Sensitization to foods in gastroesophageal reflux disease and its relation to eosinophils in the esophagus: is it of clinical importance?

Background: Refractory gastroesophageal reflux disease (GERD) can be related to greater sensitization to foods. Objective: To evaluate sensitization to foods in patients with refractory GERD. Methods: Patients with refractory GERD after using at least 40 mg of a proton pump inhibitor were given a restriction diet based on the results of skin prick testing and atopy patch testing with foods. The characteristics of sensitized patients were compared with those of nonsensitized patients in relation to atopy and number of eosinophils in the esophageal mucosa. Results: The prevalence of sensitization to foods was 27.7%. Asthmatic patients showed higher sensitization to foods (P = .008). Eosinophils were determined to be present in the esophageal mucosa in 15.8% of patients, and this correlated with greater sensitization to foods (P = .01). One case of eosinophilic esophagitis was confirmed. A diet excluding identified sensitizing foods led to clinical improvement regarding GERD symptoms (P = .004). Conclusion: The presence of eosinophils in esophageal mucosa associated with greater sensitization to foods and the response to a restriction diet in patients with positive test results suggest that refractory GERD can represent an initial stage of eosinophilic esophagitis. Ann Allergy Asthma Immunol. 2010;105:359-363.

Outcomes and safety of drug provocation tests

Drug provocation tests (DPTs) are considered the gold standard for identifying adverse drug reactions (ADRs). The aim of this study was to analyze DPT results and discuss severe systemic reactions associated with them. This was a retrospective analysis of 500 patients with ADRs who sought treatment and were submitted to DPTs when indicated between 2006 and 2010. We performed DPTs according to the European Network for Drug Allergy recommendations. Single-blind, placebo-controlled DPTs were performed with antibiotics, local anesthetics, and nonsteroidal anti-inflammatory drugs, as well as with other drugs. Patient characteristics, DPT results, and reactions were analyzed. The sample comprised 198 patients (80.8% of whom were female patients) submitted to 243 DPTs. Ages ranged from 9 to 84 years (mean, 39.9 years). The 243 DPTs were performed with local anesthetics (n = 93), antibiotics (n = 19), acetaminophen (n = 44), benzydamine (n = 33), COX-2 inhibitors (n = 26), dipyrone (n = 7), aspirin (n = 4), or other drugs (n = 17). The results of 4 tests (1.6%) were inconclusive, whereas those of 10 (4.1%) revealed positive reactions to antibiotics (2/19), COX-2 inhibitors (2/26), acetaminophen (3/44), and local anesthetics (3/93). Two severe reactions were observed: cephalexin-induced anaphylactic shock and bupivacaine-induced anaphylaxis without shock. Four patients (2.0%) reacted to the placebo before administration of the drug. Drug provocation tests are safe for use in clinical practice but they should be placebo-controlled and should be performed under the supervision of an allergist. To confirm a presumptive diagnosis and to manage allergies appropriately, it is crucial to perform DPTs. (Allergy Asthma Proc 32:301-306, 2011; doi: 10.2500/aap.2011.32.3450)

Electrophysiological characteristics of the Marshall bundle in humans

BACKGROUND Marshall bundles (MBs) are the muscle bundles within the ligament of Marshall. OBJECTIVE This trial sought to the electrophysiological characteristics of the MB and the anatomical connections between MB and left atrium (LA) in patients with persistent atrial fibrillation (AF). METHODS We enrolled 72 patients (male: female 59: 13, age 59.9 +/- 9.4 years) who underwent MB mapping and ablation for AF. MB mapping was done via an endocardial or epicardial approach during sinus rhythm and AF. RESULTS Recordings were successful in 64 of 72 patients (89%). A single connection was noted in 11 of 64 patients between the MB and the coronary sinus (CS) muscle sleeves. The MB recordings showed distinct MB potentials with a proximal-to-distal activation pattern during sinus rhythm. During AF, organized passive activations and dissociated slow MB ectopic activities were commonly observed in this type of connection. Double connections to both CS and LA around left pulmonary veins were noted in 23 of 64 patients (36%). After the ablation of the distal connection, MB recording showed typical double potentials as in single connection. Multiple connections were noted in 30 of 64 patients (47%). During sinus rhythm, the earliest activation was in the middle of the MB. The activation patterns were irregular and variable in each patient. During AF, rapid and fractionated complex activations were noted in all patients of this group. CONCLUSION We documented 3 different types of MB-LA connections. Rapid and fractionated activations were most commonly observed in the MB that had multiple LA connections.

