Dose-dependent relationship between nocturnal gastroesophageal reflux and chronic rhinosinusitis in a middle-aged population: results from the SCAPIS pilot.

BACKGROUND: Gastroesophageal reflux (GER) has been associated with several upper- and lower-airway diseases. It would be plausible if nightly occurring reflux via laryngopharyngeal reflux (LPR) might affect the upper airways. Still, the role of nocturnal gastroesophageal reflux (nGER) in chronic rhinosinusitis (CRS) is not fully established. The aim of this population-based study was to investigate the association between nGER and CRS. METHODOLOGY: This cross-sectional population-based study comprises 1,111 randomly selected subjects from Gothenburg, Sweden, aged 50-64 years. The study is based on self-reported validated questionnaires. CRS was defined according to EPOS criteria. nGER was reported in relation to frequency. RESULTS: CRS was more common among subjects with nGER than in those without (13 vs. 4.8%). There was a dose-response association between the frequency of nGER episodes and the risk of having CRS. In the logistic regression adjusted for (age, sex, BMI, educational level, smoking, and asthma). CRS was associated with nGER, OR 1.43 and the odds ratio increased if episodes were reported 'almost every night' OR 4.6. CONCLUSIONS: The study shows an association between nocturnal GER and CRS in a middle-aged population. The revealed dose dependency supports, though does not prove causality.

Utilidad del monitoreo hemodinámico con espectroscopia cercana infrarroja en pediatría / Use of near infrared spectroscopy for hemodynamic monitoring in pediatrics

La espectroscopia cercana infrarroja (NIRS, por su sigla en inglés), es una técnica óptica no invasiva y no ionizante utilizada para medir la oxigenación tisular regional a través de sensores transcutáneos. En los últimos años, han aumentado de manera exponencial las publicaciones sobre este tema; esto refleja el creciente interés de investigadores y clínicos por la utilización de esta nueva tecnología y los beneficios que podría ofrecerles a los pacientes pediátricos. El objetivo de esta revisión es dar a conocer el funcionamiento y las posibles aplicaciones de la saturación regional medida por NIRS, así como los desafíos en el futuro.

Near infrared spectroscopy (NIRS) is a non-invasive optical technique for the evaluation of regional tissue oxygenation using transcutaneous detectors. In recent years, publications about this topic have increased exponentially; this reflects the growing interest among investigators and clinicians about this new technology and its potential benefits for pediatric patients. The objective of this review is to know the functioning and potential uses of regional saturation measured by NIRS and establish future challenges.

Relationship between extralaryngeal endoscopic findings, proton pump inhibitor (PPI) response, and pH measures in suspected laryngopharyngeal reflux.

Laryngopharyngeal reflux (LPR) is a clinical entity diagnosed by history laryngoscopic findings that has a variable response to empiric proton-pump inhibitor (PPI) therapy. While the reflux finding score (RFS), an endoscopic scoring scheme, has been advanced as a measure of LPR, it has not been externally validated against symptom severity in practice. Extralaryngeal pharyngeal endoscopic findings may have diagnostic utility but remain underexplored. This study assesses the correlation between extralaryngeal findings and (1) 24-hour oropharyngeal pH & (2) PPI response in patients with suspected LPR. Subjects presented to a tertiary care center with laryngeal symptoms ≥1 month and reflux symptom index (RSI) ≥13. Following baseline questionnaires, laryngoscopy, and a 24-hour oropharyngeal pH probe study, subjects were prescribed 8-12 week omeprazole trials. Baseline endoscopic findings were scored in a blinded fashion using the RFS and extralaryngeal score criteria, summatively the 'ELS.' PPI response was defined as ≥50% improvement in RSI. Thirty-three subjects with flexible endoscopic recordings completed baseline and follow-up questionnaires. The cohort's baseline mean RSI was 23.0 ± 7.2 with a ΔRSI = 9.8 after PPI therapy. The baseline RFS score averaged 5.3 ± 2.7. 45% of our subjects was found to be PPI responsive. The Cohen's kappa for the ELS but not the RFS was significant. There were no significant differences between the RFS (P = 0.10) or ELS (P = 0.07) for PPI responders & nonresponders. Oropharyngeal pH measures did not correlate with the RFS or ELS. In conclusion, endoscopic scores of laryngeal and extralaryngeal findings did not predict PPI response or oropharyngeal acid exposure in suspected LPR.

The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples.

