Clinical decisions in the care of elderly persons with AIDS.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
R W Wood
Publications and source records attributed to R W Wood.
pH regulation of an egg cortex tyrosine kinase.
Fertilization of the echinoderm egg is known to result in the phosphorylation, on tyrosine, of a high-molecular-weight cortical protein (HMWCP) localized in the egg cortex. Studies using various parthenogenic agents indicate that this phosphorylation event occurs in response to the alkaline shift in cytoplasmic pHi which normally occurs 1 to 2 min after fertilization. In the present study, the purified egg cell surface complex was used as in vitro system to determine whether a small alkaline shift in pH, such as occurs upon fertilization, could stimulate the activity of the egg cortex-associated tyrosine kinase toward endogenous protein substrates. The results demonstrated that the cell surface complex is highly enriched in a tyrosine kinase activity which accounts for the majority of the protein kinase activity in this preparation. The activity of this tyrosine kinase toward the HMWCP and other cortical proteins was highly dependent on pH over the range pH 6.8 to 7.3. This indicates that the fertilization-associated change in cytoplasmic pH would be sufficient to trigger increased tyrosine phosphorylation of the high-molecular-weight cortical protein in vivo. The regulation of tyrosine phosphorylation by small changes in pH represents a novel control mechanism in which a tyrosine protein kinase may act as a pH-sensitive transducer.
Animals↗
In vitro dissolution and in vivo bioavailability of commercial levothyroxine sodium tablets in the hypothyroid dog model.
The objective of this study was to determine whether a correlation exists between the rate of in vitro dissolution and bioavailability of levothyroxine sodium (T4) tablets. Dissolution versus time profiles for Synthroid, the Flint brand of levothyroxine sodium, and two competitors' tablets (brands A and B) were generated using an official dissolution apparatus (USP), and 0.05 M phosphate buffer (pH 7.4) as the medium. These tablets were also utilized in single-dose crossover bioavailability studies in the hypothyroid dog model (n = 6). The average areas under the serum T4 concentration versus time curve from 0 to 8 h (AUC) for Synthroid, brand A, and brand B were 8.22, 6.32, and 8.70 ng-h/mL per dose (micrograms per kg body weight), respectively. Respective peak serum concentrations (Cmax) for each tablet formulation were 1.26, 1.07, and 1.36 ng/mL per dose. The corresponding dissolution rates, expressed as t50%, were 20.5, 3.06, and 14.1 min, respectively. Data analysis indicated no correlation between dissolution kinetic parameters and the bioavailability parameters AUC and Cmax. However, a linear relationship was observed between dissolution kinetics and both the time to reach maximal serum concentration (tmax) and the observed absorption rate constant (ka).
Animals↗
Biphasic changes in mouse motor activity during exposure to toluene.
There are few careful studies of the effects of solvents on unlearned animal behavior during acute exposure, despite the importance of the prevention of acute behavioral or neurological effects in the workplace. To examine the effects of toluene on the locomotor activity of mice, we divided a plastic vacuum desiccator into six wedge-shaped compartments with diffusing plena above and below. A phototransistor in each wedge measured the movement of individual mice, thus each mouse could serve as its own control. Six groups of six mice were exposed to each of five concentrations of toluene (300-3000 ppm) or air in a Latin-square design for 1 hr on Tuesdays and Fridays. Individual animals differed in their sensitivity to toluene, and the use of each subject as its own control permitted the detection of effects at lower concentrations. The magnitude of the effect was related to concentration, the duration of exposure, and the control rate of activity. Activity increases were obvious at 560 ppm, and decreases at 3000 ppm. The concentrations at which these reversible activity increases occurred are the lowest reported to date and are only slightly greater than those that have been reported to alter human reaction time. This preparation displays sensitivity comparable to that observed in published studies of the effects of toluene on learned behavior in the rat.
Analysis of Variance↗
Analysis of 5' flanking regions of the gamma globin genes from major African haplotype backgrounds associated with sickle cell disease.
There are at least three major African haplotype backgrounds on which the beta s mutation arises. Sequence changes in the immediate 5' flanking area of the gamma-globin genes may account for differences in fetal hemoglobin expression among the three haplotypes. We determined the sequence from -350 to 10 bp 5' of the G gamma and A gamma fetal globin genes from one beta s-containing chromosome on each of the three major haplotype backgrounds. The Senegal chromosome had a T at -158 5' to the G gamma gene; the Benin (BEN) chromosome had an A to G change at -309 5' to the G gamma gene; and the Central African Republic (CAR) chromosome had a C to T change at -271 5' to the A gamma gene. Genomic DNA from patients with sickle cell disease was analyzed using the polymerase chain reaction and radiolabeled allele-specific oligonucleotide probes. The -309 G variant 5' to the G gamma gene is associated with BEN chromosomes, and the -271 T variant 5' to A gamma with CAR. The -309 change was also found on beta A-containing chromosomes, while the -271 change was not. The -309 change may have predated the beta s mutation on the BEN chromosome.
