Quantitative assays of pharmacologic aerosols used in studying asthma

To more nearly accurately quantitate the dose of pharmacologic agents delivered to human and animal airways via aerosols, we have developed a monodisperse aerosol containing either methacholine or histamine that permits a light scattering device (tyndallometry) to measure accurately the quantity of inspired and expired particles. These aerosols (described in previous studies) are simultaneously tagged with a radioactive label (technetium 99m) to permit the use of external gamma camera imaging. Present work focuses on the development of assay techniques to measure the quantity of methacholine delivered in these aerosols. The lack of specific radioimmune or radioenzyme assays coupled with the cross-reaction of organic contaminants with conventional chemical reagents for measuring methacholine required the development of separative techniques to isolate the methacholine from the organic aerosol contaminants. With aqueous extraction and column separation we have been able to completely isolate the methacholine from these contaminants. This allows the application of standard spectrophotometric assays for methacholine to quantitate the methacholine in the resulting solution. These separative techniques will permit the use of these aerosols in quantitative studies of airway reactivity.     

Skin tests and blood leukocyte histamine release of patients with allergies to laboratory animals

Skin tests and in vitro histamine-release reactions were used to evaluate 130 patients observed in an employee allergy clinic at a biomedical research facility. The allergens used included extracts from pollens (ragweed, grasses, trees, weeds), molds, mixed feathers, house dust, cat, dog, mouse, rat, rabbit, guinea pig, and hamster. Of all patients, 66% complained of allergic symptoms on laboratory animal exposure, although only 52% worked directly with animals. Among patients with symptoms, 91% were positive by skin test to at least one laboratory animal, and 46% had asthma. The median length of exposure to laboratory animals before onset of symptoms was 2.8 yr with 60% of the patients developing their symptoms within 3 yr. Among patients who had allergic symptoms before exposure to laboratory animals, 79% were skin test positive to laboratory animals when they were evaluated in this study. There was a close association found between the skin test and histamine-release results with the laboratory animal allergens: 91% of the 4+ skin reactors had leukocytes positive for histamine release versus 5% of the leukocyte donors with less than 1+ skin reactions. A close relationship in positive reactions to different laboratory animal allergens was also found. For example, individuals positive to mouse were positive also to rat (95%), rabbit (79%), guinea pig (83%), and hamster (88%). Patients who reacted to laboratory animals also reacted to some extent to house dust and cat and dog allergens, and about one half of the animal-allergic individuals reacted to pollens. Although nonpollen-allergic individuals can develop sensitivity to laboratory animals, the group at higher risk are allergic individuals, especially those sensitive to house dust, cats, or dogs.     

Different specificities of an HLA-DRw6 haplotype detected by alloreactive T lymphocytes

DRw6 has been difficult to define serologically. In the present experiments we have developed T cell lines in order to characterize the components of a DRw6 haplotype. This was accomplished by priming T cells with allogeneic mononuclear cells mismatched for DRw6, Dw6, and MT2. Subsequently, three sublines with distinct reactivity patterns were derived by limiting dilution. The specificities detected by these sublines included: (a) a specificity found on a subset of cells positive for DRw6 which was inhibited by monoclonal antibodies against DS(DC), the human homologue of the murine IA-encoded molecules, (b) another DRw6-associated specificity blocked by an MT2-like antibody, and (c) an MT2-like specificity blocked by monoclonal antibodies reactive with a different MT2-associated determinant. These results show that more than one IE-like, as well as the DS/DC (IA-like) molecules, carry distinctive antigenic epitopes that can be recognized by allogeneic T cells. Primed T cell lines may be useful for a better definition of certain haplotypes which are at present difficult to characterize with serological reagents alone.     

