Biomedical subjects
D A Taylor
Publications and source records attributed to D A Taylor.
A new crop of concerns: Congress investigates pesticide safety.
A March 2000 report by the General Accounting Office, Pesticides: Improvements Needed to Ensure the Safety of Farmworkers and Their Children, states that much remains unknown about the risks faced by children in agriculture, and that enforcement of pesticide protection standards for farmworkers is patchy and unsystematic. Many cases of farmworkers' pesticide-related illnesses go unreported, leaving health workers with an inadequate basis for tracking patterns and fine-tuning pesticide standards, says the report. In addition, children are known to be more vulnerable to the effects of pesticides, but there is a lack of data regarding children's exposures and the precise effects of pesticides on children's health.
Effects of long term resistance training on left ventricular morphology.
OBJECTIVES: To assess the effects of long term (mean +/- SD 10+/-5 years, range three to 25 years) resistance training on left ventricular (LV) dimensions and mass. METHODS AND RESULTS: The study participants were 21 elite male power-lifters (age 33.4+/-5.9 years) and 10 sedentary male control subjects (age 30.9+/-4.2 years). Two-dimensionally guided transthoracic M-mode echocardiograms were obtained at rest to quantify LV diastolic cavity dimension, posterior wall thickness, ventricular septal wall thickness and LV mass. Long term resistance training was not associated with an alteration in LV diastolic cavity dimension (resistance trained 54. 4+/-4.3 mm versus control 51.8+/-5.6 mm), ventricular septal wall thickness (resistance trained 9.7+/-1.0 mm versus control 10.1+/-0.7 mm), posterior wall thickness (resistance trained 9.6+/-1.5 mm versus control 9.3+/-1.4 mm) or LV mass (resistance trained 200. 3+/-32.5 g versus control 186.5+/-39.6 g). In addition, no resistance-trained athlete was found to have an LV mean wall thickness above clinical normal limits (12 mm or less). CONCLUSION: Contrary to common beliefs, long term resistance training as performed by elite male power-lifters does not alter LV morphology.
Cardiac tamponade as the first clinical manifestation of metastatic adenocarcinoma of the lung.
A 62-year-old woman presented in the emergency department with new onset of dyspnea and clinical signs of cardiac tamponade. She had a history of cigarette smoking and a family history of adenocarcinoma, pancreatic and breast carcinoma. An emergency two-dimensional echocardiogram confirmed the diagnosis of cardiac tamponade. Therapeutic pericardiocentesis resulted in prompt relief. Cytology confirmed malignant glandular cells, consistent with a metastatic adenocarcinoma. Computerized chest tomography confirmed pulmonary involvement.
Alterations in neuronal gamma-aminobutyric acid(A) receptor responsiveness in genetic models of seizure susceptibility with different expression patterns.
The genetically epilepsy-prone rat (GEPR) is a unique animal model of seizure predisposition with substrains (i.e., GEPR-NE, GEPR-3, and GEPR-9) that exhibit different seizure patterns in response to the same stimulus. Among many deficits identified in these animals, reduced responses to GABA(A) receptor agonists have been described in several brain regions of the GEPR-9. However, few studies have quantitatively analyzed this difference in responsiveness or have examined and compared the responsiveness of GEPR-3 neurons with the other strains. Using intracellular recording, we determined and compared the responsiveness of Purkinje neurons from GEPR-3 animals with those of control (both Sprague-Dawley and GEPR-NE) and GEPR-9 rats at different developmental ages. In GEPR-9 animals, the EC(50) value for GABA and muscimol was shifted 3-fold to the right, with no reduction in maximum. In contrast, GEPR-3 animals showed a significant reduction in the maximum hyperpolarizing response to only GABA and muscimol with no change in the EC(50) values. Responsiveness to glutamate, aspartate, norepinephrine, and diazepam was unchanged in both strains, indicating that the change in responsiveness was highly selective for GABA(A) receptor agonists. Changes in responsiveness in animals <15 days of age suggests that deficits in GABAergic function exist before the development of seizure susceptibility. In addition, the data are the first to reveal that the GEPR-3 and GEPR-9 exhibit different changes in GABA(A) receptor function and may provide significant insight into the cellular mechanism underlying differences between these two strains.
