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Biomedical subjects

D B Thomson

Publications and source records attributed to D B Thomson.

At least 37 records · Page 2Linked to original sources
PubMed1992

Neuromuscular organization of feline anterior sartorius: II. Intramuscular length changes and complex length-tension relationships during stimulation of individual nerve branches.

The feline anterior sartorius is a long strap-like muscle composed of short muscle fibers. Nerve branches that enter this muscle contain the axons of motor units whose constituent muscle fibers are distributed asymmetrically within the muscle. In the present study, twitch and tetanic isometric contractions were evoked by stimulating individual nerve branches while muscle force was recorded and intramuscular length changes were monitored optically by the movement of reflective markers on the muscle. Contractions elicited by stimulating the parent nerve produced little change in the positions of the surface markers. Contractions elicited by stimulating the proximally or distally directed nerve branches caused the muscle to shorten at the end closest to the nerve branch and lengthen at the opposite end. Some muscles were supplied by a centrally directed nerve branch whose stimulation produced variable effects: in some cases a portion of the muscle shortened whereas the rest lengthened, but in other cases, the positions of the surface markers showed little change. The intramuscular length changes produced by stimulating single nerve branches were greater during isometric contractions at short whole-muscle lengths than at long whole-muscle lengths. The twitch and tetanic length-tension relationships obtained by stimulating the individual nerve branches were not congruent with the length-tension relationship produced when the parent nerve was stimulated. At short whole-muscle lengths, stimulation of a single nerve branch generated only a small fraction of the force that could be generated by the muscle when the parent nerve was stimulated. As whole-muscle length increased, an increased fraction of total muscle force could be generated by stimulating a single nerve branch. The results suggest that a complex relationship between passive and active elements contributes to the total muscle force and depends on the distribution of active and passive muscle units throughout the muscle.

Animals↗
PubMed1992

Electromyographic studies of neck muscles in the intact cat. I. Patterns of recruitment underlying posture and movement during natural behaviors.

Natural head movements in alert, unrestrained cats were studied using video-filming, videofluoroscopy and electromyographic (EMG) recording methods. In each cat, up to sixteen neck muscles or neck-muscle compartments were implanted with recording electrodes. Patterns of muscle recruitment were examined during systematically-selected behavioral epochs in which the cat held a range of stationary postures, and when it performed volitional and exploratory behaviors such as flexion-extension or turning, grooming, eating, or headshaking. Patterns of muscular activity were interpreted with reference to simultaneous video images of head and neck movements. In separate, videofluoroscopic analysis, flexion-extension movements were examined to gain insight into the underlying movements of the skull and cervical vertebrae. These and other movements were found commonly to depend upon changes in joint angles between lower as well as upper cervical joints. Stationary postures in which the neck was held vertically were consistently associated with tonic EMG activity in only two long dorsal muscles, biventer cervicis and occipitoscapularis. Less consistent activity was also present in dorsal intervertebral muscles crossing lower cervical joints. When the neck was held horizontally, the long dorsal muscles increased their EMG activity and moderate activity was also recorded in deeper intervertebral and suboccipital muscles. When flexion-extension occurred around upper cervical joints, greatest activity was recorded in rectus capitis posterior and complexus, but when it involved the lower cervical joints, large changes in EMG activity could also be detected in biventer cervicis, occipitoscapularis, and the intervertebral muscles crossing lower cervical joints. During specialized, sagittal-plane movements such as grooming, well-defined patterns of synergy could be recognized that varied according to the degree of involvement of upper and lower cervical joint-sets. Movements in the horizontal plane were associated with EMG activity in a largely different subset of neck muscles including splenius, longissimus capitis and obliquus capitis inferior. The levels of EMG activity during flexion-extension or turning movements were much lower than those observed during other more vigorous behaviors, such as head shaking. Some neck muscles, such as clavotrapezius and sternomastoideus, could only be recruited during forceful or ballistic head movements. Results showed that the patterns of muscular activation were linked not only to the speed and trajectory of the movements of the skull, but also to the kinematics of the motion occurring across different parts of the cervical column.

Animals↗
PubMed1991

Neuromuscular organization of feline anterior sartorius: I. Asymmetric distribution of motor units.

