Effects of electrotactile vestibular substitution on rehabilitation of patients with bilateral vestibular loss

The present study evaluated the effectiveness of electrotactile tongue biofeedback (BrainPort (R)) as a sensory substitute for the vestibular apparatus in patients with bilateral vestibular loss (BVL) who did not have a good response to conventional vestibular rehabilitation (VR). Seven patients with BVL were trained to use the device. Stimulation on the surface of the tongue was created by a dynamic pattern of electrical pulses and the patient was able to adjust the intensity of stimulation and spatially centralize the stimulus on the electrode array. Patients were directed to continuously adjust head orientation and to maintain the stimulus pattern at the center of the array. Postural tasks that present progressive difficulties were given during the use of the device. Pre- and post-treatment distribution of the sensory organization test (SOT) composite score showed an average value of 38.3 +/- 8.7 and 59.9 +/- 11.3, respectively, indicating a statistically significant improvement (p = 0.01). Electrotactile tongue biofeedback significantly improved the postural control of the study group, even if they had not improved with conventional VR. The electrotactile tongue biofeedback system was able to supply additional information about head position with respect to gravitational vertical orientation in the absence of vestibular input, improving postural control. Patients with BVL can integrate electrotactile information in their postural control in order to improve stability after conventional VR. These results were obtained and verified not only by the subjective questionnaire but also by the SOT composite score. The limitations of the study are the small sample size and short duration of the follow-up. The current findings show that the sensory substitution mediated by electrotactile tongue biofeedback may contribute to the improved balance experienced by these patients compared to VR. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Brain structure and symptom dimension relationships in obsessive-compulsive disorder: A voxel-based morphometry study

Background: Obsessive-compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. Methods: GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. Results: Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls > patients), and bilateral midbrain (patients > controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. Limitations: The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. Conclusions: These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples. (C) 2008 Elsevier B.V. All rights reserved.

Placental transmogrification of the lung presenting as giant bullae with soft-fatty components

A 44-year-old man presented with progressive dyspnea and a previous pneumothorax. Chest CT scan showed a mediastinal shift due to giant bullae containing soft tissue and fatty components in the left lower lung Lobe, and a right upper lung lobe partially collapsed. The pulmonary function tests revealed forced vital capacity (FVC) 53% (of the predicted) and forced vital capacity in 1 s (FEV1) 52%. Then, resection of the lower lobe was performed with intention to prevent other pneumothoraxes and to revert the upper lobe collapse. The pathological examination showed a placental. transmogrification of the lung (PTL). One month after the surgery, the patient was asymptomatic, the pulmonary function tests normalized and the upper lobe was well expanded. In conclusion, we described the first CT finding of soft tissue and fatty components within the PTL-related bullae, and the PTL should be considered in the differential diagnosis of pulmonary lesions with soft-fatty and air components. (c) 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Toxoplasma gondii: The severity of toxoplasmic encephalitis in C57BL/6 mice is associated with increased ALCAM and VCAM-1 expression in the central nervous system and higher blood-brain barrier permeability

In order to investigate the differential ALCAM, ICAM-1 and VCAM-1 adhesion molecules mRNA expression and the blood-brain barrier (BBB) permeability in C57BL/6 and BALB/c mice in Toxoplasma gondii infection, animals were infected with ME-49 strain. It was observed higher ALCAM on day 9 and VCAM-1 expression on days 9 and 14 of infection in the central nervous system (CNS) of C57BL/6 compared to BALB/c mice. The expression of ICAM-1 was high and similar in the CNS of both lineages of infected mice. In addition, C57BL/6 presented higher BBB permeability and higher IFN-gamma and iNOS expression in the CNS compared to BALB/c mice. The CNS of C578L/6 mice presented elevated tissue pathology and parasitism. In conclusion, our data suggest that the higher adhesion molecules expression and higher BBB permeability contributed to the major inflammatory cell infiltration into the CNS of C57BL/6 mice that was not efficient to control the parasite. (C) 2010 Elsevier Inc. All rights reserved.

Harris-Benedict equation for critically ill patients: Are there differences with indirect calorimetry?

