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Biomedical subjects

L Adams

Publications and source records attributed to L Adams.

At least 37 records · Page 2Linked to original sources
PubMed1996

Does oxygen help dyspnea in patients with cancer?

Dyspnea in patients with advanced cancer is a common symptom that is difficult to treat. This study investigated whether oxygen helps to relieve rest dyspnea in patients with advanced cancer. In a single-blind controlled trial, oxygen and air were administered in random order to hospice patients reporting dyspnea at rest. Measurements of arterial oxygen saturation, lung function, and dyspnea (using a visual analogue scale [VAS] and Borg score) were made before and after each gas had been given for 15 min. Data from 38 patients were used: analysis of variance revealed that mean VAS levels during baseline conditions, breathing room air (59 mm), were significantly reduced after administration of either air (48 mm; p < 0.001) or oxygen (45 mm; p < 0.001); there was no significant difference for the mean VAS scores between oxygen and air administration. There was no statistically significant order of treatment effect. There was no difference in the response to oxygen or air in patients with a history of cardiopulmonary disease. The improvement in dyspnea with oxygen could not be predicted from a subject's initial level of hypoxia. Results suggested that benzodiazepines may potentiate the effect of oxygen. The overall conclusion is that oxygen and air can have a significant effect in reducing dyspnea at rest in patients with advanced cancer.

Aged↗
PubMed1996

Pre-clamp cardioprotection by protein kinase C (PKC) inhibitor improves left ventricular function following canine normothermic arrest.

Since protein kinase C (PKC) has been proven to be a mediator of neutrophil activation and of intracellular calcium homeostasis, its inhibition could protect the myocardium from the deleterious effects of ischemic/reperfusion inury (IRI). The principal objective of this study was to evaluate the efficacy of the PK inhibitor SPC-100270 (2S,3S)-2-amino, 3-octadecanediol in a canine model of IRI. A double-blind study was conducted in which 19 coonhound dogs received either SPC-100270 or a vehicle before going on cardiopulmonary bypass (CPB). After 60 minutes of global normothermic (37 degree C) cardiac arrest (cross-clamp time 65-81 minutes for SPC-100270 and 65-72 minutes for control) and discontinuation of CBP, an epicardial short axis view echocardiogram was performed and reviewed by a double-blinded observer to determine the ejection fraction (EF). EF value exceeded 20% in 5 out of 9 SPC-100270 animals (27%-44%) and in 0 of 10 controls (0%-16%). These data show that SPC-10027 significantly (p=0.01 by Fisher's Exact Test) increased the probability that the animals would exhibit an EF greater than 20%.

Animals↗
PubMed1995

Hyperpnoea during and immediately after exercise in man: evidence of motor cortical involvement.

1. The neurophysiological basis for the increase in breathing associated with exercise remains obscure. The present study uses positron emission tomography (PET) to measure relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during and immediately following exercise. 2. Male volunteers underwent H2(15)O PET scanning during two complementary studies. Firstly, six subjects performed right leg exercise, adequate to increase oxygen uptake 2.5-fold. Secondly, five different subjects were scanned immediately following bicycle exercise (adequate to increase oxygen uptake 5-fold) while breathing was still increased. In each study, as a control, scanning was also performed during matched passive isocapnic positive pressure ventilation; additionally, in the first study, passive right leg movement was performed. 3. Increases in relative rCBF were obtained in each individual and co-registered with their magnetic resonance image of the brain defining individual gyral morphology. 4. During exercise, individual and group analysis revealed significant relative rCBF increases in the left and right superomedial primary motor cortex (the motor cortical 'leg' areas) and also in the left and right superolateral primary motor cortex in areas previously shown to be associated with volitional breathing. After exercise, there was no significant increase in relative rCBF in the superomedial areas but such increases were still present bilaterally in the superolateral areas which had been activated during the exercise. Other relative rCBF increases were also found, both during and after exercise, in cortical and subcortical areas known to be involved in motor control. 5. The results from PET scans during and after exercise, taken together, provide evidence for motor cortical involvement in the exercise-related hyperpnoea in man.

