Continuous bladder infusion methods for studying voiding function in ambulatory mice.
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Administration, Intravesical↗
Biomedical subjects
R W Wood
Publications and source records attributed to R W Wood.
Stability of methylecgonidine and ecgonidine in sheep plasma in vitro.
BACKGROUND: Crack smokers are exposed to a pyrolysis product, methylecgonidine (MEG), which can be used as an analytical marker for crack smoking. Ecgonidine (EC), a hydrolytic product of MEG, has been identified in urine of crack smokers. MEG undergoes conversion to EC, complicating analysis and perhaps explaining a lack of forensic blood specimens containing MEG. METHODS: We developed gas chromatography-mass spectrometry (GC-MS) assays for MEG and EC. Plasma was collected from sheep blood containing 0, 0.06, or 0.24 mol/L (0%, 0.25%, or 1%) NaF. MEG was added to these plasmas, and they were incubated at -80, 1, 21, or 37 degrees C to determine whether there were temporal, temperature, or storage effects on MEG stability over 48 h. RESULTS: Decreased temperature and increased NaF concentrations limited MEG degradation and EC formation. MEG stored in plasma at -80 degrees C was stable up to 1 month, even in the absence of NaF. CONCLUSIONS: MEG is stable in sheep plasma collected in commercially available, evacuated blood-collection tubes containing NaF and stored at -80 degrees C. In vitro formation of EC can be minimized with appropriate sample handling, and its in vivo formation may provide a better marker of crack smoking than its parent pyrolysis product.
Animals↗
Developing, implementing, and evaluating a condom promotion program targeting sexually active adolescents.
This article describes the development, implementation, and evaluation of the Condom Campaign, a 1995 HIV prevention program promoting condom use among sexually active adolescents in three King County, Washington, urban communities. This program employed three main strategies: (a) mobilizing all levels of the target communities to support and guide program development and implementation; (b) creating and implementing a mass media campaign targeting sexually active teenagers that promoted correct condom use and favorable attitudes toward condoms; and (c) recruiting public agencies, community organizations, and businesses to distribute condoms from bins and vending machines. We evaluated the program through a series of cross-sectional interviews conducted in the three communities chosen for their elevated levels of adolescent sexual risk behavior. Overall, 73% of target youth reported exposure to the Condom Campaign; exposure did not differ by age, gender, race, or level of sexual experience. Levels of sexual activity remained stable throughout the media campaign.
Adolescent↗
Nebulization of NanoCrystals: production of a respirable solid-in-liquid-in-air colloidal dispersion.
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Aerosols↗
Clinical relevance of parvovirus B19 as a cause of anemia in patients with human immunodeficiency virus infection.
Parvovirus B19 (B19) DNA was detected by dot blot hybridization in sera from 5 (17%) of 30 human immunodeficiency virus (HIV)-infected patients with hematocrits (HCT) of < or =24 and 4 (31%) of 13 HRV-infected patients with HCT of < or =20, suggesting that B19 is a reasonably common cause of severe anemia in HIV infection. The anemia promptly remitted after immunoglobulin therapy in 3 of 4 treated patients. The presence of IgM to B19, the clinical circumstance in which anemia developed, and the marrow morphology were poor predictors of chronic B19 infection. DNA hybridization studies of sera from 191 HIV-infected and 117 HIV-seronegative homosexual males attending a clinic in the Seattle area revealed that 1 (0.5%) and 2 (2%) samples, respectively, from the 2 groups contained B19. However, when assayed by polymerase chain reaction (PCR), 5% of the serum samples from HIV-infected persons and 9% from uninfected persons contained B19, although each had an HCT of > or =40. The data argue that anemia results from chronic high-titer B19 infection. Although a negative PCR assay excludes this diagnosis, DNA hybridization may be the more specific serum test.
Adult↗
Testing the neural sensitization and kindling hypothesis for illness from low levels of environmental chemicals.