Recent evidence points towards a role of oxidative stress in suicidality. However, few studies were carried out on the sources of reactive oxygen species (ROS) in subjects with suicidal behaviour. We have previously demonstrated that the NADPH oxidase NOX2-derived oxidative stress has a major role in the development of neuropathological alterations observed in an animal model of psychosis. Here, we investigated the possible increase in NOX2 in post mortem brain samples of subjects who died by asphyctic suicide (AS) compared with controls (CTRL) and subjects who died by non-suicidal asphyxia (NSA). We found that NOX2 expression was significantly higher in the cortex of AS subjects than in the other two experimental groups. NOX2 immunostaining was mainly detected in GABAergic neurons, with a minor presence of NOX2-positive-stained cells in glutamatergic and dopaminergic neurons, as well as astrocytes and microglia. A sustained increase in the expression of 8-hydroxy-2'-deoxyguanosine, an indirect marker of oxidative stress, was also detected in the cortex of AS subjects, compared with CTRL and NSA subjects. A significant elevation in cortical interleukin-6 immunoreactivity in AS subjects suggested an involvement of cytokine-associated molecular pathways in NOX2 elevations. Our results suggest that the increase in NOX2-derived oxidative stress in the brain might be involved in the neuropathological pathways leading to suicidal behaviour. These results may open innovative insights in the identification of new pathogenetic and necroscopic biomarkers, predictive for suicidality and potentially useful for suicide prevention.

Grade of eosinophilia versus symptoms in patients with dysphagia and esophageal eosinophilia.

The aim of this study was to assess whether the symptom severity and health-related quality of life (HRQL) of patients with dysphagia and esophageal eosinophilia correlate with disease activity as expressed by the number of eosinophils in the esophageal mucosa. This study included newly diagnosed (n = 58) or relapsed patients (n = 7), where 40% were diagnosed in connection with esophageal bolus impaction. The mean age was 45 years (19-88), and 74% were men. Symptoms and HRQL were recorded using the Watson Dysphagia Scale (WDS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophageal Module 18 and the Short Form-36 Questionnaire. Histological samples gathered from the proximal and distal esophageal mucosa were stained using both hematoxylin and eosin (HE) and an immunohistochemical (IHC) technique against 'Eosinophil Major Basic Protein,' and the peak number of eosinophils per high-power field was assessed. More eosinophils were detected after IHC staining than HE staining (P < 0.001). No correlation was found between symptoms or the HRQL and the number of eosinophils. However, higher numbers of eosinophils at the proximal esophagus were found in patients with concomitant bolus impaction (IHC P < 0.05 and HE P < 0.05) and could serve as a risk marker.

Bacterial flora of the human oral cavity, and the upper and lower esophagus.

This reference study aims to survey the bacterial flora of the healthy lower human esophagus and to compare it with that of the upper esophagus and oral mucosa. The use of biopsies, in addition to brush samples, allows inclusion of not only transient bacteria present on the surface but also bacteria residing in the epithelia, and the yield of the two methods can be compared. Forty patients scheduled for surgery for reasons with no known influence on esophageal flora and with no symptoms or endoscopic signs of esophageal disease were included. Samples were collected from the oral, upper esophageal, and lower esophageal mucosa using sealed brushes and biopsy forceps. Colonies cultivated on agar plates were classified and semiquantified. Twenty-three different bacterial species were identified, with similar strains present at the three sites. The most common group of bacteria was viridans streptococci, with an occurrence rate in brush samples and biopsies of 98% and 95%, respectively. The median number of species occurring in the oral cavity, upper esophagus, and lower esophagus was between 3 and 4 (range 0-7). The total number of species in the oral cavity was significantly higher when compared with either level in the esophagus, while the yields obtained by brush and biopsy sampling were highly correlated. Hence, the normal human esophagus is colonized with a resident bacterial flora of its own, which has similarities to that of the oral mucosa. There are diverse species that make up this flora, although in relatively low amounts. The most frequent inhabitants of the esophagus are streptococci, with an occurrence rate in brush samples and biopsies of 95-98%. Comparative studies of patients with eosinophilic esophagitis and gastroesophageal reflux disease are warranted.

[Acute liver failure due to human herpesvirus 6 in an infant]. / Insufficienza epatica acuta da Human Herpesvirus 6 in un lattante.

We report a case of a 4-months infant with fever in the absence of other specific symptoms that has rapidly and unexpectedly developed acute liver failure (ALF) with coagulopathy and complicated with bone marrow failure without encephalopathy. The main viral infection agents (hepatitis virus A, B, C, Citomegalovirus, Ebstain Barr virus, Parvovirus B19, Adenovirus), drug-induced hepatotoxicity and metabolic disorders associated to ALF were excluded. Quantitative determination of Human Herpesvirus 6 (HHV6) genome was positive with a significant number of copies for mL. A favorable evolution of the clinical symptoms and a progressive hematochemical resolution were obtained. Plasma and Vitamin K were administrated as a support therapy for treating coagulopathy. The present case report and the cases' review from the literature, evidence the importance of always including screening for HHV6 infection in the diagnostic approach to acute onset of liver failure. HHV6 is a common virus in the pediatric population with a greater number of cases of fulminant viral non-A, non-B, non-C hepatitis in immunocompetent patients due to this virus: these forms have often a high mortality rate and maybe necessitate liver transplantation; for this reason correct etiological agent identification is mandatory for the prognosis and it has to be based on the quantitative search of the virus's genome. Pathogenesis of liver-induced damage associated to HHV6 remains unclear; however in vitro studies demonstrate the potential hepatotoxicity effects of this virus.

