Biomedical subjects
Publications and source records attributed to J E Berger.
Employers, insurers, and other purchasers of health care services collect data to profile the practice habits of pediatricians and other physicians. This policy statement delineates a series of recommendations that should be adopted by health care purchasers to guide the development and implementation of physician profiling systems.
Pediatricians and pediatric medical and surgical subspecialists should know their legal responsibilities to protect the privacy of identifiable patient health information. Although paper and electronic medical records have the same privacy standards, health data that are stored or transmitted electronically are vulnerable to unique security breaches. This statement describes the privacy and confidentiality needs and rights of pediatric patients and suggests appropriate security strategies to deter unauthorized access and inappropriate use of patient data. Limitations to physician liability are discussed for transferred data. Any new standards for patient privacy and confidentiality must balance the health needs of the community and the rights of the patient without compromising the ability of pediatricians to provide quality care.
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Homozygous mice with a null mutation in the MMP-9/gelatinase B gene exhibit an abnormal pattern of skeletal growth plate vascularization and ossification. Although hypertrophic chondrocytes develop normally, apoptosis, vascularization, and ossification are delayed, resulting in progressive lengthening of the growth plate to about eight times normal. After 3 weeks postnatal, aberrant apoptosis, vascularization, and ossification compensate to remodel the enlarged growth plate and ultimately produce an axial skeleton of normal appearance. Transplantation of wild-type bone marrow cells rescues vascularization and ossification in gelatinase B-null growth plates, indicating that these processes are mediated by gelatinase B-expressing cells of bone marrow origin, designated chondroclasts. Growth plates from gelatinase B-null mice in culture show a delayed release of an angiogenic activator, establishing a role for this proteinase in controlling angiogenesis.
The mammalian lung develops through branching morphogenesis which is controlled by growth factors, hormones, and extracellular matrix proteins. We have evaluated the role of EGF-receptor signaling in lung morphogenesis by analyzing the developmental phenotype of lungs in mice with an inactivated the EGF-receptor gene both in vivo and in organ culture. Neonatal EGF-receptor-deficient mice often show evidence of lung immaturity which can result in visible respiratory distress. The lungs of these mutant mice had impaired branching and deficient alveolization and septation, resulting in a 50% reduction in alveolar volume and, thus, a markedly reduced surface for gas exchange. The EGF-receptor inactivation also resulted in type II pneumocyte immaturity, which was apparent from their increased glycogen content and a reduced number of lamellar bodies. The defective branching was already evident at Day 12 of embryonic development. When explants of embryonic lungs from Day 12 embryos were cultured under defined conditions, the branching defect in EGF-receptor-deficient lungs was even more pronounced, with only half as many terminal buds as normal lungs. EGF treatment stimulated the expression of surfactant protein C and thyroid transcription factor-1 in cultured normal lungs, but not in EGF-receptor-deficient lungs, suggesting that EGF-receptor signaling regulates the expression of these marker genes during type II pneumocyte maturation. Taken together, our data indicate that signal transduction through the EGF receptor plays a major role in lung development and that its inactivation leads to a respiratory distress-like syndrome.
The activity of LY288513, an investigational cholecystokinin (CCK)B antagonist, was evaluated in a wide range of pharmacological tests in mice and rats. The anxiolytic benzodiazepine, diazepam, served as a reference standard for LY288513 in many of the tests. In the elevated plus-maze, LY288513 (3, 10 mg/kg, IP; 10, 30 mg/kg, PO) produced an anxiolytic-like action in mice with a magnitude of effect similar to that of diazepam. However, unlike diazepam, LY288513 produced no overt clinical signs and did not affect muscle tone, neuromuscular coordination, or sensorimotor reactivity. Also, in contrast to diazepam, LY288513 did not produce changes in the thresholds for electroshock- or pentylenetetrazol-induced convulsions. High doses of LY288513 (1000 mg/kg, PO) were required to reduce spontaneous activity levels, decrease body temperature, or potentiate the CNS-depressant effects of hexobarbital. LY288513 had no analgesic activity in mouse writhing or tail-flick tests. Electrophysiological studies in anesthetized rats showed that acute administration of LY288513 decreased the number of spontaneously active dopamine neurons in the substantia nigra and ventral tegmental area. However, LY288513 did not produce catalepsy. These data indicate that LY288513 possess both anxiolytic and antipsychotic potential.
Since the discovery that epidermal growth factor (EGF) can accelerate opening of the eyelids, the EGF receptor (EGF-R) has been extensively studied and is now considered to be a prototype tyrosine kinase receptor. Binding of EGF or of transforming growth factor-alpha (TGF-alpha) or other related factors activates the receptor and induces cell proliferation and differentiation. Although it is not found on haematopoietic cells, the EGF-R is widely expressed in mammals and has been implicated in various stages of embryonic development. Here we investigate the developmental and physiological roles of this receptor and its ligands by inactivating the gene encoding EGF-R. We find that EGF-R-/- mice survive for up to 8 days after birth and suffer from impaired epithelial development in several organs, including skin, lung and gastrointestinal tract.
