Refuse incinerator particulate emissions and combustion residues for New York City during the 20th century.

Refuse incineration data for New York City (NYC) have been compiled as a function of time during the 20th century to assess the historical significance of this pollutant source in a densely populated area. Thirty-two municipal and 17,000 apartment house refuse incinerators were identified. Approximately 1.1 x 10(8) t of refuse (wet weight) were combusted in NYC incinerators between 1908 and 1993, producing 3.4 x 10(7) t(dryweight) of combustion residue disposed in local landfills. Refuse incinerators were operated for most of this period without air pollution control and emitted 1.0 x 10(6) t of particles (a total of 120 mg for each cm2 of land in NYC). Incinerator particle emission (PE) rates per unit area of land were highest in Manhattan (equivalent total deposition of 530 mg cm(-2)). Incinerator PE exceeded 1.2 x 10(4) t yr(-1) between 1930 and 1975, with maximum emission rates (>2.2 x 10(4) t yr(-1)) in the late 1930s and 1960s. These and other factors support the conclusion that refuse incineration without air pollution control was an important source of airborne, respirable pollutants in NYC for many decades during the 20th century. Rates of particle emissions from Manhattan incinerators estimated here correlate stronglywith Pb accumulation rates as a function of depth (time) in Central Park Lake sediments, consistent with refuse incineration emitting large amounts of atmospheric lead in NYC for many decades afterthe 1920s.

Effect of topically applied evening primrose oil on epidermal barrier function in atopic dermatitis as a function of vehicle.

The aim of this study was to establish the effect on barrier function in atopic dermatitis of topical evening primrose oil in an amphiphilic and a stable water-in-oil emulsion. The studies were vehicle-controlled in two populations of 20 atopic subjects. Barrier function was assessed in terms of transepidermal water loss and stratum corneum hydration after a 4-week treatment period and a 1-week treatment-free period. A barrier function test with sodium lauryl sulphate (SLS) and nicotinic acid ester was also carried out. Evening primrose oil proved to have a stabilising effect on the stratum corneum barrier, but this was apparent only with the water-in-oil emulsion, not the amphiphilic emulsion. The choice of vehicle is therefore an extremely important factor in the efficacy of topically applied evening primrose oil.

Trends in chlorinated hydrocarbon levels in Hudson River basin sediments.

Analysis of sections from dated sediment cores were used to establish geographic distributions and temporal trends of chlorinated hydrocarbon contaminant levels in sediments from natural waters of the Hudson River basin. Radiometric dating was based primarily on the depth distribution of 137(Cs) in the cores and on the occurrence of detectable levels of 7(Be) in surface sediment samples. Eighteen sampling sites included several along the main stem of the Hudson, its major tributaries, and components of the New York/New Jersey (NY/NJ) harbor complex. Drinking-water reservoirs were sampled to place upper limits on atmospheric inputs. Core sections were analyzed for polychlorinated biphenyls (PCBs), 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane (DDT)-derived compounds, chlordane, and dioxins. Sediment concentrations of most contaminants at most sites have decreased significantly since the mid-1960s. The data provide a basinwide perspective on major point-source inputs of PCBs to the upper Hudson River and of 2,3,7,8-tetrachlorodibenzo-p-dioxin and DDT to the lower Passaic River. Evidence was found for significant but poorly characterized sources of PCBs and chlordane to the western NY/NJ harbor, and of highly chlorinated dioxins to the upstream sites on the main stem of the Hudson. The results indicate that analysis of dated sediment samples is a most effective and efficient monitoring tool for the study of large-scale geographic and temporal trends in levels of particle-associated contaminants.

Null alleles reveal novel requirements for Bic-D during Drosophila oogenesis and zygotic development.

In the Drosophila ovary, the Bicaudal-D (Bic-D) gene is required for the differentiation of one of 16 interconnected cystocyte sister cells into an oocyte. A new class of Bic-Dnull alleles reveals a novel requirement for Bic-D for zygotic viability. In the germ line, the null mutations show that developmental processes that take place in germarial region 1, even those that create asymmetry, are independent of Bic-D function. Bic-D is then required to establish oocyte identity in one cystocyte and is essential, not only for the oocyte-specific accumulation of all oocyte markers that we have tested so far, but also for the posterior migration of the oocyte. In addition, normal polarity amongst the nurse cells requires Bic-D, indicating that the creation of different nurse cell identities may depend on oocyte determination. Our results show that different processes in early oogenesis require different amounts of Bic-D in a process-specific way and certain later processes can proceed at low levels of Bic-D. This suggests that the patterning of the female germ line and the development of an oocyte depend on differential responses to a single activity that is capable of initiating distinct oogenesis processes and can establish different cell fates.

