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Biomedical subjects

D L Morgan

Publications and source records attributed to D L Morgan.

At least 109 records · Page 6Linked to original sources

Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis.

STUDY OBJECTIVE: To compare the analgesic effect of IM ketorolac tromethamine with that of oral indomethacin in the treatment of acute gouty arthritis. DESIGN: Prospective, randomized, double-blind, controlled, parallel group clinical trial. SETTING: Two urban emergency departments. PARTICIPANTS: Twenty consecutive patients who presented to the ED with acute gout. INTERVENTIONS: Each patient was randomly assigned to receive in the ED (1) 60 mg of IM ketorolac and oral placebo or (2) 50 mg of oral indomethacin and IM placebo. The patients rated the intensity of their pain on a Wong-Baker pain scale (which runs from 0 to 5) before treatment and 30, 60, 90, and 120 minutes after treatment. All the patients were discharged with instructions to take oral indomethacin and to complete pain score cards at home at 6, 12, and 24 hours. RESULTS: The 10 patients in each group were similar with regard to age, sex, race, and initial mean pain score. After 2 hours, the mean pain scores (+/- SD) for the ketorolac group had decreased from 4.5 +/- .71 to 1.4 +/- 1.43 (P < .05), and the mean score for the indomethacin group had decreased from 4.4 +/- .70 to 1.5 +/- 1.18 (P < .05). The difference between the two groups was not significant. At 6 hours, there was some pain rebound in the ketorolac group. CONCLUSION: IM ketorolac and oral indomethacin are similar in the relief of the pain of acute gouty arthritis in the ED.

Administration, Oral↗

The intracellular Ca2+ transient and tension in frog skeletal muscle fibres measured with high temporal resolution.

1. The purpose of this study was to determine, with high temporal resolution, the relationship between the intracellular Ca2+ transient (ICT) and the mechanical responses of intact, single skeletal muscle fibres of frogs following stimulation by a single, brief depolarization. 2. The time course of the ICT was monitored using the Ca(2+)-sensitive fluorescent dyes mag-fura-2 (furaptra) and mag-fura-5. The mag-fura dyes have a low affinity for Ca2+ and have been shown to track the ICT with no appreciable kinetic delay. Continuous records of mag-fura fluorescence, tension and stiffness responses were obtained simultaneously at high time resolution at a sarcomere length of 2.9 microns. Experimental temperature was 3 degrees C. 3. When a delay of 0.4 ms due to the low-pass filter associated with the photodetector was included, the onset of the fluorescence response preceded the onset of latency relaxation (the small fall in tension that precedes positive tension generation) by 3.1 +/- 0.2 ms (mean +/- S.E.M., n = 8). After its onset, the mag-fura fluorescence signal continued to change rapidly (indicating increasing intracellular [Ca2+]) to an extreme level that occurred 1.5 +/- 0.5 ms (mean +/- S.E.M., n = 7) before tension had recovered to its resting level following latency relaxation. The time delay from the extreme of the fluorescence signal to the peak of the tension signal was 239 +/- 27 ms (mean +/- S.E.M., n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cytogenetic and germ cell effects of phosphine inhalation by rodents: II. Subacute exposures to rats and mice.

Phosphine (PH3) is a highly toxic grain fumigant to which there is significant human workplace exposure. To determine the in vivo cytogenetic effects of inhalation of PH3, male F344/N rats and B6C3F1 mice were exposed to target concentrations of 0, 1.25, 2.5, or 5 ppm PH3 for 6 hr/day for 9 days over an 11-day period. Approximately 20 hr after the termination of exposures, blood was removed from the mice and rats by cardiac puncture and the lymphocytes cultured for analyses of sister chromatid exchanges and chromosome aberrations in rats and mice, and micronuclei (MN) in cytochalasin B-induced binucleated lymphocytes from mice. In addition, bone marrow (rats) and peripheral blood (mice) smears were made for the analysis of MN in polychromatic and normochromatic erythrocytes. No significant increase in any of the cytogenetic endpoints was found at any of the concentrations examined. These results indicate that concentrations of PH3 up to 5 ppm are not genotoxic to rodents when administered by inhalation for 9 days during an 11-day period as measured by several cytogenetic assays. To evaluate the effects of PH3 on male germ cells, a dominant lethal test was conducted in male mice exposed to 5 ppm PH3 for 10 days over a 12-day period and mated to groups of untreated females (2 females/male) on each of 6 consecutive 4-day mating intervals. None of the 6 groups of females exhibited a significant increase in percent resorptions. These results indicate that exposure to 5 ppm PH3 by inhalation does not induce dominant lethality in male mouse germ cells at steps in spermatogenesis ranging from late differentiating spermatogonia/early primary spermatocytes through mature sperm.

