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Biomedical subjects

D MacGregor

Publications and source records attributed to D MacGregor.

51 records · Page 3Linked to original sources
PubMed1987

Adoptive transfer of insulitis and diabetes in neonates of diabetes-prone and -resistant rats. Tissue localization of injected blasts.

Intravenous transfusion of concanavalin A-activated splenic cells from acutely diabetic BB or diabetic BB/hooded hybrid donor rats into 6- to 36-h-old neonate recipients of diabetes-prone and -resistant rat lines induced insulitis and in some severe diabetes. These effects were observed 10-20 days after the injection of the blasts. Focal lesions of insulitis were absent in neonates killed 1 and 3 days after the blast injection but were observed in neonates killed on the 5th and 8th day. As determined by autoradiography after the injection of [3H]thymidine-labeled blasts, numerous blast cells migrated and settled in various immature lymph nodes and in the spleen within 24 h after injection. Focal mononuclear infiltrations in the islets containing labeled and unlabeled cells were again observed on the 5th and 8th day but not on the 1st and 3rd day after injection. These experiments indicate that target-specific blasts undergo a short phase of proliferation and maturation in lymphoid organs of the recipients, before initiating the autoimmune process in the pancreatic islets. They further suggest that specific immune cells rather than humoral anti-islet antibodies are more likely to play the major role in this autoimmune animal model of diabetes.

Animals↗
PubMed1987

Palatability and relative bioavailability of an extemporaneous carbamazepine oral suspension.

The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspensions was tested, and the bioavailability of the unflavored suspension relative to that of the tablet used in its manufacture was determined in a randomized, crossover study of 12 healthy volunteers. Carbamazepine 400 mg was administered with a glass of water as either 20 mL of unflavored oral suspension (20 mg/mL) or two 200-mg tablets. Subjects were randomly assigned to receive first either the tablets or the suspension in crossover fashion on two days separated by at least two weeks. Blood samples were taken just before and at various times up to 72 hours after the carbamazepine dose. Serum samples were assayed for carbamazepine content by high-performance liquid chromatography. Of five flavored and unflavored carbamazepine suspensions tested in eight volunteers, the cherry-mint formulation was the least palatable. There was no trend in preference among the remaining suspensions (banana, tutti-frutti, grape, and unflavored). Mean values of maximum serum concentration and absorption rate constant were significantly greater for the unflavored suspension (5.7 mg/L [24 mumol/L] and 0.832 hr-1, respectively) than for the tablet (4.9 mg/L [20.8 mumol/L] and 0.266 hr-1, respectively). The mean time to maximum concentration was significantly shorter after suspension administration (3.87 hours) than after tablet administration (11.8 hours). There was no significant difference in the extent of absorption of the tablet and suspension formulation as reflected by the corrected values of the area under the serum concentration-versus-time curves. The mean (+/- S.D.) bioavailability of the suspension relative to the tablet was 94.46% +/- 20.42 (range 76.35-132.72%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1986

Perceived acceptability of risk analysis as a decision-making approach.

Three methods for making a consumer product safety decision were evaluated on scales relating to their perceived acceptability, logical soundness, completeness, and sensitivity to moral and ethical concerns. Two of the methods were formalized techniques: cost-benefit analysis and risk analysis. The third method involved abiding by standard industry practices. Other factors in the decision-making context were also varied. The results indicated that formalized techniques were preferred over the standard practices method. Within the formalized methods, cost-benefit analysis was judged less acceptable than a comparable method that did not involve making explicit value tradeoffs. All methods were judged more acceptable when they led to improved product safety. Knowledge of consequences did not exert direct effect on judgments, though it did interact significantly with other variables. The results are discussed in terms of judgmental processes that people apply when evaluating decision methods.

Accident Prevention↗
PubMed1986

Family responses to developmentally delayed preschoolers: etiology and the father's role.

Parents of 59 developmentally delayed preschoolers (18 with Down syndrome, 19 with neurological problems, and with 22 unknown etiologies) responded to questionnaires and structured interviews to assess parental stress and support, locus of control, and self-esteem. There were group differences in maternal reports of positive experience with the child, self-esteem, reported support, and relations with grandparents. With the exception of self-esteem, all comparisons favored the Down syndrome group. Fathers reported fewer distress symptoms, higher self-esteem, more internal locus of control, and less support than did mothers. These findings indicate a need to understand individual differences among families of delayed children and illustrate that the effects of a child's handicap on fathers differ from those upon mothers.

Adult↗
PubMed1985

Perceived driving safety and seatbelt usage.

