Sputum induction versus fiberoptic bronchoscopy in the diagnosis of tuberculosis.
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Bronchoscopy↗
Biomedical subjects
J L Larson
Publications and source records attributed to J L Larson.
Purification, characterization, cDNA cloning and expression of a novel ketoreductase from Zygosaccharomyces rouxii.
A novel ketoreductase isolated from Zygosaccharomyces rouxii catalyzes the asymmetric reduction of selected ketone substrates of commercial importance. The 37.8-kDa ketoreductase was purified more than 300-fold to > 95% homogeneity from whole cells with a 30% activity yield. The ketoreductase functions as a monomer with an apparent Km for 3,4-methylenedioxyphenyl acetone of 2.9 mM and a Km for NADPH of 23.5 microM. The enzyme is able to effectively reduce alpha-ketolactones, alpha-ketolactams, and diketones. Inhibition is observed in the presence of diethyl pyrocarbonate, suggesting that a histidine is crucial for catalysis. The 1.0-kb ketoreductase gene was cloned and sequenced from a Z. rouxii cDNA library using a degenerate primer to the N-terminal sequence of the purified protein. Furthermore, it was expressed in both Escherichia coli and Pichia pastoris and shown to be active. Substrate specificity, lack of a catalytic metal, and extent of protein sequence identity to known reductases suggests that the enzyme falls into the carbonyl reductase enzyme class.
Alcohol Oxidoreductases↗
The reproductive and developmental toxicity of the antifungal drug Nyotran (liposomal nystatin) in rats and rabbits.
Nyotran is a liposomally encapsulated i.v. formulation of the antifungal polyene nystatin. This drug was evaluated in a series of reproductive toxicity studies, according to the guidelines outlined by the International Conference on Harmonization (ICH). A fertility and early embryonic development study (SEG I) and a prenatal and postnatal development (SEG III) study were conducted in rats, and embryo-fetal development (SEG II) studies were conducted in rats and rabbits. Nyotran was administered iv in all studies. In SEG I and SEG III, rats were administered daily doses of 0.5, 1.5, or 3.0 mg/kg Nyotran. In both studies, parental mortality and toxicity in the 3.0 mg/kg dose group necessitated the lowering of the high dose to 2.0 mg/kg/day. Parental toxicity, in the form of decreased body weights, decreased food consumption, and piloerection were also observed at the 1.5 mg/kg/day dose level in the SEG I and SEG III studies. Despite the parentally toxic doses in the SEG I study, there was no effect of Nyotran on F0 male or female fertility or early embryonic development of F1 offspring. In the SEG III study, lactational body weights of the F1 generation were decreased at all Nyotran dose levels. There was no effect on pre-wean developmental landmarks, but post-wean development was affected by Nyotran administration at all dosage levels. Preputional separation was delayed in the 1.5 and 3.0/2.0 mg/kg/day F1 offspring, auditory startle function was decreased in F1 females at all dose levels, and motor activity was decreased in male F1 offspring at all dose levels. However, there were no treatment-related effects on the subsequent mating of the F1 generation and resulting F2 offspring. In SEG II studies, rats and rabbits were also administered 0.5, 1.5, or 3.0 mg/kg/day of Nyotran during gestation. The high dose in these SEG II studies was not lowered, as the maternal animals were able to tolerate the shorter duration of dosing. Maternal effects in rabbits were observed only in the high-dose group and were limited to decreased food consumption and decreased absolute and relative liver weight. Decreased food consumption in high-dose dams and clinical weight loss in some animals at the mid- and high-dose levels evidenced maternal toxicity in rats. Nyotran did not have any effect on Caesarian section parameters in either rats or rabbits and no effect on the incidence of fetal malformations in rabbits. A statistically significant increase in mild hydrocephaly, observed in 4 rat fetuses, was seen at the highest dose level of 3.0 mg/kg/day. The biological significance and relationship to Nyotran treatment of this finding is not clear. This finding may represent a change in the background incidence or a change in the pattern of responsiveness of this strain of rat fetus to the test chemical. Toxicokinetic data were also collected in the SEG II rabbit and rat studies for comparison to human exposures. In both species, systemic exposure to the nystatin at effective antifungal concentrations was demonstrated. The systemic exposures in rats and rabbits were, however, considerably less than have been reported in humans administered clinical doses of 2 or 4 mg/kg/day Nyotran. Thus, humans tolerate higher dosages and systemic exposures of Nyotran relative to rats and rabbits and there is no margin of safety in either dosage level or systemic exposure to drug. Given this lack of a margin of safety and the effects on postnatal development in F1 rats, caution should be exercised when using this drug in females of childbearing potential.
