Formaldehyde concentrations in household air of asthma patients determined using colorimetric detector tubes.

Formaldehyde is a colorless, pungent gas commonly found in homes and is a respiratory irritant, sensitizer, carcinogen, and asthma trigger. Typical household sources include plywood and particleboard, cleaners, cosmetics, pesticides, and others. Development of a fast and simple measurement technique could facilitate continued research on this important chemical. The goal of this research is to apply an inexpensive short-term measurement method to find correlations between formaldehyde sources and concentration, and formaldehyde concentration and asthma control. Formaldehyde was measured using 30-min grab samples in length-of-stain detector tubes in homes (n = 70) of asthmatics in the Boston, MA area. Clinical status and potential formaldehyde sources were determined. The geometric mean formaldehyde level was 35.1 ppb and ranged from 5 to 132 ppb. Based on one-way ANOVA, t-tests, and linear regression, predictors of log-transformed formaldehyde concentration included absolute humidity, season, and the presence of decorative laminates, fiberglass, or permanent press fabrics (P < 0.05), as well as temperature and household cleaner use (P < 0.10). The geometric mean formaldehyde concentration was 57% higher in homes of children with very poorly controlled asthma compared to homes of other asthmatic children (P = 0.078). This study provides a simple method for measuring household formaldehyde and suggests that exposure is related to poorly controlled asthma.

Assessment of relative tumor burden in patients with clinical T1c prostate cancer treated with either external beam or radical prostatectomy.

The choice between external beam radiation therapy (EBRT) or retropubic radical prostatectomy (RPX) as potentially curative treatment for localized carcinoma of the prostate gland (CaP) has not been delineated in randomized studies. Both treatments are more effective if tumor burden is low. We sought to compare these two treatments in patients who had clinical stage T1c (cT1c) lesions and who were thought to have limited tumor burdens pretreatment. Sixty cT1c patients referred to the Department of Radiation Oncology received 66 Gy in 33 sessions of EBRT to localized prostate ports and 59 cT1c patients had RPX. No neoadjuvant nor early adjuvant therapies were prescribed. Radiotherapy success was defined biochemically as a nonrising prostate-specific antigen (PSA) of +/- 1.5 ng/ml. RPX success required a postoperative PSA that was undetectable (PSA <0.2 ng/ml by the Hybritech or Abbott IMx technics). Analysis for nonrising posttreatment PSA levels was performed using Kaplan-Meier and Cox regression methods. Mantel-Haenszel methods were used to determine odds ratios for treatment groups adjusting for potential confounders. We ultimately assessed the relative tumor burden by histologic examination of the RPX specimens. The two treatment groups, although not randomized, were statistically similar in biopsy Gleason Scores, transrectal ultrasonography calculated gland volumes, number of positive biopsy cores, and estimated amount of cancer identified on initial biopsies. Pathologic stage T3 was identified in 25% of RPX patients. Fifty to 60% of RPX specimens histologically had substantial tumor burden and by inference also the EBRT patients. At a median follow-up (F/U) of 36 months, 76% of RPX patients maintained an undetectable PSA, whereas 62% of EBRT patients had a PSA < 1.5 ng/ml at a median F/U of 29 months. The pretreatment PSA values significantly affected EBRT patients' risk of a rising posttreatment PSA level. Twenty-four months after treatment, RPX patients were 3.7 times more likely to maintain a nonrising PSA level (RPX patients posttreatment PSA < 0.2 ng/ml), than EBRT patients (posttreatment PSA < or = 1.5 ng/ml) (p = 0.006). Sixty-six gray in 33 sessions to localized EBRT ports is not sufficiently aggressive therapy for one third or more of patients with cT1c CaP. RPX alone is insufficient therapy for one fourth of cT1c patients. Analysis of the RPX specimens showed that many cT1c tumors have a significant tumor burden. Selection methodologies to separate out patients who require more than conventional dose or type of radiotherapy or more than RPX as monotherapy are needed. Pretreatment PSA and number of positive biopsies may assist this selection process.

Stability studies and high-performance liquid chromatographic procedures for L-648,548 and its major degradates in an animal health formulation.

