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Biomedical subjects

S Taylor

Publications and source records attributed to S Taylor.

At least 415 records · Page 23Linked to original sources

Changes in intracellular Ca2+ induced by shortening imposed during tetanic contractions.

Calcium transients, monitored by aequorin, and force were recorded simultaneously during tetanic contractions of isolated frog skeletal muscle fibers. Quick length changes were applied to the fibers during contractions at sarcomere lengths on the descending limb of the length-tension relationship. Previous experiments showed that regulatory Ca2+ binding sites are apparently saturated during a plateau of tetanic force development at these sarcomere lengths. However, quick releases of greater than 4 to 5% of fiber length produced a momentary fall in the calcium transient that followed a time course similar to the redevelopment of force. The fall in the Ca2+ transient after a release was maximum at striation spacings about half way along the descending limb (2.6-2.7 microns), which suggests it is not related to an increase in the number of Ca2+ binding sites distributed uniformly along the filaments. The effect was absent or barely detectable when highly stretched fibers were released during contraction. The fall in the Ca2+ transient was unrelated to the time during a tetanus that a release was made or to the velocity of the release. One explanation of these results is that complexes between actin and myosin are broken by a sudden reduction of length, and as they reform during the recovery of force the affinity of troponin for Ca2+ increases. Quick stretch had no effect on the rapid decay of Ca2+ transients, but stretch increased peak force and slowed relaxation for almost a second after the end of stimulation. Evidently the decrease in the rate of relaxation produced by stretch is unrelated to changes in the amount of Ca2+ released or the rate of Ca2+ removal, which supports suggestions that the kinetics of muscle relaxation are determined by more than one mechanism. The apparent increase in the overall duration of mechanical activity after stretch probably results from the longitudinal inhomogeneity in the duration of activity - known to occur during relaxation - coupled with the decreased compliance of stretched fibers.

Aequorin↗

The kinetics of cross-bridge attachment and detachment studied by high frequency stiffness measurements.

Muscle fiber stiffness, supposedly an indication of attached cross-bridges, was measured throughout tetanic contraction and subsequent relaxation. Stiffness increased at a rate faster than the development of force during the rise of tetanic contraction and decreased more slowly than force during relaxation. One explanation for these results is that long-lived cross-bridge states may exist between attachment, force generation and detachment.

Animals↗

Phase I evaluation of AT-125 single dose every three weeks.

A Phase I trial of AT-125 was completed for the bolus dose every three week schedule. Dose limiting toxicity was primarily central nervous system (CNS) in the form of ataxia, confusion, hallucinations and dysarthria. Although this was most severe at doses of 150 mg/m2, lesser symptoms were reported at all dose levels. Nausea and vomiting were moderate to severe at higher doses. Myelosuppression did not occur. This schedule is not recommended for Phase II studies until methods are developed to reduce drug-related CNS toxicity.

Adult↗

Protamine: a powerful in vivo inhibitor of bone resorption.

Protamine is shown to be a powerful disrupter of calcium homeostasis, acutely inducing a severe hypocalcemia in both rabbits and rats. The magnitude of its effect correlates with bone turnover. Protamine does not significantly alter the renal excretion of calcium, and is effective whether or not there is calcium present in the gut. Protamine causes a significant fall in the specific activity of 45Ca in the blood in animals whose bone has been prelabeled with 45Ca. These data suggest that protamine induces hypocalcemia by blocking calcium efflux from bone. Further work seems indicated to define the biochemical mechanism of this action.

Animals↗

Clinical experience with alfentanil for induction of anaesthesia; a comparison with thiopentone.

Alfentanil, a new short-acting narcotic was clinically evaluated as an intravenous anaesthetic induction agent in 19 patients and compared to 20 patients receiving thiopentone. Alfentanil was superior to thiopentone in cardiovascular stability, both during induction of anaesthesia and tracheal intubation. However, alfentanil does not behave like a typical induction agent, time to unconsciousness is longer and more variable and is often accompanied by muscle rigidity. The results of this study suggest that alfentanil is more difficult to use as an induction agent than thiopentone, but alfentanil is recommended for short procedures when haemodynamic stability is important.

Alfentanil↗

Gilbert's syndrome as a cause of postoperative jaundice.

A case of postoperative jaundice due to Gilbert's syndrome in a previously healthy 19-year-old female is presented. Signs and symptoms of jaundice developed on the second postoperative day and resolved spontaneously after 5 days. The diagnosis and characteristics of Gilbert's syndrome and other related abnormalities and factors relevant to anaesthesia which affect bilirubin metabolism are discussed.

Adult↗

Plasma catecholamine concentrations. The effects of infiltration with local analgesics and vasoconstrictors during nasal operations.

