Cerebral circulation revisited: an historical essay.

Three centuries of investigations relevant to cerebral circulation, from the discoveries of circulation by Harvey (1628) and Willis (1664) to the 2-deoxyglucose methods of Sokoloff (1977), have been surveyed. Perspective is provided from discussion of such developments as: the discovery of oxygen and its role in combustion, respiration and cellular metabolism; recognition of the blood-brain barrier especially as selective exchange transport systems; introduction of the concept of metabolism and elucidation of details of glycolysis and oxidative phosphorylation; the discovery of neurotransmitters and an understanding of the ionic bases for conduction and neural activity; and introduction of modern techniques for studying cerebral circulation and metabolism, specifically, the Kety-Schmidt N2O method and the Sokoloff [14C]deoxyglucose autoradiographic method for regional and local applications, with subsequent adaptation to PET studies in situ.

Faculty practice plans: the organization and characteristics of academic medical practice.

The contemporary academic medical center is a complex organization providing medical and other professional health education, biomedical and behavioral research, and a comprehensive range of patient care services. This paper presents data from the Association of American Medical Colleges' 1989 survey of 125 member faculty practice plans. The survey data showed that 62% of the 74 responding plans were units or associations within the medical school corporate structure. Plans were organized along a broad continuum from the autonomous, departmental model with decentralized governance and management to the group model with centralized governance and management. The growth of managed care, increased competition, and a greater reliance by the medical school on clinical practice income as a financing source are causing the practice plan to expand beyond billing of professional fees. The survey data showed that 75% of the practice plans operated satellite centers, and 61% planned to build new ambulatory care facilities in order to expand and improve services to patients. The practice plans also have adapted to changes in third-party reimbursement and are establishing mechanisms to negotiate managed care contracts involving multiple clinical departments to increase referrals and maintain patient shares; 86% of the plans participate in at least one managed-care organization. The role of the practice plan will continue to evolve in response to the needs of the academic medical center for a cooperative and supportive environment in which to conduct its traditional missions of teaching, research, and patient care.

The impact of the NINCDS on the neurosciences: an essay written for the centennial of the NIH.

This essay, written as a contribution to the June 1987 participation by the NINCDS in the celebration of the centennial of the NIH (dated from the founding of the Hygienic Laboratory at Staten Island in 1887), discusses the impact of the NINDB/NINCDS on the neurosciences. Contrasts are drawn with the status of basic and clinical neurosciences in the late 19th century and prior to 1950, when the NINDB was established. This impact has involved its role as advocate and focal point for the support of research and research training in the neurosciences; the training of research and academic personnel and the funding of research projects, both significant factors in the postwar proliferation of methods and technologies; and the catalyzing of the steady progress in scientific knowledge, as reflected in examples from various facets of the programs of the neurological institute, in a continuum from the very basic and fundamental to the very clinical and pathological neurosciences.

The American Society for Neurochemistry (ASN): antecedents, founding, and early years.

Events leading to and the influences on the founding of the American Society for Neurochemistry are recounted, with emphasis on early activities of neurochemists in the United States, as well as the international activities, that led to the founding of both the International and American societies (in 1965 and 1969, respectively). The founding of the American Society for Neurochemistry in the period 1968-1969 and its first annual meeting in 1970 are described, together with significant developments during the early years of the Society.

Impressions of neurology and neurosurgery in the People's Republic of China.

During July, 1979, the authors visited the neurological and neurosurgical services of eight major hospitals and associated medical schools in Peking, Tientsin, and Shanghai, and viewed many of their teaching and research facilities. From these visits and our discussions with the staffs of these units, we came away with the impressions reported here. In the People's Republic of China today there are more than 2,000 neurologists and 1,300 neurosurgeons. At present there are two major clinical centers: the Peking Institute of Neurosurgery, directed by Prof Wang Chung-Cheng and located in the Xuan Wu Hospital affiliated with the Peking First Medical College; and the Shanghai Institute of Neurology, directed by Prof Chang Yuan-Cheng and located in the Hua San Hospital affiliated with the Shanghai First Medical College. In every hospital, patient loads are formidable (e.g., several thousand outpatients weekly), but the variety of clinical problems does not differ from those seen elsewhere in the world. The most common problems are head injuries, brain tumors, cerebrovascular disorders, infections, and epilepsy. Each of the centers is heavily engaged in undergraduate and postgraduate training, and research has been resumed after the major disruptions of the 1966-76 "Cultural Revolution." Research continues on acupuncture, but present emphasis is directed toward pain mechanisms, notably at the Shanghai Institute of Physiology, directed by Prof Feng De-Pei. We were most impressed by this, the principal neurophysiology and neuroscience research center in the country. Clearly, the People's Republic of China has a wealth of clinical material and many competent neurologists and neurosurgeons with stimulating research ideas-characteristics which offer real potentials for collaborative research.

Inhibition of renal tubular transport of methotrexate by probenecid.

The mechanism of excretion of methotrexate (MTX) has been investigated in the monkey. Under steady-state conditions of varied plasma levels of MTX, it was determined that MTX was excreted by renal tubular transport as well as by glomerular filtration. The maximum rate of renal tubular transport of MTX (81 mug/min) was attained at plasma levels of MTX from 6 to 8 mug/ml. Correspondingly, the rate of clearance of MTX from plasma was shown to diminish from a value that was 3-fold greater than the glomerular filtration rate at plasma levels of MTX from 6 to 32 mug/ml. Pretreatment of animals with probenecid (700 mg/sq m) totally inhibited renal tubular transport of MTX when MTX was administered in doses from 1.8 to 621 mg/sq m. Following inhibition of renal tubular transport of MTX by probenecid, steady-state plasma levels of MTX in animals pretreated with probenecid (700 mg/sq m) was reduced by a factor of 2.6 from values determined in non-probenecid-pretreated control animals receiving similar varied doses of MTX (1.8 P to greater than 600 mg/sq m). The mode of i.v. injection of MTX was seen to effect the concentration of MTX in plasma. Initial loading followed by continuous sustaining infusion of MTX provided stable and higher levels of MTX in plasma than was determined in controls or in experimental animals pretreated with probenecid and receiving identical doses of MTX by single bolus injection.