Postradiation sarcomas: 20 cases and a literature review.
PURPOSE: To analyze 20 cases of postradiation sarcoma (PRS) to determine dose levels at which this condition developed, the pathology of the initial and postradiation tumors, latency period, and outcome; and to review the literature and propose modified criteria for diagnosis. METHODS AND MATERIALS: Patient records were reviewed. Previous radiation fields and isodose charts were reconstructed to determine the dose received in the tissue in which the PRS subsequently developed. RESULTS: There were 16 female patients and 4 male patients. Mean age at the time of initial radiotherapy was 28 years. Mean latency was 14 years, with no difference in latency between the adult and pediatric group (t = 0.45, p = 0.37), but shorter latency in the retinoblastoma than in the nonretinoblastoma patients (t = 3.18, p = 0.003). The outcome was poor; 2 patients were alive and disease-free at 2 and 5 years. The 18 patients who died as a result of PRS had a median survival of 1 year. CONCLUSION: PRSs are rare. Unnecessary radiation must be avoided. Cases should be reported with full details so that risk factors can be ascertained. PRSs usually arise in moderate to higher dose areas. Diagnostic criteria should allow soft tissue tumors and short latency.
Modulatory effect of p-chlorophenylalanine microinjected into the dorsal and median raphe nuclei on cocaine-induced behaviour in the rat.
The present study examined whether a potentiation of cocaine-induced behaviour in rats following peripheral pretreatment with the 5-hydroxytryptamine (5-HT) biosynthesis inhibitor p-chlorophenylalanine may be due to depletion of 5-HT in the dorsal raphe nucleus and/or median raphe nucleus. Following peripheral pretreatment with p-chlorophenylalanine (100 mg/kg, i.p.) for 3 consecutive days, a potentiation of cocaine-induced locomotor activity and rears was observed. To investigate a possible involvement of serotonergic neurones arising in the midbrain raphe nuclei in the observed potentiation, p-chlorophenylalanine (0.5 microg) was microinjected in either the dorsal raphe nucleus or median raphe nucleus followed by behavioural testing 48 h later. Application of p-chlorophenylalanine in the dorsal raphe nucleus resulted in an enhancement of cocaine-induced locomotor activity and head bobs. In contrast, the stimulant effect of cocaine on behaviour was not altered by microinjection of p-chlorophenylalanine in the median raphe nucleus. Peripheral and central administration of p-chlorophenylalanine did not consistently alter the baseline behaviour of saline-treated animals. Biochemical results indicated only a moderate depletion of 5-HT in the midbrain raphe nuclei following peripheral p-chlorophenylalanine administration. Surprisingly, the central application of p-chlorophenylalanine in the dorsal raphe nucleus and median raphe nucleus did not alter the 5-HT levels in the midbrain raphe nucleus investigated. In addition, peripheral and central administration of p-chlorophenylalanine did not alter the 5-HT levels in the nucleus accumbens. In conclusion, the behavioural results suggest that the potentiation of cocaine-induced behaviour following peripheral p-chlorophenylalanine administration may be attributed to the dorsal raphe nucleus but not the median raphe nucleus suggesting that, serotonergic dorsal raphe nucleus neurones may normally mediate a tonic inhibitory effect on cocaine-induced behaviour. Furthermore, the biochemical data may indicate the existence of neurochemical resistance of the midbrain raphe nuclei to the 5-HT depleting effects of p-chlorophenylalanine.
The role of the sodium pump in the developmental regulation of membrane electrical properties of cerebellar Purkinje neurons of the rat.