Plasma catecholamine concentrations were measured in 19 patients allocated randomly to receive submucous infiltration with 4 ml of either 0.5% lignocaine with adrenaline 1:200 000 or prilocaine 0.5% with octapressin 0.03 iu per ml. Venous blood samples were obtained before and at 2, 5, and 10 minutes following infiltration. Plasma adrenaline increased from 0.35 to 1.72 p mol/ml at 2 minutes infiltration with the former solution whilst there was little change in plasma noradrenaline concentration. No similar peak in adrenaline concentration occurred after infiltration with prilocaine/ octapressin solutions but with both solutions there was a small increase in plasma noradrenaline and adrenaline concentrations 10 minutes after infiltration, at the time of surgical stimulation.

Adolescent↗

Neurophysiological changes following traumatic spinal lesions in man.

Neurophysiological observations were made on normal subjects and on 57 patients who had had injuries to the spinal cord. The amplitude of the muscle compound action potential (M response) recorded from triceps surae in response to supramaximal stimulation of the tibial nerve was reduced in the patients indicating that there are changes in motor units below the level of a spinal lesion in man. In the patients who were clinically spastic it was found that: (1) The proportion of the triceps surae motoneuron pool reflexly activated either by tapping the Achilles tendon or by stimulating the tibial nerve just below the threshold of the alpha motoneuron axons (H reflex) was greater than in normal subjects. This can be explained by an increase in the excitability of central reflex pathways. (2) Vibration of the tendo Achilles depressed the H reflex less effectively than in normal subjects. This may indicate altered transmission in the premotoneuronal portion of the H reflex pathway. (3) The H reflex elicited 50 and 100 ms after a standardised conditioning stimulus to the tibial nerve and expressed as percentage of the unconditioned reflex was greater than in normal subjects. This could reflect a change in the excitability of motoneurons or of interneurons.

Adolescent↗

A disposable double-lumen tracheostomy tube--a prototype.

A prototype disposal double-lumen tracheostomy tube made of plastic has been developed and used successfully in two cases. It has definite advantages over a conventional double-lumen tube in facilitating suction and minimising the risk of kinking by virtue of its shorter length.

Disposable Equipment↗

Assessing the market for long-term care services.

Traditionally, long-term care services have been used by a diverse marketplace. The chronically ill, developmentally disabled, mentally ill and aging population has looked to long-term care support services as a means of physical and emotional support. Much of the time these services were housed together for the sake of efficiency. The enormous burden these services are creating on the economy, and the growing aging population, have forced the recognition that long-term care service delivery systems must change. Alternate programming for long-term care services that reach out into the community and into individual homes is becoming an attractive approach to meeting the growing demands of the marketplace. Home health, specialized housing and creative funding mechanisms such as HMOs, are examples of initiatives undertaken by healthcare organizations that view diversification as a vehicle for survival. Market research techniques that have been used in other industries are being adapted to the healthcare industry to ensure the proper mix of services that are demanded by older, more knowledgeable consumers. The programs of the future will be market driven, with the ability of the individual to pay for such services playing a significant role. The healthcare provider of today is in a position to serve the community in new ways. By becoming an integral link in the long-term care system and by developing new programs, the organization can serve as a catalyst for change. It is up to the governing bodies and managers of these facilities to become visionaries and to accept responsibility for assessing the market for long-term care services and to guide their organization into the future.

Aged↗

Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. The effects of halothane and dantrolene.

Calcium-induced calcium release and halothane-induced calcium release from pig sarcoplasmic reticulum (SR) were studied. The SR prepared from pigs susceptible to malignant hyperthermia (MH) was shown to release calcium at a much lower level of calcium content than in normal pig SR. The concentration above which halothane can release calcium is 40 microM for both MH-SR and normal SR, although the latter required a high calcium content to demonstrate the calcium release. Dantrolene was shown to inhibit the halothane-induced calcium release. Results suggest that SR plays an important role in pathogenesis of MH.

Animals↗

Angiogenesis inhibition and tumor regression caused by heparin or a heparin fragment in the presence of cortisone.

Heparin or a heparin fragment administered with cortisone inhibited angiogenesis, caused regression of large tumor masses, and prevented metastases. Oral administration of heparin resulted in the release of non-anticoagulant heparin fragments in the serum which, in the presence of cortisone, had similar anti-angiogenic and antitumor effects. Of all the heparin fragments tested, the most potent inhibition of angiogenesis in the presence of cortisone was provided by a hexasaccharide with a molecular weight of about 1600.

Animals↗

Human cardiac beta-adrenergic receptors: subtype heterogeneity delineated by direct radioligand binding.