Sensitization in the neuroscience and pharmacology literatures is defined as progressive increase in the size of a response over repeated presentations of a stimulus. Types of sensitization include stimulant drug-induced time-dependent sensitization (TDS), an animal model related to substance abuse, and limbic kindling, an animal model for temporal lobe epilepsy. Neural sensitization (primarily nonconvulsive or subconvulsive) to the adverse properties of substances has been hypothesized to underlie the initiation and subsequent elicitation of heightened sensitivity to low levels of environmental chemicals. A corollary of the sensitization model is that individuals with illness from low-level chemicals are among the more sensitizable members of the population. The Working Group on Sensitization and Kindling identified two primary goals for a research approach to this problem: to perform controlled experiments to determine whether or not sensitization to low-level chemical exposures occurs in multiple chemical sensitivity (MCS) patients; and to use animal preparations for kindling and TDS as nonhomologous models for the initiation and elicitation of MCS.
Animals↗
Methylecgonidine coats the crack particle.
Crack is a form of cocaine base self-administered by smoking. When heated, it volatilizes and may partially pyrolyze to methylecgonidine (MEG). Upon cooling, a condensation aerosol forms. Heating cocaine base in model crack pipes produced particles of about 1 micron in diameter, regardless of the amount heated; however, MEG concentration increased from < or = 2% at 10 mg per heating to as much as 5% at 30 mg per heating. Methylecgonidine was < or = 1% of the recovered material when cocaine was vaporized off a heated wire coil, but the particles were larger (2-5 microns), and the distribution disperse. The vapor pressure of MEG was higher [log P(mm Hg) = 9.994 - 3530/T] than cocaine base, consistent with MEG coating the droplet during condensation, and with evaporation during aging or dilution. Disappearance of MEG from a chamber filled with crack smoke was a two-component process, one proceeding at the rate of cocaine particle removal, and the other at the desorption rate from other surfaces. Particle diameter influences the deposition site in the respiratory tract; thus, the likely different patterns of deposition in the respiratory tract of humans and animals of crack aerosols produced by different techniques warrant consideration, as they may influence our understanding of immediate and delayed sequelae of the inhalation of cocaine and its pyrolysis product, MEG.
Administration, Inhalation↗
Generation of stable test atmospheres of cocaine base and its pyrolyzate, methylecgonidine, and demonstration of their biological activity.
Generating controlled test atmospheres of known chemical identity and airborne concentration upon demand is a significant technical obstacle that limits the scope and repeatability of studies of inhaled substances. We addressed this problem as applied to the generation of atmospheres that result from heating crack cocaine, which include both cocaine and its pyrolyzate methylecgonidine (MEG). A condensation aerosol generator was used to generate atmospheres comprised of monodisperse particles of cocaine, MEG, or mixtures of both that are of submicron size suitable for deposition in the alveolar region of primates. Compressed air seeded with nanometer-size sodium chloride particles was passed through a constant depth of molten cocaine or MEG in a bead bed, reheated, and condensed to an aerosol within an annulus of cold air. To achieve control of a mixture of both compounds, MEG was condensed onto cocaine particles in a separate coating step. On-line analytical instruments provided verification of airborne concentration, estimates of particle size, and dispersion as well as chemical identity. Specific airway conductance (SGaw), heart rate, and rectal and skin temperatures were measured in squirrel monkeys breathing atmospheres containing condensation aerosols of cocaine or MEG free base. SGaw was reduced after inhalation of either base, and both induced temperature and cardiovascular changes, demonstrating that the aerosols so generated had biological activity.
Administration, Inhalation↗
A repeated measures approach to the detection of the acute behavioral effects of toluene at low concentrations.