A 1-year longitudinal study of severe traumatic brain injury in Australia using the Sickness Impact Profile

Objective: To document outcome and to investigate patterns of physical and psychosocial recovery in the first year following severe traumatic brain injury (TBI) in an Australian patient sample. Design: A longitudinal prospective study of a cohort of patients, with data collection at 3, 6, 9, and 12 months post injury. Setting: A head injury rehabilitation unit in a large metropolitan public hospital. Patients: A sample of 55 patients selected from 120 consecutive admissions with severe TBI. Patients who were more than 3 months post injury on admission, who remained confused, or who had severe communication deficits or a previous neurologic disorder were excluded. Interventions: All subjects participated in a multidisciplinary inpatient rehabilitation program, followed by varied participation in outpatient rehabilitation and community-based sen ices. Main Outcome Measures: The Sickness impact Profile (SIP) provided physical, psychosocial, and total dysfunction scores at each follow-up. Outcome at 1 year was measured by the Disability Rating Scale. Results: Multivariate analysis of variance indicated that the linear trend of recovery over time was less for psychosocial dysfunction than for physical dysfunction (F(1,51) = 5.87, P < .02). One rear post injury, 22% of subjects had returned to their previous level of employability, and 42% were able to live independently. Conclusions: Recovery from TBI in this Australian sample followed a pattern similar to that observed in other countries, with psychosocial dysfunction being more persistent. Self-report measures such as the SIP in TBI research are limited by problems of diminished self-awareness.

Fast-track rehabilitation for lung cancer lobectomy: a five-year experience

Objective: Fast-track rehabilitation is a group of simple measures that reduces morbidity, postoperative complication and accelerates postoperative rehabilitation reducing hospital stay. It can be applied to lung cancer lobectomy. Fast-track rehabilitation cornerstones are: minimally invasive surgical techniques using video-assisted and muscle sparring incisions, normovolemia, normothermia, good oxygenation, euglicemia, no unnecessary antibiotics, epidural patient-controlled analgesia, systemic opiods-free analgesia, early ambulation and oral feeding. Our objective is to describe a five-year experience with fast-track rehabilitation for lung cancer lobectomy. Patients and methods: A retrospective non-controlled study including 109 consecutive patients submitted to fast-track rehabilitation in the postoperative care of lung cancer lobectomy was performed. Only collaborative patients who could receive double-lumen intubation, epidural. catheters with patient-controlled analgesia, who had Karnofsky index of 100, previous normal feeding and ambulation, absence of morbid obesity, diabetes or asthma, were eligible. Postoperative oral feeding and aggressive ambulation started as soon as possible. Results: Immediate postoperative extubation even in the operation room was possible in 107 patients and oral feeding and ambulation were possible before the first hour in 101 patients. Six patients could not receive early oral feeding or ambulate due to hypnosis secondary to preoperative long effect benzodiazepines. Two patients could not ambulate immediately due to epidural catheter misplacement with important postoperative pain. Ninety-nine discharges occurred at the second postoperative day, four of them with a chest tube connected to a Heimlich valve due to air teak. No complication of early feeding and ambulation was observed. Postoperative hypnosis due to long duration benzodiazepines or pain does not allow early oral feeding or ambulation. Avoiding long duration preoperative benzodiazepines, immediate postoperative extubation, regional thoracic PCA and early oral feeding and ambulation were related to a lesser frequency of complication and a shorter hospital stay. Conclusion: Fast-track rehabilitation for lung cancer lobectomies can be safety performed in a selected group of patients if a motivated multidisciplinary group of professionals is available and seems to reduce postoperative complication and hospital stay. (C) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Hyperdopaminergia and NMDA Receptor Hypofunction Disrupt Neural Phase Signaling

Neural phase signaling has gained attention as a putative coding mechanism through which the brain binds the activity of neurons across distributed brain areas to generate thoughts, percepts, and behaviors. Neural phase signaling has been shown to play a role in various cognitive processes, and it has been suggested that altered phase signaling may play a role in mediating the cognitive deficits observed across neuropsychiatric illness. Here, we investigated neural phase signaling in two mouse models of cognitive dysfunction: mice with genetically induced hyperdopaminergia [dopamine transporter knock-out (DAT-KO) mice] and mice with genetically induced NMDA receptor hypofunction [NMDA receptor subunit-1 knockdown (NR1-KD) mice]. Cognitive function in these mice was assessed using a radial-arm maze task, and local field potentials were recorded from dorsal hippocampus and prefrontal cortex as DAT-KO mice, NR1-KD mice, and their littermate controls engaged in behavioral exploration. Our results demonstrate that both DAT-KO and NR1-KD mice display deficits in spatial cognitive performance. Moreover, we show that persistent hyperdopaminergia alters interstructural phase signaling, whereas NMDA receptor hypofunction alters interstructural and intrastructural phase signaling. These results demonstrate that dopamine and NMDA receptor dependent glutamate signaling play a critical role in coordinating neural phase signaling, and encourage further studies to investigate the role that deficits in phase signaling play in mediating cognitive dysfunction.

