroups of women with PCOS when compared to the subgroups of normal women. No significant differences were seen in the total cholesterol (p = 0.307), low-density lipoprotein cholesterol (LDL-C; p = 0.283) and TGs (p = 0.113) levels among the subgroups. An independent effect on HDL-C was detected for glucose (p = 0.004) and fasting insulin (p = 0.01); on TG for age (p = 0.003) and homeostatic model assessment insulin resistance (p = 0.03) and on total cholesterol and LDL-C for age (p = 0.02 and p = 0.033, respectively). In conclusion, dyslipidemia is common in women with PCOS, mainly due to low HDL-C levels. BMI has a significant impact on this abnormality.

Metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein in young obese and normal-weight patients with polycystic ovary syndrome

Objective: To clarify whether the metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein (HDL) are altered in patients with polycystic ovary syndrome (PCOS). Design: Case control study. Setting: Endocrinology clinics. Patient(s): Eight normal-weight (NW) and 15 obese (013) patients with PCOS were compared with 10 NW and 10 Ob women without PCOS paired for age and body mass index. Intervention(s): Determination of triglyceride-rich lipoprotein metabolism and lipid transfer to HDL. Main Outcome Measure(s): Participants were injected triglyceride-rich emulsions labeled with (14)C-cholesteryl esters and (3)H-triglycerides and the fractional clearance rate (FCR, in min(-1)) of labels was determined. Lipid transfer from artificial nanoemulsions to HDL was performed by incubating radioactively labeled lipid nanoemulsions with plasma during 1 hour, followed by radioactive counting of HDL-containing supernatant after chemical precipitation. Result(s): Lipolysis estimated by triglyceride FCR was equal in PCOS groups (NW = 0.043 +/- 0.032, Ob = 0.033 +/- 0.009) and respective controls (NW = 0.039 +/- 0.015, Ob = 0.044 +/- 0.019). However, the remnant removal as estimated by cholesteryl ester FCR was reduced in both PCOS groups (NW = 0.005 +/- 0.006, Ob = 0.005 +/- 0.005) compared with controls (NW = 0.016 +/- 0.006, Ob = 0.011 +/- 0.072). Lipid transfer rates were not different among groups, but triglyceride transfer rates were positively correlated with homeostasis model assessment estimate of insulin resistance in PCOS. Conclusion(s): PCOS patients showed decreased removal of atherogenic remnants even when fasting glucose was <100 mg/dL. This reinforces the usefulness of the measures taken to prevent cardiovascular events in PCOS patients. (Fertil Steril (R) 2010;93:1948-56. (C)2010 by American Society for Reproductive Medicine.)

HDL concentration, lipid transfer to HDL, and HDL size in normolipidemic nonobese menopausal women

Objective: To determine the impact of menopause on lipid transfer from donor lipoproteins to high-density lipoproteins (HDLs)-a process that is related to the protective function of HDL-and the size of HDL particles. Method: Plasma from 22 prernenopausal and 18 postmenopausal nonobese, normolipidemic women paired for age (40-50 years) was incubated in an artificial nanoemulsion labeled with radioactive lipids. Then the HDL fraction was assessed for radioactivity; the percentage of radioactive lipids transferred from the nanoemulsion to HDL was determined; and the size of HDL particles was measured by laser light scattering. Results: There were no differences between the 2 groups in serum concentration of HDL cholesterol (61 12 mg/dL vs 61 +/- 14 mg/dL) or apolipoprotein A(1) (1.5 +/- 0.3 g/L vs 1.5 +/- 0.2 g/L); lipid transfer to HDL; or size of HDL particles (8.8 +/- 0.8 vs 9.0 +/- 0.5 nm). Conclusion: Menopause was not found to affect HDL cholesterol plasma concentration, lipid transfer to HDL, or size of HDL particles in normolipidemic nonobese women. (C) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd.All rights reserved.