Abnormalities, Drug-Induced↗
Effect of hyperbaric oxygen on neutrophil CD18 expression.
Previous work has shown that treatment with hyperbaric oxygen significantly reduces neutrophil adhesion to postcapillary venules in a rat microcirculation model of ischemia-reperfusion injury. The mechanism of this process is unknown. The purpose of this study was to evaluate the effect of hyperbaric oxygen on neutrophil CD18 adhesion sites by flow cytometry in an animal model of ischemia-reperfusion injury. The gracilis muscle flap was raised in three groups of male Wistar rats: (1) a sham group (n = 25), (2) a group that underwent 4 hours of ischemia (n = 25), and (3) a group that underwent 4 hours of ischemia and received hyperbaric oxygen (100% 02, 2.5 atmospheres absolute, during the last 90 minutes of ischemia) (n = 25). Samples from one subgroup of each group (n = 5) were divided into two portions, and one portion was stimulated with phorbol-12 myristate 13-acetate (PMA). Samples from another subgroup of each group (n = 5) were treated in the same manner, and a flap flush was added at the end of reperfusion to determine the number of CD18 adhesion sites on adherent neutrophils remaining in the flap. Venous blood was drawn 10 minutes after the operation, at 5 minutes of reperfusion, and at 90 minutes of reperfusion. Hematocrit and white blood cell count were measured. Samples were analyzed by flow cytometry, and the antibody binding capacity was assessed using microbead standards and linear regression (antibody binding capacity was expressed as the mean number of sites per cell +/- SEM). Microbeads were used to align the flow cytometer and to provide external and internal standards. Ischemia-reperfusion injury increased the expression of CD18 by neutrophils (p < 0.05). Expression of CD18 was not decreased by hyperbaric oxygen treatment. Stimulation with PMA increased the expression of CD18 in all groups (p < 0.01). These results suggest that ischemia-reperfusion injury does increase the expression of CD18 by neutrophils. Hyperbaric oxygen, as administered in this experiment, did not prevent the increase in CD18 expression.
Animals↗
Direct measurement of islet amyloid polypeptide fibrillogenesis by mass spectrometry.
A novel method for monitoring fibrillogenesis is developed and applied to the amyloidogenic peptide, islet amyloid polypeptide (IAPP). The approach, based on electrospray ionization mass spectrometry, is complementary to existing assays of fibril formation as it monitors directly the population of precursor rather than product molecules. We are able to monitor fiber formation in two modes: a quenched mode in which fibril formation is halted by dilution into denaturant and a real time mode in which fibril formation is conducted within the capillary of the electrospray source. Central to the method is the observation that fibrillar IAPP does not compromise the ionization of monomeric IAPP. Furthermore, under mild ionization conditions, fibrillar IAPP does not dissociate and contribute to the monomeric signal. Critically, we introduce an internal standard, rat IAPP, for analysis on the mass spectrometer. This standard is sufficiently similar in sequence in that it ionizes identically to human IAPP. Furthermore, the sequence is sufficiently different in that it does not form fibrils and is distinguishable on the basis of mass. Applied to IAPP fibrillogenesis, our technique reveals that precursor consumption in seeded reactions obeys first-order kinetics. Furthermore, a consistent level of monomer persists in both seeded and unseeded experiments after the fibril formation is complete. Given the inherent stability of fibrils, we expect this approach to be applicable to other amyloid systems.
Amyloid↗
Can relative spermatozoal galactosyltransferase activity be predictive of dairy bull fertility?
The best and poorest bovine semen samples used commercially for artificial insemination in dairy cattle typically differ in pregnancy rates by 20 to 25% but are within a range that pregnancy rates cannot be predicted consistently by commonly used laboratory assays. Sperm motility and morphology are the characteristics most often evaluated. Laboratory assays that measure other functional traits of sperm may be useful as supplemental assays to increase the reliability of predicting fertility. One such functional trait is the ability of sperm to bind to the zona pellucida, a process mediated by complementary receptors on each gamete. On mouse sperm, beta1,4-galactosyltransferase acts as a receptor for the zona pellucida. Beta1,4-galactosyltransferase is expressed on sperm from many mammals, including bovine sperm, and is a candidate for a zona pellucida receptor. The ability of sperm to bind to the zona pellucida may be related to the amount of beta1,4-galactosyltransferase present on sperm. The aim of this work was to determine if bull sperm beta1,4-galactosyltransferase activity was related to fertility. Beta1,4-galactosyltransferase enzyme assays were performed on sperm from 24 bulls whose fertility was estimated by nonreturn rate and on sperm from a second group of seven bulls whose fertility was ranked by in vivo competitive fertilization. Beta1,4-galactosyltransferase activity varied between individual bulls but was not correlated to fertility as estimated by nonreturn rate or by competitive fertilization. These results demonstrate that beta1,4-galactosyltransferase activity on sperm varies between animals, but that beta1,4-galactosyltransferase activity alone is not an accurate indicator of fertility in dairy bulls.
