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Biomedical subjects

D L Morgan

Publications and source records attributed to D L Morgan.

At least 145 records · Page 8Linked to original sources

Earliest mechanical evidence of cross-bridge activity after stimulation of single skeletal muscle fibers.

The stiffness of single fibers from frog skeletal muscle was measured by the application of small 2-kHz sinusoidal length oscillations during twitch and tetanic contractions at a range of initial sarcomere lengths. The earliest mechanical signs of activation were a fall in tension (latency relaxation) and a rise in stiffness. The earliest stiffness increase and the earliest tension fall occurred simultaneously at all sarcomere lengths. This suggests a cross-bridge origin for the latency relaxation. The lead of stiffness over tension seen during the rise of tension was substantially established during the latent period. Reducing the size of the twitch by reducing calcium release with D-600 (methoxyverapamil) reduced the latency relaxation and the stiffness development during latency much less than it reduced the twitch tension. For very small twitches the peak of the stiffness response occurred during the latent period and the times of onset of both latency relaxation and stiffness rise were delayed, but remained coincident. This suggests a strong connection between the latency relaxation and the rise of stiffness during the latent period, whereas the connection between these events and positive tension generation appears to be less strong.

Animals↗

Tension in frog single muscle fibers while shortening actively and passively at velocities near Vu.

Experiments were undertaken to determine the contribution of passive tension to total tension during rapid shortening in a stimulated muscle fiber. Results were obtained by applying shortening movements at constant velocities slightly less than Vu (the velocity of unloaded shortening) to intact twitch fibers isolated from the frog (Rana temporaria). The tension maintained by unstimulated fibers during such shortening movements ("dynamic passive tension") from moderately long lengths was greater than zero but much less than the passive tension measured under static conditions ("static passive tension") at the same lengths. Fibers maximally activated by electrical stimulation and then shortened at the same velocity over the same range of average sarcomere lengths maintained tension that was greater than zero but less than the dynamic passive tension. For average sarcomere lengths up to approximately 3.1 microns, the dynamic passive tension appeared to be substantially abolished by activation. The onset of the apparent disappearance of dynamic passive tension was studied by initiating the stimulation and the shortening movement simultaneously. The resulting tension response exhibited a latency relaxation that was increased in amplitude compared with the isometric case, followed by a brief tension rise, giving way to a steady tension level equal to that expected if stimulation had been initiated well before the release. These changes are qualitatively explained in terms of the establishment of a steady state distribution of deformations of attached cross-bridges.

Animals↗

Effects of muscle history on the stretch reflex in cat and man.

1. This is a report of experiments on cat and man which demonstrate effects of a muscle's previous history of contraction and length changes on the size of the stretch reflex. 2. In adult human subjects the size of the tendon jerk was measured in ankle extensor muscles by tapping the Achilles tendon. Muscle conditioning consisted of a maximum voluntary contraction with the foot dorsiflexed or plantarflexed by 30 deg from the test position, after which the subject was asked to relax while the foot was held still for several seconds before being returned to the test position and a tendon tap given. After a contraction of the lengthened muscle the tendon jerk was smaller than after a contraction of the shortened muscle. 3. The experiment was then repeated, but instead of a tendon jerk an H (Hoffmann) reflex was elicited by transcutaneous electrical stimulation of the tibial nerve in the popliteal fossa. The reflex after a conditioning contraction of the lengthened muscle was larger than after a contraction of the shortened muscle. In other words muscle conditioning produced opposite effects on the tendon jerk and H reflex. 4. These findings were confirmed in cats anaesthetized with chloralose. After a conditioning contraction of triceps surae at a length 5 mm longer than the test length (hold-long) a quick tendon stretch produced a smaller reflex response than following a conditioning contraction with the muscle 5 mm shorter than the test length (hold-short). The reverse trend was seen with a reflex elicited by direct electrical stimulation of the muscle nerve, which stimulates the H reflex. 5. One consequence of a conditioning contraction is that it leads to an alteration of the level of resting discharge of muscle spindles. We propose that the larger tendon jerk after a contraction of the shortened muscle is the result of changes in stretch sensitivity of muscle spindles. The reverse effect on the H reflex we attribute to a rise in the level of resting discharge of muscle spindles, which, we propose, leads to reflex inhibition of motoneurones. 6. We support this conclusion with evidence from an experiment in which the size of the conditioning step was systematically altered. Even quite small hold-short conditioning steps led to depression of the H reflex in man and the monosynaptic reflex in cats. Recordings from single afferents showed that such small steps were also accompanied by a detectable rise in spindle resting discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Prospective study of concurrent ploidy analysis and routine cytopathology in body cavity fluids.