The neuromuscular organization of feline anterior sartorius was examined using three experimental approaches. First, the branching pattern of the nerve supplying anterior sartorius was inspected in muscles taken from a large number of feline cadavers. All muscles were found to be supplied by two major nerve branches, one directed proximally and the other directed distally, and most muscles (42/51) had a third distinct branch that entered the muscle centrally. Second, the motoneuronal populations supplying the three nerve branches were investigated by electrophysiological techniques. Motoneurons that supplied axons to the distally-directed branch did not appear to have collaterals in more proximally-located branches. In contrast, other motoneurons supplying the proximally-directed branch also appeared to supply axon collaterals to the centrally-directed branch. This result suggested that the motoneuronal population of the distally-directed branch was largely separate from that supplying the proximally- and centrally-directed branches. Third, the motor unit territories supplied by different nerve branches were mapped using glycogen-depletion methods. Muscle fibers supplied by the distally-directed nerve branch were mostly distributed to the medial portion of anterior sartorius, whereas the fibers supplied by the other two branches were generally found more anteriorly. Further, the muscle fibers supplied by an individual nerve branch were present in greater numbers at the end of the muscle closest to the entry point of that branch. Thus, the motor units supplied by discrete nerve branches were found to be distributed asymmetrically within anterior sartorius, but were arranged neither strictly in-parallel nor strictly in-series.

Adenosine Triphosphatases↗
PubMed1991

Bilateral labyrinthectomy in the cat: motor behaviour and quiet stance parameters.

The purpose of this study was to examine the effect of bilateral labyrinthectomy on quiet stance in the freely-standing cat. Since loss of the vestibular end organs produces marked deficits in motor behaviour, including ataxia and problems with balance, we hypothesized that labyrinthectomized animals would show impairment in quantitative measures of stance. Stance was quantified in terms of the ground reaction forces under each limb and the tonic electromyographic (EMG) activity of selected muscles. Animals were labyrinthectomized by drilling into the vestibule and removing the vestibular epithelium. Following lesion, animals were able to stand unsupported on the force platform within 2 days. To our surprise, the lesioned animals showed little change in stance parameters from the control, pre-lesion state. Thus, our hypothesis of changes in stance parameters was not supported. There was no change in the distribution of vertical forces under the limbs and no increase in sway, as measured by the area of excursion of the centre of pressure over time. The horizontal plane forces, which were diagonally directed prior to lesion, became more laterally directed and larger in amplitude. The change in direction persisted even after the animals had fully compensated for the lesion, but the force amplitudes returned to control values within 10-12 days. The change in horizontal force direction was similar to that observed in normal animals that were required to stand with their paws closer than preferred in the sagittal plane (unpublished observations). EMG activity changed in some muscles but not others, and usually transiently.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Treatment of advanced malignant melanoma with recombinant interferon alfa-2a in combination with DTIC: long-term follow-up of two phase II studies.

The present studies were designed to examine whether treatment of disseminated melanoma with a combination of recombinant interferon alpha (rIFN alpha-2a) and DTIC may provide better results than either agent alone. Two dose levels of rIFN alpha-2a were examined with the same dose and schedule of DTIC administration. In the first study 76 patients were treated with rIFN alpha-2a (3 x 10(6) IU days 1-3, 9 x 10(6) IU days 4-70 then 9 x 10(6) IU TIW) plus DTIC (i.v. 200 mg/m2, escalating to 800 mg/m2 each 21 d) for 6 months or longer or until failure. Responses were seen in 26% of patients overall (7CR, 13PR) with the highest responses being seen in those assessed as having a good prognosis and in patients with skin and/or lung metastases. It was notable that males showed a better response than females and that patients with metastases in lymph nodes showed low responses. Response rates in 30 patients treated with high-dose rIFN alpha-2a (18 x 10(6) IU days 7-70) were not superior to that seen at the lower dose and was accompanied by significant increase in bone marrow toxicity. The duration of responses appeared longer than expected from responses to DTIC alone and four patients remain progression free at periods in excess of 3 years. Failure in nine of the responders was due to the development of brain metastases which emphasizes the need for additional treatment approaches to treat micrometastases at this site. The results of a randomized control study comparing DTIC alone with DTIC plus 'low' dose rIFN alpha-2a are awaited with interest.

Adolescent↗
PubMed1990

Clinical evaluation of interferons in malignant melanoma.

The evaluation of interferons in the treatment of malignant melanoma has been mainly in the treatment of advanced disease using interferons as the sole agent or in combination with other agents. Studies of the value of interferons as adjuvant therapy in high-risk primary melanoma patients are necessary, but no results have been published to date. Human interferon alpha produces low response rates as a sole agent, but in combination with cimetidine, a 30% response rate has been achieved. Recombinant alpha interferons give responses of 15%-20% in advanced melanomas, and combination with cimetidine does not enhance the response rate. Recombinant alpha interferons have been used in combination with other interferons, cimetidine, monoclonal antibodies, and cytotoxics, with either no or small improvement in response rates. DTIC with recombinant interferon alpha-2a has been shown to produce objective response rates of 26%, with low toxicity and maintenance of quality of life. A randomized trial with DTIC as the sole agent, compared with combination treatment, is being conducted to determine the significance of this finding.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Sustainable inspiratory pressures over varying flows, volumes, and duty cycles.

