Problematic renal calculi presenting during pregnancy.
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Female↗
Biomedical subjects
T Thompson
Publications and source records attributed to T Thompson.
Architectural features and perceptions of community residences for people with mental retardation.
Architects, group home administrators, people with mental retardation, family members of people with mental retardation, and college undergraduates substantially agreed regarding the rated homelikeness of slides of interiors of 20 community residences for people with mental retardation ranging from institutional to homey, mean r = .87. Clusters of physical features identified using an architectural inventory were found to be associated with homelikeness ratings. Adjectives applied to rooms with these features were determined using a Q-sort method. Two factors were identified from Q-sort correlations: Homelikeness-Institutionality and Spatial Organization as well as a third variable, privacy.
Adolescent↗
Interdependence of architectural features and program variables in community residences for people with mental retardation.
In an earlier study, we found that architects, group home administrators, people with mental retardation, family members of people with mental retardation, and college undergraduates rated the homelikeness of slides of community residences for people with mental retardation similarly. In addition, clusters of physical features were identified that were specifically associated with homelikeness ratings. In the present study, behavior of residents with mental retardation living in those residences was assessed using the Aberrant Behavior Checklist and direct behavioral observations. After statistically controlling for confounding variables, we found that adaptive and maladaptive behavior covaried with homelikeness ratings. In addition, we were able to identify associations between specific architectural features of residential settings and the behavior of residents living in those settings.
Activities of Daily Living↗
In vivo disposition and metabolism by liver and enterocyte microsomes of the antitubercular drug rifabutin in rats.
The in vivo disposition and in vitro metabolism of rifabutin, a new spiropiperidylrifamycin, were studied in rats and in microsomes from rat liver and enterocytes, respectively. After i.v. doses of 1,5, 10 and 25 mg/kg the systemic clearance was 0.7 to 1.0 liters/hr/kg; the volume of distribution was 4.4 liters/kg for the 1 mg/kg dose and 7.4 to 7.7 liters/kg for the 5 to 25 mg/kg doses, and the half-life ranged from 4.4 to 9.1 hr. Urinary and fecal excretion over 0 to 96 hr after i.v. administration of 25 mg/kg [14C]rifabutin accounted for 40.1 and 52.2% of the dose, respectively. Exteriorization of the bile duct showed that approximately 24% of the dose was eliminated in bile, > or = 98% as metabolites. Bioavailability after oral administration of 25 and 1 mg/kg rifabutin was > 90% and 44%, respectively, suggesting significant first-pass metabolism of the lower dose. Concentrations of rifabutin in gastric juice were 10 to 17 times higher than in blood, indicating extensive secretion into the stomach. Experiments with the isolated small intestinal loop demonstrated direct exsorption of the drug into the lumen. The rate of rifabutin metabolism by enterocyte microsomes was > 10 times higher than that by liver microsomes, i.e., 84 and 8 pmol/min/mg protein, respectively. Biotransformation of rifabutin in vivo and in vitro was markedly induced by dexamethasone and inhibited by erythromycin, suggesting that CYP3A is involved in the metabolism of rifabutin. Several metabolites, including 20-OH-rifabutin and 27-O-demethyl-rifabutin, isolated from urine and microsomes were identified by mass spectrometry and nuclear magnetic resonance spectroscopy.
Administration, Oral↗
Cytochromes CYP1A1 and CYP1B1 in the rat mammary gland: cell-specific expression and regulation by polycyclic aromatic hydrocarbons and hormones.
Cultured rat mammary cells express both CYP1A1 and CYP1B1 in response to polycyclic aromatic hydrocarbons (PAH) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a cell type-specific manner. The expression of each P450 was determined functionally (regioselective PAH metabolism), as apoprotein (immunoblots) and as mRNA (Northern hybridization). The epithelial rat mammary cells (RMEC) expressed CYP1A1, however only after PAH or TCDD treatment. CYP1B1 protein was scarcely detected in these induced RMEC but was surprisingly active as a participant in 7,12-dimethylbenz[a]anthracene (DMBA) metabolism shown through selective antibody inhibition (40% of total activity). CYP1B1 was selectively expressed in the stromal fibroblast population of rat mammary cells to the exclusion of CYP1A1. In the rat mammary fibroblasts (RMF), CYP1B1 protein and associated activity were each present at low levels constitutively and were highly induced by benz[a]anthracene (BA) to a greater extent than by TCDD (12- versus 6-fold). However, BA (10 microM) and TCDD (10 nM) stimulated the 5.2-kb CYP1B1-specific mRNA equally. These increases are consistent with the involvement of the aryl hydrocarbon (Ah) receptor in the transcription of the CYP1B1 gene and with the additional stabilization of CYP1B1 protein by BA, previously observed in embryo fibroblasts. Exactly this regulation of CYP1B1-dependent activity was seen in RMEC suggesting that this arises from exceptionally active CYP1B1 in a small proportion (5%) of residual RMF. The constitutive expression and PAH inducibility of CYP1B1 and CYP1A1 proteins in RMF and RMEC, respectively, were each substantially decreased (approximately 75%) by a hormonal mixture (17 beta-estradiol (0.2 microM) progesterone (1.5 microM) cortisol (1.5 microM) and prolactin (5 micrograms/ml)). Progesterone and cortisol, added singly to RMF suppressed CYP1B1 protein expression (approximately 80%) in both untreated and BA-induced cells, while cortisol also suppressed the 5.2-kb CYP1B1 mRNA. In contrast, 17 beta-estradiol stimulated constitutive expression of CYP1B1 protein (50-75%) and mRNA level (2- to 3-fold), but did not affect CYP1B1 expression in BA-treated RMF. The expression of CYP1A1 and CYP1B1 is therefore highly cell specific even though each is regulated through the Ah receptor. Each P450 exhibits a surprisingly similar pattern of hormonal regulation even though expressed in different cell types.