Adult↗
PubMed1995

Evidence for limbic system activation during CO2-stimulated breathing in man.

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

Adult↗
PubMed1995

Phase I clinical and pharmacokinetic study of 3'-deamino-3'-(2-methoxy-4-morpholinyl)doxorubicin (FCE 23762).

Methoxymorpholinyldoxorubicin (FCE 23762) is a novel, highly lipophilic doxorubicin analogue. It possesses potent in vitro and in vivo antitumor activity including efficacy in multidrug-resistant tumor cell lines. It is also metabolically activated in vivo resulting in an 80-fold increase in potency over the parent drug. In this phase I study the drug was administered by i.v. bolus injection at 3-week intervals. Fifty-three patients with refractory solid tumors were treated; 133 courses of FCE 23762 were administered at doses ranging from 30 to 2250 micrograms/m2. The dose limiting toxicity was reversible myelo-suppression (granulocytopenia and thrombocytopenia), demonstrating a delayed nadir and recovery in comparison to doxorubicin. Other toxicities included transient elevation of hepatic transaminases, delayed and prolonged nausea and vomiting, mucositis, anorexia, fatigue, and diarrhea. Heavily pretreated patients demonstrated more myelosuppression than previously untreated patients at 1250 micrograms/m2. No cardiotoxicity was observed. Four objective tumor responses were seen: one complete response in a patient with pelvic recurrence of cervical cancer; one partial response in a patient with cutaneous and lymph gland metastases from head and neck cancer; and two minor responses in patients with liver metastases from colorectal cancer. Plasma concentrations of FCE 23762 and its 13-dihydro metabolite, FCE 26176, were measured in 20 patients at doses > or = 675 micrograms/m2, using HPLC with fluorescence detection. The area under the plasma concentration-time curve ranged from 30 to 80 ng/h/ml; plasma data suggested linear kinetics in the range of tested doses (although there was considerable interpatient variability). The maximum tolerated dose defined in this study using this schedule is 1500 micrograms/m2. A safe phase II dose for previously untreated patients using this schedule is 1250 micrograms/m2; however, this may actually be below the optimal dose for this patient population.

Adult↗
PubMed1995

Imagination of dynamic exercise produced ventilatory responses which were more apparent in competitive sportsmen.

1. The cardiorespiratory response to imagination of previously performed treadmill exercise was measured in six competitive sportsmen and six non-athletic males. This was compared with the response to a control task (imaging letters) and a task not involving imagination ('treadmill sound only'). 2. In athletes, imagined exercise produced increases in ventilation which varied within and between subjects. The mean maximal increase (11.71 min-1) was approximately 20% of the ventilatory response to actual exercise. This was primarily due to treadmill speed-related increases in respiratory frequency (mean maximal increase, 14.8 breaths min-1) and resulted in significant reductions in end-tidal PCO2 (mean maximal fall, 7 mmHg). These effects were greater (P < 0.01) than any observed during the control tasks. 3. Changes in heart rate (mean increase, 12 beats min-1) were not significantly different from those observed during the control tasks (P > 0.2). 4. In non-athletes, imagination of exercise produced no changes in cardiorespiratory variables. No significant differences were detected in subjective assessments of movement imagery ability between athletes and non-athletes (P = 0.17). 5. This study demonstrates that ventilatory effects, when observed, are specific to imagination of exercise. The greater likelihood of generating ventilatory responses in highly trained athletes, experienced in 'rhythmic' sports, may be related to awareness of breathing and its role in exercise imagination strategy. A volitional component of the response cannot be discounted.

Adult↗
PubMed1995

Modulation by "central" PCO2 of the response to carotid body stimulation in man.

