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Biomedical subjects

T McDonald

Publications and source records attributed to T McDonald.

88 records · Page 5Linked to original sources
PubMed1979

Familial pheochromocytoma, hypercalcemia, and von Hippel-Lindau disease. A ten year study of a large family.

Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the clinical presentations of the disease.

Adolescent↗
PubMed1979

Development and testing of new hypoxic cell radiosensitizers.

Several new electron-affinic compounds have been shown to possess radiosensitizing ability in hypoxic mammalian cells. The correlation between chemical structure and biological activity can aid in the design and synthesis of new agents with potentially greater hypoxic cell radiosensitizing ability.

Animals↗
PubMed1976

Intraocular irritation evaluation of benzalkonium chloride in rabbits.

The purpose of this study was to define the threshold for intraocular irritation of benzalkonium chloride, a preservative used in some formulations which enter the anterior segment of the eye during ocular surgery. Various concentrations of benzalkonium were injected into anterior chambers of albino rabbit eyes. Conjunctivitis, flare, iritis, and corneal changes occurred in a dose response pattern. The threshold of irritation was 0.03%, with highest nonirritating concentration being 0.01%. In other works in this laboratory, threshold of irritation for topical ocular benzalkonium was 0.05%, but the nature of ocular changes was less substantial than those observed intraocularly. Because the threshold for intraocular irritation is less than that topically, the nature of ocular changes was different for two routes, and there is a paucity of clinical data for intraocular benzalkonium chloride, a safety factor of 10 was utilized in setting the highest safe concentration of 0.001% for intraocular use. The preservative efficacy of 0.001% is questionable; therefore, we cannot endorse benzalkonium chloride as a preservative for formulations which will enter the anterior segment of the eye.

Administration, Topical↗
PubMed1975

Electrical activity in embryonic heart cell aggregates. Pacemaker oscillations.

Aggregates were formed from dissociated heart cells of 7-day chick embryos. When spontaneous action potentials were blocked with 10-8 to 10-7 g/ml tetrodotoxin (TTX) oscillatory pacemaker potentials were sometimes seen. The emergence of these pacemaker potentials was critically dependent on the external potassium concentration. In 1.3 mM potassium medium TTX suppression of action potential generation always led to a stable resting potential close to the threshold level (-55 to -50 mV). In 4.3 mM potassium TTX suppression was followed by a train of pacemaker potentials which usually gave way to a stable resting potential of about -70 mV. Raising the calcium concentration from 1.8 to 5 mM often induced long lasting (3 hrs) pacemaker oscillations of 20 to 30 mV peak to peak amplitude. These were abolished by raising the potassium concentration to 8.3 mM or upon the addition of 1.5 mM Mn2 plus. The responses of TTX-treated aggregates are discussed in terms of Noble and Tsien's pacemaker theory for Purkinje fibers. The results are well described by assuming the existence of an ik2-like potassium current in embryonic heart cells. The role of calcium is unclear but it may help provide the inward current against which the outward potassium current can function.

Action Potentials↗
PubMedDate not supplied

On the nature of rheumatoid rice bodies: an immunologic, histochemical, and electron microscope study.

The nature of rice bodies was studied, utilizing histochemistry, immunofluorescence, and scanning and transmission electron microscopy. Rice bodies were found to consist primarily of fibrous material, most of which was fibrin with small amounts of collagen. Channels containing a variety of viable cells permeated the rice bodies. Blood vessels occurred in a few rice bodies indicating a former connection with the synovial membrane. Nonvascularized rice bodies might represent a further degeneration of the vascular type. Rice bodies seem to be a nonspecific response to inflammation.

Arthritis, Rheumatoid↗
PubMedDate not supplied

Thalamic modulation of aggression.

This experiment extends Pavlov's method of contrasts for 8 components of aggression were quantitatively evaluated in 11 freely moving adult cats. Aggression was elicited from the perifornix septohypothalamic areas by a series of progressively increasing and decreasing stimulation parameters. Three levels of thalamic stimulation (low, medium, and high) were combined with the perifornix stimulations. High level thalamic stimulation tended to facilitate the aggressive response elicited by low level perifornix stimulation. Thalamic lesions attenuated the aggression response, especially those elicited during high level perifornix stimulation. It was suggested that within the hypothalamic induced aggression circuitry the center median nucleus modulates the excitatory state of the system. The discussion concerns anatomic and physiologic pathways through which the center median nucleus may modulate the sensory, motor, and affective-autonomic subsystems into a well integrated aggressive state. These experimental findings are supported by the clinically established treatment of aggression by stereotaxic lesions placed in the center median nucleus.

Aggression↗
PubMedDate not supplied

Application of Raney nickel to measure adducts of styrene oxide with hemoglobin and albumin.

Adducts of styrene 7,8-oxide (SO) with the blood proteins, Hb and albumin (Alb), were measured following treatment of the proteins with Raney nickel (Ra-Ni) to cleave 2-phenylethanol, which was subsequently assayed. Internal standards were prepared by modifying Hb and Alb with 4-methyl-SO to produce similar adducts. In a preliminary experiment with human blood, which had been modified with [14C]SO in vitro, it was determined that Ra-Ni released 6% of the total binding to globin and 76% of the total binding to Alb. Since Ra-Ni primarily cleaves covalently-bound sulfur species, this suggests that much more binding to human serum Alb occurred at a free cysteine residue than to human Hb. The overall rate of reaction of SO at 37 degrees C in vitro had a half-time of 0.70 h in human blood and of 0.36 h in blood from Sprague-Dawley rats. Adducts of SO with Hb and Alb were measured following SO modification of blood from humans and rats in vitro at 37 degrees C. Slopes of the linear relationships between adduct level and SO concentration allowed the following second-order rate constants [(L/mol of protein)/h] to be estimated: rat Hb, 72; human Hb, 2.4; rat Alb, 63; human Alb, 32. These rate constants show that intrinsic reactivity of SO toward the cysteine residue of human Hb is much lower than that of rat Hb or of Alb from either species. Adducts of Hb and Alb were also measured following administration of both SO and styrene to rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Acrylamide: review of toxicity data and dose-response analyses for cancer and noncancer effects.