Anemia, Sickle Cell↗
Poverty and HIV seropositivity: the poor are more likely to be infected.
We analyzed demographic and behavioral risk factors for HIV seropositivity using data from 3601 clients of the main HIV counseling and testing clinic for high-risk people in Seattle, Washington, USA. Clients with lower income were found to be more likely to be HIV seropositive, before and after controlling for other demographic and risk factors with logistic regression. This result supports the hypothesis that the impoverished are at increased risk for HIV infection due to the physical and social circumstances in which their poverty places them. These may include poor access to risk-reduction information and less support for implementation of risk-reduction strategies.
Acquired Immunodeficiency Syndrome↗
Animal models of drug self-administration by smoking.
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Animals↗
Oral mucosal lesions: association with the presence of antibodies to the human immunodeficiency virus.
To assess the relationship between oral lesions and antibodies to the human immunodeficiency virus, oral examinations of 803 homosexual males were conducted at the time of serologic testing. Nineteen percent were HIV seropositive. Thirty percent of antibody-positive subjects had one or more oral lesion(s), as compared with 7% of antibody-negative subjects (p less than 0.001). The presence of oral lesions was significantly associated with HIV seropositivity: a subject was 5.7 times as likely to have serum antibodies if he had one or more oral lesions (95% confidence interval, 3.5 to 9.1; p less than 0.001). This significant association with HIV seropositivity was only partially explained by cigarette smoking (adjusted odds ratio 3.1; 1.4-6.8; less than 0.006). Specific conditions that were significantly associated with seropositivity included candidiasis, hairy leukoplakia, periodontal disease, and Kaposi's sarcoma. Other diseases identified included acute necrotizing ulcerative gingivitis, mucocutaneous ulcerations, and oral warts. Oral findings may occur earlier in the natural history of infection than previously reported.
Adult↗
Evidence of tolerance following repeated exposure to toluene in the rat.
Toluene shares pharmacological properties with other abused central nervous system depressants such as ethanol and the barbiturates. Although tolerance has been clearly demonstrated for these classic CNS depressants, evidence of tolerance following repeated toluene exposure is equivocal. The present work examined if tolerance would develop to the effects of repeated toluene exposure on learned behavior and examined the possibility that external discriminative stimuli could influence these effects. Two variants of a fixed-consecutive-number schedule of reinforcement were used as components in a multiple schedule. The components differed in whether or not behavior within them was under the control of external discriminative stimuli. Rats were exposed daily for two hours to toluene (1780 to 4500 ppm). Different patterns of effects emerged from repeated exposure; some rats displayed tolerance while the performance of others deteriorated. Behavior controlled by external discriminative stimuli was more resistant to disruption and showed tolerance more readily than did behavior not under such control.
Animals↗
National policy on AIDS.
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Acquired Immunodeficiency Syndrome↗
"Crack smoke" is a respirable aerosol of cocaine base.
The smoking of cocaine base [corrected] ("crack") has emerged as a significant substance abuse problem. A detailed characterization of cocaine smoke is a prerequisite for studies of its pharmacokinetics, abuse potential and toxicity. Model pipes were used to generate cocaine smoke analogous to that inhaled by human "crack" abusers. Using procedures to minimize pyrolysis, cocaine base smoke was determined to be 93.5% cocaine particles with the remainder being cocaine vapor. The average particle size generated from all model pipes was 2.3 mu which is small enough to ensure deposition into the alveolar region of the human lung. Although this particle size is eminently respirable [corrected] by primates, a much smaller fraction will reach the alveolar region of rodents. Special generating procedures would therefore be required to expose rodents to meaningful doses of airborne cocaine that mimic the rapid absorption achieved by "crack" smokers.
Aerosols↗
Carbon disulfide effects on the visual system. II. Retinogeniculate degeneration.
We examined the morphological effects of carbon disulfide exposure on neurons and vasculature of the visual system of macaque monkeys. Five monkeys were exposed to 256 ppm carbon disulfide (CS2) by inhalation for 6 hr a day, 5 days a week. One monkey, sacrificed immediately after exposure, had numerous axonal swellings in the distal optic tract. Four other monkeys survived the exposure period for at least 1 year and were found to have suffered marked degeneration of central retinal ganglion cells, with little or no effect on other neurons in the retina. No evidence was found for arteriosclerotic or aneurysmal changes, suggesting that visual system injury in primates induced by carbon disulfide exposure is not dependent on the occurrence of structural changes in retinal blood vessels.