9,10-Dimethyl-1,2-benzanthracene↗
Effects of genetic background on tumorigenesis in p53-deficient mice.
Mice with disrupted germline p53 alleles have been engineered by us and others and have been shown to have enhanced susceptibility to spontaneous tumors of various types. We monitored a large number of p53-deficient mice (p53+/- and p53-/-) and their wild-type littermates (p53+/+) of two different genetic backgrounds (129/Sv and mixed C57BL/6 x 129/Sv) up to 2 yr of age. p53+/- and p53-/- 129/Sv mice show accelerated tumorigenesis rates compared with their p53-deficient counterparts of mixed C57BL/6 x 129/Sv genetic background. The tumor spectra of the two strains of mice are similar except that almost half of 129/Sv p53-/- males develop malignant teratomas, whereas these tumors are rarely observed in C57BL/6 x 129/Sv mice and never in 129/Sv p53+/- males. In the study reported here, we further characterized the lymphomas that arose in the p53-nullizygous mice and found that over three-quarters of the lymphomas were of thymic origin and contained primarily immature (CD4+/CD8+) T-cells, whereas the remainder originated in the spleen and peripheral lymph nodes and were of B-cell type. The high incidence of early-onset lymphomas in the nullizygous mice makes these animals a good lymphoma model, whereas the heterozygous mice may be a useful model for Li-Fraumeni syndrome, a human inherited cancer predisposition.
Alleles↗
Effects of neuropeptide Y, insulin, 2-deoxyglucose, and food deprivation on food-motivated behavior.
The current study demonstrates the ability of neuropeptide Y (NPY) to increase break points under a progressive ratio 1 (PR1) reinforcement schedule. An initial response resulted in delivery of a food reinforcer (45 mg pellet) under the PR1, and an additional response was required for each successive reinforcer. The break point, the number of responses emitted to obtain the last reinforcer, is considered a measure of reinforcing efficacy or motivational strength of the food reinforcer. NPY (0.3-10 micrograms) significantly increased break point to levels comparable to those produced by 36-48 h of food deprivation. Although insulin (3-8 U/kg) and 2-deoxyglucose (150-250 mg/kg) also increased food intake, neither increased break points to levels produced by NPY or food deprivation. These data suggest that NPY may change the value of food in ways that cannot be accounted for by changes in insulin, glucose levels or intracellular glucoprivation. These results emphasize that simply measuring the amount of freely available food eaten is not a fully adequate measure of the strength of the feeding behavior.
Animals↗
Double-blind 1-year follow-up of 1540 infants with respiratory distress syndrome randomized to rescue treatment with two doses of synthetic surfactant or air in four clinical trials. American and Canadian Exosurf Neonatal Study Groups.
Synthetic surfactant has been shown to reduce neonatal and 1-year mortality and neonatal morbidity in infants with respiratory distress syndrome. However, less is known about the effects of synthetic surfactant on developmental outcome and long-term morbidity. Four multicenter, randomized, placebo-controlled trials of synthetic surfactant administered as rescue therapy were conducted in the United States and Canada, with a total enrollment of 2224 patients. Double-blind developmental evaluations of survivors were conducted at 1 year of age (adjusted for prematurity) in all four trials. Of the 1802 patients enrolled in the placebo-controlled rescue trials who survived to 1 year, 1540 (85%) completed the 1-year follow-up evaluation. Height, weight, and head circumference measurements were not different in the treatment and control groups. Mean and median Bayley Scores of Infant Development for both the Mental Development Index and the Psychomotor Development Index were also equivalent. The incidence of impairments was not different in the two groups (mild to moderate impairment, 12% (92 of 745) for the air placebo group vs 11% (86 of 771) for the synthetic surfactant group; severe impairment, 15% (114 of 745) for the air placebo group vs 13% (102 of 771) for the synthetic surfactant group). No differences in rates of retinopathy of prematurity or hearing impairment were found in the treatment groups. The need for surgery after day 28 of life (relative risk, 0.779; 95% confidence interval, 0.665, 0.927) and the need for respiratory support at 1 year (relative risk, 0.525; 95% confidence intervals, 0.303, 0.911) were both reduced in the synthetic surfactant group. These results indicate that developmental outcome at 1 year of age is at least as good among infants with respiratory distress syndrome who received rescue therapy with synthetic surfactant as it is in infants who received air placebo; the results also indicate that the incidence of long-term morbidity is reduced.