Acrylamide (ACR) is used in the manufacture of polyacrylamides and has recently been shown to form when foods, typically containing certain nutrients, are cooked at normal cooking temperatures (e.g., frying, grilling or baking). The toxicity of ACR has been extensively investigated. The major findings of these studies indicate that ACR is neurotoxic in animals and humans, and it has been shown to be a reproductive toxicant in animal models and a rodent carcinogen. Several reviews of ACR toxicity have been conducted and ACR has been categorized as to its potential to be a human carcinogen in these reviews. Allowable levels based on the toxicity data concurrently available had been developed by the U.S. EPA. New data have been published since the U.S. EPA review in 1991. The purpose of this investigation was to review the toxicity data, identify any new relevant data, and select those data to be used in dose-response modeling. Proposed revised cancer and noncancer toxicity values were estimated using the newest U.S. EPA guidelines for cancer risk assessment and noncancer hazard assessment. Assessment of noncancer endpoints using benchmark models resulted in a reference dose (RfD) of 0.83 microg/kg/day based on reproductive effects, and 1.2 microg/kg/day based on neurotoxicity. Thyroid tumors in male and female rats were the only endpoint relevant to human health and were selected to estimate the point of departure (POD) using the multistage model. Because the mode of action of acrylamide in thyroid tumor formation is not known with certainty, both linear and nonlinear low-dose extrapolations were conducted under the assumption that glycidamide or ACR, respectively, were the active agent. Under the U.S. EPA guidelines (2005), when a chemical produces rodent tumors by a nonlinear or threshold mode of action, an RfD is calculated using the most relevant POD and application of uncertainty factors. The RfD was estimated to be 1.5 microg/kg/day based on the use of the area under the curve (AUC) for ACR hemoglobin adducts under the assumption that the parent, ACR, is the proximate carcinogen in rodents by a nonlinear mode of action. When the mode of action in assumed to be linear in the low-dose region, a risk-specific dose corresponding to a specified level of risk (e.g., 1 x 10-5) is estimated, and, in the case of ACR, was 9.5 x 10-2 microg ACR/kg/day based on the use of the AUC for glycidamide adduct data. However, it should be noted that although this review was intended to be comprehensive, it is not exhaustive, as new data are being published continuously.

Acrylamide↗
PubMedDate not supplied

Changes in health risks among the participants in the United Auto Workers--General Motors LifeSteps Health Promotion Program.

PURPOSE: To examine health risk changes among participants of a multicomponent worksite health promotion program. DESIGN: A study using health risk changes among health risk appraisal (HRA) participants linked to program participation records. Baseline risk and participation in multiple programs were examined in relation to risk change in multivariate models. SETTING: Worksite health promotion programming sponsored by the United Auto Workers (UAW) and General Motors (GM). SUBJECTS: Active employees (12,984) who voluntarily participated in an HRA in each of two program years. INTERVENTION: The nationwide program was a mailed HRA and a 1-800 nurse line. A pilot program (implemented in two cities) added screening, wellness programs, a materials resource, and, for high risk participants, health coaching and vouchers for medical office visits. MEASURES: Using 13 selected health risk factors from the HRA, changes in overall health risks were measured as program outcomes in three ways: one-directional, net, and risk status change. RESULTS: A greater decrease in the number of health risks was observed with increased program participation. The decrease was significantly related to the number of baseline risk factors and eligibility for high risk programs. Associated with program participation, the number of people at low risk status increased from 70.1% to 71.3% at year 2 among nationwide participants and from 52.4% to 58.9% among pilot participants. CONCLUSIONS: Participation was associated with a significant impact on health risk. Baseline risk of participants and eligibility for high risk programs were necessary factors to control when measuring program effects on health risk changes.

Health Promotion↗
PubMedDate not supplied

Internal associations among health-risk factors and risk prevalence.

OBJECTIVE: To explore risk associations between health variables and to compare these associations with the prevalence of each risk. METHODS: Manufacturing-company employees (N=16,879) completed a self-reported health risk appraisal with on-site biometric screening. RESULTS: Risk prevalence and risk association findings differed by gender, age, and overall risk level. Risks that were most highly associated with other risks were different from risks that were most prevalent. CONCLUSIONS: The findings suggest that in addition to risk prevalence, individual characteristics and the level of association between risks are also important to consider when planning health interventions.

Adult↗
PubMedDate not supplied

Predicting the learning and consultation time in a computerized primary healthcare clinic.

Managers would like to know how long it takes healthcare service providers to achieve the same throughput of patients per day that they were used to with a pen-and-paper system. This study has been undertaken to derive a model for predicting the time it takes a service provider from a previously disadvantaged community to enter a patient's record in terms of his or her experience and the number of data units that have to be captured. A model was also derived to predict the average consultation time in terms of the number of data units that are captured by an experienced service provider. It can be inferred that healthcare service providers should be allowed at least 6 months of computerized system experience before any decisions about the success of the technology introduction can be made.

Ambulatory Care Information Systems↗