Cough receptor sensitivity in children with acute and non-acute asthma

BACKGROUND: Cough is a major symptom in some children with asthma. The relationship between cough and the severity of asthma is ill defined. A study was undertaken to test the hypotheses that, in children with asthma who cough as a major part of their asthma symptoms, cough receptor sensitivity (CRS) is heightened during an acute severe exacerbation of asthma but not in the non-acute phase and airway calibre or its change correlates with CRS. METHODS: Spirometric measurements and the capsaicin CRS test were performed on children admitted to hospital for an acute severe exacerbation of asthma. Nasal secretions were tested for viruses. The children were grouped into those who usually cough with asthma episodes and those who do not. The tests were repeated 7-10 days and 4-6 weeks later. The CRS outcome measure used was the concentration of capsaicin required to stimulate two (Cth) and five coughs (C5). RESULTS: The CRS of the group who coughed (n = 15) was significantly higher than those who did not cough (n = 16) (mean difference log Cth 0.77 mumol (95% CI 0.35 to 1.18), C5 0.72 mumol (95% CI 0.26 to 1.18)) during acute asthma but not after the exacerbation. CRS was not significantly different between groups based on the presence of a viral infection. Neither forced expiratory volume in one second (FEV1) nor its change correlated with CRS nor its change. CONCLUSIONS: In children with asthma CRS is heightened in acute severe asthma in the subgroup of children who have cough as a significant symptom with their asthma episodes. In acute and non-acute asthma CRS does not correlate with FEV1.


     

Therapeutic ratings and end-of-phase II conferences: initiatives to accelerate the availability of important new drugs

To facilitate the availability of important new therapeutic agents, the Food and Drug Administration (FDA) in the mid-1970s began assigning therapeutic ratings to investigational new drugs and holding end-of-phase II conferences with drug sponsors. To determine whether these initiatives are associated with faster approvals, we examined new drug application (NDA) review times of new chemical entities (NCEs) approved during the 12-year period 1978 through 1989. Mean NDA review time for 1A drugs (22.5 months) was 22% shorter than that for 1B drugs (28.7 months), which in turn was 25% shorter than that for 1C drugs (38.4 months). For drugs approved during the recent 4-year period 1986 through 1989, however, the gap between 1A and 1C review times has narrowed considerably from 19 to 9 months. When drugs were grouped by FDA reviewing division, 1A drugs had the shortest mean review time in each division except the Cardio-Renal Division; in that division, 1B drugs had the shortest mean review time. Mean NDA review time for drugs that had end-of-phase II conferences (28.6 months) was 15% shorter than that for drugs without such conferences (33.7 months). These results suggest that NCEs that receive 1A or 1B ratings and are the subject of end-of-phase II conferences benefit by having shorter review times.     

Hippocampal formation and related structures of the limbic lobe: anatomic-MR correlation. Part I. Surface features and coronal sections

Correlation of magnetic resonance (MR) images with cryomicrotome sections and formalin-fixed sections of human brain documents that spin-echo MR imaging with short repetition time/short echo time pulse sequences can display the surface gyri of the inferomedial temporal lobe, including the temporal pole, the parahippocampal gyrus, the isthmus of the cingulate gyrus, the lateral and medial occipitotemporal gyri, and the inferior temporal gyrus; the associated sulci including the rhinal and collateral sulci, the occipitotemporal sulcus, and the anterior calcarine sulcus; the components and fiber tracts of the hippocampal formation including the pes hippocampi, the hippocampus, the subiculum, the dentate gyrus, the subsplenial gyri, the alveus, the fimbria, and the fornix; the fissures and sulci associated with the hippocampal formation, including the hippocampal fissure, dentatofimbrial fissure, and the choroidal fissure; the continuity between the cingulate gyrus and the parahippocampal gyrus through the isthmus of the cingulate gyrus; and the continuity between the callosal sulcus and the hippocampal fissure.     