Animals↗
Simple histochemical stain for acrosomes on sperm from several species.
The acrosome reaction is an exocytotic process that enables a sperm to penetrate the zona pellucida and fertilize an egg. The process involves the fenestration and vesiculation of the sperm plasma membrane and outer acrosomal membrane releasing the acro somal contents. Many different methods have been devel oped to detect the acrosomal status of sperm. These techniques are sometimes complicated, costly, and can be used on only a few species. The aim of this study was to develop an efficient and inexpensive method to assess the acrosomal status of sperm from a variety of species. We prepared and fixed sperm from humans, cattle, swine, rabbits, guinea pigs, and mice and stained them with Coomassie G250. The acrosomes were stained intensely blue in color. Following capacitation, some sperm were incubated for 1 hr with 10 microM calcium ionophore A23187 to induce the acrosome reaction. They were also stained with Coomassie G-250. Ionophore-treated sperm lacked Coomassie staining over the acrosomal region. Differential interference contrast (DIC), bright field microscopy or Pisum sativum agglutinin staining confirmed that the acrosomes of sperm from these species were reacted in response to calcium ionophore treatment and the acrosome reaction frequencies matched results with Coomassie staining. These results demonstrate that the acrosomal status of mammalian sperm from several species can be determined easily and reliably using this simple Coomassie Blue G-250 staining method.
Acrosome↗
Reliability of submaximal exercise tests in patients with COPD. Chronic obstructive pulmonary disease.
UNLABELLED: Submaximal constant work rate exercise tests are often used to measure the efficacy of an exercise intervention, but the reliability of these tests in patients with chronic obstructive pulmonary disease (COPD) has not been established. PURPOSE: To examine the reproducibility of submaximal exercise responses of COPD patients compared with those of healthy elderly subjects. METHODS: Sixteen COPD patients and 15 healthy subjects performed four weekly submaximal exercise tests against two different constant work rates: 20 W and 50% of the peak work rate (PWR). Spirometry was performed before each exercise test. COPD patients and healthy subjects were: age 69 +/- 5 and 65 +/- 5 yr, body mass index 26.4 +/- 3.9 and 26.7 +/- 3.0 kg x m(-2), respectively. RESULTS: Both groups had no change in minute ventilation (V(E)), oxygen uptake (VO2), breathlessness (RPB), and leg fatigue (RPLF) for either work rate over repeated measures (P > 0.05). At 50% PWR test-retest reliability coefficients for V(E) and VO2 ranged from r = 0.88 to r = 0.96 for COPD patients and from r = 0.72 to r = 0.97 for healthy subjects; for RPB and RPLF test-retest reliability ranged from r = 0.76 to r = 0.89 for COPD patients and from r = 0.70 to r = 0.91 for healthy subjects. Intrasubject mean absolute differences for repeated measures of V(E), VO2, RPB, or RPLF were low and there were no group differences (P > 0.05). Percent error for V(E) and VO2 ranged from 6 +/- 3 to 9 +/- 7%, and for RPB and RPLF ranged from 19 +/- 18 to 68 +/- 65% for both groups at each work rate. CONCLUSIONS: Submaximal exercise responses were reliable over a 1-month period, and measures of the physiological and psychophysical responses of COPD patients were as reliable as those of healthy subjects.
Aged↗
Cycle ergometer and inspiratory muscle training in chronic obstructive pulmonary disease.