We describe a method to assess the effects of PCO2, around and below eucapnia, on the neuromuscular ventilatory response to a standard peripheral chemoreceptor stimulus. Subjects were "passively" hyperventilated (without respiratory muscle activity), at a constant level of ventilation. Stimuli (3-7 breaths N2) were delivered over a range of steady-state PETCO2 (25-43 mmHg). Stimuli during hypocapnia were coupled with a transient increase in FICO2 so that the stimulus to the peripheral chemoreceptors was always "hypoxia at eucapnia". Responses to the stimuli (quantified from the reduction in peak inflation pressure and the magnitude of the evoked diaphragm electromyographic activity) decreased in a graded manner as steady-state PETCO2 fell, disappearing at 7.5 mmHg below eucapnia. Carotid body chemoreceptor recordings from two anaesthetised cats, indicated that the peak firing rate during such stimuli was independent of steady-state PETCO2. The results suggest that the central sensitivity to a peripheral chemoreceptor input may be modulated by changes in steady-state PCO2 around eucapnia and during mild hypocapnia.

Adult↗
PubMed1995

Somatotopy of human hand somatosensory cortex revealed by dipole source analysis of early somatosensory evoked potentials and 3D-NMR tomography.

Somatosensory evoked potentials (SEPs) to median nerve and finger stimulation were analyzed by means of spatio-temporal dipole modelling combined with 3D-NMR tomography in 8 normal subjects. The early SEPs were modelled by 3 equivalent dipoles located in the region of the brain-stem (B) and in the region of the contralateral somatosensory cortex (T and R). Dipole B explained peaks P14 and N18 at the scalp. Dipole T was tangentially oriented and explained the N20-P20, dipole R was radially oriented and modelled the P22. The tangential dipole sources T were located within a distance of 6 mm on the average and all were less than 9 mm from the posterior bank of the central sulcus. In 6 subjects the tangential sources related to finger stimulation arranged along the central sulcus according to the known somatotopy. The radial sources did not show a consistent somatotopic alignment across subjects. We conclude that the combination of dipole source analysis and 3D-NMR tomography is a useful tool for functional localization within the human hand somatosensory cortex.

Adult↗
PubMed1995

Is voluntary control of breathing impaired in patients with chronic obstructive pulmonary disease?

1. To assess whether voluntary control of breathing is impaired in patients with chronic obstructive pulmonary disease, a group of such patients performed a tracking task, requiring volitional control of respiratory muscles. 2. Eight patients (mean age 60 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 31%) took part in the study. Five of the seven patients in whom blood gas measurements were made were mildly hypoxaemic (PaO2 = 53-71 mmHg), and one of these was hypercapnic (PaCO2 = 55 mmHg). Each subject performed a compensatory ventilatory tracking task using a tracking system which comprised a fixed target displayed on a monitor screen and a cursor moving in a line bisecting the target. The position of the cursor was perturbed by a forcing function and patients were required to keep the cursor on the target by breathing in and out of a spirometer. 3. To allow for any non-specific deficiency in motor control, patients performed a similar manual tracking task, using their dominant arm to move a joystick. As a control group, 11 healthy subjects (mean age 58 years; mean ratio of forced expiratory volume in 1 s to forced vital capacity = 77%) underwent an identical experimental protocol. 4. Motor control performances were measured in terms of the error between the target position and the subject's positioning of the cursor. Indices of performance were the root mean square of the error and the averages of the zero errors (i.e. end expiration/arm movement towards the trunk) and the peak errors (i.e. end inspiration/arm movement from the trunk).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Adaptation of nicotinic acetylcholine receptor, myogenin, and MRF4 gene expression to long-term muscle denervation.

