Development of a calibration chamber to evaluate the performance of low-cost particulate matter sensors.

Low-cost particulate matter (PM) air quality sensors are becoming widely available and are being increasingly deployed in ambient and home/workplace environments due to their low cost, compactness, and ability to provide more highly resolved spatiotemporal PM concentrations. However, the PM data from these sensors are often of questionable quality, and the sensors need to be characterized individually for the environmental conditions under which they will be making measurements. In this study, we designed and assessed a cost-effective (∼$700) calibration chamber capable of continuously providing a uniform PM concentration simultaneously to multiple low-cost PM sensors and robust calibration relationships that are independent of sensor position. The chamber was designed and evaluated with a Computational Fluid Dynamics (CFD) model and a rigorous experimental protocol. We then used this new chamber to calibrate 242 Plantower PMS 3003 sensors from two production lots (Batches I and II) with two aerosol types: ammonium nitrate (for Batches I and II) and alumina oxide (for Batch I). Our CFD models and experiments demonstrated that the chamber is capable of providing uniform PM concentration to 8 PM sensors at once within 6% error and with excellent reliability (intraclass correlation coefficient > 0.771). The study identified two malfunctioning sensors and showed that the remaining sensors had high linear correlations with a DustTrak monitor that was calibrated for each aerosol type (R2 > 0.978). Finally, the results revealed statistically significant differences between the responses of Batches I and II sensors to the same aerosol (P-value<0.001) and the Batch I sensors to the two different aerosol types (P-value<0.001). This chamber design and evaluation protocol can provide a useful tool for those interested in systematic laboratory characterization of low-cost PM sensors.

NVP-QBE170: an inhaled blocker of the epithelial sodium channel with a reduced potential to induce hyperkalaemia.

BACKGROUND AND PURPOSE: Inhaled amiloride, a blocker of the epithelial sodium channel (ENaC), enhances mucociliary clearance (MCC) in cystic fibrosis (CF) patients. However, the dose of amiloride is limited by the mechanism-based side effect of hyperkalaemia resulting from renal ENaC blockade. Inhaled ENaC blockers with a reduced potential to induce hyperkalaemia provide a therapeutic strategy to improve mucosal hydration and MCC in the lungs of CF patients. The present study describes the preclinical profile of a novel ENaC blocker, NVP-QBE170, designed for inhaled delivery, with a reduced potential to induce hyperkalaemia. EXPERIMENTAL APPROACH: The in vitro potency and duration of action of NVP-QBE170 were compared with amiloride and a newer ENaC blocker, P552-02, in primary human bronchial epithelial cells (HBECs) by short-circuit current. In vivo efficacy and safety were assessed in guinea pig (tracheal potential difference/hyperkalaemia), rat (hyperkalaemia) and sheep (MCC). KEY RESULTS: In vitro, NVP-QBE170 potently inhibited ENaC function in HBEC and showed a longer duration of action to comparator molecules. In vivo, intratracheal (i.t.) instillation of NVP-QBE170 attenuated ENaC activity in the guinea pig airways with greater potency and duration of action than that of amiloride without inducing hyperkalaemia in either guinea pig or rat. Dry powder inhalation of NVP-QBE170 by conscious sheep increased MCC and was better than inhaled hypertonic saline in terms of efficacy and duration of action. CONCLUSIONS AND IMPLICATIONS: NVP-QBE170 highlights the potential for inhaled ENaC blockers to exhibit efficacy in the airways with a reduced risk of hyperkalaemia, relative to existing compounds.

ENaC-mediated effects assessed by MRI in a rat model of hypertonic saline-induced lung hydration.

BACKGROUND AND PURPOSE: The epithelial sodium channel (ENaC) regulates airway mucosal hydration and mucus clearance. The lack of such regulation in cystic fibrosis patients leads to desiccation of the airway lumen, resulting in mucostasis that establishes the environment for infections. Osmotic agents and negative ENaC regulators can be used to restore mucosal hydration. We aimed to assess whether: (i) osmotically driven fluid flux into the rat lung could be quantified in vivo by magnetic resonance imaging (MRI); and (ii) the MRI signals could be modulated through the regulation of ENaC function. EXPERIMENTAL APPROACH: Lung images from spontaneously breathing rats were acquired following intra-tracheal (i.t.) administration of physiological or hypertonic saline (HS). Compounds known to modulate the ENaC function were given i.t. prior to saline. Volumes of fluid signals were quantified on the images. KEY RESULTS: A tonicity-dependent increase in lung fluid was demonstrated following HS administration. Pretreatment with the ENaC blockers, amiloride or 552-02, resulted in an enhancement of HS-induced lung fluid signals, which were detectable for up to 4 h, consistent with a role for ENaC in fluid clearance. Aprotinin, a serine protease inhibitor that attenuates ENaC function, likewise enhanced the HS-induced increase in lung fluid signal, while alpha(1)-anti-trypsin was without significant effect. CONCLUSIONS AND IMPLICATIONS: Proton MRI provides a non-invasive technique for studying modulators of lung fluid hydration in rat lung in vivo. The pharmacological sensitivity of MRI-detected fluid signals is consistent with ENaC-mediated fluid reabsorption after HS. This target-related readout may be used to characterize new ENaC modulators.

Optimizing drugs for local delivery.

An international panel of speakers together with approximately 70 delegates were brought together by The Society for Medicines Research's symposium on Optimising Drugs for Local Delivery, held on June 11, 2009 at the Novartis Institutes for Biomedical Research, Horsham, UK. The focus of the conference was on the delivery of drugs direct to the site of action and the consequences of this delivery route on delivery technologies, formulation science and molecular design.