Acute behavioral effects of solvents are frequently the critical parameter considered for the recommendation of exposure limit values. Studies of toluene's acute effects on animal behavior during exposure have not been particularly sensitive; increasing the number of observations at low concentrations and the number of animals studied is a reasonable approach to increasing the ability to detect small acute effects. The effects of toluene (178-3000 ppm) were determined in 12 rats trained to nose poke on a probabilistic schedule of food delivery in a small exposure chamber that was highly ventilated with air or a toluene test atmosphere. Animals served as their own controls and were exposed to toluene twice a week for 2 hr during behavioral evaluation. At least six determinations of the effects of toluene were made at concentrations of 178, 300, and 560 ppm, and at least three determinations at 1000, 1780, and 3000 ppm. Biphasic concentration-effect, time-effect, and concentration-response functions were observed. Rates of nose poking increased in 4 of 12 animals at 178 ppm and in 9 of 12 animals at 300 ppm; all animals were affected at 560 ppm. The concentration at which a 10% rate increase occurred was determined by regression analysis to be 156 ppm with the lower 95% confidence limit or "benchmark" concentration being 116 ppm. Weighted regression analysis produced slightly higher estimates of these parameters, 182 and 157 ppm, respectively, while conventional logistic regression revealed that 10% of animals would be affected at a concentration of 114 ppm with a lower confidence limit of 63 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Behavioral evaluation of the irritant properties of formaldehyde.
The effects of formaldehyde were determined using a behavioral technique that permits the estimation of the aversiveness of airborne chemical irritants. Eight mice were initially trained to terminate presentations of ammonia by poking their nose into a conical sensor; five pokes terminated the presentation and produced a facial shower of clean air. Ammonia (1000 ppm) or formaldehyde (1.0-10 ppm) was delivered to the mice for a maximum of 60 sec followed by a 60-sec washout period; this cycle repeated 25 times per session. All animals consistently terminated 100% of ammonia deliveries. Mice also terminated delivery of formaldehyde. At the lowest concentration examined (1.0 ppm), significantly (p < 0.0005) more deliveries of formaldehyde were terminated than were deliveries of air. Mice differed in their sensitivity to formaldehyde: one mouse failed to terminate any more than 10% of deliveries of formaldehyde up to concentrations of 10 ppm; graded concentration-related increases in the number of deliveries terminated were observed in five mice; the two remaining mice consistently terminated 80% or more of the deliveries at each concentration of formaldehyde. As the concentration of formaldehyde increased, the amount of time taken to terminate the exposure decreased. A significant shift to the left of the concentration-effect curves occurred on the second exposure to the series of formaldehyde concentrations. These studies indicate that formaldehyde is aversive to mice at concentrations which approximate those at which humans also report sensory irritation, and that enhanced sensitivity is associated with repeated exposure.
Aerosols↗
Pulmonary effects of the cocaine pyrolysis product, methylecgonidine, in guinea pigs.
The pulmonary effects of the cocaine pyrolysis product, methylecgonidine (MEG; anhydroecgonine methyl ester), were assessed in guinea pigs. Specific airway conductance (SGaw), which decreases during bronchoconstriction, was measured in guinea pigs exposed to atmospheres containing a condensation aerosol of MEG free base (13 +/- 1 mg/liter of air), nebulized MEG fumarate (3 and 12% in phosphate buffered saline) or nebulized acetylcholine chloride (0.2 and 0.4% in phosphate buffered saline). A decrease in SGaw to 24.0 +/- 4.2% (mean +/- 2 S.E.M.) of baseline levels was observed in guinea pigs breathing MEG free base. A decrease to 28.4 +/- 4.5% of baseline was observed following administration of 0.4% acetylcholine. No change in SGaw was measured in guinea pigs exposed to 3% MEG fumarate but SGaw was reduced to 69.3 +/- 5.3% of baseline after exposure to 12% MEG fumarate. MEG free base poses an alkaline challenge to the lung, 3% MEG fumarate is neutral (pH approximately 7.4) and 12% MEG fumarate is acidic (pH approximately 4.3); thus, MEG free-base and 12% MEG fumarate might provoke a reflex bronchoconstriction due to direct pulmonary irritant effects. These results suggest that MEG free base produced during crack pyrolysis may play a role in bronchoconstriction observed in crack smokers.
Animals↗
Effects of methylecgonidine on acetylcholine-induced bronchoconstriction and indicators of lung injury in guinea pigs.