In patients with chronic obstructive pulmonary disease (COPD) the intensity of aerobic training is limited by dyspnea. Improving strength of the inspiratory muscles could enhance aerobic exercise training by reducing exercise-related dyspnea. We examined effects of home-based inspiratory muscle training (IMT) and cycle ergometry training (CET) in 53 patients with moderate to severe COPD (FEV(1)% pred, 50 +/- 17 [mean +/- SD]). Patients were randomly assigned to 4 mo of training in one of four groups: IMT, CET, CET + IMT, or health education (ED). Patients were encouraged to train to the limits of their dyspnea. Inspiratory muscle strength and endurance increased in IMT and CET + IMT groups compared with CET and ED groups (p < 0. 01). Peak oxygen uptake increased and heart rate, minute ventilation, dyspnea, and leg fatigue decreased at submaximal work rates in the CET and CET + IMT groups compared with the IMT and ED groups (p < 0. 01). There were no differences between the CET and CET + IMT groups. Home-based CET produced a physiological training effect and reduced exercise-related symptoms while IMT increased respiratory muscle strength and endurance. The combination of CET and IMT did not produce additional benefits in exercise performance and exercise-related symptoms. This is the first study to demonstrate a physiological training effect with home-based exercise training.
Aged↗
Discontinuous incremental threshold loading test: measure of respiratory muscle endurance in patients with COPD.
STUDY OBJECTIVE: To assess the discontinuous incremental threshold loading (DC-ITL) test as a measure of respiratory muscle endurance for patients with COPD in terms of perceived breathing difficulty, reliability, and validity. DESIGN: The DC-ITL test was repeated three times at weekly intervals under identical test conditions. SETTING: Clinical research laboratory. PATIENTS: Forty-eight patients with moderate to severe COPD. MEASUREMENTS AND RESULTS: Rating of perceived breathing difficulty (RPBD) was measured at the end of each stage of the DC-ITL test with a Borg category-ratio scale. The maximal inspiratory pressure (PImax) was measured before and after the DC-ITL test. Breathing patterns were measured during the DC-ITL test. The mean (+/-SD) for RPBD at the maximal load was 6.3 (3.1), 6.6 (2.8), and 6.7 (2.7) for visits one, two, and three, respectively (not significant). The mean relative maximal load for the DC-ITL test (peak mouth pressure as a percent of PImax) at the last completed stage was 59+/-23%, 62+/-20%, and 63+/-19% for visits one, two, and three, respectively (not significant). Test-retest reliability was r1,2=0.82 and r2,3=0.69 for relative maximal load and r1,2=0.90 and r2,3=0.90 for absolute maximal load (peak mouth pressure). Tidal volume decreased (p < 0.01) and respiratory rate increased (p < 0.01) from the next-to-the-last to the last completed stage. PImax decreased after the DC-ITL test (p < 0.01). CONCLUSIONS: Moderate breathing difficulty was experienced during the DC-ITL test. The test was reliable and the results of this study support its validity as a measure of respiratory muscle endurance.
Aged↗
Chronic obstructive pulmonary disease: strategies to improve functional status.
People with chronic obstructive pulmonary disease (COPD) experience deterioration in functional status, therefore improving functional status is a major goal of treatment. We reviewed interventions to improve functional status in people with COPD published from 1980 through September 1996. Randomized controlled clinical trials were reviewed to document outcomes in terms of functional capacity and functional performance for the following interventions: pharmacologic therapy including theophylline, inhaled bronchodilators, steroids, antianxiolytics and antidepressants; general exercise strategies including exercise training, exercise and comprehensive pulmonary rehabilitation, and upper extremity training; inspiratory muscle therapy including inspiratory muscle training and inspiratory muscle rest; nutritional therapy; oxygen therapy; and specialized nursing care. Improvements for functional capacity were documented in terms of strength of the inspiratory muscles and upper extremities, walking tests, and peak oxygen uptake. Most interventions were targeted to enhance functional capacity, and few were aimed at enhancing functional performance. Further research is needed to examine the relationship between functional capacity and functional performance and to design and test interventions to improve functional performance.
Humans↗
Reliability and validity of the functional performance inventory in patients with moderate to severe chronic obstructive pulmonary disease.
The Functional Performance inventory (FPI) is a new instrument designed to measure functional status in terms of activities that people perform on a daily basis. Psychometric characteristics were examined by a survey of 45 men and 27 women with chronic obstructive pulmonary disease (COPD). Internal consistency reliability was high and no ceiling and floor effects were observed for the Total FPI. Concurrent validity was demonstrated by correlations with the Total Sickness Impact Profile (r = -.59). Construct validity was supported by correlations with the Medical Outcomes Study Short Form-36, Physical Functioning (r = .69), the Physical Activity Scale for the Elderly (r = .62) and American Thoracic Society-Division of Lung Disease Breathlessness scale (r = -.62). The Total FPI is a reliable and valid measure of functional performance in persons with COPD.
Activities of Daily Living↗
Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine.
