Haemoglobin adducts from isoprene and isoprene monoepoxides.

1. Isoprene is metabolised in vitro by oxygenation of either double bond to 2-ethenyl-2-methyloxirane (epoxide A) and 2-(1'-methylethenyl)oxirane (epoxide B). The reactivity in vitro and formation in vivo of the monoepoxides of isoprene were studied by the formation of adducts to N-terminal valines in haemoglobin (Hb). These adducts were analysed by mass spectrometry after cleavage and derivatization by a modified Edman degradation method. 2. When red blood cells were incubated with commercial isoprene oxide (about 95% epoxide A, < or = 5% epoxide B) adducts from both epoxides were formed. 3. It is confirmed that epoxide A is hydrolysed much faster than epoxide B. The rates are enhanced by phosphate buffer (epoxide A), probably through acid catalysis, and by the presence of red blood cells (both epoxides), due to enzymatic detoxification. 4. Comparison of total valine adduct levels in Hb from isoprene and isoprene oxide injected i.p. led to the conclusion that 23 and 1% of injected isoprene was metabolized to the epoxides in mouse and rat, respectively.

Species differences in the stereochemistry of the metabolism of isoprene in vitro.

1. Comparative studies on the stereochemistry of the metabolism of isoprene in vitro have been carried out using liver microsomes from rats, mice, monkeys, dogs, rabbits and humans. Differences between strains and gender were also investigated. 2. In the production of the isoprene monoepoxides, microsomes from the livers of the male Sprague-Dawley or Wistar rat showed an approximately 2:1 preference for the formation of (S)-2-(1-methylethenyl)oxirane compared with the (R)-enantiomer. No enantioselectivity was observed for mouse or rabbit. In contrast, liver microsomes from dog, monkey or male human preferentially formed (R)-2-(1-methylethenyl)oxirane. There was no enantioselectivity observed with microsomes from female human liver. 3. The significant differences between species in the in vitro metabolism of isoprene indicate that stereochemical and mechanistic data should be taken into account when evaluating the results of animal studies designed to assess the carcinogenic risks to humans that may be associated with exposure to isoprene.

Studies on the molecular toxicology of buta-1,3-diene and isoprene epoxides.

Reactions of ethenyloxirane with amino (RNH2) and thiol (R'SH) nucleophiles occur by an SN2 mechanism involving competing ring cleavage at C-2 and C-3. In contrast, 2-ethenyl-2-methyloxirane reacts with amino (RNH2) and thiolate (R'S-) nucleophiles in methanol by regioselective SN2 attack at C-3 ("neo-pentyl" position). However, in pure water or methanol SN1 reaction occurs mainly at C-2.

Fuel loads in U.S. cities.

Sources of burnable material within U.S. cities are analyzed. Based on a detailed evaluation of construction practices, storage of burnable contents, building function and layout, and density of buildings in city districts, we derive urban fuel load densities in terms of land use type and geographic location. Residential building fuel loads vary regionally from 123 to 150 kg m-2; nonresidential building classes have loads from 39 to 273 kg m-2. The results indicate that average U.S. urban area fuel loads range from 14 to 21 kg m-2.

Pharmacokinetic evaluation of stable piecewise cubic polynomials as numerical integration functions.

A numerical integration method based on piecewise cubic polynomial for computing the area under the curve in pharmacokinetics is presented. The method has been found to produce stable and monotone interpolations irrespective of experimental error. Spurious oscillations occasionally associated with cubic splines are eliminated. Comparisons with the previously available methods suggest that more reliable and less biased areas under the plasma concentration curve, AUC, or areas under the first moment of plasma curve, AUMC, can be generated by the present method.

Epidemiologic programs for computers and calculators. Exact binomial confidence intervals for the relative risk in follow-up studies with sparsely stratified incidence density data.

The authors present a computer program for hypothesis testing and calculation of exact binomial confidence intervals for the adjusted relative risk in follow-up studies involving multiple strata with incidence density (person-time) denominators and small or zero person-count numerators. The program is an extension to multiple tables of a single-table method by Rothman and Boice (NIH publication no. 79-1649, Washington, DC: US GPO, 1979) and represents a counterpart for person-time denominators to the program of Thomas (Comput Biomed Res 1975;8:423-46) for exact analysis of multiple tables with person-count denominators. Comparisons with asymptotic analyses of real and simulated data are given. Copies of the program are available from the authors on request.

Tests of significance using regression models for ordered categorical data.

Regression models of the type proposed by McCullagh (1980, Journal of the Royal Statistical Society, Series B 42, 109-142) are a general and powerful method of analyzing ordered categorical responses, assuming categorization of an (unknown) continuous response of a specified distribution type. Tests of significance with these models are generally based on likelihood-ratio statistics that have asymptotic chi 2 distributions; therefore, investigators with small data sets may be concerned with the small-sample behavior of these tests. In a Monte Carlo sampling study, significance tests based on the ordinal model are found to be powerful, but a modified test procedure (using an F distribution with a finite number of degrees of freedom for the denominator) is suggested such that the empirical significance level agrees more closely with the nominal significance level in small-sample situations. We also discuss the parallels between an ordinal regression model assuming underlying normality and conventional multiple regression. We illustrate the model with two data sets: one from a study investigating the relationship between phosphorus in soil and plant-available phosphorus in corn grown in that soil, and the other from a clinical trial comparing analgesic drugs.

