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Biomedical subjects

J McGee

Publications and source records attributed to J McGee.

At least 55 records · Page 3Linked to original sources

Arm and leg cycle cross-training effect on anaerobic threshold and heart rate in patients with coronary heart disease.

It has been suggested that the anaerobic threshold (AT) represents a minimal intensity for eliciting an exercise training adaptation. Thirteen men (age = 66 +/- 9; weight = 81 +/- 13kg) and two women (age = 58 +/- 21; weight = 70 +/- 3kg) with coronary heart disease (CHD) trained for 12 weeks to determine the effect of an exercise regimen composed of three- to six-minute intervals of alternating arm and leg cycling (cross-training) on AT. The patients cross-trained for a total of 30 minutes per session, three days per week. Maximal cycle ergometer tests with breath by breath ventilatory gas analyses were performed before and after training. Peak oxygen uptake increased by 8.9% and peak power output increased (p < .05) by 28.3%, whereas resting heart rate (HR) decreased (p < .05) by 9.6% as a result of the cross-training regimen. Cross-training did not effect a significant change in AT but HR at AT was decreased by 6.3% (p < .05). Arm and leg cross-training produced a physiological adaptation and may have reduced the HR threshold for effective exercise training.

Aged↗

Comparisons of the development of auditory brainstem response latencies between cats and humans.

Developmental changes in the peak latencies of auditory brainstem responses (ABR) recorded from humans and kittens were compared to test the hypothesis that developmental time courses among mammals are the same when appropriately normalized. Response latencies were computed as the difference from adult latency and conceptional ages were represented as percentages relative to the age that ABR wave latencies achieved a criterion value within 0.2 ms of asymptotic latency (i.e., adulthood). An underlying assumption of this exercise is that far-field response latency is an appropriate index of overall 'auditory development'. Results of this analysis suggest that developmental changes in latency of responses arising within the auditory periphery are similar between humans and cats, when appropriately normalized, and that more central changes show less correspondence. Consequently, absolute time course differences for specific developmental parameters must be considered and caution should be exercised when extrapolating results acquired from one species to the other.

Acoustic Stimulation↗

14, 15-cis-episulfide-eicosatrienoic acid, an 'epoxygenase' eicosanoid analog, inhibits ionophore- but not thrombin-induced platelet aggregation.

An 'epoxygenase' eicosanoid analog, 14, 15-cis-episulfide-eicosatrienoic acid, has several unique pharmacological effects on platelets. These include (i) inhibition of ionophore A23187- but not thrombin-induced activation, (ii) inhibition of thromboxane B2 biosynthesis derived from endogenous but not exogenous arachidonic acid, and (iii) attenuation of ionophore-mediated increases in cytosolic Ca2+ when extracellular or membrane Ca2+ is available but not when these pools are excluded. Neither elevation of cyclic AMP levels, a potent inhibitory process, nor direct antagonism of the prostaglandin H2/thromboxane A2 receptor is responsible for the actions of 14, 15-cis-episulfide-eicosatrienoic acid. These properties distinguish 14, 15-cis-episulfide-eicosatrienoic acid from other antiaggregatory substances.

8,11,14-Eicosatrienoic Acid↗

GABA actions within the caudal cochlear nucleus of developing kittens.

1. The effects of gamma-aminobutyric acid (GABA), microionophoretically applied onto neurons within the dorsal and posteroventral divisions (i.e., caudal regions) of the cochlear nucleus (CN), were studied during postnatal development in kittens with the use of extracellular recording techniques. Approximately 80% of all neurons encountered within the caudal CN responded to exogenously applied GABA regardless of neuronal response type or postnatal age. 2. GABA reduced acoustically evoked as well as spontaneous discharge rates in a dose-dependent manner at all ages studied, and generally abolished discharge activity at sufficiently high doses (i.e., ejection currents). Dose-response curves generated during acoustic stimulation by varying GABA ejection current were sigmoidal at all ages studied, and the range of slopes relating discharge rate to applied currents increased during the first 10 postnatal days. 3. Neural thresholds to acoustic stimuli were elevated, and slopes of discharge-rate-versus-sound-pressure-level curves were depressed regardless of age when GABA was microionophoresed onto CN neurons. 4. GABA's capacity to reduce spontaneous or acoustically evoked discharge rates was a voltage-dependent phenomenon directly related to control discharge rates (i.e., efficacy was high when discharge rates were high) for neurons recorded from both immature and mature animals. 5. A small set of neurons recorded from animals younger than 2 wk exhibited prolonged GABA "activation" and "deactivation" times (i.e., times required to achieve 90% of the maximal effect evoked by GABA and to recover from that effect, respectively) and may represent a group of actively differentiating units. 6. Bicuculline microionophoresis effectively blocked the actions of exogenously applied GABA and endogenous GABA, which, presumably, was synaptically released as a result of acoustic stimulation. The actions of bicuculline were dose dependent in animals ranging in age from 2 postnatal days to adulthood. These results suggest that recognition sites for GABA and bicuculline and the ionophore associated with the GABA receptor are present and functionally coupled in the caudal CN before the developmental period during which the full complement of inhibitory projections form synaptic contacts with these cells.