A total of 390 body cavity fluids were analyzed by both cytopathologic examination and flow cytometric DNA analysis. The two methods gave compatible results in analyses of 304 fluids (78%). In 24 patients, cytopathologic studies found the specimens to contain malignant cells, but the DNA content was diploid. This illustrates an area where flow cytometric studies do not extend tumor detection. In 56 fluids from 48 patients, cytologic methods revealed no malignant cells but flow cytometry distinguished aneuploid cell populations; additional clinical information allowed the identification of malignant tumors in 24 (50%) of these patients. Because flow cytometry was able to detect aneuploidy in cases where conventional cytologic examination could not detect malignant cells, the number of patients with tumors detected was increased by 39% beyond those detected by cytologic methods alone in this series.

Aneuploidy↗

Thirteen-week toxicity studies of 3,3'-dimethoxybenzidene and C.I. Direct Blue 15 in the Fischer 344 rat.

The benzidine congener 3,3'-dimethoxybenzidine (DMOB), and C.I. Direct Blue 15 (Blue 15), a prototypical compound of the DMOB-derived class of dyes, were evaluated in 13-week studies to characterize the toxicity and establish dose levels for subsequent chronic studies. Groups of 10 Fischer 344 rats of each sex were administered either DMOB, or Blue 15, at 1 of 5 concentrations in drinking water for 13 weeks. DMBO concentrations were 0, 0.017, 0.033, 0.063, 0.125, and 0.25% for males and females. For Blue 15, the concentrations were 0.063, 0.125, 0.25, 0.50, and 1.0% for females and 0, 0.125, 0.25, 0.50, 1.0, and 3.0% for male rats. Rats showed dose-related decreases in water consumption and weight gains. All DMOB-treated rats and their controls survived the 13-week treatment. There were 7 deaths in the 3% level of male rats treated with Blue 15. Liver and kidney weights were increased in rats treated with both compounds. Target organs for DMOB-treated rats were the kidney and thyroid. These lesions were characterized by chronic nephropathy, and increased pigment in the follicular cells of the thyroid. The kidney and liver were identified as target organs for Blue 15-treated rats. In the high-dose rats that died before termination of the study, renal effects were characterized by degeneration and focal necrosis of proximal tubular epithelial cells. Liver lesions in this group consisted of degeneration and necrosis of hepatocytes, fatty metamorphosis, and minimal megalocytosis. Mild chronic nephropathy was the principal histological effect in Blue 15-treated rats surviving to study termination.

Animals↗

14-day and 90-day toxicity studies of C.I. Pigment Red 3 in Fischer 344 rats and B6C3F1 mice.

Treatment of F344 rats and B6C3F1 mice with C.I. Pigment Red 3 in the diet (10, 5.0, 2.5, 1.25, 0.6 or 0.3%) for 14 and 90 days resulted in haematological alterations consistent with haemolytic anaemia. Rats appeared to be more sensitive than mice to the haematological effects. Histological lesions were observed in rats and mice after exposure for 90 days. Target organs in the rat were the spleen, bone marrow, liver and kidney. Lesions in the spleen consisted of a haematopoietic cell proliferation, iron-positive pigment and congestion of the red pulp, and inflammation of the splenic capsule. Changes in the livers of rats consisted of haematopoietic cell proliferation and iron-positive pigment in Kupffer cells. Haematopoietic cell proliferation also occurred in the bone marrow of treated rats. The presence of iron-positive pigment and a slightly increased incidence of protein casts were seen in the kidney. Target organs in mice were the spleen, liver and kidney. Histological lesions in mice after exposure for 90 days included increased haematopoietic cell proliferation in the liver and spleen, and iron-positive pigment in the spleen. Mild cytomegaly of the renal tubular epithelia was also observed in exposed mice.