Administration, Inhalation↗

The responses of secondary endings of cat soleus muscle spindles to succinyl choline.

This report describes the effects of succinylcholine (SCh) on the secondary endings of cat soleus muscle spindles and attempts to explain them in terms of the action of the drug on intrafusal fibres. All but 2 of 41 secondary endings studied in detail showed a significant response to a single intravenous injection of 200 micrograms kg-1 SCh. This consisted of a rise in the resting rate or development of a resting discharge if the spindle had previously been silent and an increase in the response to stretch. The increases in the responses to stretch were weaker than those observed for primary endings of spindles, but were much larger than those of tendon organs, which showed very little effect with this concentration of drug. The response to SCh showed two features consistent with its action being mediated via an intrafusal muscle fibre contraction rather than a direct depolarising action on the afferent nerve ending. In the presence of SCh, secondary endings were able to maintain a discharge during muscle shortening at rates, on average, more than 5 times greater than under control conditions. Secondly, the increase in spindle discharge produced by SCh showed a length dependence similar to that for fusimotor stimulation. Further support for the action of SCh being principally via an intrafusal fibre contraction was provided by the observation that its effects were abolished by the neuromuscular blocker gallamine triethiodide.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Fusimotor activity and the tendon jerk in the anaesthetised cat.

This is a study of the tendon jerk reflex elicited by a brief stretch applied to the triceps surae muscle group in the chloralose-anaesthetised cat. The size of the recorded reflex depended on stretch parameters (optimum at 300 microns amplitude at a rate of 100 mm/s) and on how the muscle had been conditioned. A reflex elicited after a conditioning contraction at the test length was often twice as large as after a contraction carried out at a length longer than the test length. This difference was attributed to the amount of slack introduced in the intrafusal fibres of muscle spindles by conditioning. The question was posed, did ongoing fusimotor activity exert any influence on the size of the tendon jerk? Depolarization indices (DPI) were calculated from responses of muscle spindles to stretch and correlated with the level of reflex tension. Values of DPI obtained from afferent responses with and without repetitive stimulation of identified fusimotor fibres suggested that with the stretch parameters used here the main influence of fusimotor activity was that it removed any pre-existing slack in muscle spindles and thereby increased reflex tension. In the absence of intrafusal slack, stimulation of static and dynamic fusimotor fibres had little additional influence on the size of the reflex. It is concluded that much of the variability typically seen with tendon jerks is due to muscle history effects. Since in muscles which have not been deliberately conditioned there is commonly some slack present in spindles, activity in fusimotor fibres is likely to reduce slack and therefore increase reflex size.

Anesthesia↗

Sharing the caring: family caregivers' views of their relationships with nursing home staff.

Using data from focus groups and individual interviews with family caregivers who had a spouse or a parent with Alzheimer's disease, we examined their reports of interactions with staff in formal care settings. Families most often discussed nurses' aides; they emphasized their desire for an ongoing relationship with staff members; and, they interpreted staff behaviors in terms of high-quality care that was based on the social and emotional care given to their resident as much as on the technical tasks involved in caring for them. These results point to the families' desire for emotionally sensitive care and not just for technically competent performance of tasks.

Adult↗

Blockade of intrafusal neuromuscular junctions of cat muscle spindles with gallamine.