Acoustic Stimulation↗

Aeroallergen-induced immediate asthmatic responses and late-phase associated pulmonary eosinophilia in the guinea pig: effect of methylprednisolone and mepyramine.

Guinea pigs were sensitized by intraperitoneal injection of ovalbumin, 10 micrograms mixed with 100 mg A1(OH)3 in saline. On days 15-30 sensitized guinea pigs were challenged with ovalbumin aerosol (0.5 mg/ml, 30 s, 15 psi) which produced immediate asthmatic responses characterized by dyspnea, convulsions, and some deaths during the first 14 min. Twenty to 24 h later the animals were sacrificed with an overdose of pentobarbital, and lungs, bronchi, and lower trachea were dissected and fixed in 10% neutral buffered formalin. Histopathological examination of randomly coded tissues of the respiratory tract revealed a pulmonary eosinophilic cellular infiltrate in the epithelium/subepithelium of trachea, bronchi, and bronchioles as well as the peribronchial, peribronchiolar, and perivascular areas of the lungs. Oral administration of mepyramine (10 mg/kg) 2 h before aeroallergen challenge provided complete protection against immediate asthmatic responses and prevented deaths during the first 14 min without influencing the late phase associated lung eosinophilic cellular infiltrate. The immediate asthmatic responses were not influenced by methylprednisolone (30 mg/kg) administered orally 24 and 2 h before aeroallergen challenge. Following an additional dose of methylprednisolone 4 h after challenge, there was a significant inhibition of pulmonary eosinophilia (30 mg/kg; -24 h, -2 h, and +4 h). These observations suggest that histamine is the principal mediator of immediate asthma attacks in guinea pigs. Methylprednisolone may be acting by inhibiting the production of eosinophil chemotactic factor of anaphylaxis (platelet-activating factor or leukotriene B4) from the alveolar macrophages, T lymphocytes, and perhaps other cells, thus preventing pulmonary eosinophilia.

Administration, Oral↗

Interdisciplinary approach to assessing the health risk of air toxic chemicals: an overview.

To assist the regulatory branch of the Environmental Protection Agency in addressing the risk assessment of air toxics, the Health Effects Research Laboratory initiated a comprehensive inhalation toxicology program to provide key health effects data missing from the current data base. A priority ranking of chemicals based on the potential for substantial human exposure and the need for health effects data was developed to identify candidate chemicals for toxicological research. The major goal of the program is to evaluate the concentration-response from acute, intermittent and subchronic inhalation exposures to developmental, genetic, hepatic, immunologic, neurologic, pulmonary and reproductive toxicity in a manner that provides data for the regulatory health assessment of air toxic chemicals. Extrapolation and dosimetry research is also conducted to improve the basis for human risk assessment. Determination of biological endpoints to be examined will be decided on a compound-by-compound basis, depending on the physical, chemical and structural characteristics of the chemical and evaluation of the existing health data base. Although the main emphasis is on inhalation as the primary route of exposure, some of the laboratories will compare inhalation to other routes, such as oral, to better understand the influence of route of exposure and hence the potential applicability of existing health data. Acute and intermittent exposures will be done for all compounds. Upon evaluation of the acute results, a decision will be made as to whether subchronic studies are needed. Endpoints that show unusual sensitivity may be investigated in greater detail. The total length of exposure will vary from 1 to 21 days. The daily length of exposure will range from 1 to 8 hr. If adverse effects are observed at ambient levels, the time to recovery after exposure will be investigated.

