Kenan Haver

The utility of endoscopy and multichannel intraluminal impedance testing in children with cough and wheezing

Gastroesophageal reflux (GER) has been implicated as a causal factor in respiratory disease but prior studies have focused on the role of acid alone in the genesis of symptoms. Prior studies have relied on pH probe testing but this is blind to non‐acid reflux which has been implicated in the genesis of extraesophageal symptoms. The objective of this prospective, cross‐sectional study is to determine the utility of gastroesophageal reflux testing, including multichannel intraluminal impedance with pH (pH‐MII) and upper gastrointestinal endoscopy (EGD), in the child with intractable cough and wheezing. We hypothesize that there is a high rate of pathologic reflux testing in these patients.

Case 10-2008: A 10-Year-Old Girl with Dyspnea on Exertion

From the Pediatric Pulmonary Unit (K.E.H.) and the Departments of Pediatric Surgery (D.P.R.), Radiology (R.S.), and Pathology (E.J.M.), Massachusetts General Hospital; Pediatric Otolaryngology, Massachusetts Eye and Ear Infirmary (C.J.H.); and the Departments of Pediatrics (K.E.H.), Otology and Laryngology (C.J.H.), Surgery (D.P.R.), Radiology (R.S.), and Pathology (E.J.M.), Harvard Medical School.

Brain clathrin complex: II. Immunofluorescent correlation and biochemical affinity for actin.

The interaction of clathrin with cytoskeletal proteins was studied cytochemically by immunofluorescent staining and biochemically by the binding of actin to clathrin on the surfaces of polystyrene particles. Using a cytoskeletal-disrupting agent, the linear arrangement of clathrin lattices along actin fibers was altered. As a result of cell retraction, the fluorescent dots of clathrin redistributed, conforming to the new cellular shape. Cytoplasmic areas, largely devoid of fluorescent dots, were observed at the cells periphery. In vitro, the native clathrin complex (clathrin plus clathrin-associated proteins (CAPs)) bound up to 1 mol of actin, but when the clathrin polypeptide was separated from accompanying proteins it bound up to 2 mol of actin from solution. It appears that clathrins molecular lattices have an affinity for arrays of actin microfilaments, following them closely, and that clathrin lattices display lateral mobility during cytoplasmic reorganization.

Case 10-2008

From the Pediatric Pulmonary Unit (K.E.H.) and the Departments of Pediatric Surgery (D.P.R.), Radiology (R.S.), and Pathology (E.J.M.), Massachusetts General Hospital; Pediatric Otolaryngology, Massachusetts Eye and Ear Infirmary (C.J.H.); and the Departments of Pediatrics (K.E.H.), Otology and Laryngology (C.J.H.), Surgery (D.P.R.), Radiology (R.S.), and Pathology (E.J.M.), Harvard Medical School.

Utilization of lipid‐laden macrophage index in evaluation of aerodigestive disorders

The utility of the lipid‐laden macrophage index (LLMI) in the evaluation of airway inflammatory processes remains controversial. There is a paucity of normative data in both pediatric and adult populations, and there is wide variability in the reported cases. The goal of this project was to review the LLMI levels in a large series of patients with a wide range of well‐documented pulmonary and airway diseases (cystic fibrosis, aspiration, tracheo/bronchomalacia, recurrent pneumonia, asthma, immunosuppressed conditions, and laryngeal clefts) to develop a better understanding of the clinical utility of the LLMI.

Brain Clathrin: A Study of Its Properties

In 1968, Puszkin, Berl and coworkers reported the presence of contractile proteins in whole brain (1). Subsequent work showed the presence of contractile proteins in nerve-endings (2,3,4). The properties of various contractile proteins found in brain tissue resembled, to a large extent, those from muscle tissue (2,4). As a result, it was proposed that contractile activities are involved in neurotransmitter release (5). With the advantage of sodium dodecyl sulfate polyacrylamide gel electrophoresis as a procedure for distinguishing and comparing the size of various proteins, many researchers working with other tissues or cells began to report the presence and involvement of contractile proteins in motility-related cell functions (6).

