Functional organization of the central cough generation mechanism

Recent studies evaluating the effects of pulmonary afferents, chemoreceptors, and antitussive drugs on the cough motor pattern indicate that this reflex is regulated in a different manner than breathing. Furthermore, regulatory differences exist between tracheobronchial and laryngeal cough. We propose a functional model of the brainstem elements participating in the production of cough that accounts for these regulatory differences. The model incorporates known brainstem interneuronal pathways as well as novel regulatory elements for tracheobronchial and laryngeal cough. Each of these novel regulatory elements controls the excitability of a common motor pattern generation network. Given that cough and breathing are associated with profoundly different spatiotemporal alterations in motor drive to respiratory motoneurons, brainstem elements common to the generation of both behaviours must be capable of a high degree of plasticity.     

The SWAL–QOL and SWAL–CARE Outcomes Tool for Oropharyngeal Dysphagia in Adults: III. Documentation of Reliability and Validity

Advances in the measurement of swallowing physiologic parameters have been clinician-driven, as has the development of intervention techniques to modify swallowing pathophysiology. However, a critical element to determining the success of such efforts will be established by the patients themselves. We conceptualized, developed, and validated the SWAL–QOL, a 93-item quality-of-life and quality-of-care outcomes tool for dysphagia researchers and clinicians. With 93 items, the SWAL–QOL was too long for practical and routine use in clinical research and practice. We used an array of psychometric techniques to reduce the 93-item instrument into two patient-centered outcomes tools: (1) the SWAL–QOL, a 44-item tool that assesses ten quality-of-life concepts, and (2) the SWAL–CARE, a 15-item tool that assesses quality of care and patient satisfaction. All scales exhibit excellent internal-consistency reliability and short-term reproducibility. The scales differentiate normal swallowers from patients with oropharyngeal dysphagia and are sensitive to differences in the severity of dysphagia as clinically defined. It is intended that the standardization and publication of the SWAL–QOL and the SWAL–CARE will facilitate their use in clinical research and clinical practice to better understand treatment effectiveness as a critical step toward improving patients' quality of life and quality of care.     

Plasma shedding by the canine oxyntic and pyloric glandular mucosa induced by topical action of acetylcholine. Effect of atropine and physostigmine.

Irrigation of the canine oxyntic or pyloric glandular mucosa in vagally denervated pouches with a solution of acetylcholine causes the mucosa to shed plasma proteins and the potential difference across the mucosa to fall. The response is dose-related with the threshold concentration of acetylcholine bromide ranging from 0.1 to 1 g per 100 ml. Topical application or intravenous injection of atropine prevents both plasma shedding and decline in potential difference. The minimal effective intravenous dose of atropine sulfate is about 0.007 mg per kg. The effect of irrigation with low concentrations of acetylcholine is enchanced by concurrent irrigation with physotigmine. The action of topical acetylcholine is not affected by concurrent irrigation with hexamethonium chloride (0.5 g per 100 ml) or by intravenous injection (5 mg per kg). Topical application of gallamine triethiodide (0.5 g per 100 ml) or d-tubocurarine (0.15 g per 100 ml) does not prevent the effects of acetylcholine in causing plasma shedding. Topical application of succinylcholine chloride (1 g per 100 ml) does not cause plasma shedding or a fall in potential difference.     

Phase I/II dose escalation study of recombinant human interleukin-11 following ifosfamide, carboplatin and etoposide in children, adolescents and young adults with solid tumours or lymphoma: a clinical, haematological and biological study

Thrombocytopenia remains the major dose-limiting toxicity of myelosuppressive chemotherapy in children with solid tumours. Recombinant human interleukin-11 (rhIL-11) has been approved by the Food and Drug Administration as treatment for adults with solid tumours and lymphomas with severe chemotherapy-induced thrombocytopenia. We conducted a phase I/II trial of rhIL-11 following ifosfamide, carboplatin and etoposide (ICE) chemotherapy in children with solid tumours or lymphomas. Patients received ifosfamide 1800 mg/m(2)/d for 5 d, carboplatin 400 mg/m(2)/d for 2 d and etoposide 100 mg/m(2)/d for 5 d with rhIL-11 subcutaneous (s.c.) at 25-125 microg/kg/d on days 6-33. Forty-seven patients with median age 10.5 years (range, 0.7-26 years) were studied. Median days to absolute neutrophil count >/=0.5 x 10(9)/l, platelet count >/=50 x 10(9)/l and platelet transfusions were 23, 18, 18, 16.5 and 18.5, 21, 20, 18 and 3, 3, 4, and 2 d at doses 25, 50, 75 and 100 Schulteg/kg respectively. There was a dose-dependent increase in C(max) (7.6-25.5 ng/ml), AUC(0-rho) (57-209 ng.h/ml) and T(1/2) (4-8.2 h) respectively. There was a 4% incidence of anti-IL-11 antibody formation. Clinically important adverse events to rhIL-11 were papilloedema and periosteal bone formation. In summary, rhIL-11 was well tolerated at doses of 相似文献   