Administration, Inhalation↗

Physician need. An alternative projection from a study of large, prepaid group practices.

To model a base level of physician demand in a managed health care system, we examined in 1983 the ratios by specialty of full-time equivalent physicians to health maintenance organization members in seven large, closed-panel health maintenance organizations, each with more than 100,000 members. The medical director of each plan was surveyed by mailed questionnaire and telephone interview to determine the plan's number of full-time equivalent physicians by specialty and members served. Out-of-plan physicians contracted by the group were included within the specialty distribution wherever possible. We compared our findings (4779.4 full-time equivalent physicians serving 4,297,790 members) with Graduate Medical Education National Advisory Committee and others' projections of physician need and supply. Based on this model and unknowns that might affect utilization, our study suggests that at least 111 physicians per 100,000 population would be necessary in a system that emphasized reduced utilization of services and that more primary care physicians would be needed than the Graduate Medical Education National Advisory Committee predicted would be available.

Forecasting↗

Vestibular evoked potentials in response to direct unilateral mechanical stimulation.

Evoked potentials produced by direct unilateral mechanical stimulation of the cannulated horizontal semicircular canal were investigated parametrically in anesthetized adult cats (40 mg/kg pentobarbital). Stimuli were fluid pressure pulses in a closed hydraulic system (no net flow), which was coupled to the lateral semicircular canal near the ampulla. Hydraulic waveform output and fluid pressure was monitored in situ via a parallel hydraulic circuit during experiments. Maximum fluid displacement at the level of the horizontal canal was 0.025 microliters. The intensity, duration, and presentation rate of the stimulus were varied during experiments. Field potentials were recorded differentially using subdermal electrodes, with the active lead in the region of the mastoid referenced to a distant nasal site. A total of 256 trials was accumulated for each run using an averaging computer. Evoked responses were physiologically vulnerable and reproducible, with little variance among animals. Response amplitude increased monotonically until saturation was noted and responses followed the temporal structure of the pressure wave. Polarity reversal with differing electrode placement suggests that the generator site lies within the mastoid. Further, intense broad-band acoustic stimuli and eighth nerve sectioning did not affect the vestibular evoked potentials, but could be shown to abolish the auditory evoked potentials. Results of these experiments support the notion that vestibular evoked potentials are related to the first derivative of the pressure pulse waveforms. Future experiments will be directed toward the assessment of vestibular physiology and pharmacology with this evoked response method.

Acoustic Stimulation↗

Temporal relationship of hepatocellular dysfunction and ischemia in sepsis.

To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production.

Animals↗

Rhythmic discharge properties of caudal cochlear nucleus neurons during postnatal development in cats.

Action potentials recorded extracellularly from neurons within the caudal cochlear nuclei of developing cats exhibited distinctive temporal characteristics (i.e., rhythmic responses) in response to long-duration acoustic stimuli including both tone and noise bursts. Unlike the homogeneous response characteristics of auditory nerve fibers, cochlear nucleus neurons exhibited many variations in rhythmic discharge patterns. The majority of neurons within the caudal CN of kittens younger than 10 days of age responded rhythmically to long-duration acoustic stimuli, however, the percentage of neurons responding rhythmically steadily decreased thereafter, and by the end of the second postnatal week most tonically-responding neurons maintained sustained steady-state discharge rates throughout stimulation. Discharges of neurons recorded during the transitional ages (around 13 days) were rhythmic at low sensation levels and exhibited adultlike sustained patterns at higher levels. Using constant sensation level stimuli (re individual neuron thresholds), burst frequencies remained essentially constant during the period of development in which rhythmic responses were observed. Intervals separating discharge bursts decreased as stimulus intensities increased for all neurons studied during the relevant period, but were not related in an orderly way to stimulus frequency. The effects of intensity on response periodicity were not mimicked by altering the amount of neurotransmitter present at the postsynaptic cell through microiontophoresis of excitatory amino acids and their antagonists onto the surface of neurons within the caudal CN. In addition, some immature neurons which responded phasically to acoustic stimuli responded rhythmically during the simultaneous presentation of acoustic stimuli and neuroexcitatory agents (i.e., glutamate). These results suggest that the source of the rhythmicity is not intrinsic to neurons in the caudal CN. Based on these and other observations we conclude that the most probable source of response periodicity observed early in development is the domination of inner hair cell output by efferent projections of the olivocochlear bundle, the temporal discharge patterns of which are also periodic.