Muscle activity alters the expression of functionally distinct nicotinic acetylcholine receptors (nAChR) via regulation of subunit gene expression. Denervation increases the expression of all subunit genes and promotes the expression of embryonic-type (alpha 2 beta delta gamma) nAChRs, while electrical stimulation of denervated muscle prevents this induction. We have discovered that the denervation-induced increases in alpha, beta, gamma, and delta subunit gene expression do not persist in muscles that have been denervated for periods extending beyond a couple of months. However, expression of RNA encoding the epsilon-subunit remains elevated suggesting a return to expression of predominantly adult-type (alpha 2 beta delta epsilon) nAChR in long-term denervated muscles; a finding confirmed by single channel patch-clamp analysis. Since the nAChR subunit genes are regulated by the MyoD family of muscle regulatory factors, and the genes encoding these factors are also induced following short-term muscle denervation, we determined their level of expression in long-term denervated muscle. Although MyoD and myf-5 RNA levels remained elevated, myogenin and MRF4 RNAs were induced only transiently by muscle denervation. Surprisingly, Id-1, a negative regulator of transcription, was gradually induced in denervated muscle with RNA levels peaking about two months after denervation. It is likely that this maintained level of increased Id expression, in conjunction with the returning levels of myogenin and MRF4 expression, account for the reduced level of embryonic receptors in long-term denervated muscle. These changing patterns of gene expression may have important consequences for the ability of muscle to recover function after denervation.

Adaptation, Physiological↗
PubMed1995

Effect of hyperglycemia duration on rabbit corneal thickness and endothelial ATPase activity.

This study compares corneal thickness and corneal endothelial Na,K ATPase activity in normal and age-matched diabetic rabbits with up to 10 weeks of hyperglycemia. Corneal endothelial Na,K ATPase activity in normal rabbits increased between 10 and 20 weeks of age. Corneal thickness increased after 5 weeks of hyperglycemia. Decreased corneal endothelial homogenate Na,K ATPase activity was first seen after 10 weeks of hyperglycemia, though an earlier onset was possible due to sampling restrictions. Corneal endothelial homogenate Mg++ ATPase activity showed a transient increase after 2 to 5 weeks of hyperglycemia. This study shows that hyperglycemia in rabbit is associated with complex dynamic interactions between corneal thickness and corneal endothelial Mg++ ATPase and Na,K ATPase activities.

Aging↗
PubMed1995

Oral efficacy of a leukotriene B4 receptor antagonist in colitic cotton-top tamarins.

Leukotriene B4 (LTB4) is a potent neutrophil activator and chemotaxin that is present in increased concentrations in the colonic tissue and rectal dialysates of acute ulcerative colitis patients. Cotton-top tamarins (CTTs) with confirmed active colitis were treated with the second generation LTB4 receptor antagonist, SC-53228 ((+)-(S)-7-[3-(2-cyclopropyl-methyl)-3-methoxy-4-[(methylamino) carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2- propanoic acid), 20 mg/kg bodyweight by gavage, twice daily for 56 days. End points were body weights, stool consistency, colonic endoscopy, assay of inflammatory mediators, and haematology and clinical chemistry tests. LTB4 and prostaglandin E (PGE) values were measured in rectal dialysates at pretreatment, 28 day and 56 day time points. LTB4 concentrations were reduced from pretreatment mean (SEM) values of 37.3 (0.8) ng/ml to 3.7 (0.8) ng/ml (p < 0.001) and 2.3 (0.5) ng/ml (p < 0.01) at days 28 and 56, respectively. On the other hand, mucosal protective PGE values remained constant or slightly increased during SC-53228 treatment (pre: 6.9 (2.2) ng/ml; day 28: 6.7 (1.4) ng/ml; day 56: 9.9 (1.6) ng/ml). Furthermore, assessment of a panel of 35 clinical chemistry and haematology parameters throughout the treatment showed there were no significant untoward effects of drug treatment. Six CCTs finished the eight week treatment and five of six gained weight (ranging from 27-121 grams each) while one CTT lost weight (50 g). Stool condition improved in five of six animals while one of six remained unchanged. All CCTs showed dramatic improvement histologically, with no or only minimally active colitis after treatment. The histological changes plus significant weight gains and improvement of stool condition (quality of life parameters) after eight weeks of SC-53228 treatment were remarkable. Furthermore, in follow up biopsies seven months after treatment ceased, three of six CTTs had no active colitis. This is the first time afflicted CTTs have not had recurring colitic exacerbations after a treatment regimen was stopped. It is concluded that in colitic CTTs, SC-53228 has shown both an immediate and a long acting anticolitic activity. It is also concluded that reduced LTB4 concentrations during treatment inhibited neutrophil infiltration of the colonic tissue and this, coupled with the maintenance of mucosal protective prostaglandins, contributed to the dramatic anticolitic efficacy. The treatment was safe over eight weeks. A compound such as SC-53228 may be useful in the medical treatment of human inflammatory bowel disease.