Reimplantation in infection. Elution of gentamicin from cement and beads.

A prospective study was performed to evaluate the arthroplasty fluid, serum, and urine antibiotic levels in 38 patients implanted with gentamicin-impregnated cement and in 18 patients with gentamicin-impregnated beads. Radioimmune assays were performed on arthroplasty fluid, serum, and urine samples at various times after surgery. On day 1, high arthroplasty fluid levels of gentamicin were eluted from bead-implanted patients (mean, 36.9 micrograms/ml; range, 19.6-69.5) and cement-implanted patients (mean, 14.9 micrograms/ml; range, 2.7-38.9) with very low serum and urine levels. The arthroplasty levels of gentamicin obtained in bead-implanted patients on day 1 were 17 times higher, and in cement-implanted patients, seven times higher, than those obtained with intravenous administration of gentamicin. The serum and urine levels were approximately ten to 20 times less in patients with gentamicin-impregnated cement or beads compared to those levels obtained after intravenous administration. These very low systemic levels should preclude nephrotoxic and ototoxic effects. No toxic effects were observed in these patients. Bioactivity of gentamicin in the specimens was confirmed. Staphylococci were exquisitely sensitive, while Streptococci were moderately resistant to gentamicin. Both gentamicin-impregnated beads and cement appear safe and provide substantial local in vivo antibacterial activity.

The CAD hip arthroplasty. Five to ten-year follow-up.

One hundred and fourteen total hip arthroplasties in 100 patients were performed using the CAD (computer-assisted design) prosthesis at The Hospital for Special Surgery between 1975 and 1977. Sixty-one of these patients (seventy-four hips) have been followed both clinically and radiographically for a minimum of five years (average, 7.1 years). While no hip required revision before five years, seven hips were revised between six and ten years postoperatively. Ten hips had an excellent result; forty-eight, good; eight, fair; and one, poor. Radiographic analysis revealed narrowing of the cortex of the bone medially at the region of the proximal part of the stem in the hips that were operated on as compared with the contralateral side that was not operated on. Nine hips (12 per cent) had one to two-millimeter radiolucent lines at the femoral bone-cement interface, and in five the lines were progressive. Fourteen hips (19 per cent) had radiolucent lines at the femoral bone-cement interface with a maximum width of 0.5 millimeter. Thirty-four (42 per cent) had more than three millimeters of resorption of the calcar or superomedial cyst formation. Survivorship analysis of the prosthesis predicted a 77 per cent survival rate at nine years. None of the prosthetic stems fractured despite the fact that the population was young, active, heavy, and predominantly male. The incidence of calcar resorption, however, was higher than in other studies. Thus, while the revision rate compared favorably with that of similar studies using other stem designs, compromise of the bone stock of the proximal end of the femur may be a significant disadvantage of this type of prosthesis.

Smoke production from multiple nuclear explosions in nonurban areas.

The amount of smoke that may be produced by wildland or rural fires as a consequence of a large-scale nuclear exchange is estimated. The calculation is based on a compilation of rural military facilities, identified from a wide variety of unclassified sources, together with data on their geographic positions, surrounding vegetation (fuel), and weather conditions. The ignition area (corrected for fuel moisture) and the amount of fire spread are used to calculate the smoke production. The results show a substantially lower estimated smoke production (from wildland fires) than in earlier "nuclear winter" studies. The amount varies seasonally and at its peak is less by an order of magnitude than the estimated threshold level necessary for a major attenuation of solar radiation.

Group B streptococcal arthritis in adults.

Group B streptococcal arthritis in adults is uncommon. This report describes seven cases seen at these institutions over the past five years and reviews the previous 17 documented cases. Of seven adults, three were diabetics, three had prosthetic hips, and one had undergone splenectomy. Six had undergone no prior dental, genitourinary, or gastrointestinal procedures. The most common clinical presentation was fever and acute joint pain. Five patients had monoarticular arthritis; two had multiple joint involvement. Underlying joint abnormalities included osteoarthritis (two), prosthetic hip (three), and neuropathic joint (one). Bacteremia was documented in three and suspected in the remaining four patients, often without a primary source. Therapy included parenteral antibiotics, usually penicillin G, and drainage of the involved joint. Two of three patients with prosthetic implants required Girdlestone procedures; the third was apparently cured. The three diabetic patients died, one with resolution of group B streptococcal arthritis. The seventh patient was cured. Group B streptococcal arthritis is a serious infection in adults with diabetes and late prosthetic hip infections.

Boundary layer effects in optical measurements in gas dynamics.

A method for including three-dimensional boundary corrections in the analysis of interferograms of two-dimensional flows is described. An effective optical pathlength is calculated using a displacement thickness concept. Expressions and methods for determining the correction to the optical pathlength are given for laminar and turbulent boundary layers in isoenergetic or diabatic flow. An exact expression is derived for the turbulent case and results given showing the correction to be of the order of 10%.

Single beam schlieren interferometer using a wollaston prism.

A standard single pass schlieren system was converted into a single beam schlieren interferometer by replacing the knife edge with a polarizer-Wollaston prism-analyzer combination. The system is described and an analysis given that relates the fringe shifts on the interferogram to density changes in the test section. The proper location of the density difference is discussed.A complex gas dynamic flow field was investigated with this interferometer, and the results were shown to compare well with theoretical predictions.