The postnatal development of the rat cerebellum has been well described morphologically and functionally. However, information regarding the electrical characteristics of Purkinje neurons during development is sparse. Using standard intracellular recording, the basic electrical properties of Purkinje neurons in cerebellar slices were compared at different postnatal ages. There was a significant, progressive increase in the resting membrane potential (RMP) of Purkinje neurons with age as well as a small but significant decrease in the cellular input resistance (Rin). The cardiac glycoside, ouabain (1 mM), an inhibitor of the sodium pump, depolarized Purkinje neurons significantly more with age. The magnitude of the increase in depolarizing activity of ouabain was equivalent to the magnitude of the increase in membrane potential. The number of ouabain binding sites was also found to increase with age suggesting an age related increase in the number of sodium pump sites. These results suggest that the predominant cellular mechanism which underlies the increase in membrane potential of Purkinje neurons during development is an increase in the density of Na+, K+ pump sites and in the contribution of the electrogenic sodium pump.
Cellular cardiomyoplasty improves diastolic properties of injured heart.
BACKGROUND: Acute myocardial infarction leads to loss of functional myocytes and structural integrity that often decreases diastolic compliance and increases resting myocardial segment length (diastolic creep). Successfully engrafting autologous skeletal myoblasts could improve compliance and potentially reverse creep. Thus, we transplanted myoblasts into cryoinjured rabbit heart (n = 15, CRYO) and measured regional diastolic properties in the presence (n = 9, +ENG) or absence (n = 6, -ENG) of engraftment. MATERIALS AND METHODS: Left ventricular (LV) pressures (P) and myocardial segment lengths (SL) were measured in vivo by micromanometry and sonomicrometry after cryoinjury (CRYO) and again 3 weeks following transplantation of myoblasts. Performance was estimated from the relationships between end-diastolic (ED) P and strain (epsilon) or between EDP and EDSL. Compliance was characterized by strain (epsilon(8)) and dynamic stiffness (dP/dL(8)) at 8 mm Hg. Creep was characterized by resting myocardial segment length (EDSL(0)) and static stiffness at 8 mm Hg (m(stat8)). RESULTS: Successful myoblast engraftment was determined via histologic examination. In nine +ENG animals, diastolic properties improved. Regional strain (epsilon(8)) increased (0.06 +/- 0.02 CRYO vs 0.10 +/- 0.04 +ENG; P = 0.0009) while dynamic stiffness (dP/dL(8)) decreased (43 +/- 23 mm Hg/mm CRYO vs 23 +/- 14 mm Hg/mm +ENG; P = 0.009). Static stiffness (m(stat8)) was unaffected (0.78 +/- 0.2 mm Hg/mm CRYO vs 0.72 +/- 0. 1 mm Hg/mm +ENG; P = 0.08), and creep did not occur (EDSL(0) = 10.3 +/- 2.8 CRYO vs 10.4 +/- 2.3 +ENG; P = 0.74). In the absence of myoblast engraftment (n = 6, -ENG), strain decreased (epsilon(8) = 0. 06 +/- 0.02 CRYO vs 0.05 +/- 0.02 -ENG; P = 0.048), but dynamic stiffness (dP/dL(8)) did not (36 +/- 19 mm Hg/mm CRYO vs 28 +/- 12 mm Hg/mm -ENG; P = 0.20). Furthermore, static stiffness decreased (0. 78 +/- 0.3 mm Hg/mm CRYO vs 0.65 +/- 0.2 mm Hg/mm -ENG; P = 0.05) and creep was obvious (EDSL(0) = 10.8 +/- 3.6 mm CRYO vs 13.0 +/- 4. 4 mm -ENG, P = 0.04). CONCLUSIONS: Myoblast engraftment may partially overcome the loss of myocytes and structural integrity that often follow chronic myocardial ischemia. Improved compliance and reversal of diastolic creep suggest regeneration of viable muscle within once infarcted myocardium.
Modulation of cocaine-induced locomotor activity, rears and head bobs by application of WAY100635 into the dorsal and median raphe nuclei of the rat.