The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.
3,4-Dihydroxyphenylacetic Acid↗
Sperm from a variety of mammalian species express beta1,4-galactosyltransferase on their surface.
In mice, initial gamete recognition is mediated by the binding of sperm surface beta1,4-galactosyltransferase (GalTase) to a glycoprotein of the zona pellucida, ZP3. When sperm bind to the zona pellucida, ZP3 induces the acrosome reaction by aggregating GalTase. The acrosome reaction releases acrosomal enzymes allowing sperm to pass through the zona pellucida, bind to the egg membrane, and activate development. In addition to GalTase, there is evidence that other sperm proteins may also bind ZP3. Although fertilization in the mouse is morphologically similar to fertilization in most other mammalian species, the degree of parallelism at the molecular level is not well defined. Less information is available about the molecular details of fertilization in other species. The aim of this work was to determine whether sperm from other mammalian species express GalTase on their surface. We performed GalTase enzyme assays on sperm from six species, and all six expressed GalTase on their surface. The amounts of GalTase varied between species. Guinea pig, mouse, and rat sperm had higher levels of GalTase than bovine, porcine, and rabbit sperm. GalTase was localized by immunofluorescence on live and fixed sperm to the anterior portion of the sperm head in all species examined. This is the expected location for a receptor that binds the zona pellucida. Biotinylation of sperm surface proteins confirmed that GalTase detected by immunofluorescence and enzyme assay was expressed on the sperm surface. These results demonstrate that various mammalian species express GalTase on their surface and that it is found in the proper location to bind to the zona pellucida.
Acrosome↗
Levels of myc, fos, Ha-ras, met and hepatocyte growth factor mRNA during regenerative cell proliferation in female mouse liver and male rat kidney after a cytotoxic dose of chloroform.
Chloroform is a liver carcinogen in mice and a kidney carcinogen in rats. It is thought to act through a non-genotoxic-cytotoxic mode of action. Changes in expression of growth control genes accompanying chloroform-induced cytolethality and regeneration may play a part in the development of chloroform-induced tumors. In this experiment, we examined the levels of the myc, fos, Ha-ras, met and hepatocyte growth factor mRNA in livers of female B6C3F(1) mice and kidneys of male F-344 rats to detect changes in gene expression following a single, cytotoxic gavage dose of chloroform in corn oil. Poly A+ RNA was purified from homogenates of livers of mice treated with 350mg/kg chloroform and kidneys of rats treated with 180 mg/kg chloroform and used for Northern blot analysis. Livers of female mice showed large transient increases in levels of myc and fos mRNA while levels of Ha-ras, met and the hepatocyte growth factor gene mRNA remained near control levels. In the male rat kidney, levels of myc mRNA increased after treatement, while levels of mRNA of all other genes examined remained near control levels. This pattern of gene expression is consistent with that induced by other cytotoxic carcinogens and suggest that alteration of the myc and fos genes could be involved in the regenerative cell proliferation that ultimately could play a role in chloroform-induced tumors.
Animals↗
A 90-day chloroform inhalation study in female and male B6C3F1 mice: implications for cancer risk assessment.
High doses of chloroform induced liver cancer in male and female B6C3F1 mice when administered by gavage, kidney cancer in male Osborne-Mendel rats when given by gavage or in the drinking water, and kidney cancer in male BDF1 mice when administered by inhalation. The weight of evidence indicates that chloroform is acting through a nongenotoxic-cytotoxic mode of action. The present study was designed to investigate the dose-response relationships for chloroform-induced lesions and regenerative cell proliferation in B6C3F1 mice as the basis for formulation of a biologically based risk assessment for inhaled chloroform. Different groups of female and male B6C3F1 mice were exposed to atmospheric concentrations of 0, 0.3, 2, 10, 30, and 90 ppm chloroform 6 hr/day, 7 days/week for exposure periods of 4 days or 3, 6, or 13 consecutive weeks. Some additional exposure groups were exposed for 5 days/week for 13 weeks or were exposed for 6 weeks and then examined at 13 weeks. Bromodeoxyuridine was administered via osmotic pumps implanted 3.5 days prior to necropsy, and the labeling index (LI, percentage of nuclei in S-phase) was evaluated immunohistochemically from histological sections. Complete necropsy and microscopic evaluation revealed treatment-induced dose- and time-dependent lesions only in the livers and nasal passage of the female and male mice and in the kidneys of the male mice. Large, sustained increases in the liver LI were seen in the 90-ppm groups at all time points. The female mice