The discovery of neuronopathy and neuropathy as a cause of progressive paralysis in childhood. The historical origins of modern differential diagnosis in neuromuscular disease

The concept of the differential diagnosis has a central place in all clinical medicine. In neurology and paediatrics, evolution of thought concerning the differential diagnosis of the child presenting with symptoms of neuromuscular disease was far in advance of similar diagnostic approaches to problems of infectious, infective and neoplastic disease; and as such forms a significant historical model for the development of modern clinical approaches to the sick or disabled child. The account presented in this paper provides a detailed historical review of the development of thought relating to the causes of neuromuscular disease. Nosological developments concerning diseases of the motor unit can be conveniently classified into three periods: (a) a "state of the art" period to 1850; (b) 1850-1890 - a period of parallel and interdependent advances in both normal neuro-anatomy and neurophysiology, and diseases recognized as variations from such norms. In this era Duchenne was the first to write about the differential diagnosis of the progressive muscular paralysis in childhood; and Gowers was the first to write specifically on the hereditary transmission of this group of diseases; (c) in 1891 was described the first case of childhood neuronopathy recognized as such, and with this development was ushered in the modern era of clinical differential diagnosis of childhood neuromuscular disease. The "splitters" have won the great debate concerning the clinical approach to neurological diseases. The continual further refining of an exact diagnosis is the only way in which a realistic prognosis can be forecast, correct genetic counseling can be offered, and (if the condition is treatable) optimal therapy can be introduced.     

Machine Learning Algorithms to Predict Mortality and Allocate Palliative Care for Older Patients With Hip Fracture

ObjectivesTo evaluate a machine learning model designed to predict mortality for Medicare beneficiaries aged >65 years treated for hip fracture in Inpatient Rehabilitation Facilities (IRFs).DesignRetrospective design/cohort analysis of Centers for Medicare & Medicaid Services Inpatient Rehabilitation Facility–Patient Assessment Instrument data.Setting and ParticipantsA total of 17,140 persons admitted to Medicare-certified IRFs in 2015 following hospitalization for hip fracture.MeasuresPatient characteristics include sociodemographic (age, gender, race, and social support) and clinical factors (functional status at admission, chronic conditions) and IRF length of stay. Outcomes were 30-day and 1-year all-cause mortality. We trained and evaluated 2 classification models, logistic regression and a multilayer perceptron (MLP), to predict the probability of 30-day and 1-year mortality and evaluated the calibration, discrimination, and precision of the models.ResultsFor 30-day mortality, MLP performed well [acc = 0.74, area under the receiver operating characteristic curve (AUROC) = 0.76, avg prec = 0.10, slope = 1.14] as did logistic regression (acc = 0.78, AUROC = 0.76, avg prec = 0.09, slope = 1.20). For 1-year mortality, the performances were similar for both MLP (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.96) and logistic regression (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.95).Conclusion and ImplicationsA scoring system based on logistic regression may be more feasible to run in current electronic medical records. But MLP models may reduce cognitive burden and increase ability to calibrate to local data, yielding clinical specificity in mortality prediction so that palliative care resources may be allocated more effectively.     

社区卫生服务信息系统之健康档案研究

建立一套标准、规范、电子化的城市社区家庭个人健康档案模式及可接通互联网络的电脑管理信息系统,为社区工医生提供完整的、系统的居民健康状况数据,是社区医生掌握居民健康状况的基本工具,进行社区诊断的主要依据,是进行社区卫生管理的重要前提,也是我国卫生事业发展必然趋势。     

地段医院转为社区卫生服务中心后的工作思路

论述了地段医院转为社区卫生服务中心后的工作思路:适应形势,转变观念,将工作重点放在加快硬件建设,强化人才培养,进行科室重组。同时还要合理设置社区卫生服务点积极开设家庭病床,实行上门服务,推广户籍医生制度,逐步建立家庭健康基础档案。     

Measuring quality and outcomes in intensive care

While quality measures are integral to the maintenance of a high standard of patient care, high-quality care remains a complicated concept to define in the context of acute care. In this article we explore how quality can be measured in the intensive care unit. Standard outcome metrics such as mortality are tangible comparators, but do not offer a comprehensive assessment of quality for the complex heterogeneity of the intensive care population. We explore the Donabedian model as a means to describe the importance of outcomes, processes, structure and environment to inform the measurement of quality. These concepts can be more abstract and difficult to measure but can provide significant insight into the culture of a unit and the resulting performance, and thus provide a more comprehensive measure of quality.