The present study investigated the role of somatodendritic 5-HT1A autoreceptors located in the dorsal and median raphe nuclei on the stimulant effect of cocaine on locomotor activity, rears and head bobs in female Glaxo Wistar rats. Cocaine was administered at a submaximal dose of 15 mg/kg i.p. to enable either a potentiation or attenuation to be observed. The selective 5-HT1A antagonist WAY100635 (0.21 ng or 21 ng) or saline was microinjected in the dorsal or median raphe nuclei followed by the peripheral administration of cocaine 60 min later. WAY 100635 microinjected in the dorsal or median raphe nuclei did not consistently alter the locomotor activity and the number of rears of saline-treated animals. Microinjection of WAY100635 in the dorsal raphe nucleus potentiated cocaine-induced locomotor activity and the number of head bobs. The number of rears induced by cocaine was not significantly altered by WAY100635 microinjected in the dorsal raphe nucleus. In contrast, microinjection of WAY100635 in the median raphe nucleus did not alter the stimulant effect of cocaine on locomotor activity, rears or head bobs. It may be suggested from these results that stimulation of somatodendritic 5-HT1A autoreceptors located in the dorsal raphe nucleus mediates an inhibitory effect on cocaine-induced locomotor activity and head bobs, whereas somatodendritic 5-HT1A autoreceptors in the median raphe nucleus are not involved in the inhibitory role of 5-HT on the stimulant effect of cocaine on locomotor activity and head bobs. A differential involvement of the midbrain raphe nuclei may exist controlling the stimulant effect of cocaine on locomotor activity and head bobs.
Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ.
BACKGROUND: Adult heart lacks stem cells and cannot effectively regenerate. In contrast, skeletal muscle is constantly undergoing repair. We proposed to transplant immature skeletal myoblasts into injured myocardium. METHODS: Approximately 7x10(6) soleus skeletal myoblasts were expanded in vitro from adult New Zealand White rabbits (n = 23) whose posterior left ventricle was cryoinjured to create a transmural lesion. Autologous myoblasts (n = 18) or saline (n = 5) was transplanted into the central cryolesion at the time of injury (n = 6) or 1 week later (n = 12). Hearts were harvested 2 weeks after injection. RESULTS: Myoblast transfer did not incur further morbidity. After cryolesion, grossly, a 1.6-cm epicardial hemorrhagic lesion could be seen. Histologically, the transmural lesion contained inflammatory cells and active scarring but no viable cardiomyocytes. Electron microscopy demonstrated a predominance of collagen and fibroblasts. Nine hearts contained multinucleated cells within the cryolesion that covered approximately 75% of the central cryolesion in 17% of animals. Immunohistochemical analysis confirmed their skeletal muscle origin. At the periphery of the lesion, isolated clusters of nonskeletal muscle cells could be visualized (n = 12) that resembled immature cardiocytes. CONCLUSIONS: Autologous skeletal myoblasts can regenerate viable striated tissue within damaged myocardium. Myoblast transfer warrants further investigation as a new method for improving myocardial performance within infarcted myocardium.
Pain report and the relationship of pain to physical factors in the first 6 months following spinal cord injury.
A prospective, longitudinal study of 100 people with traumatic spinal cord injury (SCI) was performed to determine the time of onset. prevalence and severity of different types of pain (musculoskeletal, visceral, neuropathic at level, neuropathic below level) at 2, 4, 8, 13 and 26 weeks following SCI. In addition, we sought to determine the relationship between physical factors such as level of lesion, completeness and clinical SCI syndrome and the presence of pain. At 6 months following SCI, 40% of people had musculoskeletal pain, none had visceral pain, 36% had neuropathic at level pain and 19% had neuropathic below level pain. When all types of pain were included, at 6 months following injury, 64% of people in the study had pain, and 21% of people had pain that was rated as severe. Those with neuropathic below level pain were most likely to report their pain as severe or excruciating. There was no relationship between the presence of pain overall and level or completeness of lesion, or type of injury. Significant differences were found, however, when specific types of pain were examined. Musculoskeletal pain was more common in people with thoracic level injuries. Neuropathic pain associated with allodynia was more common in people who had incomplete spinal cord lesions, cervical rather than thoracic spinal cord lesions, and central cord syndrome. Therefore, this study suggests that most people continue to experience pain 6 months following spinal cord injury and 21% of people continue to experience severe pain. While the presence or absence of pain overall does not appear to be related to physical factors following SCI, there does appear to be a relationship between physical factors and pain when the pain is classified into specific types.