L-648,548 is a new avermectin which was evaluated for the development of an animal health formulation. A stability-indicating method for the essay of 5% (w/v) L-648,548 in an animal health formulation has been developed using reversed-phase high-performance liquid chromatography (HPLC) with UV detection (245 nm). The procedure to determine L-648,548 is linear and accurate over the range 80-120% of the target concentration with a limit of quantitation of 0.2%. Validation data are presented. Also two related degradates of this compound were observed during the stability studies of the L-648,548 formulation. These degradates were determined to be the 2-epimer formed in the presence of base and the 8a-oxo degradate formed by oxidation. Identification of these compounds following direct chemical synthesis was based on mass, UV and NMR spectroscopy. The mechanistic pathways for the formation of these degradates are discussed. The 8a-oxo degradate has a modified chromophore, thus requiring a second HPLC method with detection at 280 nm that was also validated.

Identification of the secondary degradates of L-648,548 in an animal health formulation.

L-648,548 is a semisynthetic analog of avermectin. During stability investigations of this compound in an animal health formulation, two new degradates were discovered. These degradates (L-648,548 phenol and its 8,9-Z isomer) were identified as the reaction products of 5-oxo-L-648,548 formed by oxidation of L-648,548. Addition of base to the reaction medium containing 5-oxo-L-648,548 was found to catalyze the formation of L-648,548 phenol via a postulated dehydration by an E1cb elimination followed by the rapid tautomerization of the C5 carbonyl. Photolysis of L-648,548 phenol with visible light (including ambient laboratory lighting) was found to readily produce 8,9-Z-L-648,548 phenol. This transformation was confirmed to be exclusively a photoinduced process.

Density-dependent regulation of ramet recruitment by the red:far-red ratio of solar radiation: a field evaluation with the bunchgrass Schizachyrium scoparium.

Depressions in the red to far-red ratio (R:FR) of solar radiation arising from the selective absorption of R (600-700 nm) and scattering of FR (700-800 nm) by chlorophyll within plant canopies may function as an environmental signal directly regulating axillary bud growth and subsequent ramet recruitment in clonal plants. We tested this hypothesis in the field within a single cohort of parental ramets in established clones of the perennial bunchgrass, Schizachyrium scoparium. The R:FR was modified near leaf sheaths and axillary buds at the bases of individual ramets throughout the photoperiod without increasing photosynthetic photon flux density (PPFD) by either (1) supplementing R beneath canopies to raise the naturally low R:FR or (2) supplementing FR beneath partially defoliated canopies to suppress the natural R:FR increase following defoliation. Treatment responses were assessed by simultaneously monitoring ramet recruitment, PPFD and the R:FR beneath individual clone canopies at biweekly intervals over a 12-week period. Neither supplemental R nor FR influenced the rate or magnitude of ramet recruitment despite the occurrence of ramet recruitment in all experimental clones. In contrast, defoliation with or without supplemental FR beneath clone canopies reduced ramet recruitment 88% by the end of the experiment. The hypothesis stating that the R:FR signal directly regulates ramet recruitment is further weakened by evidence demonstrating that (1) the low R:FR-induced suppression of ramet recruitment is only one component of several architectural modifications exhibited by ramets in response to the R:FR signal (2) immature leaf blades, rather than leaf sheaths or buds, function as sites of R:FR perception on individual ramets, and (3) increases in the R:FR at clone bases following partial canopy removal are relatively transient and do not override the associated constraints on ramet recruitment resulting from defoliation. A depressed R:FR is probably of greater ecological significance as a signal of competition for light in vegetation canopies than as a density-dependent signal which directly regulates bud growth and ramet recruitment.

Dissociation between early loss of actin fibres and subsequent cell death in serum-deprived quiescent Balb/c-3T3 cells.

Serum withdrawal from either growing or quiescent Balb/c-3T3 murine fibroblasts causes a loss of F-actin fibres and focal adhesions within 30 min. Cells that are growing survive serum deprivation, whereas the great majority of density-arrested quiescent cells die during a period of up to 5 h from serum withdrawal. During this time an approximately constant fraction of the quiescent cell population dies per unit time. The population half-life is 60-70 min during this time. Addition of an appropriate cell growth factor or second messenger agonist at the time of serum withdrawal or within 2 h after serum withdrawal protects a similar fraction of viable cells. These findings suggest a model according to which withdrawal of serum (i.e. growth factors) initiates the death process in cells of the population with kinetics that approximate first-order kinetics. We postulate that appropriate growth factors or second messenger agonists block the initiating event that starts the cell death process.