Determination of fluoxetine and norfluoxetine in human plasma by capillary gas chromatography with electron-capture detection.

A capillary gas chromatographic method with 63Ni electron-capture detection is reported for the determination of fluoxetine (Prozac) and its metabolite norfluoxetine in human plasma. A liquid-liquid extraction is used, followed by derivatization with heptafluorobutyric anhydride to increase the sensitivity of detection. A 30 m x 0.25 mm I.D. DB-17 capillary column resolves the compounds from endogenous matrix interferences. The limit of quantitation by this method is 5 ng/ml for each compound. Stability studies show that fluoxetine and norfluoxetine are stable in human plasma for up to 96 h at room temperature and up to one year at -20 degrees C.

New aspects in the staging of lung cancer. Prospective validation of the International Union Against Cancer TNM classification.

BACKGROUND AND METHODS: To validate the new TNM definitions for lung cancer (International Union Against Cancer [UICC] TNM classification, 4th edition, 1987), the data of 3823 patients were analyzed prospectively in terms of concordance between clinical (TNM) and pathologically confirmed classification (pTNM), the value of the various diagnostic techniques in estimating the pathologically confirmed classification, and the prognostic relevance of the new TNM definitions. RESULTS: With regard to the primary tumor (T), clinical and pathologic classifications were identical in 63%; with regard to lymph node involvement (N), the agreement was 47%; for distant metastasis agreement occurred in 91% of cases and for the stages it occurred in 56%. As to the primary tumor (T), the accuracy of radiography (59%) was nearly identical to that of computed tomography (CT) (58%). Both techniques were less precise in determining the extent of lymph node involvement (CT, correct assessments in 50%; radiography, correct assessments in 43%). The statistically significant differences in the prognosis for the T, N, and M categories and for the stages and the categories of the new R classification could be confirmed. Allowance should be made for the different prognosis between T1N0M0 and T2N0M0 by the new Substages IA and Ib of Stage I. CONCLUSIONS: By the new TNM definitions for bronchus carcinoma, international conformity became feasible and practical, and the improvement of its prognostic relevance provided a more reliable basis for establishing guidelines for individual oncologic concepts.

Sensitive method for the quantitation of nortriptyline and 10-hydroxynortriptyline in human plasma by capillary gas chromatography with electron-capture detection.

A method for the determination of nortriptyline and 10-hydroxynortriptyline concentrations in human plasma by capillary gas chromatography with electron-capture detection is described. The procedure requires 1.0 ml of plasma and uses maprotiline as an internal standard. The compounds are extracted from alkalinized plasma with hexane-2-butanol (98:2) and back-extracted into hydrochloric acid. The acid solution is then made basic and the compounds are re-extracted into n-butyl chloride. The extract is evaporated to dryness, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography on a fused-silica capillary column coated with phenylmethyl silicone. The calibration curves for nortriptyline and 10-hydroxynortriptyline are linear in the ranges 3-40 and 7-90 micrograms/l, respectively, with coefficients of variation for within-day and between-day precision of less than 12%. The quantitation limits for nortriptyline and 10-hydroxynortriptyline are 1 and 3 micrograms/l, respectively. This procedure was used to analyze more than 1400 samples following sub-therapeutic doses of nortriptyline in human subjects. The assay was sufficiently sensitive for use in pharmacokinetic analysis.

Chiral drugs: an industrial analytical perspective.

In the pharmaceutical industry, chiral drug candidates introduce a unique set of challenges to all disciplines involved in the drug development process. For the analytical chemist in particular, the generation of relevant information about a variety of stereoisomeric issues is necessary. Chiral drug candidates, whether a single isomer or a mixture of isomers, require more analytical information than achiral drug candidates. This information can be derived from enantioselective spectroscopic and chromatographic techniques. Chiral analytical methods require proper development and validation to ensure accurate results. Issues related to method development and validation for complete stereochemical characterization are discussed, with primary emphasis on the generation of analytical data required for the registration of a chiral drug candidate. The presentation of pertinent analytical data depends on an awareness of the problems encountered during the development process and the appropriate use of methodology for the determination of stereoisomeric purity.

Nizatidine disposition in subjects with normal and impaired renal function.