This study identifies the influence of flow (0.5-2.0 l/s), duty cycle (0.29-0.57), and tidal volume (1.08-2.16 liters) on sustainable inspiratory muscle pressure (Pmus) and transdiaphragmatic pressure (Pdi) development. Six normal humans performed endurance tests using an isoflow method, which allowed for measurements of maximum dynamic Pmus and Pdi, with controlled lung inflation. The subjects repeated maximum dynamic voluntary inspirations for 10 min. Pressures dropped exponentially from initial measurements at rest (Pmusi or Pdi) to sustainable values (Pmus or Pdis). As flow and tidal volume increased, maximum initial and sustainable pressures decreased significantly. However, at a constant duty cycle, the sustainable dynamic pressures remained predictable fractions of initial dynamic pressures (i.e., Pmuss/Pmusi or Pdis/Pdii), regardless of changes in flow and tidal volume. In contrast, as duty cycle increased, the sustainable fractions significantly decreased for both Pdi and Pmus. For example, at a duty cycle of 0.29, Pmuss/Pmusi was approximately 0.71, and at a duty cycle of 0.57, Pmuss/Pmusi was approximately 0.62. Calculated sustainable pressure-time indexes varied significantly between 0.16 to 0.32 for Pmus and 0.11 to 0.22 for Pdi over the breathing patterns studied. We conclude that 1) the maximum dynamic pressure that can be sustained at a given duty cycle is a predictable fraction of the maximum dynamic pressure that can be generated at rest when measured under the same conditions of inspiration and 2) the sustainable fraction of initial dynamic pressure significantly decreases with increasing duty cycle.

Abdomen↗
PubMed1988

Loss of alleles on the short arm of chromosome 11 in a hepatoblastoma from a child with Beckwith-Wiedemann syndrome.

The Beckwith-Wiedemann syndrome (BWS) is characterised by multiple congenital abnormalities, including exomphalos, macroglossia, and gigantism. It is also associated with an elevated risk of embryonal neoplasia and occasionally with constitutional anomalies of chromosome band 11p15. A common pathogenetic mechanism for the development of several embryonal tumours has been proposed involving the loss of somatic heterozygosity for a locus on the short arm of chromosome 11. In support of this hypothesis, we have recently reported generation of homozygosity for the c-Ha-ras-1 protooncogene in an adrenal adenoma from an adult BWS patient. In this study we report the generation of homozygosity for a region on the short arm of chromosome 11 defined by the calcitonin (11p13-15) and insulin (11p15-15.1) genes in a hepatoblastoma from a child with BWS.

Alleles↗
PubMed1988

The mechanical response of active human muscle during and after stretch.

Five subjects contracted forearm supinator muscles which were stretched after development of maximal isometric torque. The ratio of torque at the end of stretch over isometric torque at that position was calculated as excess torque. Excess torque increased with stretch velocity and decreased with stretch amplitude, and it was not dependent upon final muscle length. The rate of decay of torque following stretch could not be shown to depend upon stretch variables. The absence of significant changes in myoelectric activity suggested that with high initial forces, reflex activity did not account for the observed changes. Time-constants of decay (0.15 s to 1.8 s) were much greater than time-constants of rise (approx. 0.07 s) of isometric torque at the same muscle length. This indicates that interaction of series elastic and contractile elements is not the sole cause of prolonged torque following stretch. It is concluded that stretch temporarily enhances the intrinsic contractile properties of a group of human muscles in a manner similar to, but quantitatively different from that seen in isolated muscle preparations.

Analysis of Variance↗
PubMed1988

Encephalopathy following cisplatin, bleomycin and vinblastine therapy for non-seminomatous germ cell tumour of testis.

A 22-year-old man developed severe encephalopathy, grand mal seizures and visual disturbance after combination chemotherapy with cisplatin, vinblastine and bleomycin for metastatic testicular carcinoma. After excluding treatable causes, only supportive management was given, and the symptoms and signs resolved over several months. We suggest a clinical syndrome of encephalopathy, seizures and visual disturbance represents a rare toxicity of cisplatin-based therapy. Given the wide spread usage of cisplatin, this should be drawn once again to the attention of medical oncologists.