Air↗
Causes of alcoholism: a qualitative study of traditional Muscogee (Creek) Indians.
Traditional Native American people are experiencing serious health, economic, and social problems resulting from alcoholism. Native Americans maintain a worldview of health and illness that conflicts with the dominant culture's approach to treatment. The purposes of this study were to describe the health beliefs of traditional Muscogee (Creek) Indians concerning the causes of illness and learn how these beliefs relate to alcoholism. The researchers conducted in-depth interviews of 55 traditional Muscogee (Creek) participants to learn traditional beliefs about illness and alcoholism. Data were analyzed using content analysis. Results indicate that both illness and alcoholism are perceived as having natural and unnatural (supernatural) causes. A challenge facing nurses is how to provide culturally sensitive care when clients' and nurses' beliefs about the cause of alcoholism may be in conflict. The authors discuss preservation, accommodation, and repatterning of health care beliefs as a basis for planning culturally sensitive nursing care.
Adult↗
Effects of blended lithium-zinc heparin on ionized calcium and general clinical chemistry tests.
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Adult↗
Insulin, 2-deoxy-D-glucose, and food deprivation as discriminative stimuli in rats.
Using a two-lever drug discrimination procedure, two groups of four rats each were trained to discriminate the stimulus effects of 1.0 U/kg insulin or 125 mg/kg 2-deoxy-D-glucose (2-DG) from saline. A third group was trained to discriminate food deprivation produced by feeding 23 h prior to sessions from satiation produced by feeding 2 h prior to sessions. Differential responding was a direct function of dose or deprivation level in each group. Rats trained to discriminate insulin responded as if they had received insulin when they received 2-DG and vice versa. Insulin and 2-DG produced deprivation-appropriate responding in two of four rats trained to discriminate food deprivation. Low insulin and 2-DG doses produced drug-appropriate responding in rats deprived 47 h, but not in rats deprived 23 h. Blood glucose level was altered by the training doses of insulin and 2-DG, but not by 23-h deprivation. These results indicate that operations that induce feeding produce discriminable stimuli, and that these effects overlap or interact. Thus, drug discrimination procedures can be useful in the analysis of ingestive behavior.
Animals↗
Changes in food-maintained progressive-ratio responding of rats following chronic buprenorphine or methadone administration.
Seven rats lever pressed under a progressive ratio 3 (PR 3) schedule of food presentation; the number of responses per reinforcer systematically increased during each session. Break point (i.e., the number of responses in the last completed ratio before session termination) was measured under daily methadone (4.5 mg/kg and 3.0 mg/kg) or buprenorphine (0.3 mg/kg) administered prior to experimental sessions. Both drugs initially eliminated rats' food-maintained progressive-ratio responding. Break points during chronic methadone did not return to baseline levels after 80 drug sessions and a dose reduction. In contrast, break points during chronic buprenorphine administration were considerably above baseline control levels for two rats and returned to baseline levels for the third.
Animals↗
Methadone and feeding: sources of differences between home cage and operant chamber assessment procedures.
Methadone administration is reported to increase food intake in studies examining free feeding and to decrease food reinforced operant responding. In light of this apparent paradox, the present study evaluated methadone's effects on food reinforced operant responding under conditions more typical of free feeding studies than operant studies. The effect of methadone (5 mg/kg) on food intake was examined in rats maintained at 100% of their free feeding weights. Methadone did not increase food intake with food available under a fixed ratio 1 (FR 1) reinforcement schedule. Methadone did not alter response rate when each lever press produced a larger reinforcer (225 mg as opposed to 45 mg), but did increase food intake. When response requirements were changed from lever pressing to interruption of an infrared beam, increases in food intake following methadone administration were observed. Thus, the differences between methadone's effects on free feeding vs. operant chamber food intake may be due to procedural factors such as magnitude of reinforcement and response requirements.
Animals↗
Behavioral and neurochemical mechanisms of opioid-antidepressant interactions.