were most sensitive, with a no-observed-adverse-effect level (NOAEL) for induced hepatic cell proliferation of 10 ppm. The hepatic LI in the 5 days/week groups were about half of those seen in the 7 days/week groups and had returned to the normal baseline in the 6-week recovery groups. Induced renal histologic changes and regenerative cell proliferation were seen in the male mice at 30 and 90 ppm with 7 days/week exposures and also at 10 ppm with the 5 days/week regimen. Nasal lesions were transient and confined to mice exposed to 10, 30, or 90 ppm for 4 days. In a previous cancer bioassay, a gavage dose of 477 mg/kg/day produced a 95% liver tumor incidence in female B6C3F1 mice. This gavage dose is equivalent to a daily 6 hr/day inhalation exposure of approximately 80 ppm, based on the observed induced increases in the LI as an internal dosimeter. The United States Environmental Protection Agency currently uses the linearized multistage model applied to the mouse liver tumor data from the chloroform gavage study to estimate a virtually safe dose (VSD) as a one in a million increased lifetime risk of cancer. The resulting value is an airborne exposure concentration of 0.000008 ppm. Assuming that chloroform-induced female mouse liver cancer is secondary to events associated with necrosis and regenerative cell proliferation, then no increases in liver cancer in female mice would be predicted at the NOAEL of 10 ppm or below based on the results reported here. Applying an uncertainty factor of 1000 yields an estimate of a VSD at 0.01 ppm. This estimate relies on inhalation data and is more consistent with the mode of action of chloroform.
Administration, Inhalation↗
A 90-day chloroform inhalation study in F-344 rats: profile of toxicity and relevance to cancer studies.
Chloroform acts via a nongenotoxic-cytotoxic mode of action to produce cancer if given in doses and at dose rates sufficiently high to produce organ-specific toxicity. In a recent study, chloroform failed to induce cancer in male or female F-344 rats when administered by inhalation for 2 years at 90 ppm, 5 days/week. The present study was undertaken to define the concentration-response curves for chloroform-induced lesions and regenerative cell proliferation in the F-344 rat when exposed by inhalation and to correlate those patterns of toxicity with the results from the inhalation cancer bioassay. Male and female F-344 rats were exposed to airborne concentrations of 0, 2, 10, 30, 90, or 300 ppm chloroform 6 hr/day, 7 days/week for 4 days or 3, 6, 13 weeks. Additional treatment groups were exposed 5 days/week for 13 weeks or were exposed for 6 weeks and held until Week 13. Bromodeoxyuridine was administered via osmotic pumps implanted 3.5 days prior to necropsy and the labeling index (LI, percentage of nuclei in S-phase) was evaluated immunohistochemically. A full-screen necropsy identified the kidney, liver, and nasal passages as the only target organs. This study confirmed that 300 ppm is extremely toxic and would be inappropriate for longer-term cancer studies. The primary target in the kidney was the epithelial cells of the proximal tubules of the cortex, with significantly elevated increases in the LI at concentrations of 30 ppm and above. However, only a marginal increase in the renal LI in the males was seen after exposures of 90 ppm, 5 days/week. Chloroform induced hepatic lesions in the midzonal and centrilobular regions with increases in the LI throughout the liver, but only at 300 ppm exposures. An additional liver lesion seen only at the highly hepatotoxic concentration of 300 ppm was numerous intestinal crypt-like ducts surrounded by dense connective tissue. Enhanced bone growth and hypercellularity in the lamina propria of the ethmoid turbinates of the nose occurred at the early time points at concentrations of 10 ppm and above. At 90 days there was a generalized atrophy of the ethmoid turbinates at concentrations of 2 ppm and above. Cytolethality and regenerative cell proliferation are necessary but not always sufficient to induce cancer because of tissue, sex, and species differences in susceptibility. A combination of a lack of direct genotoxic activity by chloroform, only a marginal induction of cell proliferation in the male rat kidney, and lower tissue-specific susceptibility in the female rat is apparently responsible for the reported lack of chloroform-induced cancer in a long-term inhalation bioassay with F-344 rats.
Administration, Inhalation↗
Peer review in a shared governance model.
Peer review is a process by which professional nurses measure the quality of nursing practice in relation to established standards of practice. Shared governance provides a framework in which professional nurses self-regulate practice in their domain. Quality of nursing care is assessed through the peer review process in a shared governance model. This article describes the development, implementation, and evaluation of a peer review process and tool designed for postanesthesia nursing practice.
Clinical Competence↗