Anemia↗

Effects of passive tension on unloaded shortening speed of frog single muscle fibers.

Experiments were performed to determine the influence of sarcomere length and passive tension on the velocity of unloaded shortening (Vu) as measured by the slack test technique. Slack test results were obtained from intact twitch fibers isolated from the frog (Rana temporaria). Measurements were made both in the absence and presence of passive tension using two different protocols. In one, all releases were initiated from the same sarcomere length and passive tension level; in the other, all releases ended at the same sarcomere length. In the absence of passive tension, no difference was observed between the results from the two slack test protocols. When passive tension was present, performing all releases from the same initial sarcomere length and passive tension level resulted in linear step size-slack time relationships in which the slopes (Vu) were independent of length over a sarcomere length range extending to 3.1 microns, and the intercepts increased with increasing sarcomere length. Performing all releases to the same final sarcomere length in the presence of passive tension produced nonlinear step size-slack time relationships. The results presented here show that, in the presence of significant levels of passive tension, the traditional interpretation of the slope of the slack test plot as the constant unloaded shortening velocity is only correct when all length steps are initiated from the same initial sarcomere length and level of passive tension.

Animals↗

Adjusting to widowhood: do social networks really make it easier?

Positive and negative aspects of relations with friends and family were examined among groups of widows in focus-group discussions, where relationships mentioned were coded as positive or negative. Approximately 40% of all mentions were negative, with family members receiving more negative mentions. Family relations showed commitments involving both problematic obligations and an inability to avoid undesirable behavior. Non-family relations showed flexibility, with increases in positive relationships and decreases in negative ones.

Aged↗

Efficacy and safety of pentoxifylline in geriatric patients with intermittent claudication.

The effects of pentoxifylline on intermittent claudication were evaluated at a dose of 1200 mg/day in an open-label twelve-week study on geriatric patients with chronic occlusive arterial disease (COAD). Standardized treadmill testing and clinical signs and symptoms of COAD were followed up before and during drug administration. Twenty-four subjects with a mean age of 73.5 years, capable of walking between 20 and 200 meters on the treadmill, were entered into the trial; 22 participated for eight weeks and 19 completed the study in terms of treadmill walking distance measurements at 12 weeks. The mean walking distance for all patients was increased 111% over baseline at week 12. Thirteen subjects were considered drug responders (greater than or equal to 50% increase in treadmill walking distance) and 9 were considered nonresponders (less than 50% increase). Improvements in clinical signs and symptoms of COAD were noted. Decreases in elevated systemic systolic pressures (but not diastolic) were unexpectedly observed in many drug responders. Seven of 19 males reported sexual function improvements while receiving pentoxifylline. Fourteen (58%) of the 24 subjects reported mild side effects of dyspepsia, nausea, vomiting, dizziness, headache, or insomnia; no subjects were withdrawn from the study because of side effects. In summary, pentoxifylline improved function and symptoms in 13 of 22 geriatric patients with intermittent claudication; the drug was safe and well tolerated at the usual dosage in this geriatric patient population.

Aged↗

Metal-reinforced glass ionomers: their flexural and bond strengths to tooth substrates.

This study compared the flexural strengths and bond strengths to dentin and enamel of two brands of silver-reinforced glass ionomers with their respective unfilled glass-ionomer cements for luting. The results led to the following conclusions. 1. No significant differences in bond strengths to tooth substrates were recorded between silver-reinforced and unfilled glass ionomers. 2. Although the mean bond-strength values of enamel were higher than those of dentin, no statistically significant differences were observed. 3. No significant differences in bond strengths to tooth substrates were observed between the two brands of glass ionomers studied. 4. No differences in flexural strengths were recorded between the silver-reinforced glass ionomer and glass ionomer of a similar brand for luting. 5. Ketac-Silver and Ketac-Cem cements had significantly higher flexural strength than Fuji II Lumi Alloy and Fuji I cements.