Animals↗
PubMed1995

Changes in total pulmonary resistance and PCO2 between wakefulness and sleep in normal human subjects.

We investigated the possible role of an increase in total pulmonary resistance in the sleep-related hypoventilation that occurs in healthy subjects. Eight nonsnoring volunteers were studied during quiet wakefulness and stage IV sleep. Airflow was measured via a nasal mask with a low dead space, and breathing pattern, end-tidal PCO2 (PETCO2), and a continuous estimate of total pulmonary resistance were estimated. From wakefulness to sleep, mean inspiratory resistance increased from 5.5 +/- 2.4 (SD) to 8.1 +/- 4.3 cmH2O.l-1.s, PETCO2 increase from 38.7 +/- 3.0 to 40.7 +/- 3.5 Torr, and ventilation decreased from 7.12 +/- 1.15 to 6.47 +/- 1.68 l/min. In five of the eight subjects, low levels of continuous positive airway pressure were applied during stage IV sleep to reverse any increase in resistance. In these subjects, continuous positive airway pressure reduced mean inspiratory resistance from 9.3 +/- 4.3 +/- 3.0 cmH2O.l-1.s but had little effect on mean PETCO2 (from 39.8 +/- 4.0 to 39.6 +/- 4.0 Torr) and mean ventilation (from 6.79 +/- 1.93 to 6.91 +/- 1.80 l/min). These findings suggest that in nonsnoring subjects reductions in alveolar ventilation cannot be accounted for by an increase in airway resistance.

Adult↗
PubMed1995

Promoting secure attachment patterns in infancy and beyond.

The attachment an infant makes to its mother* has a powerful influence over subsequent development. Attachment patterns may be secure, insecure avoidant or insecure ambivalent. They are already established by the age of one year, and are likely to affect future adult relationships, including the marital relationship and relationships with the person's own children. Children with insecure attachments may be more prone to psychological or psychiatric ill health. Family therapy can recognise the relevance of attachment theory and incorporate it when helping families to find new patterns of relating to one another and resolving their difficulties. Early intervention by midwives, health visitors and other primary health care professionals can help prevent faulty attachment patterns from becoming established and so being transmitted from one generation to the next.

Adult↗
PubMed1994

Calcium-dependent regulation of rat and chick muscle nicotinic acetylcholine receptor (nAChR) gene expression.

Muscle depolarization leads to decreased expression of nicotinic acetylcholine receptor (nAChR) genes in extrajunctional regions of the muscle fiber with little effect on their expression at the neuromuscular junction (NMJ). Depolarization-dependent decreases in nAChR gene expression have been linked to a cAMP-dependent signaling system in rat (Chahine, K. G., Baracchini, E., and Goldman, D. (1993) J. Biol. Chem. 2893-2898), and a calcium-dependent protein kinase C (PKC) signaling system in chick (Klarsfeld, A., Laufer, R., Fontaine, B., Devillers-Thiery, A., Bubreuil, C., and Changeux, J. P. (1989) Neuron 2, 1229-1236). We report here on experiments investigating the role of calcium and PKC in regulating rat muscle nAChR gene expression. These studies indicate that depolarization-dependent regulation of rat muscle nAChR gene expression is independent of PKC activity. However, these genes are regulated by a calcium-dependent signal transduction system. Calcium influx across the plasma membrane decreases nAChR gene expression in inactive rat myotubes. Surprisingly, this influx of extracellular calcium is most effective at reducing nAChR epsilon-subunit gene expression. We also provide evidence that a similar signal transduction system is capable of regulating nAChR gene expression in chick muscle. Based on these data we propose that calcium, in addition to mediating depolarization-dependent regulation of nAChR expression, may also participate in restricting their expression to the neuromuscular junctions of adult muscle fibers.

Animals↗