Purpose: The aim of this study was to compare the measured energy expenditure (EE) and the estimated basal EE (BEE) in critically ill patients. Materials and Methods: Seventeen patients from an intensive care unit were randomly evaluated. Indirect calorimetry was performed to calculate patient`s EE, and BEE was estimated by the Harris-Benedict formula. The metabolic state (EE/BEE x 100) was determined according to the following criteria: hypermetabolism, more than 130%; normal metabolism, between 90% and 130%; and hypometabolism, less than 90%. To determine the limits of agreement between EE and BEE, we performed a Bland-Altman analysis. Results: The average EE of patients was 6339 +/- 1119 kJ/d. Two patients were hypermetabolic (11.8%), 4 were hypometabolic (23.5%), and 11 normometabolic (64.7%). Bland-Altman analysis showed a mean of -126 +/- 2135 kJ/d for EE and BEE. Only one patient was outside the limits of agreement between the 2 methods (indirect calorimetry and Harris-Benedict). Conclusions: The calculation of energy needs can be done with the equation of Harris-Benedict associated with lower values of correction factors (approximately 10%) to avoid overfeeding, with constant monitoring of anthropometric and biochemical parameters to assess the nutritional changing and adjust the infusion of energy. (C) 2009 Elsevier Inc. All rights reserved.

Prevalence of Insulin Resistance and Related Risk Factors for Cardiovascular Disease in Patients With Essential Hypertension

BACKGROUND There is evidence that the subgroup of patients with essential hypertension who are also insulin resistant is at increased risk of cardiovascular disease (CVD). We are unaware of the frequency of insulin resistance in patients with essential hypertension as well as the CVD risk in this subgroup of patients. This analysis was aimed at providing the prevalence of insulin resistance and associated CVD risk factors in treated and untreated patients with essential hypertension. METHODS The study population consisted of 126 patients with hypertension: 56 untreated and 70 in a stable treatment program. Body mass index (BMI), blood pressure, plasma glucose and insulin responses to an oral glucose challenge, lipid and lipoprotein concentrations, and steady-state plasma glucose (SSPG) concentration during the insulin suppression test were measured. Insulin resistance was defined operationally as a SSPG concentration >180 mg/dl. RESULTS Demographic characteristics and metabolic CVD risk factors were comparable in both groups, with 30-50% of both treated and untreated patients having abnormalities of all risk factors measured. Approximately 50% of patients met the criteria for insulin resistance in both groups, and the prevalence of abnormal CVD risk factors in this group was increased two to threefold as compared to the other half of the subjects. CONCLUSIONS Approximately 50% of patients with essential hypertension, both treated and untreated, appear to be insulin resistant, and CVD risk factors are greatly accentuated in this subset of patients.

Postprandial gastric antral contractions in patients with gastro-oesophageal reflux disease: a scintigraphic study

Disturbed gastric contractility has been found in manometric studies in patients with gastro-oesophageal reflux disease (GORD), but the pathophysiological role of this abnormality is unclear. We aimed at assessing postprandial gastric antral contractions and its relationships with gastric emptying and gastro-oesophageal reflux in GORD patients. Fasted GORD patients (n = 13) and healthy volunteers (n = 13) ingested a liquid meal labelled with 72 MBq of (99m)Technetium-phytate. Gastric images were acquired every 10 min for 2 h, for measuring gastric emptying half time. Dynamic antral scintigraphy (one frame per second), performed for 4 min at 30-min intervals, allowed estimation of both mean dominant frequency and amplitude of antral contractions. In GORD patients (n = 10), acidic reflux episodes occurring 2 h after the ingestion of the same test meal were determined by ambulatory 24-h oesophageal pH monitoring. Gastric emptying was similar in GORD patients and controls (median; range: 82 min; 58-126 vs 80 min; 44-122 min; P = 0.38). Frequency of antral contractions was also similar in both groups (3.1 cpm; 2.8-3.6 vs 3.2 cpm; 2.4-3.8 cpm; P = 0.15). In GORD patients, amplitude of antral contractions was significantly higher than in controls (32.7%; 17-44%vs 23.3%; 16-43%; P = 0.01), and correlated positively with gastric emptying time (R-s = 0.58; P = 0.03) and inversely with the number of reflux episodes (R-s = -0.68; P = 0.02). Increased amplitude of postprandial gastric antral contractions in GORD may comprise a compensatory mechanism against delayed gastric emptying and a defensive factor against acidic gastro-oesophageal reflux.

Interleukin-18 and interferon-gamma polymorphisms in Brazilian human immunodeficiency virus-1-infected patients presenting with lipodystrophy syndrome

Cytokines play important roles in the pathogenesis of lipodystrophy syndrome (LS). Single nucleotide polymorphisms (SNPs) at positions -607(C/A) and -137(C/G) in the promoter region of the interleukin-18 (IL-18) gene and at position +874(T/A) of the interferon-gamma (IFN-gamma) gene are related to the expression of these cytokines. To examine whether IL-18 and IFN-gamma polymorphisms are associated with LS, these SNPs were genotyped in 88 human immunodeficiency virus (HIV)-infected patients presenting LS, 79 HIV-infected without LS, and 133 healthy controls. The -607A allele, -607AA genotype, and -137G/-607A and -137C/-607A haplotypes in the IL-18 gene were over-represented in HIV patients presenting LS. The -137G/-607C haplotype was associated with protection against LS. These results indicate that the -607(C/A) SNP is associated with LS development in HIV-infected patients.