Twelve pigeons key-pecked under a multiple variable interval 15-s, 150-s schedule of food reinforcement. The effects of methadone were studied alone and in combination with chronic daily administration of either imipramine (IMI) or desipramine (DMI). Chronic IMI was also given following reductions in response rates by unsignaled delay-to-reinforcement (UDR). Acute administration of methadone produced dose-dependent reductions in response rates under both schedules of reinforcement. Chronic daily administration of IMI or DMI alone did not result in lasting changes in baseline responding. When administered in combination, chronic daily IMI significantly attenuated the rate-reducing effects of methadone, whereas neither a low nor a high dose of chronic daily DMI was effective. The same dose of chronic daily IMI failed to ameliorate response rate reductions under delayed reinforcement. The behavioral and neurochemical specificity of the antidepressant effect is discussed.
Animals↗
12-lead and continuous ECG recordings of subjects during inpatient administration of smoked cocaine.
Cocaine can cause myocardial ischemia or infarction. The incidence of these events, and the influence of specific dosing routes or regimens on their occurrence is not established. In the current study, we obtained frequent 12-lead electrocardiograms (ECGs) and continuous 2 or 3 channel ECGs from 20 subjects participating in a behavioral study of smoked cocaine. Subjects received 10 or 11 doses of cocaine 0.4 mg/kg per dose, or 10 doses of 35 mg per dose at 30 min intervals (range 233-408 mg total dose per session). ECGs were also recorded on control days on which subjects received no cocaine. The mean peak plasma cocaine concentration on cocaine days was 640 +/- 262 ng/ml. There were no changes in digitized ST segment amplitude on 12-lead ECGs obtained during cocaine administration (P = 0.098). Of 17 subjects who had technically satisfactory continuous ECGs, four had significant ST segment depression (> 1 mm below the PR segment); two on cocaine days and two on control days (P > 0.5). One subject had frequent premature beats on both cocaine and control days. One subject had an asymptomatic run of 4 ventricular beats 30 s after cocaine administration that could have been due to cocaine. All episodes of ST depression or premature beats were asymptomatic. No evidence of either symptomatic or subclinical cardiac ischemia related to cocaine administration was found. Thus no clinically important adverse events were found as a result of smoked cocaine administered by this dosing regimen to healthy males with a history of heavy cocaine use. Additional study with larger numbers of subjects will be helpful in further assessing the safety of administering smoked cocaine to research subjects.
Administration, Inhalation↗
A descriptive study of physically aggressive behavior in dementia by direct observation.
OBJECTIVE: To study, by direct observation, physically aggressive behavior (PAB) in a cohort of older persons with dementia. DESIGN: Cross-sectional survey. SETTING: A locked special care unit for Alzheimer's Disease and an ordinary skilled unit of two suburban nursing homes. PARTICIPANTS: Twenty men and women with a history of PAB. MEASUREMENTS AND MAIN RESULTS: Portable bar-code-readers and daily diaries were used to determine the frequency of PAB as well as to elucidate the antecedents and consequences of it. PAB was most often directed toward staff (23/28 episodes), usually in the context of personal care (15/23 episodes). In the majority of cases, verbal aggression or non-compliance preceded the PAB. Most often PAB was followed by a rapid return to non-aggressive behavior. CONCLUSIONS: Very little PAB was truly spontaneous, nor was it usually the participant's normal behavior. Most PAB occurred in response to intrusion into the participant's personal space by staff or other residents. The PAB is better understood as a defensive response than an expression of anger.
Activities of Daily Living↗
Methotrexate therapy for autoimmune hearing loss: a preliminary report.
The management of autoimmune sensorineural hearing loss (SNHL) continues to challenge the otologist. Steroids and cyclophosphamide, the two traditional medications for this malady, are often associated with serious adverse reactions. In an effort to use a less toxic medication, the authors treated five autoimmune SNHL patients with low-dose oral methotrexate. Methotrexate has been found to be very effective in rheumatoid arthritis patients with acceptable adverse reactions. Preliminary results from this study indicate that methotrexate has the potential of being effective for autoimmune SNHL and associated otologic symptoms. Tolerance has been very good and side effects have been minimal.
Administration, Oral↗
Opioid antagonist effects on self-injury in adults with mental retardation: response form and location as determinants of medication effects.
The opioid antagonist naltrexone was administered to 8 adults with severe or profound mental retardation and extensive histories of self-injurious behavior. Five-minute behavioral samples were observed randomly out of every hour from 8 a.m. through 3 p.m., Monday through Friday, for four 2-week phases (baseline, placebo, 50 mg, and 100 mg). During naltrexone administration, there were fewer days with frequent head-banging and self-biting, whereas there were more days on which blows to the head or self-biting were infrequent. Self-injurious participants slept 1.38 hours less per night during baseline, which was unaffected by naltrexone.
Adult↗