Age Factors↗

Effect of chronic treatment with the calcium antagonist diltiazem in Duchenne muscular dystrophy.

We conducted a double-blind trial with the calcium antagonist, diltiazem (8 mg/kg/d), for 24 to 32 months in 22 boys with Duchenne muscular dystrophy, who were paired by functional activity and age. No adverse clinical or ECG effects of diltiazem were detected. In eight matched pairs, completing 28 months, manual muscle testing scores fell somewhat less in the diltiazem group (from 5.5 to 4.6) than in the placebo group (from 5.3 to 4.2), although the difference between groups was not significant (p = 0.06). The 95% confidence interval for the difference in slopes of regression lines obtained from trimonthly manual muscle tests on all subjects was markedly asymmetric in favor of the diltiazem group, but this difference was also not significant. There was less deterioration of functional activity of lower extremities in the diltiazem-treated group, when beginning and end values were analyzed (p = 0.03). However, the difference in slopes of regression lines obtained from trimonthly determinations was nonsignificant. Similarly, the beginning versus end comparisons of systolic and diastolic blood pressure showed a significantly (p less than 0.05) smaller elevation of blood pressure in the diltiazem-treated group, but no difference was observed when the slopes of all values were analyzed. All other clinical and laboratory variables were unaffected by diltiazem treatment. The findings in manual muscle tests and functional activity suggest a beneficial trend with chronic diltiazem treatment in DMD.

Adolescent↗

Protection by physostigmine against the pressor effect of soman in the rat.

Intravenous injection of soman, 30 ug/kg, increased mean arterial blood pressure by 57 mmHg in urethane-anesthetized rats. The response declined slightly after a few minutes and then remained stable at about 39 mmHg for the next 20 minutes. The increase in pressure was accompanied by marked inhibition of brain acetylcholinesterase (AChE). In rats pretreated with a threshold pressor dose of physostigmine (50 ug/kg, i.v.), the peak pressor response to soman rose to the same level as that in the control group, but showed a more rapid recovery, reaching 17 mmHg at 20 minutes. The recovery of blood pressure was accompanied by partial recovery of brain AChE.

Acetylcholinesterase↗

Postnatal development of auditory nerve and cochlear nucleus neuronal responses in kittens.

Neurons located within the auditory periphery of kittens (i.e., primary auditory nerve fibers and neurons of the cochlear nucleus (CN) exhibit similar response properties throughout the early stages of postnatal development. Neural thresholds to acoustic stimuli are uniformly high, spontaneous and acoustically-evoked discharge rates are low, input/output slopes are shallow, and temporal discharge patterns are markedly immature. Phase-locking abilities are poor in developing mammals and all neurons exhibit broad bandpass tuning curves, with center frequencies clustering near 1.5 kHz. Throughout the first week, response thresholds, maximum discharge rates, rate-intensity slopes, dynamic ranges and other response indices remain essentially unchanged. Thereafter, between the 7th and 20th postnatal days, peripheral auditory development proceeds rapidly, such that thresholds, tuning properties, temporal discharge patterns, and input/output functions achieve maturity. The role of synaptogenesis in the development of adult response properties has been studied through microionophoresis of neuroactive molecules onto the surface of neurons in the caudal divisions of the cochlear nuclei of developing kittens. Results of preliminary experiments suggest that inhibitory postsynaptic receptor function precedes intrinsic excitatory neurotransmission. Furthermore, during the first two weeks of postnatal development in kittens, GABA microionophoresis onto immature caudal CN neurons, exhibiting sustained responses to acoustic stimuli, converts response patterns to the onset type in the majority of neurons encountered.

Action Potentials↗

Influence of nutrition and aging on the composition and function of rat skeletal muscle.