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In order to explore the potential clinical utility of CCK-B antagonists for the treatment of benzodiazepine withdrawal symptoms, the auditory startle reflex was examined in rats undergoing withdrawal from the chronic administration of diazepam. Animals were exposed to diazepam continuously for 12 days (20 mg kg-1 per day) via osmotic minipumps. After 12 days the pumps were removed and the animals were allowed to go through spontaneous withdrawal for 4 days. Acute pretreatment with either diazepam or the selective CCK-B antagonist LY288513 dose-dependently blocked withdrawal-induced increases in the auditory startle response. These results support the hypothesis that the selective CCK-B antagonist LY288513 may be an effective treatment for alleviating at least some benzodiazepine withdrawal symptoms in man.
1. Several selective and non-selective muscarinic agonists (McN-A-343, RS-86, arecoline, oxotremorine-M, pilocarpine, cis-dioxolane, and acetylcholine) were examined for relaxant activity in the isolated guinea-pig ileum at pharmacologically low concentrations. 2. The concentrations studied include: 1 x 10(-12) M, 3 x 10(-12) M, 1 x 10(-11) M, 3 x 10(-11) M and 1 x 10(-10) M. 3. None of the compounds exhibited relaxant activity in both the field and non-field stimulated ileum. 4. All of the above compounds exert muscarinic agonist activity in a concentration range of 1 x 10(-9) M to 1 x 10(-6) M (Williams et al., 1992). 5. Thus, in the isolated guinea-pig ileum, muscarinic agonists do not exert relaxant activity of the gastrointestinal tract at low concentrations.
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An electron microscope study is reported of structural changes during ATP-induced contraction of glycerinated rabbit psoas. In the absence of ATP, A-band length is constant at sarcomere lengths above 1.9 micron, with average length of 1.54 mu. In ATP-treated fibers, A-band length is also constant at sarcomere lengths above 2.0 microns, but the apparent length of A-band decreases to approximately 1.3 micron, as sarcomere length decreases from 1.9 micron to 1.5 mu. The occurrence of short A-bands cannot be attributed to crumpling of thick filaments against Z-lines, since I-bands remain patent; nor to the presence of heterogeneous filaments, since resting muscle does not show comparable heterogeneity, nor to compressive artifacts, which are minor when knife edge is oriented parallel with fiber axis during microtomy . The decrease of A-band length appears related, at least in part, to disarray of terminal cross-bridges as the thick filaments encroach upon the N-line, a structure which becomes evident within the I-band during contraction of glycerinated fibers. In preliminary studies, optical transforms of A-bands from individual sarcomeres reveal a characteristic myosin layer-line pattern as low as 1.5 micron sarcomere length. A cross-bridge repeat of 143 A is obtained for sarcomeres above 1.6 micron length; however, an appreciable proportion of sarcomeres in the range from 1.5 micron to 1.9 mu length generate meridional reflections less than 143 A, and as low as 130 A.
One specific concern that has received public attention in recent times is the possible risk of cancer from exposure to industrial chemicals. Although it is not known presently how much cancer is caused by exposure to chemicals from industry, and although the amount is believed by many to be low, responsible corporate actions to reduce the threat of industrially related cancer must be a part of daily business. Even though the personal and emotional impacts of cancer pose a great difficulty in dealing with its risk, if we take a realistic view, it is possible to place the risk into a more manageable perspective and thereby not impede our efforts toward abating it. To that end, we have developed a four stage process for making decisions about cancer risk and actions to reduce it, together with a system for classifying risks as "high," or "low," or "insignificant." The four stages are: hazard identification, hazard evaluation, risk evaluation and risk response. A proper understanding and use of this systematic process by legislative and regulatory bodies could lead to more rational decisions about how to best allocate society's finite resources so as to reduce cancer risks as soon as possible for the largest number of people. Use of this process will also accelerate the handling of the most significant risks first and, until our complex societal mechanisms move to determine what is acceptable risk, it will give us in industry a means for setting priorities and moving in a clearly desirable direction.
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Group practices need to be wary of assuming that the anticipated surplus of physicians will make recruiting any easier. Problems previously associated with candidate identification will give way to how to best manage the screening, interviewing and evaluation of prospective candidates. Furthermore, increasing numbers of physicians competing for patients in the medical care marketplace will pose a direct threat to established groups. This is already occurring in many areas of the country. A recent example of this is occurring with an 85-person multispecialty group in a city of 120,000 with a service of 220,000. A nearby town of 50,000 with a 200-bed hospital is actively recruiting its own physicians. The result will be a steadily eroding referral base for the large multispecialty group over the next five years.
Although gasoline blending streams exhibit widely varying sulfur concentrations, significant quantities of low-sulfur motor gasoline cannot be manufactured by reallocation of existing components without substantial sacrifices in the useful properties of the remaining fuels having normal sulfur levels. To meet the anticipated demand for low-sulfur unleaded gasoline which may be required for catalyst-equipped automobiles it will be necessary to install process equipment based on known hydrotreating technology. The effects which this construction program would exert on the activities, abilities and needs of one petroleum refiner are sketched for two degrees of sulfur removal. The impacts of installing the process facilities which would be necessary are discussed in terms of time requirements, capital needs, and added energy expenditures.
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