Dental Bonding↗

Ozone-initiated changes in erythrocyte membrane and loss of deformability.

In vivo O3 exposure followed by in vitro incubation was observed to cause inhibition of mouse RBC deformability. The requirement for in vitro incubation to allow expression of these effects and the potential role for oxidizable membrane components were investigated. Membrane sulfhydryls (SHs) and membrane ATPase are both susceptible to oxidation by O3 and are essential for maintaining RBC membrane deformability. RBC SH levels and ATPase activity were unchanged immediately after exposure of mice to filtered air (controls) or 1 ppm O3. After a subsequent 6-hr in vitro incubation, RBCs from control mice exhibited significant increases in membrane SH and ATPase activity, while SH levels and ATPase activity in RBCs from O3-exposed mice remained unchanged. Although the stimulus for increasing membrane SH and ATPase activity is unclear, these changes appear to be essential to maintaining RBC deformability in vitro and are inhibited by in vivo O3 exposure.

Adenosine Triphosphatases↗

The use of red cell distribution width in the detection of iron deficiency in chronic hemodialysis patients.

Forty patients on maintenance hemodialysis were studied to determine the usefulness of the red blood cell distribution width (RDW) in screening these patients for iron deficiency. Serum ferritin was used as the indicator of body iron stores. The sensitivity of RDW elevation in determining the likelihood of iron store depletion was 89%; and the negative predictive value of a normal RDW was 93%. The specificity of RDW elevation for iron deficiency was only 45%, and the positive predictive value was 32%. This study has confirmed the usefulness of the RDW as a screening test for iron deficiency in chronic hemodialysis patients. However, the low specificity and positive predictive value of the test also suggests the need for further studies when there is an unexplained elevation of the RDW.

Erythrocyte Indices↗

Age differences in social network participation.

Differences in participation in social networks were analyzed as a function of age, drawing on a theoretical model of substitution processes. Using an empirical approach from the study of participation in voluntary organizations, I separated the direct effects of age from indirect effects via age-based declines in resources. The results show that a substantial proportion of the age-based decrease in level of activity in social networks was due to declines in resources, but similar analyses for the sources of participation in networks showed effects of age that persisted after controlling for resources. These results point to some important distinctions among measures of social networks.

Aged↗

Aftereffects in the responses of cat muscle spindles and errors of limb position sense in man.

1. This is a report of two series of experiments, one, observations on muscle spindles in the anesthetized cat, the other, based on the animal observations, concerned with limb-position sense in human subjects. 2. When the cat soleus muscle is contracted at a short length and then after a brief period is brought to an intermediate length, the integrated afferent activity recorded in dorsal roots is maintained at a high level. If the contraction is applied while the muscle is held at a long length, the subsequent level of afferent activity back at the intermediate length is much lower. A similar result is obtained if large amplitude vibration of the muscle is used instead of contraction. Recordings from single afferents confirm that these alterations in discharge could be attributed to the primary and secondary endings of muscle spindles. 3. Following the proposal that the resting discharge of muscle spindles contributes to the sense of limb position in man, we have used a sequence of contractions or periods of vibration of biceps and triceps brachii followed by an arm-matching task to look for errors in limb position consistent with the patterns of muscle afferent discharge observed in the animal experiments. 4. Blindfolded subjects were told to contract biceps of one, the test arm, with the arm flexed. After the arm had relaxed, it was placed by the experimenter at an intermediate angle that the subject was asked to match with the other, indicator arm. Then the subject was asked to contract triceps with the arm extended, and the matching task was repeated. 5. The hypothesis was that contracting a muscle while it was short raised the level of afferent discharge coming from it when the arm was moved to an intermediate position so that the muscle would be perceived as more stretched and the arm felt to be displaced further than it really was. Thus, when biceps was contracted with the arm flexed, this would lead the arm in the intermediate position to be perceived as more extended than it really was. When triceps was contracted with the arm extended, this would lead the arm in the intermediate position to be perceived as more flexed than it really was.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Tendon stiffness: methods of measurement and significance for the control of movement. A review.