Animals↗
The acute toxicity of nitrite inhalants.
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Administration, Inhalation↗
Carbon disulfide effects on the visual system. I. Visual thresholds and ophthalmoscopy.
The visual effects of carbon disulfide exposure were studied in macaque monkeys with measurements of visual thresholds, fluorescein angiography and fundus photography. Five monkeys were exposed by inhalation for 6 hr a day, 5 days a week to 256 ppm carbon disulfide (CS2). The motor dysfunction observed in these monkeys appeared to be entirely reversible. All five suffered severe reductions in visual acuity and contrast sensitivity although flicker resolution was not affected. Visual loss was found to be irreversible, with degeneration of substantial numbers of retinal ganglion cells (companion paper) in those monkeys permitted to survive after the termination of exposure. None of the monkeys developed retinal microaneurysms or hemorrhages, major accepted signs of visual toxicity in CS2 exposed humans; thus, permanent visual loss may result from carbon disulfide exposure even in the absence of retinal vascular effects.
Animals↗
Acquired immunodeficiency syndrome.
Acquired immunodeficiency syndrome (AIDS) is the lethal end stage of a sexually transmitted disease caused by a virus that is producing the major epidemic of our century. In this article we describe the history and epidemiology of AIDS and the disease states associated with infection with the human immunodeficiency virus (HIV), the apparent cause of AIDS. We review what is known about disease pathogenesis and present an overview of clinical management issues. In the absence of vaccine or therapy to prevent and eradicate this viral infection, we present formative educational approaches for its control.
Acquired Immunodeficiency Syndrome↗
Stimulus control and the development of behavioral tolerance to daily injections of d-amphetamine in the rat.
We examined whether daily d-amphetamine administration affected behavior under the control of external stimuli differently than behavior not under such control. Two variants of a fixed-consecutive-number reinforcement schedule were combined in a multiple schedule. An external discriminative stimulus indicated when the schedule requirement for reinforcement had been satisfied in one component, no such stimulus was used in the other component. Reinforcement frequency was roughly equated between the components by reducing the probability of reinforcement in the added stimulus component. Two groups of animals were given daily i.p. injections with equivalent doses of drug. Tolerance to the drug's behavioral effects developed when injections occurred before behavioral evaluation but did so only to a limited extent when injections were given only after the sessions. This indicated that behaving in the presence of the drug facilitated the development of such tolerance. It developed under both stimulus control conditions at both doses; at 3.0 mg/kg, it developed predominantly in those aspects of behavior that were under the control of external discriminative stimuli. Although drug-related decreases in reinforcement frequency in some animals were correlated with behavioral tolerance development, differential tolerance development was not associated consistently with such reductions. Establishing discriminative control of behavior by external stimuli can both reduce sensitivity to repeated d-amphetamine administration and facilitate the development of tolerance to its behavioral effects.
Animals↗
Abdominoplasty: agony and ecstasy.
A review of 102 consecutive patients was made. Stress is given to the standard of excellence, which should be an attempt to re-create an hour-glass contour (certainly in all thin patients and perhaps to a certain extent even in the obese patient). A row of sutures (approximately 3 mm apart) is placed in the rectus fascia tightening it as much as each suture will tolerate. With this row of numerous sutures, the intense pull that gives the superb contour is distributed more evenly than in a lesser number of sutures. In the obese patient the superior flap must be defatted for about a centimeter, just to the subdermal level, in order to correct the asymmetry of thickness of the superior flap as opposed to the thinness of the pubic skin.
Abdominal Muscles↗
Behavioral evaluation of the irritating properties of ozone.
The sensory irritant properties of ozone have been considered to be responsible for symptoms that occur in humans after exposure. This assumption has not been studied explicitly. One way to assess the aversive properties of airborne irritants is to give the exposed individual an opportunity to control the duration of exposure, i.e., escape from the irritant. Mice were trained to turn off 1000-ppm ammonia, a concentration that, in humans, is irritating to the upper airways. Each mouse could terminate irritant delivery for 1 min by inserting its nose five times into one of two conical response sensors. Daily exposure was limited to a maximum of twenty-five 1-min exposures, every other minute. After the determination of ammonia concentration-effect curves, ozone was substituted for ammonia. Ozone exposures were alternated every other day with ammonia as a control for any changes that might occur as a result of repeated ozone exposure. Ozone reliably maintained escape behavior. Additional mice with no history of ammonia termination were trained to terminate ozone exposure, indicating that the aversive properties of ozone were not dependent on previous experience with other airborne irritants. As the concentration of ozone increased from 0.25 to 24 ppm, the number of escape responses increased, and the duration of ozone tolerated decreased. Ozone concentrations of 0.5 ppm or greater were significantly more aversive than control.
Ammonia↗