Human myocardial beta-adrenergic receptors were directly identified and characterized using the high affinity antagonist radioligand [125I]iodocyanopindolol. Beta 1 and beta 2 adrenergic receptors were found to coexist in both the left ventricle and right atrium. The relative proportions of the two receptor subtypes were determined by the use of competition radioligand binding and computer modelling techniques employing the subtype selective agents atenolol (beta 1 selective) and zinterol (beta 2 selective). The left ventricle contains 86 +/- 1% beta 1 and 14 +/- 1% beta 2 adrenergic receptors while the right atrium contains 74 +/- 6% beta 1 and 26 +/- 6% beta 2 adrenergic receptors. The direct demonstration of beta 2 adrenergic receptors in the human heart, with a higher proportion in the right atrium agrees with pharmacologic data and supports the notion that chronotropic effects of adrenergic agonists in man may be mediated by both beta 1 and beta 2 adrenergic receptors.

Adrenergic beta-Agonists↗

Phase I trial of Indicine-N-Oxide on two dose schedules.

Indicine-N-Oxide is the water soluble N-oxide of the pyrolizidine alkaloid indicine recently evaluated in Phase I trials. Initially in a weekly times four schedule, twenty-nine patients were treated with a dose range of 1.0 to 7.5 g/m2 per week. Fifteen of 40 of the courses of four doses were interrupted by myelosuppression which prohibited completion of the course. Therefore, an intermittent schedule was evaluated utilizing single doses repeated every 3-4 weeks. Twenty-six patients were treated at doses of 5 to 10 g/m2. Myelosuppression is the dose limiting toxicity of both schedules with thrombocytopenia being more severe than leukopenia. Myelosuppression is predictable and reversible on the intermittent schedule. It is more severe in patients with heavy prior treatment. Partial responses were seen in four patients, one with a mucoepidermoid carcinoma of the salivary gland and three with adenocarcinoma of the colon. Phase II studies are planned at a starting dose of 7.5 g/m2 every 3-4 weeks in patients with no prior treatment and 5 g/m2 in patients with prior treatment.

Adult↗

Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir. A randomized double-blind controlled trial in normal subjects.

We performed a double-blind placebo-controlled trial of oral acyclovir in the treatment of first episodes of genital herpes simplex virus infections in 48 young adults (31 women and 17 men). Subjects were randomized to receive either placebo or acyclovir (200 mg per dose) five times daily for 10 days; they were examined on at least eight visits until healed and at monthly visits thereafter. Acyclovir treatment, as compared with placebo, significantly reduced virus shedding, new lesion formation after 48 hours, and the duration of genital lesions in both men and women. The total duration and severity of clinical symptoms (such as pain, adenopathy, dysuria, and malaise) were significantly reduced by acyclovir in both men and women by the third and fourth day, respectively (P less than or equal to 0.025), as compared with placebo. No toxicity was observed. Recurrence rates have so far been similar in placebo and acyclovir recipients. Oral acyclovir treatment of first-episode genital herpes simplex virus infections is clinically effective, but it does not seem to prevent virus latency or associated recurrent disease.

Acyclovir↗

The role of heparin in angiogenesis.

A series of experiments is described in which: (i) mast cells were found to accumulate at a tumour site before the ingrowth of new capillaries; (ii) heparin released by mast cells increased the migration of capillary endothelial cells in vitro; and (iii) heparin enhanced tumour angiogenesis in vivo. These experiments led to the discovery that protamine and platelet factor 4 are angiogenesis inhibitors. This finding suggests a central role for heparin or related glycosaminoglycans in the growth regulation of capillary blood vessels.

Angiogenesis Inducing Agents↗

The effect of reduced viewing time on colour vision in normal subjects and those with abnormal ocular conditions.

The effect of restricting viewing time to 3.75 ms in normal subjects is to produce a tritan-like colour response on the City University colour vision test. This response pattern is consistent and is repeatable for standard illuminant C at 600 lx. Supplementary tests suggest that the effect is due to a defect of the blue/yellow opponent system rather than a true tritan defect. The same test when repeated on subjects with amblyopia or retinal pathology provides different results which may aid in the differential diagnosis of some visual disorders.

Amblyopia↗

Muscular contraction: kinetics of crossbridge attachment studied by high-frequency stiffness measurements.

Instantaneous stiffness of frog skeletal muscle, an indication of the proportion of attached crossbridges, was determined drug the tetanus rise and after a step length change imposed during the tetanus plateau. During the onset of contraction as well as after a step, the ratio of stiffness to force differed from that determined during the tetanus plateau. The data after a step are predicted by the Huxley-Simmons model of muscular contraction, but the results during the rise suggest that a long-lived state may exist between crossbridge attachment and force generation.

Animals↗