The fumarate salt of methylecgonidine (MEG; anhydroecgonine methylester), a pyrolysis product of cocaine, has previously been shown to antagonize contractions of guinea pig isolated trachea induced by acetylcholine (ACh) and other spasmogenics. We determined the effects of MEG fumarate on ACh-induced bronchoconstriction in vivo. Specific airway conductance (SGaw) was measured in guinea pigs receiving 30-300 mg/kg s.c. MEG fumarate and exposed one hour later to nebulized ACh (0.2-3.2%; by inhalation). MEG fumarate did not induce any changes in SGaw; neither did it antagonize dose-dependent decreases in SGaw induced by ACh. However, tremors, salivation, startle and increased numbers of fecal boli were observed after MEG administration. Thus, unlike antagonism of ACh-induced contractions of guinea pig isolated trachea observed in vitro, MEG fumarate does not antagonize ACh-induced bronchoconstriction in vivo, even at doses which induced changes in grossly-observable behavior. Inhalation of a condensation aerosol of MEG base induced lung damage as evidenced by the presence of blood and higher levels of protein and lactate dehydrogenase in the lung lavage fluid of MEG-treated animals than of control animals. Aerosols of MEG fumarate, on the other hand, did not induce lung damage when inhaled. These results extend previous observations that MEG base may contribute to detrimental pulmonary effects of crack smoking.
Acetylcholine↗
Comparison of simulated and in-vivo plasma levels of cilastatin following intravenous in-line drug administration.
The primary objective of this work was to establish a method to simulate the plasma levels of cilastatin, a model drug, following an intravenous in-line delivery scheme. In-vivo data in dogs obtained from this work were used to demonstrate the validity of the proposed approach. The in-line drug delivery system consists of a drug containing device which is placed between a large volume parenteral and a patient. Numerous advantages have been identified for this automatic in-line reconstitution delivery system. The numerical convolution integral algorithm was used in this work to perform plasma profile simulation. The results indicated that the simulated cilastatin plasma profile following in-line delivery closely agreed with the in-vivo data.
Animals↗
Foreign bodies in spinal syringes.
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Anesthesia, Spinal↗
Airway smooth muscle relaxant effects of the cocaine pyrolysis product, methylecgonidine.
Methylecgonidine (anhydroecgonine methylester; MEG) is produced when cocaine base ("crack") is heated. Since crack smoking can produce significant airway toxicity and the role of MEG in this toxicity is unknown, we determined the effects of MEG on guinea pig isolated tracheal rings. Trachea do not contract in response to MEG; rather, MEG (10(-9) to 10(-3) M) dose-dependently relaxed tissue precontracted with 2 x 10(-3) M acetylcholine (ACh). MEG (10(-9) to 10(-6) M) reduced the magnitude of contractions induced by ACh, carbachol, histamine and KCl in a nonsurmountable manner; the maximal response to these agents was not restored after repeated washing. MEG did not affect contractions induced by BaCl2. 4-Diphenyl acetoxymethyl piperidine methiodide (4-DAMP; 10(-7) M), in the presence or absence of MEG (10(-7) M), shifted the dose-effect curve for ACh 30-fold to the right. After washing, sensitivity to ACh was fully recovered in tissues exposed to 4-DAMP alone, but was still reduced to 50% of control in tissues exposed to 4-DAMP and MEG. The effects of MEG were unlike those of cocaine which, at 10(-7) to 10(-5) M, increased the magnitude of contractions induced by ACh (10(-9) to 2 x 10(-3) M); MEG (10(-7) M) abolished this increase. The mechanism by which MEG relaxes tracheal smooth muscle has not been established, but it is likely to be independent of direct interaction with sites that mediate the effects of the bronchoconstrictor agents used in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Attitudes toward assisted suicide and euthanasia among physicians in Washington State.