This is a report on the resistance to block of the motor terminals on intrafusal fibres of cat soleus muscle spindles using the drug gallamine triethiodide (Flaxedil). To minimize diffusion barriers and to permit accurate measurements of time courses, rather slow rates of gallamine infusion were used (0.15 mg min-1). The main finding made was that after gallamine infusion, when extrafusal tension had dropped to half, all dynamic fusimotor effects and eight of twenty static effects had fallen to 40% or less of their control value. The remaining static effects persisted at 60-80% of their control value. Where fusimotor fibres were stimulated together with one or two skeletomotor fibres, the influence of the skeletomotor axons was significant only after spindle biasing had fallen to low levels. When gallamine infusion was stopped extrafusal tension returned to control levels within 20-75 min, depending on the length of the block, while fusimotor responses did not fully recover within the recording period of up to 150 min. The combination for some fusimotor responses of an early fall and a late recovery when compared with extrafusal tension, suggested a greater sensitivity of these endings to the drug. A comparison of spindle responses to the drug succinyl choline (SCh) and to fusimotor stimulation in the presence of gallamine showed that SCh responses were rapidly reduced by gallamine and had a long recovery time course, as were some fusimotor responses. From this it is argued that fusimotor effects with a high sensitivity to gallamine blockade were associated with nuclear bag fibre contractions and the more resistant effects with nuclear chain fibre contraction. It is generally believed that intrafusal neuromuscular junctions are more resistant to neuromuscular blockers than extrafusal junctions. The present experiments provide evidence to the contrary for some intrafusal junctions. Since muscle relaxants are often used in general anaesthesia it is interesting to speculate about the recovery of function of proprioceptive reflexes and of kinaesthesia during the immediate post-anaesthetic period, in view of the large difference in recovery time for transmission at intrafusal and extrafusal junctions.

Animals↗

Decline running produces more sarcomeres in rat vastus intermedius muscle fibers than does incline running.

Unaccustomed eccentric exercise, in which a muscle is lengthened while generating tension, is well known to cause injury and pain. A rapid training effect has been demonstrated in a number of eccentric exercises. The mechanism for both the damage and the training has been unknown. Morgan proposed that the damage is caused by sarcomere length instabilities during operation on the descending limb of the sarcomere length-tension curve and that the training effect is an increase in the number of sarcomeres connected in series in a muscle fiber, thus avoiding the descending limb (Biophys. J. 57: 209-221, 1990). We tested this proposal by exercising rats on a treadmill set at either an incline or a decline of 16 degrees, an exercise that has previously been shown to cause damage in untrained rats and a training effect. The vastus intermedius muscles were fixed and were digested in acid, and the fiber and sarcomere lengths of representative fibers were measured. From these measurements, the mean number of sarcomeres per fiber was found for the different training regimes. A clear and repeatable difference was found, supporting Morgan's prediction of more sarcomeres after decline running, although with some differences in response that depended on the age of the rats.

Adaptation, Physiological↗

Correlating resting discharge with small signal sensitivity and discharge variability in primary endings of cat soleus muscle spindles.

1. In a previous report we proposed that primary endings of cat soleus muscle spindles can be separated into two kinds. One kind, called by us silent endings, at muscle lengths shorter than Lm -10 (maximum body length -10 mm), fell silent after a 5 mm shortening step. Spontaneous endings, on the other hand, were able to resume a resting discharge after a brief pause at all muscle lengths down to Lm -20. This report examines further differences between the two kinds of endings. 2. There were consistent differences in the muscle length dependence of the maintained level of resting discharge of the two kinds of endings, measured after a conditioning contraction or a contraction followed by a shortening step. The resting discharge of spindles with spontaneous endings, after both forms of conditioning increased progressively with length. For silent endings, after a conditioning contraction, resting discharge fell slightly at longer lengths. 3. Discharge variability, measured at a number of muscle lengths, showed a dependence both on mean interimpulse interval and on spindle type, being higher in silent than spontaneous spindles. 4. Small signal sensitivity was measured with the use of 1 Hz sinusoidal stretches applied longitudinally to the tendon. Sine wave amplitude was adjusted to give a 30% depth of modulation of the resting discharge. Spontaneous endings were consistently less sensitive to the stretches than silent endings at all muscle lengths. Average sensitivities, measured over a range of lengths between Lm -4 and Lm -20 mm were 0.30 imp.s-1.microns -1 for spontaneous endings and 0.66 imp.s-1.microns -1 for silent endings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Summary of the National Toxicology Program benzidine dye initiative.

