GABA immunoreactive axons and growth cones in the developing chicken optic nerve and tract.

Immunohistochemical studies of the chicken embryo optic tract using an antibody to gamma-aminobutyric acid (GABA) reveal that the tract is initially free of GABA immunoreactive axons. During the second week of incubation, GABA+ axons appear in the tract, chiasm, and optic nerve. The number of GABA+ axons in the optic nerve increases through E18, although few are recognizable after hatching. Detailed staining of GABA+ growth cones confirmed that virtually all the GABA+ axons in the optic nerve were growing toward the retina. Taken together, the findings suggest that the GABA+ axons in the chiasm and nerve are largely a transient extension of the GABA+ optic tract cells, the tectogeniculate projection, or both.     

Association of ambient air‐pollution levels with acute asthma exacerbation among children in Singapore

BACKGROUND: Air-pollution levels have been shown to be associated with increased morbidity of respiratory diseases. METHODS: Data for ambient air-pollutant levels, meteorologic factors, and hospitalization or emergency room (ER) visits for acute asthma in Singapore children over a 5-year period (1990-4) were obtained and analyzed for associations by time-series methods. RESULTS: Throughout this period, the annual mean and 24-h mean levels for sulfur dioxide (SO2), nitrogen dioxide (NO2), and total suspended particles (TSP) and maximum 1-h daily average for ozone were generally within the air-quality guidelines established by the World Health Organization (WHO). However, positive correlation between levels of each of these pollutants and daily ER visits for asthma was observed in children aged 3-12 years, but not among adolescents and young adults (13-21 years old). The association with SO2 and TSP persisted after standardization for meteorologic and temporal variables. An adjusted increase in 2.9 ER visits for every 20 microg/m3 increase in atmospheric SO2 levels, lagged by 1 day, was observed on days when levels were above 68 microg/m3. With TSP, an adjusted increase of 5.80 ER visits for every 20 microg/m3 increase in its daily atmospheric levels, lagged by 1 day, was observed on days with levels above 73 microg/m3. Similar results were also obtained after controlling for autocorrelation by time-series analysis. CONCLUSIONS: These associations were observed even though the overall levels of all pollutants were generally within the air-quality guidelines established by the WHO. These findings suggest that asthmatic children are susceptible to increased levels of air pollutants, particularly SO2 and TSP, although the ambient levels are generally within "acceptable" ranges.     

Testing of a medical linear accelerator's computer-control system

In August of 1987, the Radiation Oncology Center at the Mallinckrodt Institute of Radiology became the first academic-medical-center user of Varian's computer-controlled therapy accelerator, a prototype version of the 2100C. Installation was accomplished by the retrofit of a computer system to our two-year-old Clinac 1800. Being well aware of the malfunctions that occurred in other computer-controlled accelerators, we took extraordinary measures to assure proper operation of the new, computerized, system. Our acceptance procedure included tests of (i) mechanical systems (isocentricity, digital readouts, etc.); (ii) radiation parameters (flatness, symmetry, output, etc.); (iii) manual safety systems (emergency off switches, etc.); (iv) the computer console systems (communications integrity, state integrity, etc.); and (v) the interlock systems (some 50 electrical, mechanical, and/or computer-controlled interlocks). As items (i), (ii), and (iii) do not differ significantly from the tests for a non-computer-controlled machine, they will not be discussed here. Rather, this report will concentrate on the methods that were devised to test the computer-control and interlock systems.     

Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast

Zafirlukast is a cysteinyl leukotriene antagonist used to treat allergic and exercise-induced asthma. This in vitro study used human liver microsomes to evaluate the inhibitory activity of zafirlukast versus six human cytochrome P450 (CYP) isoforms. Zafirlukast (0-250 microM) was co-incubated with fixed concentrations of index substrates. Zafirlukast inhibited the hydroxylation of tolbutamide (CYP2C9; mean IC(50)=7.0 microM), triazolam (CYP3A; IC(50)=20.9 microM) and S-mephenytoin (CYP2C19; IC(50)=32.7 microM), and was a less potent inhibitor of phenacetin O-deethylation (CYP1A2; IC(50)=56 microM) and dextromethorphan O-demethylation (CYP2D6; IC(50)=116 microM). Zafirlukast produced negligible inhibition of CYP2E1. In vitro inhibition of CYP2C9 by zafirlukast is consistent with clinical studies showing impaired clearance of S-warfarin and enhanced anti-thrombotic effects, although the in vitro IC(50) value is higher than the usual range of clinically relevant plasma concentrations. Zafirlukast deserves further clinical study as an inhibitor of other CYP2C9 substrates such as nonsteroidal anti-inflammatory agents, tolbutamide, phenytoin and mestranol. Clinically important inhibition by zafirlukast of other CYP isoforms is not established.     

Survival and developmental disability in infants with birth weights of 501 to 800 grams, born between 1979 and 1994

OBJECTIVE: Because the survival rate has increased for extremely low birth weight neonates, many have raised the concern that the rate of developmental disability among survivors will also increase. To address this concern, we analyzed changes over time in survival and major neurosensory impairment in a sample of extremely low birth weight infants born between July 1, 1979, and June 30, 1994. METHODS: The study sample included 513 infants with birth weights of 501 to 800 g who were cared for in either of the two neonatal intensive care units that serve a 17-county region in northwest North Carolina and who were born to mothers residing in that region. At 1 year of age (corrected for gestation), survivors were examined by a pediatrician and were tested using the Bayley Scales of Infant Development. Major neurosensory impairment was defined as cerebral palsy, a Bayley Mental Developmental Index <68, or blindness. A total of 209/216 (97%) of survivors were examined at 1 year of age. Epoch of birth was defined as follows: epoch 1, July 1, 1979 to June 30, 1984; epoch 2, July 1, 1984 to June 30, 1989; and epoch 3, July 1, 1989 to June 30, 1994. RESULTS: Survival rates for epochs 1, 2, and 3 were, respectively, 24/120 (20%), 63/175 (36%), and 129/218 (59%). In contrast, the proportions with a major neurosensory impairment did not increase over time; rates for successive epochs were 6/24 (25%), 17/61 (28%), and 26/124 (21%). Rates of cerebral palsy were 3/24 (13%), 12/61 (20%), and 9/124 (7%); rates of delayed mental development were 4/24 (17%), 12/61 (20%), and 17/124 (14%); and rates of blindness were 2/24 (8%), 0/62, and 5/124 (4%), respectively. CONCLUSIONS: This analysis suggests that the increasing survival of extremely low birth weight neonates since the late 1970s has not resulted in an increased rate of major developmental problems identifiable at 1 year of age.