P ARAMEDIC U SE OF THE E NDOTRACHEAL T UBE I NTRODUCER IN A D IFFICULT A IRWAY M ODEL

Objectives. To determine whether advanced life support (ALS)-level prehospital providers can be taught to effectively use the Flex-Guide (FG) Endotracheal Tube (ETT) introducer in a difficult airway model by comparing success of styleted ETT intubation with Flex-Guide-assisted intubation. Methods. Intermediate and advanced providers, who brought patients to a Level 1 emergency department, were given a handout and viewed an instructional video describing the bougie and its use. A difficult airway was simulated using the CPR 5000 model mannequin from Medical Plastics Laboratory, Inc. The tongue was inflated to a pressure of 180?mm Hg to partially obscure the view of the airway and a cervical collar was placed to limit flexion and extension. Participants were then asked to intubate the mannequin using both the ETT with a stylet and the bougie-assisted method. Whether the providers used the FG or stylet method first was randomized. Success or failure was recorded and the McNemar test was used to evaluate the paired nonparametric data. Results. A total of 96 providers (66% advanced, 34% intermediate) were enrolled, 69 successfully intubated using the FG, while 64 successfully intubated with the stylet. Comparing successful bougie intubations with successful stylet intubations using the McNemar test, no significant difference was found between the groups (p = 0.486). Conclusion. Prehospital care providers were as successful intubating a difficult airway model using the newly learned bougie technique as they were using the more familiar styleted ETT technique.     

The relationships between aerobic fitness, power maintenance and oxygen consumption during intense intermittent exercise

This study examined the relationships between VO2max, power maintenance and oxygen consumption during intense intermittent work. Female recreational soccer players were assigned to either a low aerobic power group (LOW, n = 6, mean (SD) VO2max = 34.4 (2.4) mL.kg(-1)min(-1) or to a moderate aerobic power group (MOD, n = 7, VO2max = 47.6 (3.8) mL.kg(-1).min(-1)). VO2 was measured while subjects performed 10 6-s all-out sprints (30-s passive recovery) on a Monark cycle ergometer. LOW and MOD subjects generated similar peak 6-s power (p = .58) but MOD had a smaller decrement in power (% DO) over the 10 sprints (LOW vs MOD: 18.0 (7.6) vs 8.8 (3.7) % DO, p = .02). The MOD group also consumed significantly more oxygen than LOW in 9 of the 10 sprint-recovery cycles (p < .05). Significant relationships were seen between VO2max and the aerobic response to the sprint-recovery series (r = .78, p =.002) as well as between VO2max and % DO (r = -.65, p = .02), while a non-significant relationship was seen between the oxygen consumed during the sprint-recovery cycles and % DO (r = -.41, p = .16). Thus, VO2max appears to be related to both an increased aerobic contribution to sprint-recovery bouts and the enhanced ability of the MOD group to resist fatigue during intense intermittent exercise.     

Dynamic Assay for Profiling Anti-SARS-CoV-2 Antibodies and Their ACE2/Spike RBD Neutralization Capacity

Serological assays have been widely employed during the coronavirus disease 2019 (COVID-19) pandemic to measure antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to track seroconversion in populations. However, currently available assays do not allow determination of neutralization capacity within the assay protocol. Furthermore, commercial serology assays have a high buy-in cost that is inaccessible for many research groups. We have replicated the serological enzyme-linked immunosorbent assay for the detection of SARS-CoV-2 antibody isotypes, developed at the Icahn School of Medicine at Mount Sinai, New York. Additionally, we have modified the protocol to include a neutralization assay with only a minor modification to this protocol. We used this assay to screen local COVID-19 patient sera (n = 91) and pre-COVID-19 control sera (n = 103), and obtained approximate parity with approved commercial anti-nucleoprotein-based assays with these sera. Furthermore, data from our neutralization assay closely aligns with that generated using a spike-based pseudovirus infection model when a subset of patient sera was analyzed.