Insular cortex alpha(1)-adrenoceptors modulate the parasympathetic component of the baroreflex in unanesthetized rats

The insular cortex (IC) has been reported to modulate the cardiac parasympathetic activity of the baroreflex in unanesthetized rats. However, which neurotransmitters are involved in this modulation is still unclear. In the present study, we evaluated the possible involvement of local IC-noradrenergic neurotransmission in modulating reflex bradycardiac responses. Bilateral microinjection of the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nL), into the IC of male Wistar rats, increased the gain of reflex bradycardia in response to mean arterial pressure (MAP) increases evoked by intravenous infusion of phenylephrine. However, bilateral microinjection of equimolar doses of either the selective alpha(2)-adrenoceptor antagonist RX821002 or the non-selective beta-adrenoceptor antagonist propranolol into the IC did not affect the baroreflex response. No effects were observed in basal MAP or heart rate values after bilateral microinjection of noradrenergic antagonists into the IC, thus suggesting no tonic influence of IC-noradrenergic neurotransmission on resting cardiovascular parameters. In conclusion, these data provide evidence that local IC-noradrenergic neurotransmission has an inhibitory influence on baroreflex responses to blood pressure increase evoked by phenylephrine infusion through activation of alpha(1)-adrenoceptors. (C) 2009 Elsevier B.V. All rights reserved.

A crucial role for TNF-alpha in mediating neutrophil influx induced by endogenously generated or exogenous chemokines, KC/CXCL1 and LIX/CXCL5

Background and purpose: Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice. Experimental approach: Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-alpha. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy. Key results: Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-alpha, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-alpha antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-alpha production, which were inhibited by reparixin or anti-TNF-alpha treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-alpha upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-alpha or anti-LIX/CXCL5. Conclusion and implications: Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-alpha, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.

Conspecific and heterospecific alarm substance induces behavioral responses in piau fish Leporinus piau

In ostariophysan fish, the detection of alarm substance released from the skin of a conspecific or a sympatric heterospecific may elicit alarm reactions or antipredator behavioral responses. In this study, experiments were performed to characterize and quantify the behavioral response threshold of Leporinus piau, both individually and in schools, to growing dilutions of conspecific (CAS) and heterospecific skin extract (HAS). The predominant behavioral response to CAS stock stimulation was biphasic for fish held individually, with a brief initial period of rapid swimming followed by a longer period of immobility or reduced swimming activity. As the dilution of skin extract was increased, the occurrence and magnitude of the biphasic alarm response tended to decrease, replaced by a slowing of locomotion. Slowing was the most common antipredator behavior, observed in 62.5% of animals submitted to HAS stimulation. School cohesion, measured as proximity of fish to the center of the school, and swimming activity near the water surface significantly increased after exposure to CAS when compared with the control group exposed to distilled water. Histological analysis of the epidermis revealed the presence of Ostariophysi-like club cells. The presence of these cells and the behavioral responses to conspecific and heterospecific skin extract stimulation suggest the existence of a pheromone alarm system in L. piau similar to that in Ostariophysi, lending further support for the neural processing of chemosensory information in tropical freshwater fish.

Deregulation of LOXL1 and HTRA1 Gene Expression in Endometriosis

Endometriosis is a gynecologic disease characterized by the presence of endometrial tissue outside the uterine cavity. Although 15% of the female population in reproductive age is affected by endometriosis, its pathogenesis remains unclear. According to the most accepted pathogenesis hypothesis, endometrial fragments from the menstrual phase are transported through the uterine tubes to the peritoneal cavity, where they undergo implantation and growth, invading adjacent tissues. However, the establishment of the disease requires that endometrial cells present molecular characteristics favoring the onset and progression of ectopic implantation. In this investigation, we analyzed the differential gene expression profiles of peritoneal and ovarian endometriotic lesions compared to the endometrial tissue of nonaffected women using rapid subtraction hybridization (RaSH). In our study, this method was applied to samples of endometriotic lesions from affected women and to biopsies of endometrium of healthy women without endometriosis, where we could identify 126 deregulated genes. To evaluate the expression of genes found by RaSH method, we measured LOXL1, HTRA1, and SPARC genes by real-time polymerase chain reaction. Significant different expression was obtained for HTRA1 and LOXL1, upregulated in the ectopic endometrium, suggesting that these genes are involved in the physiopathology of endometriosis and may favor the viability of endometrial cells at ectopic sites.