Do nonsteroidal anti-inflammatory drugs interfere with blood pressure control in hypertensive patients?

Exacerbation of hypertension by nonsteroidal anti-inflammatory drugs in hypertensive patients remains controversial among physicians and investigators. Because of the many differences among studies of oral nonsteroidal anti-inflammatory drugs and blood pressure control in patients with hypertension, the authors critically evaluated the published clinical evidence on this subject using standardized methodologic criferia. A search of the literature from 1965 to 1986 identified 31 relevant studies, of which only eight were double-blind randomized controlled trials that provided the most clinically useful information. Of these eight best-designed studies, five of the six that studied indomethacin concluded that it may interfere with antihypertensive effectiveness in selected patients with treated, stable hypertension. The remaining double-blind randomized studies included comparisons of other nonsteroidal anti-inflammatory drugs. Their limited results suggest that sulindac is less likely than piroxicam, naproxen or indomethacin to cause an attenuation of antihypertensive therapy. More research on this subject is needed, with greater attention to methodologic details and identification of predisposing risk factors for impairment of blood pressure control by nonsteroidal anti-inflammatory drugs. Received from the Department of Internal Medicine, University of Cincinnati, Medical Center, and the Department of Pharmacy. University Hospital, Cincinnati, Ohio.     

Head Impact Exposure in Youth Football: High School Ages 14 to 18 Years and Cumulative Impact Analysis

Sports-related concussion is the most common athletic head injury with football having the highest rate among high school athletes. Traditionally, research on the biomechanics of football-related head impact has been focused at the collegiate level. Less research has been performed at the high school level, despite the incidence of concussion among high school football players. The objective of this study is to twofold: to quantify the head impact exposure in high school football, and to develop a cumulative impact analysis method. Head impact exposure was measured by instrumenting the helmets of 40 high school football players with helmet mounted accelerometer arrays to measure linear and rotational acceleration. A total of 16,502 head impacts were collected over the course of the season. Biomechanical data were analyzed by team and by player. The median impact for each player ranged from 15.2 to 27.0 g with an average value of 21.7 (±2.4) g. The 95th percentile impact for each player ranged from 38.8 to 72.9 g with an average value of 56.4 (±10.5) g. Next, an impact exposure metric utilizing concussion injury risk curves was created to quantify cumulative exposure for each participating player over the course of the season. Impacts were weighted according to the associated risk due to linear acceleration and rotational acceleration alone, as well as the combined probability (CP) of injury associated with both. These risks were summed over the course of a season to generate risk weighted cumulative exposure. The impact frequency was found to be greater during games compared to practices with an average number of impacts per session of 15.5 and 9.4, respectively. However, the median cumulative risk weighted exposure based on combined probability was found to be greater for practices vs. games. These data will provide a metric that may be used to better understand the cumulative effects of repetitive head impacts, injury mechanisms, and head impact exposure of athletes in football.     

Perceptions of Families of Individuals with Autism Spectrum Disorder during the COVID-19 Crisis

Caring for an individual with autism spectrum disorder (ASD) in ideal circumstances can be stressful, and the Coronavirus disease (COVID-19) pandemic created a high degree of disruption to life and stress to families living with an individual with ASD. We conducted an online survey of families in Michigan that revealed higher levels of stress in caregivers of younger individuals with ASD and those with greater severity of ASD symptoms. Stress around therapeutic service disruption, finances, and illness predominated and greater stress was reported for caregivers of individuals receiving greater intensity of services pre-COVID-19. Respondents voiced concerns about receiving respite care during COVID-19, and those expressing interest in respite also reported greater symptom severity in the person with ASD.