An appraisal of the role of tendons in transmitting muscle tension to skeletal parts during posture and movement requires accurate knowledge of the mechanical characteristics of the tendon. Here the most important property is tendon stiffness. While it is relatively easy to measure the stiffness of an isolated segment of tendon, more sophisticated methods must be sought to take into account the whole length of tendon, including its intramuscular portion. Two methods are currently available for measurement of whole tendon stiffness: each has a limited range of muscle tensions over which it appears to provide reliable values, one method being better at low tensions, the other at high tensions. Some controversy remains about the precise values obtained in the mid-tension range covered by both methods. Nevertheless it is now possible to achieve reasonable estimates of tendon stiffness over the whole working range of the muscle. An important consideration which has emerged from the discussion is that at low tensions the tendon is much less stiff than at higher tensions.

Animals↗

Changes in size of the stretch reflex of cat and man attributed to aftereffects in muscle spindles.

1. This is a report of experiments carried out on the cat and on man, which demonstrate that conditioning of a muscle by contraction and movement can lead to changes in amplitude of stretch reflexes elicited in that muscle. 2. In triceps surae of the cat, the reflex response to a brief stretch was recorded after conditioning with a whole-muscle contraction followed by a pause at a length either 5 mm longer or shorter than the length at which the reflex was elicited. Following conditioning at the long length the reflex response was less than half as large as that following conditioning at the short length. 3. The changes in reflex amplitude could be correlated with an altered stretch responsiveness of muscle spindles in the soleus muscle. When the muscle had been held long during conditioning, a subsequent brief stretch applied at an intermediate length elicited fewer impulses in primary endings of spindles than after conditioning at a short length. 4. The same kind of experiment was then carried out on adult human subjects. When a tendon tap was applied to the Achilles tendon after a voluntary contraction and relaxation of triceps surae with the muscle at a long length, (foot dorsiflexed) the reflex was frequently less than half the size it had been after a contraction at a short length (foot plantarflexed). It was concluded that the same kind of spindle aftereffects as observed for cat soleus spindles were responsible for the changes in reflex amplitude. 5. It was found both in the cat and in human subjects that the changes in reflex amplitude after conditioning became progressively less as the test length was made longer. 6. The explanation put forward to account for these observations is that stable cross-bridges form between actin and myosin filaments of passive intrafusal (and extrafusal) fibers. When the muscle is shortened several seconds after a contraction at a long length, the intrafusal fibers, stiffened by the presence of cross-bridges, fall slack. Slack does not develop after a contraction at a short muscle length, as the fiber is stretched to the test length. Since any slack must first be taken up by the test stretch, there is a smaller afferent response and consequently a smaller reflex contraction in response to a tendon tap after conditioning at a long length.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The artificial heart: pursuit of a noninvasive method for determining atrial pressures.

The use of conventional open-port catheters in total artificial heart (TAH) research shortens the survival time of recipients owing to sepsis and embolism caused from the catheters. Valuable data are lost when an open-port catheter clots off, and transducer position must be keyed to the level of the atria for accuracy. The need for an accurate, easily obtainable, noninvasive method for measuring atrial pressure is of obvious value. Such a method has been developed in vitro using a device that measures the stroke volume of a pneumatic ventricle. The stroke volume is obtained by quantifying the amount of air exiting a pneumatic TAH in diastole. Using this information ventricular filling rates can be calculated by the stroke volume measurement device, and these rates are correlated to measured atrial pressures. There is no need to continually adjust transducer levels in relation to the atria with this system. The data show an average percentage error of 2.4 of full scale (25 mm Hg) or 0.6 mm Hg. The method of measurement is accurate, without limitations on driving parameters. The information is available without any additional prosthetic fabrication or surgical intervention than that already needed for basic TAH implantation. This method of measuring atrial pressures now needs to be proved effective in vivo.

Heart Atria↗