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Biomedical subjects

L Adams

Publications and source records attributed to L Adams.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1994

Dose dependency of perceived breathlessness on hypoventilation during exercise in normal subjects.

To determine whether a dose-dependent relationship exists between the subjective sensation of breathlessness and hypoventilation during steady-state exercise, we measured breathlessness at six levels of volitionally suppressed ventilation. To achieve this, subjects targeted their breathing at 0, 5, 10, 15, 20, and 25% below their spontaneous exercise level. All 12 subjects were successful in hypoventilating in a graded manner. However, in general, the degree of hypoventilation achieved was less than that of the target level set; this discrepancy was greatest at the higher target levels. Volitional hypoventilation at target levels of > or = 10% caused significant decreases in ventilation and significant increases in end-tidal PCO2. All levels of volitional hypoventilation caused increased ratings of breathlessness, reaching statistical significance at a set target level of 15%. Significant increases in breathlessness intensity were associated with increases in end-tidal PCO2 of 2-3 Torr. We conclude that, during steady-state exercise, there appears to be a dose-dependent relationship between breathlessness and volitionally induced inappropriately low ventilation. The need to minimize such subjective sensations of breathlessness may play a role in the increased ventilation observed during exercise.

Adult↗
PubMed1994

Biostereometric measurement of oral tumour growth. Description of the technique and case report.

Following radiotherapy, it may be difficult to determine clinically whether tumour regression, stabilization or growth has occurred. Traditional diagnostic imaging may not be possible due to the small size of the tumour and the proximity of metallic restorations. A case of squamous cell carcinoma of the mandibular alveolar process in which these problems arose is presented. A computer-assisted biostereometric technique was used to identify volumetric change of the tumour. Polyvinylsiloxane impressions were obtained to record the anatomy of the tumour site. From these, stone models were made at four and eight weeks following radiotherapy. Using optical mapping techniques, tumour growth was demonstrated which was not evident on follow-up examinations. The methodolgy of biostereometry is presented and its advantages and potential applications are discussed.

Carcinoma, Squamous Cell↗
PubMed1994

Preoperative localization of the central sulcus by dipole source analysis of early somatosensory evoked potentials and three-dimensional magnetic resonance imaging.

Surgery of lesions within or close to the central area of the brain always carries the risk of iatrogenic motor or sensory deficits. Functional localization by means of intraoperative direct stimulation of the motor area or by recording somatosensory evoked potentials (SSEP's) from the surface of the somatosensory cortex is believed to reduce the operative risk. The authors introduce the combination of dipole source analysis of scalp-recorded SSEP's with three-dimensional (3-D) magnetic resonance (MR) imaging as a tool for preoperative localization of the central sulcus. This provides information on both functional and structural localization for preoperative planning. Four repeated measurements of right and left median nerve SSEP's were obtained from 20 subjects. Dipole source analysis showed a retest reliability of the 3-D localization error of 2.9 +/- 2.0 mm. Compared to the MR evaluation, dipole source analysis was found to mark the central sulcus within 3 mm for 15 conditions (subjects x side of stimulation), while the 3-D MR measurement was accurate to within 6 mm for 10 conditions and 9 mm for 14 conditions. Dipole locations were confirmed in six patients who underwent surgery of the central region. With respect to this application, dipole source analysis combined with 3-D MR imaging appears to be a valuable tool for preoperative functional localization. The accuracy in localization will be further improved when realistic head models become available that can take into account individual head geometry. Further development of the proposed new method holds promise that evoked potentials and electroencephalography will gain greater use in presurgical functional localization.

Brain Diseases↗
PubMed1993

Effects of inspiratory support upon breathing in humans during wakefulness and sleep.

We have compared the effects on breathing of inspiratory mechanical support during wakefulness and sleep in healthy subjects. Nine awake volunteers breathed through a nose mask connected to a machine supplying variable levels of inspiratory positive airway pressure (IPAP). Tidal volume (VT), breath duration (TTOT) and end-tidal PCO2 (PETCO2) were measured over 1 min steady state periods with IPAP set at a minimal level (approx. 2 cmH2O) and at approx. 10 cmH2O. This protocol was repeated in 6 of the subjects during non-REM sleep. When awake, "10 cmH2O IPAP" caused a significant increase in mean VT from 513 to 842 ml and a significant fall in PETCO2 from 39.7 to 32.7 mmHg. During sleep, "10 cmH2O IPAP" caused no significant changes in VT (388 to 390 ml) or PETCO2 (41.8 to 39.8 mmHg). In each state, "10 cmH2O IPAP" had no significant effect on TTOT. Three subjects repeated the protocol with diaphragmatic surface EMG recorded as an index of efferent inspiratory activity. "10 cmH2O IPAP" had no consistent effect on EMG when awake but caused a reduction in each subject during sleep. We conclude that during non-REM sleep, inspiratory mechanical support is associated with a compensatory decrease in efferent inspiratory activity to achieve a similar tidal volume with maintenance of arterial PCO2. When awake, a "wakefulness drive to breathe" may be associated with maintained inspiratory activity such that mechanical support results in an increased tidal volume despite a fall in arterial PCO2.

Adult↗
PubMed1993

Plant and marine n-3 fatty acids inhibit experimental metastasis of rat mammary adenocarcinoma cells.

The effectiveness of dietary n-3 plant and marine fatty acids and n-6 gamma-linolenic acid (GLA) was tested as an antimetastatic modality in the experimental model of metastasis of 13762MAT:B mammary adenocarcinoma cells. Weanling female Fischer 344 rats were placed on one of the following diets: 1-23.52% blackcurrant oil (BCO), II-23.52% corn oil (CO), III-15.52% BCO + 8% fish oil (FO), IV-20.52% FO + 3% CO, and V-5% CO. After 8 weeks, 15 rats per group were injected i.v. with 10(5) cells and diets were continued until sacrifice. In the 23.52% CO group (II), the number of small (< 2 mm) and large (> 2 mm) lung metastatic foci and their total volume were significantly greater than the BCO- and/or FO-fed groups (I, II and IV). Although the number of small metastatic foci was comparable in the 5% and 23.52% CO groups, the number of large foci and the total tumor volume were reduced in the 5% CO group. These results suggest that, compared to a low-corn oil diet or a high-fat diet containing a mixture of marine and plant n-3 fatty acids plus n-6 GLA, a 23.52% corn oil diet can enhance experimental metastasis of mammary adenocarcinoma cells. Total number of metastatic foci and tumor volume were the smallest in group III, receiving a combination of plant and marine n-3 fatty acids.

Adenocarcinoma↗