Adult↗
PubMed1987

Recombinant interferon alfa-2a in advanced malignant melanoma. A phase I-II study in combination with DTIC.

There is a rising incidence of malignant melanoma world-wide and, despite major improvements in its early diagnosis and treatment, the 10-year death rate remains at 20-25%. Evidence that the immune system has a role in the control of melanoma growth has encouraged immunological intervention. The results of phase II trials of recombinant interferon alfa-2a in advanced melanoma justified further studies. A review of trials of various interferons used as sole agents showed an overall objective response rate of 16.3%, one-third of the responses being complete responses of long duration. The use of cimetidine together with recombinant interferon alfa-2a remains controversial. Trials of both beta- and gamma-interferons are incomplete and information on their effect in advanced melanoma is not yet available. Recombinant interferon alfa-2a in combination with chemotherapy is now being used in trials and the early results are encouraging. In a combined series from Brisbane and Newcastle, Australia involving 44 patients treated with recombinant interferon alfa-2a and DTIC, 13 objective responses including 6 complete responses have been obtained. These response rates compare favourably with those of earlier trials using interferon alone. Further work is necessary to determine the best combined dosage and method of administration for optimum immunobiological effect.

Adolescent↗
PubMed1987

Plasma oxipurinol concentrations during allopurinol therapy.

The plasma concentrations of oxipurinol, the chief metabolite of allopurinol, were studied in 66 patients with gout in whom the dose of allopurinol varied between 100 and 400 mg per day. Renal function ranged from normal to moderately impaired. Plasma oxipurinol concentrations correlated directly with both allopurinol dosage and with renal glomerular function as reflected by the plasma creatinine concentration. Plasma oxipurinol concentrations between 30 and 100 mumol/l were generally effective in controlling hyperuricaemia. However, oxipurinol concentrations usually rose above this range if the daily dose of allopurinol exceeded 300 mg in patients with plasma creatinine concentrations of 0.2 mmol/l or more. In patients with normal renal function, a rise of the plasma xanthine concentration to between 6 and 9 mumol/l suggested a satisfactory degree of xanthine oxidase inhibition. These measurements are particularly useful in patients who are still hyperuricaemic despite the usual doses of allopurinol.

Allopurinol↗
PubMed1987

Chlorambucil allergy--a series of three cases.

Three cases of chlorambucil-related skin eruption in patients with low-grade non-Hodgkin's lymphoma are described. Cases were confirmed by exclusion of other drugs, rechallenge, skin testing and histology. One patient died due to florid erythema multiforme. Only two other adequately documented cases are described.

Aged↗
PubMed1986

A simple dosimeter for bronchial provocation testing using a solid-state electronic timing module.

In conducting inhalational challenge tests of airway responsiveness to methacholine, we prefer to deliver the challenge aerosol intermittently, using a dosimeter that turns the nebulizer on for about 0.5 to 0.6 second to deliver each "puff." To avoid the considerable expense of commercially available dosimeters, we constructed our own electronically controlled device, which, in conjunction with a DeVilbiss Model 646 nebulizer, is easily calibrated and permits reproducible and precise timing of challenge puffs. The device was constructed of readily available components and cost us only $100. An experienced technician can use it to trigger on the nebulizer within 0.5 second of the start of inspiration, and in more than one year's experience we have found the system to be completely satisfactory and reliable.

Bronchial Provocation Tests↗
PubMed1986

Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma.

Tamoxifen was evaluated as initial hormone therapy for metastatic breast cancer in 85 premenopausal patients. Tamoxifen responders continued on tamoxifen, while tamoxifen failures and initial responders who later progressed were to receive ovarian ablation next. Of 74 evaluable patients, 5 had complete responses (CR) and 15 had partial responses (PR) while 12 remained stable (ST), giving response rates of 27% (CR + PR) or 43% (CR + PR + ST). Of the 23 patients who initially responded (CR + PR + ST) to tamoxifen but then progressed and received ovarian ablation alone, 15 are assessable. Nine (60%) responded (CR + PR + ST) to ovarian ablation. Sixteen patients who failed tamoxifen had ovarian ablation alone, and of 14 assessable patients 2 had ST while 12 progressed. Thus response to tamoxifen strongly predicted response to ovarian ablation (P = 0.021). Serial follicle stimulating hormone, prolactin, and estradiol levels suggested that tamoxifen does not act by induction of a "medical ovariectomy" or by alteration of prolactin levels in premenopausal patients.

Breast Neoplasms↗