To test the hypothesis that renal insufficiency alters nizatidine disposition, we determined the pharmacokinetics of nizatidine and its major metabolite after a single oral dose in normal volunteers and patients with various degrees of renal dysfunction, after a single intravenous dose in normal volunteers and patients with severe renal failure and during hemodialysis. After intravenous administration the elimination half-life increased from 1.5 +/- 0.2 hours in normal volunteers to 6.9 +/- 3.3 hours in patients with renal failure. The plasma clearance decreased from 0.59 +/- 0.07 L/kg/hr in normal volunteers to 0.14 +/- 0.02 L/kg/hr in patients with renal failure. Nizatidine bioavailability was nearly 100% in normal volunteers but decreased to 75% in patients with renal failure. The volume of distribution was 1.3 +/- 0.1 L/kg in normal volunteers and was not different in patients with renal failure. Nizatidine protein binding was about 30% in normal and uremic plasma. The drug was not substantially removed by hemodialysis. Patients with creatinine clearances less than 50 ml/min/1.73 m2 should receive 150 mg nizatidine once each evening. Patients with creatinine clearances less than 20 ml/min/1.73 m2 should receive 150 mg nizatidine every other night.

Liquid chromatographic analysis of enviradene, a new antiviral agent, in plasma and its application in bioavailability studies in the dog.

A rapid and specific high-performance liquid chromatographic (HPLC) assay has been developed for the determination of enviradene, 1, at concentrations of 2-5 ng/mL in plasma. The drug was extracted from the samples using benzene. The benzene extract was evaporated and the residue dissolved in the mobile phase. The HPLC system consisted of a reversed-phase column and a 75% methanol:25% 0.2 M sodium acetate mobile phase. Either a UV detector set at 268 nm or an electrochemical (EC) detector set at a potential of +0.9 V (versus Ag/AgCl/3 M NaCl) was used to monitor the drug. A column-switching system was used to remove late-eluting plasma constituents that interfered in subsequent chromatograms. The limit of sensitivity was 2 ng/mL for the HPLC-EC procedure and 5 ng/mL for the HPLC-UV procedure. Recovery from plasma was approximately 97%; the procedure had a relative error of approximately 3% and a relative standard deviation of 4.5% over the range of 20-200 ng of 1/mL of plasma. Following intravenous administration of 1 or 2 mg/kg of 1 to dogs, the parent drug was quantitated in plasma for 24 h using this procedure. The terminal phase half-life in plasma was calculated to be 10 h. Oral administration to dogs of single 8 mg/kg doses of 1, formulated with povidone-30 or polysorbate 80 and microcrystalline cellulose, produced high and persistent plasma concentrations of drug. At doses below 2 mg/kg, plasma concentrations were found to be nonlinearly related to the amount of the dose administered. The bioavailability of the drug in dogs was found to be increased by the concomitant administration of food.

Determination of enviroxime in a variety of biological matrixes by liquid chromatography with electrochemical detection.

A simple and specific method has been developed for determination of enviroxime in biological samples. Enviroxime, a substituted benzimidazole, its coisomer zinviroxime, and the internal standard hexestrol were extracted from the samples with benzene. The benzene layer was evaporated and the residue was reconstituted and injected onto a liquid chromatograph. Reversed-phase chromatography on an octylsilane column with a 65% methanol-35% 0.14 M sodium acetate mobile phase separated the components. The compounds were detected electrochemically using a glassy carbon electrode held at +0.85 V. The assay could detect as little as 4 ng of enviroxime/ml of plasma, 15 ng/ml of nasal wash, and 20 ng/ml of urine or tissue homogenate. For plasma assays, the procedure was greater than 97% accurate and had a relative standard deviation of less than 4%. This method has proven to be applicable and reliable for the determination of enviroxime in many types of biological samples. Several problems encountered during the routine use of electrochemical detection were explored and minimized.

Determination of fluoxetine and norfluoxetine in plasma by gas chromatography with electron-capture detection.

This gas-chromatographic method for assay of fluoxetine and norfluoxetine in human plasma involves extraction of the drugs and use of a 63Ni electron-capture detector. The linear range of detection is 25 to 800 micrograms/L for each drug. Overall precision (CV) in the concentration range of 10 to 100 micrograms/L for both drugs was approximately 10%. Accuracy (relative error) in the same concentration range was approximately +10%. None of the commonly prescribed antidepressants or tranquilizers that we tested interfere with the assay.

Rehabilitation literature: a guide to selection materials.