Increased cell proliferation in experimentally induced endometriosis in rabbits

Objective: To characterize the pattern of cell proliferation and apoptosis of eutopic and ectopic endometrium in rabbits after endometrium implantation for the experimental induction of endometriosis. Design: Animal experimental study. Setting: Sector of experimental surgery. Animal(s): Twenty-female New Zealand rabbits. Intervention(s): All animals underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of 10 animals were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma determination. Main Outcome Measure(s): Cell proliferation and apoptosis were determined in the eutopic and ectopic endometrium, and the cell proliferation index (CPI) and apoptotic index (AI) were calculated as the number of labeled cells per 1,000 cells. The tissue homeostasis index was the CPI/AI ratio. Glands and stroma were analyzed separately. Result(s): The CPI for ectopic tissue was increased compared with eutopic tissue, but there was no difference in the ectopic lesions between 4 and 8 weeks of induction. Considering only the AI, eutopic and ectopic endometrium did not differ after 4 weeks, but differed significantly in glandular tissue after 8 weeks. The tissue homeostasis index revealed cell proliferation in these tissues, with a CPI/AI more than 1. Conclusion(s): Ectopic lesions seem to have a higher CPI than eutopic endometrium, with uncontrolled tissue growth occurring in induced endometriotic lesions. (Fertil Steril (R) 2010;93:1637-42. (C)2010 by American Society for Reproductive Medicine.)

Clinical and Immunological Insights on Severe, Adverse Neurotropic and Viscerotropic Disease following 17D Yellow Fever Vaccination

Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-gamma R in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3(+) CD16(+/-) CD56(+/-)/CD3(+) ratio), activated T cells (CD4(+) and CD8(+) cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated ex vivo intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-gamma(+)], tumor necrosis factor alpha positive [TNF-alpha(+)], and IL-4 positive [IL-4(+)]), CD8(+) T cells (IL-4(+) and IL-5(+)), and B lymphocytes (TNF-alpha(+), IL-4(+), and IL-10(+)). The analysis of CD4(+) T cells revealed a complex profile that consisted of an increased frequency of IL-12(+) and IFN-gamma(+) cells and a decreased percentage of TNF-alpha(+), IL-4(+), and IL-5+ cells. Depressed cytokine synthesis was observed in monocytes (TNF-alpha(+)) following the provision of antigenic stimuli in vitro. These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD.

Interaction of purinergic and nitrergic mechanisms in the caudal nucleus tractus solitarii of rats

The interaction of purinergic and nitrergic mechanisms was evaluated in the caudal nucleus tractus solitarii (cNTS) using awake animals and brainstem slices. In awake animals, ATP (1.25 nmol/50 nL) was microinjected into the cNTS before and after the microinjection of a selective neuronal nitric oxide synthase (nNOS) inhibitor N-propyl-L-arginine (NPLA, 3 pmoles/50 nL, n=8) or vehicle (saline, n=4), and cardiovascular and ventilatory parameters were recorded. In brainstem slices from a distinct group of rats, the effects of ATP on the NO concentration in the cNTS using the fluorescent dye DAF-2 DA were evaluated. For this purpose brainstem slices (150 pm) containing the cNTS were pre-incubated with ATP (500 mu M; n=8) before and during DAF-2 DA loading. Microinjection of ATP into the cNTS increases the arterial pressure (AP), respiratory frequency (f(R)) and minute ventilation (V(E)), which were significantly reduced by pretreatment with N-PLA, a selective nNOS inhibitor (AP: 39 +/- 3 vs 16 +/- 14 mm Hg; f(R): 75 +/- 14 vs 4 +/- 3 cpm; V(E): 909 159 vs 77 39 mL kg(-1) m(-1)). The effects of ATP in the cNTS were not affected by microinjection of saline. ATP significantly increased the NO fluorescence in the cNTS (62 +/- 7 vs 101 +/- 10 AU). The data show that in the cNTS: a) the NO production is increased by ATP; b) NO formation by nNOS is involved in the cardiovascular and ventilatory responses to microinjection of ATP. Taken together, these data suggest an interaction of purinergic and nitrergic mechanisms in the cNTS. (C) 2009 Elsevier B.V. All rights reserved.