Myogenic cell transplantation improves in vivo regional performance in infarcted rabbit myocardium.
BACKGROUND: Although cardiac transplantation is an ideal treatment for end-stage heart disease, inadequate donor availability has stimulated efforts to manage terminally injured myocardium by other innovative methods. Autologous skeletal myoblast transplantation, or cellular cardiomyoplasty, is one method to potentially mediate myocardial repair within chronically injured hearts. However, few investigators have documented the ability of myogenic cells to alter load-insensitive indices of systolic and diastolic performance in vivo. In this study, both systolic and diastolic regional myocardial function were evaluated following left ventricular cryoinjury and compared with function after myogenic cell transplantation. METHODS: Left ventricular pressure and segment length were determined in 9 rabbits by micromanometry and sonomicrometry 1 week following cryoinjury and 3 weeks after myoblast transplantation. At study termination, the extent of myoblast engraftment was determined by histologic analysis. Systolic performance was based on the linear regression of stroke work and end-diastolic segment length. Diastolic properties were evaluated by the curvilinear relationships between left ventricular pressure and strain, and left ventricular pressure and end-diastolic segment length. RESULTS: Although mean indices of systolic performance were unchanged after cell transplantation, systolic performance improved in 3 animals. In contrast, myoblast engraftment was associated with significantly improved diastolic properties (strain and dynamic stiffness) in all animals. CONCLUSIONS: These data quantify temporal changes in regional myocardial performance and suggest that cellular cardiomyoplasty improves diastolic compliance prior to affecting systolic performance. Cellular cardiomyoplasty, a potential therapeutic option for ischemic heart disease, appears to reverse diastolic creep and thus may represent a clinical alternative to transplantation in the near future.
Modulation by fluoxetine of striatal dopamine release following Delta9-tetrahydrocannabinol: a microdialysis study in conscious rats.
1. The present study was undertaken to investigate the effect of Delta9-tetrahydrocannabinol (Delta9-THC) and possible serotoninergic involvement on the extracellular level of dopamine (DA) in the striatum using microdialysis in conscious, freely-moving rats. 2. A dose-dependent increase in striatal DA release occurred after i.v. administration of 0.5 - 5 mg kg-1 Delta9-THC when compared with vehicle (n=5 - 8, P<0.05). Maximum increases, ranging from 42.1+/-5. 4% to 97.4+/-5.9% (means+/-s.e.mean) of basal levels occurred 20 min after Delta9-THC. This effect was abolished by pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716 (2.5 mg kg-1 i.p.). 3. Pretreatment with fluoxetine (10 mg kg-1 i.p.) abolished the Delta9-THC-induced DA release. Fluoxetine 10 mg kg-1 i.p. administered 40 min after Delta9-THC had no significant effect on Delta9-THC-induced DA release. However, fluoxetine perfused locally into the striatum by adding it to the microdialysis perfusion fluid (10 microM) 40 min after Delta9-THC significantly potentiated the Delta9-THC-induced DA release (n=6 - 8, P<0.05). 4. These results suggest that DA release induced by Delta9-THC is modulated by serotoninergic changes induced by fluoxetine, the effect of which depends on the time of its administration relative to that of Delta9-THC. Fluoxetine induces an acute increase in extracellular 5-HT through reuptake inhibition, which can activate autoreceptors which may decrease serotoninergic neuronal activity. This may be the reason fluoxetine pretreatment abolished the Delta9-THC-induced DA release. The potentiation of Delta9-THC-induced DA release by fluoxetine perfusion added 40 min after Delta9-THC may be due to an acute increase in 5-HT produced by reuptake inhibition.
Mechanism of mosaic attenuation of the lungs on computed tomography in induced bronchospasm.