The rehabilitation of physically disabled persons is an expanding and interdisciplinary field, and the literature on this topic has grown rapidly in recent years. Bibliographic control of rehabilitation literature is poor, and selection of materials about physically disabled persons can be a difficult undertaking. The present article describes and evaluates various selection tools on the basis of their coverage of rehabilitation literature and their usefulness to academic, public, and special librarians.

High-performance liquid chromatographic assay for fenoprofen in human plasma.

A high-performance liquid chromatographic method is described for the quantitation of fenoprofen, dl-2-(3-phenoxyphenyl)-propionic acid, in human plasma. The proteins in plasma were precipitated by the addition of hydrochloric acid. Fenoprofen and the internal standard, dl-2-(4-phenoxyphenyl)valeric acid, were extracted into butyl chloride and then back-extracted into sodium hydroxide. The aqueous solution was injected onto a reversed-phase alkylphenyl column, and the compounds were eluted using a mobile phase of acetonitrile-water-acetic acid (50:50:2 v/v/v). At a flow rate of 1 ml/min, the retention times of fenoprofen and the internal standard were 8 and 12 min, respectively. The absorbance was monitored at 272 nm. The method requires 1.0 ml of plasma and is sensitive to 0.5 microgram/ml. This procedure has been used for routine assay of multiple samples from bioavailability and compliance studies.

Stereoselective inversion of (R)-(-)-benoxaprofen to the (S)-(+)-enantiomer in humans.

The enantiomeric composition of benoxaprofen [(RS)-2-(P-chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid] in plasma and urine was determined after oral administration of both the racemic mixture and the (R)-(-)-enantiomer to normal human volunteers. Resolution of the diastereomeric amides, formed by the reaction of the enantiomers with (S)-(-)-apha-methylbenzylamine, was accomplished by gas chromatography. The (R)-(-1)-enantiomer of the parent drug was stereoselectively inverted to its (S)-(+) isomer in humans.

Linear pharmacokinetics of orally administered fenoprofen calcium.

The bioavailability of fenoprofen from three different fenoprofen calcium capsule formulations containing the equivalent of 60, 165, and 300 mg of fenoprofen was determined in two studies. In the first study, 12 subjects received one capsule of each formulation according to a three-period crossover design. The second study required each of 13 subjects to receive 300 mg of fenoprofen equivalent of the 60- and 300-mg capsules and 330 mg of the 165-mg capsule. The initial study provided information on the linearity of fenoprofen pharmacokinetics, and the second study established that the three capsule formulations were bioequivalent. The bioavailability parameters Cmax, tmax, and AUC0--12 hr for the drug in plasma were consistent with a linear pharmacokinetic model, as were the amounts of fenoprofen and hydroxyfenoprofen excreted in the urine. These data show linearity of kinetics for fenoprofen in plasma throughout the 60--300-mg dosage range after a single dose. Physical measurements of each capsule formulation drug content, weight variation, and dissolution showed the products to be uniform and readily soluble.

Metabolism of the antimicrobial agent nibroxane, 5-bromo-2-methyl-5-nitro-m-dioxane, in the rat.

1. The metabolism of nibroxane, a topically effective antimicrobial agent has been studied in the rat after oral and dermal administrations. 2. Plasma level studies in vitro and in vivo showed nibroxane to be rapidly debrominated to 2-methyl-5-nitro-m-dioxane. 3. Nibroxane is rapidly absorbed and extensively metabolized in the rat regardless of the route of administration. 4. Enzymic hydrolysis of the m-dioxane ring was of major importance in the biotransformation of nibroxane. The major eliminated metabolite in the rat was 2-nitropropan-1,3-diol.

Quantitation of propoxyphene and its major metabolites in heroin addict plasma after large dose administration of propoxyphene napsylate.

A sensitive and specific GLC assay method was developed for the determination of propoxyphene, its major metabolite norpropoxyphene, and lesser known metabolites cyclic dinorpropoxyphene and/or dinorpropoxyphene in plasma of heroin addicts administered up to 800 mg of propoxyphene napsylate. The assay used a mass internal standard of pyrroliphene. The compounds were extracted from pH 9.8 carbonate-buffered plasma with butyl chloride, back-extracted into acidified water which was then washed with hexane, and reextracted with chloroform from the aqueous phase made basic. Quantitation of the drug and its metabolites was accomplished by temperature-programmed GLC. Absolute identification of the compounds chromatographed was completed by GLC-mass spectrometry.