Enhancing the phonological processing skills of children with specific reading disability

The present study evaluated the benefits of phonological processing skills training for children with persistent reading difficulties. Children aged between 9-14 years, identified as having a specific reading disability, participated in the study. In a series of three experiments, pedagogical issues related to length of training time, model of intervention and severity of readers' phonological processing skills deficit prior to intervention, were explored. The results indicated that improvement in poor readers' phonological processing skills led to a dramatic improvement in their reading accuracy and reading comprehension performance. Increasing the length of training time significantly improved transfer effects to the reading process. Children with particularly severe phonological processing skill deficits benefited from art extended training period, and both individual and group intervention models for phonological processing training proved successful. Implications for speech and language therapists are discussed.

Inducible nitric oxide synthase in pityriasis lichenoides lesions

Pityriasis lichenoides (PL) is an inflammatory skin disease of unknown etiology. Nitric oxide (NO) has emerged as an important mediator of many physiological functions. The importance of NO-mediated signaling in skin diseases has been reported by several studies. A review of clinical records and histopathological slides of 34 patients diagnosed with PL was performed. Three different groups of skin biopsies including PL chronica (24 patients), PL et varioliformis acuta (10 patients) and 15 normal skin samples were subjected to the immunohistochemistry technique for inducible nitric oxide synthase (iNOS) detection. Normal skin group exhibited a few number of iNOS-positive cells in the dermis and rare positive cells in the upper epidermis, unlike abundant epidermal and dermal iNOS expression observed in both PL groups. According to our results, we hypothesize that NO produced by iNOS could participate in PL pathogenesis. Abnormal and persistent responses to unknown antigens, probably a pathogen, associated with NO immunoregulatory functions could contribute to the relapsing course observed in PL. NO anti-apoptotic effect on T-cell lymphocytes could play a role on maintenance of reactive T cells, leading to a T-cell lymphoid dyscrasia. Di Giunta G, Goncalves da Silva AM, Sotto MN. Inducible nitric oxide synthase in pityriasis lichenoides lesions.J Cutan Pathol 2009; 36: 325-330. (C) Blackwell Munksgaard 2008.

Role of nitric oxide in hyperpnea-induced bronchoconstriction and airway microvascular permeability in guinea pigs

The present study aimed to evaluate the role of nitric oxide (NO) on hyperpnea-induced bronchoconstriction (HIB) and airway microvascular hyperpermeability (AMP). Sixty-four guinea pigs were anesthetized, tracheotonnized, cannulated, and connected to animal ventilator to obtain pulmonary baseline respiratory system resistance (Rrs). Animals were then submitted to 5 minutes hyperpnea and Rrs was evaluated during 15 minutes after hyperpnea. AMP was evaluated by Evans blue dye (25 mg/kg) extravasation in airway tissues. Constitutive and inductible NO was evaluated by pretreating animals with N(G)-nitro-1-arginine methyl ester (I-NAME) (50 mg/kg), aminoguadinine (AG) (50 mg/kg), and I-arginine (100 mg/kg) and exhaled NO (NOex) was evaluated before and after drug administration and hyperpnea. The results show that I-NAME potentiated (57%) HIB and this effect was totally reversed by I-arginine pretreatment, whereas AG did not have effect on HIB. I-NAME decreased basal AMP (48%), but neither I-NAME nor AG had any effect on hyperpnea-induced AMP. NOex levels were decreased by 50% with I-NAME, effect that was reversed by I-arginine treatment. These results suggest that constitutive but not inducible NO could have a bronchoprotective effect on HIB in guinea pigs. The authors also observed that neither constitutive nor inducible NO seems to have any effect on hyperpnea-induced AMP.