The benzidine dye initiative is a research program established by the National Toxicology Program to generate an integrated body of scientific information regarding the potential health risks associated with exposure to benzidine- and benzidine-congener-derived dyes. Because an in-depth evaluation of each of the hundreds of benzidine-congener-derived dyes was considered impractical, the research program was designed to study the metabolism and disposition, genetic toxicity, and in vivo toxicity and carcinogenicity of two primary benzidine congeners, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine, and a select group of prototypical dyes derived from those amines. It was anticipated that by applying the basic information generated in these extensive studies, it would be possible to make regulatory decisions about other dyes after conducting only a minimal number of experiments such as studies of disposition and metabolism, and in vitro mutagenicity. This paper summarizes the results of studies conducted to evaluate the metabolism, disposition, mutagenicity, toxicity, and carcinogenicity of representative benzidine congeners and derived dyes.

Animals↗

Styrene inhalation toxicity studies in mice. I. Hepatotoxicity in B6C3F1 mice.

Studies were conducted to evaluate the toxic effects of short-term repeated styrene inhalation in B6C3F1 mice. Male and female mice were exposed to 0, 125, 250, or 500 ppm styrene, 6 hr/day, for up to 14 days. Styrene toxicity was characterized by severe centrilobular hepatic necrosis and deaths after one exposure to 500 ppm or two exposures to 250 ppm. Mortality and hepatotoxicity were not increased by additional exposures, and in surviving mice, regeneration and repair of initial hepatic injury occurred in spite of continued exposure for 14 days. A marked sex difference was observed, with male mice significantly more susceptible to styrene toxicity than females. A nonlinear dose response was observed where mortality in male and female mice was greater in the 250 ppm dose group than that in the 500 ppm dose group. Severe congestion and necrosis of the liver was present in moribund mice; hepatic congestion and serum alanine aminotransferase and sorbitol dehydrogenase were significantly greater in moribund animals.

Administration, Inhalation↗

Styrene inhalation toxicity studies in mice. II. Sex differences in susceptibility of B6C3F1 mice.

Styrene is a commercially important chemical used in the production of plastics and resins. In initial short-term styrene inhalation studies, toxicity was significantly greater in male B6C3F1 mice than in females, suggesting that males may metabolize styrene more extensively and/or may be less able to detoxify reactive metabolites. In addition, a nonlinear dose-response was observed where toxicity and mortality were greater in mice exposed to 250 ppm than in those exposed to 500 ppm. These studies were conducted to investigate potential mechanism(s) for sex differences and the nonlinear dose-response in styrene toxicity by evaluating the effects of repeated styrene exposure on styrene oxide production, hepatic GSH availability, and hepatotoxicity in male and female B6C3F1 mice. Mice (36/sex/dose) were exposed to 0, 125, 250, or 500 ppm styrene 6 hr/day for up to 3 days. Styrene exposure caused increased mortality and hepatotoxicity (centrilobular necrosis, increased serum liver enzymes) in males and females after one or two exposures to 250 and 500 ppm. Hepatic GSH levels were decreased in a dose-dependent manner in males and females. After one exposure, GSH levels in males rebounded above controls in all dose groups. After three exposures to 125 or 250 ppm males appeared to maintain GSH levels; GSH was still decreased in the 500 ppm group. GSH levels in females were decreased after each exposure in all dose groups to lower levels than in males, and did not rebound above controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Styrene inhalation toxicity studies in mice. III. Strain differences in susceptibility.