Posterior glottic stenosis with a calcified interarytenoid scar band: CT and laryngoscopic correlation.

A 52-year-old man with burn injuries and prolonged intubation developed PGS with hoarseness, dyspnea, and bilateral vocal cord immobility. On CT, a calcified interarytenoid scar band was identified, corresponding to an interarytenoid scar on laryngoscopy. Endoscopic laser lysis of the calcified scar band relieved the symptoms. We present laryngoscopic and CT findings of PGS with interarytenoid calcification along with the postlysis findings. The classification, clinical findings, imaging, and management of PGS are reviewed.

The pharyngeal mucosa is not involved in eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis is thought to be an isolated oesophageal disease associated with biopsy-verified eosinophilia of the squamous cell epithelium of the oesophagus. Food- or aeroallergens have been suggested to be the cause of eosinophilic oesophagitis; however, as these allergens pass through the pharynx sharing the same squamous cell epithelium, eosinophilic infiltration could be expected also here. Whether this is true or not has hitherto not been clarified. AIM: To find out whether eosinophilia is present also within the pharyngeal epithelium in patients with eosinophilic oesophagitis. METHODS: In all, 10 patients (median age 34, range 15-70) with biopsy-verified eosinophilic oesophagitis [peak count >20 eosinophils per high power field (hpf)] were biopsied also in the pharynx. The biopsies underwent histopathological examination and at each level, the peak number of eosinophils per hpf was counted. RESULTS: None of the patients examined was found to have eosinophilia within the squamous cell epithelium of the pharynx (median peak count 0, range 0-1). CONCLUSIONS: The pronounced eosinophilic infiltration in eosinophilic oesophagitis appears to be an isolated oesophageal phenomenon not shared by the adjoining organ sites and in particular, not by the pharynx. This may have implications for future research.

Influence of inherited and acquired thrombophilic defects on the clinical manifestations of mixed cryoglobulinaemia.

OBJECTIVE: To investigate the contribution of inherited and acquired thrombophilic defects to the clinical manifestations of mixed cryoglobulinaemia vasculitis. METHODS: The following thrombophilic defects were investigated in 64 consecutive patients with HCV-associated mixed cryoglobulinaemia: aPLs, lupus anti-coagulant, homocysteinaemia, protein C and protein S concentrations, activated protein C resistance, plasminogen activator inhibitor-1 4G4G and 5G5G genotypes, and the presence of mutations of factor V (Leiden and H1299R), of prothrombin (G20210A) and of methyl tetrahydrofolate reductase (C677T and A1298C). Additional variables were demographic data, duration of the disease, cryocrit level and vascular risk factors (diabetes, hypertension, hypercholesterolaemia and smoking habit). The following clinical manifestations of mixed cryoglobulinaemia were analysed as dependent covariates: severity of purpura, presence of necrotic skin ulcers, presence of peripheral neuropathy and presence of kidney disease. RESULTS: Logistic regression analysis identified hyperhomocysteinaemia as a risk factor for severe purpura (P < 0.0001) and for the presence of skin ulcers (P < 0.0001), whereas none of the other thrombophilic defects influenced the clinical presentation of mixed cryoglobulinaemia. Purpura improved in two patients after lowering homocysteine with vitamin supplementation. CONCLUSIONS: Hyperhomocysteinaemia may be a risk factor for severe cutaneous manifestations in mixed cryoglobulinaemia.

Evaluation of toxicity from high-dose systemic administration of recombinant adenovirus vector in vector-naive and pre-immunized mice.