BACKGROUND: Despite considerable public interest in legalizing physician-assisted suicide and euthanasia, little is known about physicians' attitudes toward these practices. METHODS: We sent questionnaires to 1355 randomly selected physicians in the state of Washington, including all hematologists and oncologists and a disproportionately high number of internists, family practitioners, psychiatrists, and general surgeons. To avoid ambiguity in our survey, instead of "physician-assisted suicide," we used the phrase "prescription of medication [e.g., narcotics or barbiturates] or the counseling of an ill patient so he or she may use an overdose to end his or her own life." Instead of "euthanasia," we used the phrase "deliberate administration of an overdose of medication to an ill patient at his or her request with the primary intent to end his or her life." RESULTS: Of the 1355 eligible physicians who received our questionnaire, 938 (69 percent) responded. Forty-eight percent of the respondents agreed with the statement that euthanasia is never ethically justified, and 42 percent disagreed. Fifty-four percent thought euthanasia should be legal in some situations, but only 33 percent stated that they would be willing to perform euthanasia. Thirty-nine percent of respondents agreed with the statement that physician-assisted suicide is never ethically justified, and 50 percent disagreed. Fifty-three percent thought assisted suicide should be legal in some situations, but only 40 percent stated that they would be willing to assist a patient in committing suicide. Of the groups surveyed, hematologists and oncologists were most likely to oppose euthanasia and assisted suicide, and psychiatrists were most likely to support these practices. CONCLUSIONS: The attitudes toward physician-assisted suicide and euthanasia of physicians in Washington State are polarized. A slight majority favors legalizing physician-assisted suicide and euthanasia in at least some situations, but most would be unwilling to participate in these practices themselves.
Attitude of Health Personnel↗
The central role of case managers in early discharge planning for hospitalized persons with AIDS.
Case managers can play a pivotal role in the hospital discharge planning process for medically complex patients. This is particularly true for persons with AIDS. This prospective study quantifies the importance of this role by examining the ability of case managers, nurses, and physicians to predict (at the time of admission) whether hospitalized AIDS patients would be appropriate for transfer to long-term care facilities after their hospital stays. We studied 120 AIDS patients and their primary providers; 38 (32%) patients were found to be appropriate for discharge to long-term care facilities at the end of their hospital stays. Physicians and nurses had similar accuracy in predicting eventual appropriateness for long-term care (75% and 73% correct, respectively); however, case managers were far more accurate than the physicians and nurses (93% correct, p < .05). This finding highlights the unique ability of case managers to facilitate discharge planning early on in the hospital stays of these complex patients. In this study, case managers were more accurate than physicians or nurses in predicting appropriateness for long-term care of hospitalized persons with AIDS. Case managers should play an integral role in coordinating discharge planning of persons with AIDS; this planning should be part of the hospital admission process.
Acquired Immunodeficiency Syndrome↗
Recruitment of primary care physicians to care for patients with human immunodeficiency virus infection in a large northwestern county.
BACKGROUND: We evaluated an initiative to recruit and to educate physicians to care for persons with human immunodeficiency virus (HIV) infection in King County, Washington, and to refer patients to them through a centralized telephone referral service (the acquired immunodeficiency syndrome [AIDS]/HIV Care Access Project). METHODS: Six physicians trained in AIDS care recruited primary care physicians in clinics throughout King County; the physician cohort was monitored for behavior in accepting referrals during the ensuing year. RESULTS: Of 250 primary care physicians contacted initially, 79 of 120 who met with AIDS-trained physicians were willing to accept patient referrals. Willingness was not related significantly to age, sex, years in practice, or specialty, but was related to level of experience with HIV/AIDS care and current practice. The recruitment initiative increased the physicians available to the telephone referral service by 93% (from 85 to 164). More physicians (41) joined the referral service in the ensuing year, during which 647 patient referrals were made to these 205 physicians (median referral rate of one patient per quarter). Four physicians requested cessation of referrals, however, two later asked for referrals to continue. CONCLUSION: The recruitment initiative was successful in increasing the number of primary care physicians available to accept patients with HIV infection into their practices (thereby reducing the burden of HIV referrals on a small pool of providers), and in establishing a county-wide telephone service to coordinate these referrals. The initiative was self-sustaining, with an ongoing influx of new providers willing to take referrals.
Acquired Immunodeficiency Syndrome↗