Exercise Reduces Effects of Creatine on Lung

We recently demonstrated that creatine supplementation increased some features of lung allergic sensitization in mice. On the other hand, other studies have shown that aerobic exercise inhibited allergic airway inflammation and remodeling. We hypothesized that aerobic exercise may decrease the exacerbatory effects of the creatine supplementation in a murine model of asthma. Balb/c mice were divided into six groups: Control, Creatine (Cr), Low Intensity Exercise + Creatine (Low + Cr), Ovalbumin (OVA), Ovalbumin + Creatine (OVA + Cr) and Ovalbumin + Creatine + Low Intensity Exercise (OVA + Cr + Low). OVA-sensitized groups were sensitized with OVA intraperitoneal injections (days 0, 14, 28, and 42). Aerosol challenge (OVA 1 %) and Cr treatment (0.5 g/kg/day) were initiated on Day 21 until Day 53. Low intensity exercise began on day 22 and was sustained until day 50. Low intensity exercise in the presence of creatine supplementation in sensitized mice resulted in a decreased number of eosinophils in BALF (p < 0.001) and in the airways (P < 0.001), and a decreased density of inflammatory cells positive to IL-4 (p < 0.001) and IL-5 (p < 0.001), airway collagen (p < 0.001) and elastic fibers (p < 0.001) content, airway smooth muscle thickness (p < 0.001) and bronchoconstriction index (p < 0.05) when compared with OVA + Cr group. These results suggest that aerobic exercise reduces the exacerbatory effects of creatine supplementation in chronically sensitized mice.

Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling

Vieira RP, de Andrade VF, Duarte AC, dos Santos AB, Mauad T, Martins MA, Dolhnikoff M, Carvalho CR. Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling. Am J Physiol Lung Cell Mol Physiol 295: L670-L679, 2008. First published August 29, 2008; doi: 10.1152/ajplung.00465.2007.-Recent evidence suggests that asthma leads to inflammation and remodeling not only in the airways but also in pulmonary vessels and parenchyma. In addition, some studies demonstrated that aerobic training decreases chronic allergic inflammation in the airways; however, its effects on the pulmonary vessels and parenchyma have not been previously evaluated. Our objective was to test the hypothesis that aerobic conditioning reduces inflammation and remodeling in pulmonary vessels and parenchyma in a model of chronic allergic lung inflammation. Balb/c mice were sensitized at days 0, 14, 28, and 42 and challenged with ovalbumin ( OVA) from day 21 to day 50. Aerobic training started on day 21 and continued until day 50. Pulmonary vessel and parenchyma inflammation and remodeling were evaluated by quantitative analysis of eosinophils and mononuclear cells and by collagen and elastin contents and smooth muscle thickness. Immunohistochemistry was performed to quantify the density of positive cells to interleukin (IL)-2, IL-4, IL-5, interferon-gamma, IL-10, monocyte chemotatic protein (MCP)-1, nuclear factor (NF)-kappa B p65, and insulin-like growth factor (IGF)-I. OVA exposure induced pulmonary blood vessels and parenchyma inflammation as well as increased expression of IL-4, IL-5, MCP-1, NF-kappa B p65, and IGF-I by inflammatory cells were reduced by aerobic conditioning. OVA exposure also induced an increase in smooth muscle thickness and elastic and collagen contents in pulmonary vessels, which were reduced by aerobic conditioning. Aerobic conditioning increased the expression of IL-10 in sensitized mice. We conclude that aerobic conditioning decreases pulmonary vascular and parenchymal inflammation and remodeling in this experimental model of chronic allergic lung inflammation in mice.

Chronic American trypanosomiasis: parasite persistence in endomyocardial biopsies is associated with high-grade myocarditis

Myocyte diameter, fractional area of collagen, intensity of myocarditis and parasite persistence (explored by immunohistochemistry and PCR) were evaluated in serial sections of endomyocardial biopsies from 29 outpatients with chronic chagasic cardiopathy. The patients, 25 males and four females with a mean (S.D.) age of 43 (9) years, were subsequently followed up for 3-2861 days (median=369 days). During this follow-up, 16 (55%) of the patients died. The biopsies revealed myocarditis in 25 (86%) of the patients and high-grade myocarditis in 14 (56%). Although immunohistochemistry failed to demonstrate Trypanosoma cruzi antigens in any of the samples, five (33%) of the 15 biopsies successfully tested in the PCR-based assay for T. cruzi DNA were found positive, indicating parasite persistence. There was a significant positive association between myocardial parasite persistence and high-grade myocarditis (P= 0.014); five (71%,) of the seven endomyocardial biopsies with high-grade myocarditis that were successfully tested in the PCR assays showed persistent T. cruzi DNA. The survival time of the patients was not, however, found to be significantly associated with myocardial parasite persistence, any of the morphometric measurements taken, or the presence or intensity of myocarditis.

CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION MIMICKING HENOCH-SCHONLEIN PURPURA

Introduction: Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent symptoms for at least 3 months, such as fever, hepatosplenomegaly and lymphadenopathy. The diagnosis is established due to the presence of anti-EBV antibodies or isolation of this infectious agent in affected tissues. Three cases of CAEBV infection mimicking Henoch-Schonlein purpura (HSP) were described. Case 1: Female 3-year old patient with cervical adenomegaly, anemia and fever developed palpable purpura, haematuria and arthritis. CAEBV infection was established by serology test. She received methylprednisolone and acyclovir. She had generalized lymphadenopathy, hepatomegaly, splenomegaly, disseminated intravascular coagulation and deceased. Case 2: Male 12-year old patient with persistent anemia, lymphadenopathy, hepatomegaly and splenomegaly had CAEBV infection diagnosis by serology test. He developed purpura and arthritis and received methylprednisolone. Case 3: Male 13-year old patient had purpura, abdominal pain, haematuria, hepatomegaly, splenomegaly, lymphadenopathy, anemia and elevated liver enzymes. The cervical lymph node biopsy was positive to EBV infection. He received methylprednisolone and acyclovir, developing acute fulminant hepatitis and death. Discussion: CAEBV infection mimicking HSP was rarely observed in our population

TNF receptor-associated periodic syndrome (TRAPS): Description of a novel TNFRSF1A mutation and response to etanercept

TRAPS is the most common of the autosomal dominant periodic fever syndromes. It is caused by mutations in the TNFRSF1A gene, which encodes for the type 1 TNF-receptor (TNFR1). We describe here a Brazilian patient with TRAPS associated to a novel TNFRSF1A de novo mutation and the response to anti-TNF therapy. The patient is a 9-year-old girl with recurrent fevers since the age of 3 years, usually lasting 3 to 7 days, and recurring every other week. These episodes are associated with mild abdominal pain, nausea, vomiting and generalized myalgia. Recurrent conjunctivitis and erysipela-like skin lesions in the lower limbs also occur. Laboratory studies show persistent normocytic normochromic anemia, thrombocytosis, elevated erythrocyte sedimentation rate and C-reactive protein. IgD levels are normal. Mutational screening of TNFRSF1A revealed the association of a novel C30F mutation with the common R92Q low-penetrance mutation. The R92Q mutation is seen in 5% of the general population and is associated with an atypical inflammatory phenotype. The patient had a very good response to etanercept, with cessation of fever and normalization of inflammatory markers. Our report expands the spectrum of TNFRSF1A mutations associated with TRAPS, adding further evidence for possible additive effects of a low-penetration R92Q and cysteine residue mutations, and confirms etanercept as an efficacious treatment alternative.

Gastroesophageal reflux disease in children: efficacy of Nissen fundoplication in treating digestive and respiratory symptoms. Experience of a single center

Fundoplication has been commonly performed in neurologically impaired and normal children with complicated gastroesophageal reflux disease. The relationship between gastroesophageal reflux disease and respiratory diseases is still unclear. We aimed to compare results of open and laparoscopic procedures, as well as the impact of fundoplication over digestive and respiratory symptoms. From January 2000 to June 2007, 151 children underwent Nissen fundoplication. Data were prospectively collected regarding age at surgery, presence of neurologic handicap, symptoms related to reflux (digestive or respiratory, including recurrent lung infections and reactive airways disease), surgical approach, concomitant procedures, complications, and results. Mean age was 6 years and 9 months. Eighty-two children (54.3%) had neurological handicaps. The surgical approach was laparoscopy in 118 cases and laparotomy in 33. Dysphagia occurred in 23 patients submitted to laparoscopic and none to open procedure (P = 0.01). A total of 86.6% of patients with digestive symptoms had complete resolution or significant improvement of the problems after the surgery. A total of 62.2% of children with recurrent lung infections showed any reduction in the frequency of pneumonias. Only 45.2% of patients with reactive airway disease had any relief from bronchospasm episodes after fundoplication. The comparisons demonstrated that Nissen fundoplication was more effective for the resolution of digestive symptoms than to respiratory manifestations (P = 0.04). Open or laparoscopic fundoplication are safe procedures with acceptable complication indices and the results of the surgery are better for digestive than for respiratory symptoms.