Inhalation toxicity studies were conducted to evaluate mouse strain differences in the susceptibility to styrene vapors. Male and female B6C3F1, C57BL/6, Swiss, and DBA/2 mice (8 weeks old) were exposed to 0, 125, 250, or 500 ppm styrene 6 hr/day, for 4 days (20/sex/dose). Histopathological changes and changes in liver weights were evaluated as a measure of hepatotoxicity. Styrene uptake and styrene-7,8-oxide (SO) formation were estimated by measuring levels of styrene and SO in blood. An estimate of SO detoxification by conjugation with GSH was obtained by measuring hepatic GSH depletion. In general, mortality, increased liver weights, and hepatocellular necrosis were observed in the 250 and 500 ppm dose groups for all strains and both sexes. Considerable sex and strain differences were observed. Mortality, increased liver weights, and hepatocellular necrosis were greatest in B6C3F1 and C57BL/6 mice in the 250 ppm dose group and in males; hepatotoxicity was similar in both strains. Swiss mice exhibited dose-dependent increases in mortality, liver weights, and in hepatocellular necrosis, with only slight sex differences at early time points. Hepatotoxicity in DBA/2, B6C3F1, and C57BL/6 strains was greater at 250 than 500 ppm; however, toxicity was less severe in DBA/2 than in other strains based on absence of mortality in either sex and less extensive liver necrosis at both 250 and 500 ppm. Blood styrene and SO levels did not correlate well with strain differences in toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Reconstitution of hair follicle development in vivo: determination of follicle formation, hair growth, and hair quality by dermal cells.

Combinations of cultured and uncultured epidermal and dermal cell preparations from newborn and perinatal mice were grafted onto the backs of athymic nude mouse hosts to elucidate the cellular requirements for skin appendage formation. All epidermal populations studied, including a total epidermal keratinocyte preparation from trypsin-split skin, developing hair follicle buds isolated from epidermis, and preformed hair follicles isolated from dermis, make haired skin when grafted with fresh dermal cells. Only pre-formed hair follicles produce haired skin on grafts without an additional dermal component. Hair follicle buds grafted alone or with cultured dermal cells will reconstitute skin but without appendage formation. Thus, cells or factors present in fresh, but not cultured, dermal cells are essential for supporting hair growth from budding follicles, whereas more developed (pre-formed) follicles appear to contain all the necessary components for hair formation. Dissociation of isolated hair follicles by trypsin/ethylenediaminetetraacetic acid prior to grafting is permissive for hair growth, suggesting that follicle cells can be re-induced or reassociate in vivo. Dermal papilla cells, microdissected from rat vibrissal follicles and cultured for up to 14 passages, stimulate hair growth from follicle buds and influence the quality of hair growth from pre-formed hair follicles. Thus, dermal papilla cells maintain inductive capacity in culture and contribute to the reconstituted skin. This reconstitution model should be useful for identifying cell populations within the hair follicle compartment necessary for hair growth and for examining the effects of specific gene products on hair follicle growth and development in vivo.

3T3 Cells↗

Effects of repeated eccentric contractions on structure and mechanical properties of toad sartorius muscle.

It has been proposed that lengthening of active muscle at long lengths is nonuniformly distributed between sarcomeres, with a few being stretched beyond overlap and most hardly being stretched at all. A small fraction of the overstretched sarcomeres may fail to reinterdigitate on subsequent relaxation, leading to progressive changes in the muscle's mechanical properties. Sartorius muscles of the toad Bufo marinus were subjected to repeated lengthening (eccentric) contractions at long lengths, while controls were passively stretched and then contracted isometrically or stretched at short lengths. The muscles undergoing eccentric contractions showed a progressive shift to the right of the length-tension curve, a fall in the yield point during stretch, an increase in slope of the tension response during stretch, and a fall in isometric tension. In control muscles, changes, if any, were significantly less. In electron micrographs, muscle fibers that had been subjected to a series of eccentric contractions showed sarcomeres with A bands displaced toward one half-sarcomere, leaving no overlap in the other half. Adjacent regions often looked normal. These results are all in agreement with the predictions of the nonuniform stretch of sarcomeres hypothesis.

Animals↗

Qualitative content analysis: a guide to paths not taken.

Counting codes makes qualitative content analysis a controversial approach to analyzing textual data. Several decades ago, mainstream content analysis rejected qualitative content analysis on the grounds that it was not sufficiently quantitative; today, it is often charged with not being sufficiently qualitative. This article argues that qualitative content analysis is distinctively qualitative in both its approach to coding and its interpretations of counts from codes. Rather than argue over whether to do qualitative content analysis, researchers must make informed decisions about when to use it in analyzing qualitative data.

Abstracting and Indexing↗