Chest radiographic and CT evaluation of lung abnormalities in pediatric patients with laryngeal cleft

The purpose of this study was to (1) evaluate chest radiography (CR) and computed tomography (CT) findings in pediatric patients with laryngoscopically confirmed laryngeal cleft and (2) determine whether CT provided additional information over CR in evaluating lung abnormalities in pediatric patients with laryngeal cleft.

The time is right for an international primary ciliary dyskinesia disease registry

Rare diseases present diagnostic and management challenges to patients, healthcare providers and researchers. These diseases are often inherited, typically diagnosed upon presentation during childhood and can have deleterious long-term effects on patient wellbeing [1]. According to the regulatory and policy definition, a rare disease is any condition or disease affecting <200 000 individuals in the USA or in the European Union determined to be of low prevalence (fewer than five affected individuals per 10 000) [2]. With >7000 rare diseases estimated to affect ∼25 million people in North America and 30 million people in Europe [3, 4], even large medical centres are unlikely to have garnered sufficient patient care experience to accurately identify and effectively manage patients with these rare disorders. Diagnostic consensus is a crucial first step toward better understanding of PCD http://ow.ly/vp8j306eL8z

Similarity of chest X-ray and thermal imaging of focal pneumonia: a randomised proof of concept study at a large urban teaching hospital

Objective To assess the diagnostic accuracy of thermal imaging (TI) in the setting of focal consolidative pneumonia with chest X-ray (CXR) as the gold standard. Setting A large, 973-bed teaching hospital in Boston, Massachusetts. Participants 47 patients enrolled, 15 in a training set, 32 in a test set. Age range 10 months to 82 years (median=50 years). Materials and methods Subjects received CXR with subsequent TI within 4 hours of each other. CXR and TI were assessed in blinded random order. Presence of focal opacity (pneumonia) on CXR, the outcome parameter, was recorded. For TI, presence of area(s) of increased heat (pneumonia) was recorded. Fisher’s exact test was used to assess the significance of the correlations of positive findings in the same anatomical region. Results With TI compared with the CXR (the outcome parameter), sensitivity was 80.0% (95% CIs 29.9% to 98.9%), specificity was 57.7% (95% CI 37.2% to 76.0%). Positive predictive value of TI was 26.7% (95% CI 8.9% to55.2%) and its negative predictive value was 93.8% (95% CI 67.7% to 99.7%). Conclusions This feasibility study confirms proof of concept that chest TI is consistent with CXR in suggesting similarly localised focal pneumonia with high sensitivity and negative predictive value. Further investigation of TI as a point-of-care imaging modality is warranted.

Neutral endopeptidase activity in newborn and adult rabbit tracheas

Neutral endopeptidase (NEP, E.C. 3.4.24.11), a widely distributed ectoenzyme, cleaves and inactivates a variety of biologically active peptides, including the tachykinin, substance P (SP). This study was undertaken to determine whether the modulation of SP airway smooth muscle contraction by NEP is age-dependent. We studied the contractile response of isolated tracheal rings from newborn and 120 day old New Zealand white rabbits. We measured NEP activity and determined immunoreactive NEP content in tracheal membrane preparations. NEP activity was then localized histochemically in sections of rabbit tracheas. In the presence of the NEP inhibitor, SCH 32615, the contractile response of isolated tracheal rings to SP was increased both in the newborn and 120 day old rabbits. However, the increase was greatest in the newborn animals. NEP activity in tracheal membrane preparations increased fivefold between the newborn and 120 day old rabbits. Western blot analysis also revealed a significant increase in the immunoreactive NEP content of these tracheal membrane preparations between the newborn and 120 day old rabbits. NEP activity, localized histochemically, was most intense in the epithelial region of the newborn animals, with a shift of activity to the subepithelial region with age. The prominent epithelial localization of neutral endopeptidase in the tracheas of these 1 day old rabbits, which we have shown to have relatively low neutral endopeptidase activity, suggests that the location of neutral endopeptidase in the airway, including proximity to relevant substance P receptors, may be critical to its function.