Toxicity associated with in vivo administration of adenovirus (Ad) vectors has been linked to activation of both innate and adaptive immune responses. Pre-existing immunity to the prevalent Ad serotypes, acquired by the majority of the human population as a result of natural infections, has the potential to modulate vector efficacy and safety. Previously, we evaluated some aspects of toxicity from systemic Ad vector in vector-naive and pre-immunized rhesus monkeys. In this report, we summarize data from several studies analyzing toxic effects from systemically administered E1/E3-deleted Ad vector in vector-naive and pre-immunized C57BL/6 mice. Our results indicate that pre-immunization can be associated with increased mortality shortly after systemic administration of Ad. Transient leukopenia and thrombocytopenia were observed early post vector infusion in both vector-naive and pre-immunized animals. Pre-exposure to the vector did not prevent induction of pro-inflammatory cytokines; however, pre-immunized mice showed less tissue toxicity. Growth of bone marrow myeloid and erythroid progenitors was transiently inhibited in pre-immunized animals, but only the myeloid progenitors were affected in vector-naive animals. In summary, pre-existing immunity to Ad vector substantially modifies host immune responses to systemic Ad vector.

Sources of intra-oesophageal nitric oxide production following intraluminal acid exposure.

BACKGROUND: The aim of the present study was to assess luminal nitric oxide (NO) levels in the oesophagus during baseline and acidic conditions and to clarify the sources of such oesophageal NO formation. METHODS: Healthy volunteers received an intra-oesophageal infusion of either HCl (100 mM) or NaCl (50 mM) on two separate study days. After a low nitrate diet, nitrate load or no dietary restrictions/pretreatment, direct intraluminal measurements of NO formation were performed using a tonometric technique. Endoscopy was performed and mucosal biopsies were taken and analysed by means of immunohistochemistry, Western blot and RT-PCR. RESULTS: No intra-oesophageal NO was detected during baseline conditions with pH neutrality. During the infusion of HCI the NO levels rose dramatically to around 12000 ppb. This high rate of NO formation fell by 95% following deviation of saliva. NO formation after an acute nitrate load was almost doubled during acid perfusion compared to control. Immunohistochemistry demonstrated distinct staining for iNOS in the oesophageal squamous epithelial cells, and Western blot and RT-PCR confirmed the presence of iNOS. CONCLUSION: Two sources exist for intra-oesophageal NO formation, both dependent on the luminal acidity: 1) chemical reduction of salivary nitrite, a mechanism related to dietary intake of nitrate, and 2) NO formation within the oesophageal mucosal epithelium by enzymatic degradation of L-arginine. In the latter case, the NO synthase has antigenic characteristics, indicating the inducible isoform, although a functional behaviour suggests an unconventional subtype.

Simulations of the behavior of synaptically driven neurons via time-invariant circuit models.

This paper describes computer simulations of the behavior of Hodgkin-Huxley neurons, based on a redefinition of membrane and synaptic connections as time-invariant circuit elements. Examples are given showing that this self-consistent equivalent circuit representation allows very efficient computer simulations and could facilitate the introduction of detailed biological neurons into formal neural networks.

In vitro 2-D networks of neurons characterized by processing the signals recorded with a planar microtransducer array.

The purpose of this paper is to extensively analyze and utilize the key features that characterize the recently available electrophysiological technique of growing selected populations of neurons on planar substrate microelectrode arrays. This experimental configuration is first simulated by modeling the signal transduction operated by an array of microtransducers coupled to a network of Hodgkin-Huxley-like neurons, connected to each other with given levels of synaptic strength. Signal processing tools are then described and validated by identifying the various degrees of connectivity previously introduced into the simulated network. Finally, these software tools are utilized to characterize the activity and identify the synaptic connectivity of networks of cultured neurons extracted from dorsal root ganglia (DRG) of chick embryos and exposed to synapse inhibiting/reinforcing ions. As a result, correlations between various regimens of electrophysiological activity and synaptic strength are obtained.

Realistic simulations of neurons by means of an ad hoc modified version of SPICE.

This paper describes an ad hoc modified version of the electrical circuit analysis program SPICE, which has been optimized for detailed simulations of the behaviour of neurons. An equivalent-circuit description of the simulation building blocks is provided, and the SPICE modifications are specified. These modifications, in contrast to previous uses of SPICE, allows one to simulate the behaviour of neurons of Hodgkin-Huxley type (excitable membrane) and of postsynaptic membranes without any approximations. Simulation results are reported and compared, both with data previously analysed in the literature by other authors and with experimental data recently obtained by coupling neurons to planar extracellular microelectrodes. Details of the circuit elements used in the simulations are reported. The improvements of our proposed model are discussed in comparison with a previous SPICE-based model described in the literature.

Combined modality (ABVD plus radiotherapy) versus radiotherapy in the management of early stage (IIA) Hodgkin's disease with mediastinal involvement.

The aim of this study was to establish whether combined modality treatment (ABVD plus radiotherapy) can reduce the risk of relapse in Hodgkin's disease patients with mediastinal involvement, as compared to radiotherapy alone. The results obtained suggest that one course of ABVD before irradiation can reduce the incidence of relapse. These findings, however, should be considered preliminary and need to be confirmed in larger studies.