Swedish and U.S. subjects judged their own driving skills and safety in relation to other drivers. As in earlier studies, most subjects showed an optimism bias: a tendency to judge oneself as safer and more skillful than the average driver, with a smaller risk of getting involved and injured in an accident. Different measures of the optimism effect were strongly correlated with one another, with driving experience and with the judged importance of human factors (as opposed to technical and chance factors) in causing accidents. Degree of optimism was positively, but weakly, correlated with reported seatbelt usage and worry about traffic accidents. Seatbelt usage was positively related to the extent to which belts are judged to be convenient and popular, and more modestly related to the belt's perceived contributions to safety. These results suggest that providing more information about the effectiveness of seatbelts may not be as efficient a way of increasing seatbelt usage as emphasizing other factors, such as comfort and social norms, which cannot be outweighed by optimism.

Accidents, Traffic↗
PubMed1985

A microcomputer controlled snow ski binding system--I. Instrumentation and field evaluation.

This paper presents the design and field evaluation of the first microcomputer controlled ski binding system. This system incorporates an Intel 8086 microcomputer controller and an integral binding/dynamometer. This instrumentation system not only undertakes real time control, but also it records dynamometer data via a miniature digital cassette tape recorder. The integral binding/dynamometer offers the same operational and mounting convenience of commercially available mechanical bindings. The binding may be released either manually or electrically via the controller. Comprised of four octagonal half strain rings, the strain gage dynamometer measures the three moment load components at the boot. To enable the user to conveniently operate the computer, extensive operating software was developed. The operating software is discussed in relation to both the acquisition and storage of data from the dynamometer and the control of the electro-mechanical snow ski binding. The binding system has been used successfully to both record boot moment components and control ski binding release during actual skiing maneuvers. Moment histories typical of three common recreational skiing maneuvers are presented.

Athletic Injuries↗
PubMed1985

A microcomputer controlled snow ski binding system--II. Release decision theories.

A hierarchy of release decision theories for both tibia fracture and knee ligamentous injury are defined and simulated on a computer. Moment loading data, recorded during actual skiing by the microcomputer-based ski binding system described in Part I, are processed by the various release decision theories. At the bottom of the hierarchy is the simplest theory which treats boot loading as quasi-static and compares moment components to threshold levels. Another stage of the hierarchy defines an analytic expression for a combined loading failure locus. Note that this is the first formulation of a combined loading release decision theory. Yet another stage of the hierarchy computes bone moments via dynamic system leg models. The various release decision theories are evaluated by comparing processed results to both pain and bone failure limits. For the data generated by the field tests conducted to date, the simplest release decision theory satisfied the retention requirement for pain limits in the presence of muscle activity for both torsion and forward bending. For pain limits in the absence of muscle activity the retention requirement was not satisfied however. Another result is that leg dynamics are significant. A final result is that combined loading considerations lead to a more conservative theory.

Athletic Injuries↗
PubMed1985

Powerline frequency electric and magnetic fields: a pilot study of risk perception.

The perception of the potential risk arising from human exposure to 50/60 Hz electric and magnetic fields was studied with a quasi-random sample of 116 well-educated, opinion leaders using the risk perception framework previously developed by Slovic, Fischhoff, and Lichtenstein. These individuals rated exposure to fields from transmission lines and electric blankets on a variety of scales that have been found useful in characterizing people's risk attitudes and perceptions. These judgments allowed us to conjecture about the likely desire for regulation of these potential hazards and the likely response to a publicized problem (e.g., an accident or ominous research finding) involving these two sources of exposure. Various forms of detailed information about 50/60 Hz fields were supplied to respondents. The provision of information produced modest, but statistically significant, changes in perceptions in the direction of greater concern about the risks. In response to questions of public policy, participants desired modest regulatory control of field exposure from transmission lines and little or no control of field exposure from appliances like electric blankets.

Electric Injuries↗
PubMed1984

Biopterin synthesis defect. Treatment with L-dopa and 5-hydroxytryptophan compared with therapy with a tetrahydropterin.