Total joint replacement: implication of cancelled operations for hospital costs and waiting list management.

OBJECTIVE: To identify aspects of provision of total joint replacements which could be improved. DESIGN: 10 month prospective study of hospital admissions and hospital costs for patients whose total joint replacement was cancelled. SETTING: Information and Waiting List Unit, Musgrave Park Regional Orthopaedic Service, Belfast. PATIENTS: 284 consecutive patients called for admission for total joint replacement. MAIN MEASURES: Costs of cancellation of operation after admission in terms of hotel and opportunity costs. RESULTS: 28(10%) planned operations were cancelled, 27 of which were avoidable cancellations. Five replacement patients were substituted on the theatre list, leaving 22(8%) of 232 operating theatre opportunities unused. Patients seen at assessment clinics within two months before admission had a significantly higher operation rate than those admitted from a routine waiting list (224/232(97%) v 32/52(62%), x2 = 58.6, df = 1; p < 0.005). Mean duration of hospital stay in 28 patients with cancelled operations was 1.92 days. Operating theatre opportunity costs were 73% of the total costs of cancelled total joint replacements. CONCLUSION: Patients on long waiting lists for surgery should be reassessed before admission to avoid wasting theatre opportunities, whose cost is the largest component of the total costs of cancelled operations.

Nurse entrepreneurs.

1. Supervised Environmental Living Facility (SELF) is a nurse-developed, non-profit, community-based, supervised apartment program for the chronically mentally ill. It provides comprehensive supportive and rehabilitative services to the chronically mentally ill, allowing them to re-establish themselves as part of the community. 2. SELF is based on the philosophy that a person needs assistance according to the extent that the illness affects the individual's ability to live safely and optimally. 3. Nurses can be entrepreneurs by seeking and creating innovative models for the delivery of services to specialized populations.

Decreased adherence of interleukin 6-treated breast carcinoma cells can lead to separation from neighbors after mitosis.

Interleukin 6 (IL-6) has been shown to inhibit the proliferation, but increase the motility, of wild-type ZR-75-1 human ductal breast carcinoma cells, a line of cells that resemble closely the malignant cells cultured from the ascitic effusion. IL-6-treated cells lose their epithelial character, become stellate or fusiform in shape, and migrate away from neighbors. In the wild-type ZR-75-1 cells, IL-6 causes cell-cell separation in preformed colonies as well as postmitotically. We have now investigated the action of IL-6 in clone B ZR-75-1 cells, which are morphologically distinct from wild-type ZR-75-1 cells. In the more polygonal rather than cuboidal clone B cells, IL-6 did not cause early inhibition of DNA synthesis and it caused little cell-cell separation in preformed colonies. However, IL-6 treatment markedly prolonged the interval between mitosis and readherence of daughter cells to their neighbors and the substratum. Supernatants from IL-6-treated cultures contained detached viable cells in increased numbers. Intermitotic intervals were prolonged in IL-6-treated cultures. IL-6-treated dividing breast carcinoma cells are characterized by an increased probability of separation from neighbors and the substratum.

Effects of interferon-beta on the translocation rate and stationary time in human fibroblasts in culture.

The rate of translocation and the percent of the time that cells are stationary have been measured by computer-assisted time-lapse cinemicrography in over 1,000 freshly planted human foreskin fibroblasts (FS-4 cell strain) for periods of up to a week and the effects of interferon-beta (IFN-beta) on these parameters have been determined. Cells were planted at 2.5 X 10(3) cells/cm2 in Eagle's minimal essential medium (MEM) with 10% fetal bovine serum (FBS). Frames were taken every 2 or 4 minutes and data were collected on both cell location and cell division as a function of time. After planting FS-4 cells require approximately 48 hr to reach maximum motility both with respect to the translocation rate when moving and percent time cells are moving. Recombinant human INF-beta (800 mu/ml) caused a marked increase in the fraction of time cells were stationary and a decrease of lesser magnitude in the translocation rate, as quantitated during the period during which the stationary fraction for control cells was at a minimum. IFN-beta also decreased the rate of cell proliferation, without any evidence of degeneration or death of cells. Our results contribute new evidence that the fraction of time cells spend moving directionally is an important determinant of their locomotory behavior and that this determinant is responsive to modulation by cytokines.