The purpose of this study was to investigate whether hypoxic pulmonary vasoconstriction is the major determinant of the computed tomography (CT) pattern of mosaic attenuation in asthmatic patients with induced bronchoconstriction. Thin-section CT was performed at suspended full inspiration immediately and 30 min after methacholine bronchoprovocation in 22 asthmatic subjects, who were randomly assigned to breathe room air (group A, n = 8), oxygen via nasal prongs at 5 l/min (group B, n = 8), and oxygen via face mask at 12 l/min (group C, n = 6). CT changes were quantified in terms of global lung density and density in hypodense and hyperdense areas. Lung parenchymal density increases were greatest in group C and greater in group B than in group A, globally (P = 0.03) and in hypodense regions (P = 0.01). On bivariate analysis, the only change in cross-sectional area was related to change in global density. In hypodense regions, density change was related both to reduction in cross-sectional area (P < 0.0005) and to oxygen administration (P = 0.01). After correction for changes in global lung density, only oxygen was independently related to density increase in hypodense areas (P = 0.02). In induced bronchoconstriction, the CT appearance of mosaic attenuation can be largely ascribed to hypoxic vasoconstriction rather than to changes in lung inflation.
A dose-dependent effect of the novel inhaled corticosteroid ciclesonide on airway responsiveness to adenosine-5'-monophosphate in asthmatic patients.
Inhaled corticosteroids decrease airway responsiveness in asthma partly through suppression of airway inflammation. We have previously demonstrated that inhaled budesonide reduced airway responsiveness to the mast cell stimulus adenosine-5'-monophosphate (AMP) to a threefold greater extent than to methacholine and sodium metabisulfite, suggesting that AMP responsiveness may be a more sensitive marker of airway inflammation and steroid action in order to assess a dose-response relationship. To investigate this, we studied the effects of three doses of the novel corticosteroid ciclesonide (50 micrograms, 200 micrograms, and 800 micrograms) inhaled as a dry powder twice daily on airway responsiveness to AMP and inflammatory parameters in induced sputum. In a three-parallel-dose group, double-blind, placebo-controlled, randomized, crossover study, with a washout period of 3 to 8 wk, a total of 29 patients with mild to moderate allergic asthma underwent AMP challenge and sputum induction before and after 14 d of treatment with ciclesonide or matched placebo. Compared with placebo, ciclesonide 100 micrograms, 400 micrograms, and 1,600 micrograms daily reduced airway responsiveness to AMP by 1.6 (95% confidence interval [CI], -0.1 to 3.4, not significant [NS]), 2.0 (95% CI, 0.4 to 3.6, p < 0.05), and 3.4 (95% CI, 2.3 to 4. 4, p < 0.05) doubling doses, respectively, and this reduction in airway responsiveness was dose-dependent (p = 0.039). A significant reduction in the percentage of eosinophils in induced sputum was observed after 400 micrograms and 1,600 micrograms daily ciclesonide (p < 0. 05), but this was not dose-dependent. Sputum eosinophil cationic protein (ECP) was significantly reduced after 400 micrograms daily ciclesonide only (p < 0.05). Thus, in patients with mild to moderate asthma, assessment of airway responsiveness to AMP, rather than inflammatory parameters in induced sputum, represents a sensitive method to evaluate a dose-response relationship of an inhaled corticosteroid and may have applications in evaluating other novel inhaled corticosteroids.
Acral dermatofibrosarcoma protuberans with metastases.
Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous tumor that occurs rarely on the extremities. This tumor has a particular propensity for local recurrence following seemingly adequate excision. Metastases are rare, and usually follow repeated local recurrences. On rare occasions, fibrosarcomatous change may arise in a DFSP, and appears to affect adversely the prognosis. The adequacy of the initial resection is the most important prognostic factor; however, suggested margins vary between 1.5 and 5 cm. The ideal margin of resection on the foot is unknown. We report a patient with recurrent, acral DFSP with fibrosarcomatous change and pulmonary parenchymal metastases in a 48-year-old black male.
Biatrial myxoma: a rare cardiac tumor.
A previously healthy 48-year-old man presented to the hospital with a transient ischemic attack. Echocardiography revealed a large left atrial tumor with a second tumor in the right atrium. Surgical excision revealed a large left atrial myxoma with extension through the interatrial septum into the right atrium.