Previous studies suggest that nutrition and age affect the composition and function of skeletal muscle. We have investigated these effects in vitro using model muscle preparations obtained from SPF Fischer 344 rats of different ages. Five different dietary groups of rats were studied. In three of these groups food consumption was restricted to 60% of ad libitum intake for varying fractions of the life span. Two groups of rats were fed ad libitum, and in one of these, the protein content of the food was limited to 60% of that consumed by the control group. Composition and contractile function were measured in lateral omohyoideus and soleus muscles. The data revealed a striking absence of functional change in these muscles with age and diet. Only minor changes in composition were found. The results suggest that the fibers present in the muscles of aged rats are functionally intact and are unaffected by long-term dietary restriction. Thus, age-related deficiencies of motor function are probably related to other factors, such as those associated with neuromuscular transmission or propagation of nerve impulses.

Aging↗

Development of auditory-evoked potentials in the cat. I. Onset of response and development of sensitivity.

Auditory-evoked potentials, originating from the brain stem and the forebrain, were studied in 30 unanesthetized kittens during the first 3 months of postnatal life, and from a smaller set of animals before and after surgical exposure of their tympanic membranes. In intact animals, responses to 135-dB peak SPL clicks were first reliably discernible on the seventh postnatal day; when stimuli were presented directly to the exposed tympanic membrane, responses were observed several days earlier. Responses progressed through three stages during maturation: an early period of gross insensitivity during which responses are evoked only by high-intensity stimuli and whose response thresholds remain essentially constant (week 1); a middle period characterized by rapid acquisition of sensitivity to near-adult values (week 2); and a late period during which adult thresholds and latencies are acquired. A sequential stage model of threshold maturation is proposed, in which thresholds decline linearly during stage two and exponentially during stage three. It is hypothesized that mechanical reorganization of the cochlea during the first 2 to 3 postnatal weeks and development of the stria vascularis are primarily responsible for the linear stage, and that neural factors primarily underlie the exponential stage and account for the gradual acquisition of adult thresholds. Rates of maturation for brain stem responses are frequency dependent, with responses to high frequencies achieving adult thresholds earlier than those to low frequencies.

Aging↗

Development of auditory-evoked potentials in the cat. II. Wave latencies.

Brain stem and forebrain auditory-evoked potentials were studied parametrically during the first 90 postnatal days in unanesthetized kittens using tonal and click stimuli. This paper describes changes that occur in transmission time through the auditory pathway during development by analyses of the maturational time courses of latencies associated with waves of both auditory brain stem responses (ABR's) and late-occurring auditory-evoked potentials (AER's), recorded subdermally from the vertex. In response to click stimuli, ABR latencies were found to decay rapidly early in postnatal life and more slowly after the third postnatal week. Those trends were modeled as a two-stage sequential process, with a linear stage occurring between 7 and 18 postnatal days followed by an exponential stage during which adult latencies were achieved. AER latencies changes during development were less complicated, and followed a single-stage exponential time course. When threshold influences were taken into account--that is, when data were adjusted so that sensation level (SL) was constant across age--the latency-maturation curves associated with all ABR waves were adequately described by a single exponential, and latencies recorded from young animals were substantially shorter than latencies associated with the same aged animals when analyses were carried out with constant sound-pressure level (SPL) stimuli across age. In addition, the difference function, generated when isoasymptotic SPL and SL latency versus age functions were subtracted from one another, was also represented by an exponential curve, suggesting that at least two processes underlie the latency decay that occurs during postnatal development. Evoked responses to tonal stimuli throughout development were consistent with the basoapical developmental gradient that is observed anatomically.

Aging↗

Development of auditory-evoked potentials in the cat. III. Wave amplitudes.

Amplitudes of auditory-evoked brain stem response (ABR) and late-occurring auditory-evoked potential (AER) components were recorded from kittens between birth and 90 postnatal days. All ABR and AER wave amplitudes increased during the first postnatal month. Wave amplitudes exhibited nonmonotonic growth with increasing age, attaining a maximum at 40-60 days of age, after which amplitudes decreased. Amplitudes of waves originating in the auditory nerve matured somewhat faster than waves originating in the brain stem and forebrain, and the order in which waves reached maturity was roughly the reverse order of the latencies of their peaks. Input-output curves for ABR and AER waves displayed nonmonotonic behavior that varied as a function of postnatal age. Wave amplitudes recorded from adult cats increased between threshold and 70 dB SPL, then decreased between 70 and 100 dB SPL, and rapidly increased above 100 dB SPL. The intensity corresponding to the change from increasing to decreasing amplitudes was higher for younger animals and achieved adult values during the first postnatal month.

Aging↗