Ethnic differences in otitis media [abstract]

The comparative incidence of Otitis Media (OM) has long been difficult to ascertain as almost all previous epidemiological studies were performed in comparatively homogenous populations. In an attempt to question the racial variation of OM, a study was done in Trinidad, with a population of 1.2 million people. About 40 percent of the population is of African ancestry, 40 percent of East-Indian ancestry and 20 percent includes persons of mixed ethnicity, Caucasian, Chinese and middle-Eastern descent. All patients who presented with acute otitis media (AOM), middle ear effusion (MEE), or chronic suppurative otitis media (CSOM) either of the tubo-tympanic (TT) or attico-antral (AA) types, during the period November 1998 to May 1999, were included in the study. The three national otolaryngology Departments participated in the study suggesting that patients were representative of the whole population. A questionnaire was devised with documented ethnic and other demographic factors. This was completed once an experienced physician diagnosed the patient with one of the above conditions. Two hundred and fifty-two patients enrolled in the study. There were 128 males and 124 females and the age range was 4 months to 83 years. Sixty patients presented with AOM, 88 with MEE and 104 with CSOM. The most interesting result was the ethnic distribution of the patients. One hundred and thirty-eight were of East-Indian descent and 71 were of African origin, a ratio of nearly 2:1. In conclusion, in a national population containing nearly equal numbers of two major ethnic groups, the East Indians presented twice as commonly as the Africans with otitis media. Various proposed reasons for this will be discussed. (AU)

Inhibition by viozan of extravasation induced in rat trachea by capsaicin is mediated exclusively by beta 2-adrenoceptors.

The mechanism by which 2(3H)-benzothiazolone, 4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]-sulphonyl]ethyl]amino]ethyl]-monohydrochloride (AR-C68397AA; viozan), a dual dopamine D2/beta2-adrenoceptor agonist which has shown promise in the treatment of chronic obstructive pulmonary disease (COPD), inhibits the extravasation of plasma protein induced by capsaicin in the tracheas of Brown Norway rats has been re-evaluated. Viozan (10-30 microg/kg given intratracheally; i.t.) inhibited dose-dependently the extravasation of plasma protein tagged with Evans Blue into rat trachea induced by capsaicin (10 microg/kg i.t.). Similar effects were seen with the selective beta2-adrenoceptor agonist, salbutamol (3-10 microg/kg i.t.), but the selective dopamine D2 receptor agonist, quinagolide (10-30 microg/kg i.t.), was inactive. The effects of viozan and salbutamol were abolished by propranolol (3 mg/kg) given intraperitoneally (i.p.) but unaffected by sulpiride (3 mg/kg i.p.). Thus, in c,ontrast to claims in the literature, a functional response to dopamine D2 receptor activation in a preclinical model of oedema arising from sensory nerve fibre activation in the rat lung could not be demonstrated. Moreover, no qualitative difference could be demonstrated between the response to a dual D2/beta2-adrenoceptor agonist and a selective beta2-adrenoceptor agonist. The observations call into question whether a dual D2/beta2-adrenoceptor agonist such as viozan would bring added benefit over established selective beta2-adrenoceptor agonists in the therapy

The Internet and electronic transmission of medical records.

OBJECTIVE: To review, from a legal perspective the potential for using the Internet for inter-institutional transfer of patient medical records. METHODS: Basic issues and recent legislation that relate to protection of both medical data, and those transferring that data over public network systems is reviewed. RESULTS: Many laws already in existence can be applied to Internet transmission, but questions of jurisdiction remain. Providing signatures on requests for information, which are in essence contracts, is a problem. Signatures must both prove the identity of the participants and provide for non-repudiation of the agreement. Cryptographic digital signatures appear secure and effective, but their use is difficult to implement. Simpler methods are fraught with risks, yet are more easily accomplished. The patient's rights of privacy must be balanced against the need for access by government, physician, or healthcare institutions to confidential information. In general, information holders must put forth reasonable efforts to keep information confidential. The development of acknowledged standards will provide guidance. Multiple laws provide some deterrence and hence some reassurance to healthcare institutions, for example, by criminalizing acts of electronic interception of patient records in transit. CONCLUSION: Some believe the expense of secure transfer of medical records by electronic means is a major obstacle; this is false: such transfers are now technologically quite easy. The greatest obstacle to electronic transfer of medical records at this point is the development of workable standards for signing agreements and protecting transmissions, but the perceived advantages will likely drive the necessary developments.

Meniere's disease

Prosper Meniere more than 100 years ago in the clinical description of the disease complex that bears his name, has not been surpassed in clarity or in factual presentation of the symptoms of the disease. Modern day otorhino-laryngologists have a clearer view possibly of the condition because of more recently described specific pathology. Viz: episodic vertigo, tinnitus, hearing loss of sensorineural type due to cochlear damage(AU)

Asyptomatic maternal rubella and congenital deafness

A total of 139 congenitally deaf children were studied. Of these 87 were found to be born in the year of 1961. This sharp rise in the incidence of congenital deafness was associated with an epidemic of German measles in the latter part of 1960 and early 1961. Only 20 of these 87 cases gave a definite history of maternal rubella. (AU)

Subclinical maternal rubella and congenital deafness

At present 40 percent of congenital deafness is inexplicable. The effect of rubella on the frequency of congenital deafness was studied five years after an epidemic of rubella in an island population. Of 87 congenitally deaf children born in 1961, the year after the epidemic, 86 had deafness as the only demonstrable congenital abnormality. Only 20 gave a history of first-trimester rubella. By modern classification the remaining 67 cases should be labelled as idiopathic congenital deafness having been ruled out. Serologic tests for rubella antibodies on 30 of the idiopathic deaf children were positive in 74 per cent, as compared to 30 per cent in a control group born within the same year. This study suggests asymptomatic rubella infection in the first trimester as an etiologic factor in congenital deafness. (AU)