Structure and activity of hydrogenated derivatives of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801).

Several hydrogenated derivatives of the potent NMDA antagonist 1 have been prepared and evaluated as competitive inhibitors of [3H]-1 binding. These compounds were also tested for their ability to act as noncompetitive antagonists of NMDA in vitro. These studies indicate that two aromatic rings are not strictly required for high-affinity binding or NMDA antagonism.

Biotransformation of lovastatin. I. Structure elucidation of in vitro and in vivo metabolites in the rat and mouse.

Structures of in vitro microsomal and in vivo metabolites of lovastatin, a new cholesterol-lowering drug, were elucidated with the combined application of HPLC, UV, fast atom bombardment-MS, and NMR spectroscopy. Liver microsomes from rats and mice catalyzed the biotransformation of lovastatin, primarily at the 6'-position of the molecule, to form 6'-hydroxy-lovastatin and a novel 6'-exomethylene derivative. Hydroxylation at the 6'-position occurred stereoselectively, giving 6'-beta-hydroxy-lovastatin. Stereoselective hydroxylation at the 3"-position of the methylbutyryl side chain and hydrolysis of the lactone group to the corresponding hydroxy acid were the other two pathways of microsomal metabolism. 3'-Hydroxy-iso-delta 4',5'-lovastatin was isolated, but is not believed to be a direct metabolite since 6'-beta-hydroxy-lovastatin rearranges to this compound under mildly acidic conditions. The major metabolites excreted in bile of rats treated with the hydroxy acid form of the drug were identified as the 3'-hydroxy analog and a taurine conjugate of a beta-oxidation product of lovastatin. The pentanoic acid derivative of lovastatin, formed by beta-oxidation of the heptanoic acid moiety, was a major metabolite in livers of mice dosed with the hydroxy acid form of lovastatin. The microsomal metabolites, in their hydroxy acid forms, were active inhibitors of HMG-CoA reductase. The relative enzyme inhibitory activities of hydroxy acid forms of lovastatin, 6'-beta-hydroxy-, 6'-exomethylene-, and 3"-hydroxy-lovastatin were 1, 0.6, 0.5, and 0.15, respectively.

Interleukin 6 decreases cell-cell association and increases motility of ductal breast carcinoma cells.

Treatment of transformed breast duct epithelial cells with IL-6 produces a unique cellular phenotype characterized by diminished proliferation and increased motility. Human ductal carcinoma cells (T-47D and ZR-75-1 lines) are typically epithelioid in shape and form compact colonies in culture. Time-lapse cinemicrography shows that some untreated cells can transiently become fusiform or stellate in shape and separate from each other within a colony, but they usually rejoin their neighbors. While IL-6 suppresses the proliferation of these carcinoma cells, the IL-6-treated cells generally become stellate or fusiform and show increased motility. These changes persist as long as the cells are exposed to IL-6. This results in the dispersal of cells within colonies. The effects on cell growth, shape, and motility are reversible upon removal of IL-6. IL-6-treated T-47D cells display diminished adherens-type cell junctions, as indicated by markedly decreased vinculin-containing adhesions and intercellular desmosomal attachments. The effects on ZR-75-1 cell shape, colony number, and DNA synthesis are dependent on IL-6 concentration in the range from 0.15 to 15 ng/ml. Higher concentrations are required in T-47D cells for equivalent effects. Anti-IL-6 immune serum blocks IL-6 action. IL-6 represents a well-characterized molecule that regulates both the proliferation and junction-forming ability of breast ductal carcinoma cells.

Development of the Belfast orthopaedic information system.

A team from Musgrave Park Hospital, Belfast, describe their success in reducing the hip waiting list and introducing an information system to manage the orthopaedic waiting list.