We have identified a generalized deficiency of monoamine neurotransmitters in a patient with a defect in biopterin synthesis. Neurotransmitter precursors (L-3,4-dihydroxyphenylalanine [L-dopa]; 5-hydroxytryptophan [5-HTP] and a tetrahydropterin [6-methyltetrahydropterin (6MPH4)] were investigated for their ability to normalize monoamine neurotransmitter metabolism. Before treatment, the concentrations of dopamine (DA), norepinephrine, epinephrine, and six monoamine metabolites were very low or undetectable in plasma, cerebrospinal fluid, or urine. L-Dopa and 5-HTP replacement was begun at age 7 mo. This therapy generally corrected the deficiency of monoamines and their metabolites, and improved neurological development until the age of 25 mo. Despite these benefits, the intermittent administration of L-dopa could not produce a stable improvement of acute neurological function or DA metabolism. In the 3 h after L-dopa administration, plasma DA and the motor activity and alertness of the patient rose and fell in parallel. Doses of L-dopa that were clinically optimal produced normal plasma levels of norepinephrine and epinephrine, but excessive concentrations of DA and its metabolites. Furthermore, the clinical and biochemical effects of L-dopa were inhibited by phenylalanine and 5-HTP, respectively, demonstrating that these amino acids have antagonistic pharmacological effects. Physiological correction of the monoamine deficit and the hyperphenylalaninemia of this disorder was attempted at age 35 mo using high doses (8-38 mg/kg per d) of 6MPH4. 6MPH4, a synthetic analogue of tetrahydrobiopterin, controlled the hyperphenylalaninemia. Significant concentrations of 6MPH4 were obtained in the cerebrospinal fluid; no neurological improvement or stimulation of monoamine synthesis in the central nervous system was detected. These findings indicate the complexity in replacement therapy with L-dopa and 5-HTP, but suggest that this treatment may be partially effective in biopterin-deficient patients who are unresponsive to high doses of tetrahydropterins.

5-Hydroxytryptophan↗
PubMed1980

The effects of positive end-expiratory pressure on right and left ventricular performance.

The cardiovascular effects of positive end-expiratory pressure (PEEP) were studied in mechanically ventilated, vagotomized, Beta-blocked, anesthetized dogs. To compensate for the effect of PEEP on decreasing systemic venous return, acute plasma volume expansion was accomplished returning stroke volume and cardiac output to control values. Left and right ventricular filling pressures (LVFP and RVFP) and aortic pressure were measured relative to pressure (transmural pressure). Ventricular performance was assessed by comparing the transmural ventricular filling pressures at similar stroke volumes. Studies were performed on individual dogs with increasing LVFP produced by Beta-blockade, volume expansion, and obstruction of the descending thoracic aorta. Utilizing these methods we observed that for a given cardiac output, transmural LVFP was higher on PEEP compared to a control state with both normal and elevated control LVFP. On the right side, for a given cardiac output, RVFP was elevated only when the control LVFP was elevated. Our results suggest a nonneuronal adverse effect of PEEP on both left and right ventricular performance. This effect is probably due to mechanical heart-lung interaction since left ventricular (LV) dp/dt showed no change.

Animals↗
PubMed1978

Effects of respiration on cardiac performance.

The conventional explanation for the fall in left ventricular stroke volume (LVSV) with inspiration is that blood pools in the lungs, thereby decreasing pulmonary venous return. In anesthetized dogs, we have found an increase in left ventricular filling pressure (LVFP) with both constant and increasing lung volume during an inspiratory effort. Transmural aortic diastolic pressure rises as LVSV falls and LVFP rises consistent with the hypothesis that a fall in pleural pressure afterloads the left ventricle. Additionally the increase found in right ventricular filling pressure with inspiration may adversely affect LV performance by decreasing LV compliance and/or contractility. Our findings are incompatible with pooling of blood in the lungs being the primary determinant of the fall in LVSV with inspiration.

Animals↗
PubMedDate not supplied

Antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis after immunisation with bacterial proteins.

OBJECTIVE: There is circumstantial evidence for a role for infections in the development of the small vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA). The aim of this study was to determine whether the immunisation of rats with bacterial proteins could result in circulating ANCA, T cells with specificity for ANCA antigens, and a systemic vasculitis. METHODS: Adult male Wistar rats were immunised with pasteurised sonicated S. aureus (n = 7), E. coli (n = 8), purified protein derivative (PPD, n = 5), myeloperoxidase (MPO, n = 5) or phosphate-buffered saline (PBS, n = 5), in complete and in incomplete Freund's adjuvant. ANCA were assayed by indirect immunofluorescent (IIF) examination of normal rat neutrophils, and in ELISAs using human proteinase 3 (PR3), MPO and bactericidal/permeability-inreasing protein (BPI). The T cell response to PR3, MPO and BPI was assessed by a whole blood T cell proliferative assay in vitro, and by a delayed type hypersensitivity (DTH) response in vivo. Kidney and bowel were examined histologically for evidence of vasculitis and colitis. RESULTS: One rat from each group immunised with S. aureus or E. coli developed pauciimmune segmental glomerular sclerosis. The rat immunised with E. coli had additionally an arteritis affecting renal interlobular and gut vessels. This rat had circulating C-ANCA, that produced granular cytoplasmic neutrophil fluorescence with central accentuation, but the target antigen could not be determined in ELISAs using human PR3, MPO or BPI. In animals immunised with S. aureus or E. coli, there was no significant T cell proliferative or DTH response specific for human PR3, MPO or BPI. CONCLUSION: The development of ANCA and vasculitis in a rat immunised with bacterial proteins indicates that the relationship between infections and ANCA should be investigated further.

Animals↗