Biomedical subjects

B K Lewis

Publications and source records attributed to B K Lewis.

At least 19 recordsLinked to original sources

PubMed2001

Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells.

Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

3T3 Cells↗

PubMed2000

MRI and clinical activity in MS patients after terminating treatment with interferon beta-1b.

Monthly MRI activity and clinical disability were evaluated in two relapsing-remitting multiple sclerosis (RRMS) patients for 4 years during a cross-over treatment trial with IFNbeta-1b, and for a mean of 21 months after terminating treatment with IFNbeta-1b. Post-treatment MRI activity was compared to baseline activity in these patients. Although contrast enhancing lesions (CEL) and the bulk white matter lesion load (BWMLL) on T2-weighted images eventually returned to baseline values, there was a refractory period of 6 - 10 months after terminating treatment, before baseline MRI activity was restored. Although the mechanism for a sustained effect of IFNbeta-1b is unclear at this time, these results have important implications for enrollment of such patients into new treatment protocols that rely on contrast enhancing lesion frequency as an outcome measure.

Adjuvants, Immunologic↗

PubMed2000

Proton magnetic resonance spectroscopic imaging in children with recurrent primary brain tumors.

PURPOSE: Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) is a noninvasive technique for spatial characterization of biochemical markers in tissues. We measured the relative tumor concentrations of these biochemical markers in children with recurrent brain tumors and evaluated their potential prognostic significance. PATIENTS AND METHODS: (1)H-MRSI was performed on 27 children with recurrent primary brain tumors referred to our institution for investigational drug trials. Diagnoses included high-grade glioma (n = 10), brainstem glioma (n = 7), medulloblastoma/peripheral neuroectodermal tumor (n = 6), ependymoma (n = 3), and pineal germinoma (n = 1). (1)H-MRSI was performed on 1. 5-T magnetic resonance imagers before treatment. The concentrations of choline (Cho) and N-acetyl-aspartate (NAA) in the tumor and normal brain were quantified using a multislice multivoxel method, and the maximum Cho:NAA ratio was determined for each patient's tumor. RESULTS: The maximum Cho:NAA ratio ranged from 1.1 to 13.2 (median, 4.5); the Cho:NAA ratio in areas of normal-appearing brain tissue was less than 1.0. The maximum Cho:NAA ratio for each histologic subtype varied considerably; approximately equal numbers of patients within each tumor type had maximum Cho:NAA ratios above and below the median. Patients with a maximum Cho:NAA ratio greater than 4.5 had a median survival of 22 weeks, and all 13 patients died by 63 weeks. Patients with a Cho:NAA ratio less than or equal to 4.5 had a projected survival of more than 50% at 63 weeks. The difference was statistically significant (P =.0067, log-rank test). CONCLUSION: The maximum tumor Cho:NAA ratio seems to be predictive of outcome in children with recurrent primary brain tumors and should be evaluated as a prognostic indicator in newly diagnosed childhood brain tumors.

Adolescent↗

PubMed1999

Investigation of low frequency drift in fMRI signal.

Low frequency drift (0.0-0.015 Hz) has often been reported in time series fMRI data. This drift has often been attributed to physiological noise or subject motion, but no studies have been done to test this assumption. Time series T*2-weighted volumes were acquired on two clinical 1.5 T MRI systems using spiral and EPI readout gradients from cadavers, a normal volunteer, and nonhomogeneous and homogeneous phantoms. The data were tested for significant differences (P = 0.001) from Gaussian noise in the frequency range 0.0-0.015 Hz. The percentage of voxels that were significant in data from the cadaver, normal volunteer, nonhomogeneous and homogeneous phantoms were 13.7-49.0%, 22.1-61.9%, 46.4-68.0%, and 1.10%, respectively. Low frequency drift was more pronounced in regions with high spatial intensity gradients. Significant drifting was present in data acquired from cadavers and nonhomogeneous phantoms and all pulse sequences tested, implying that scanner instabilities and not motion or physiological noise may be the major cause of the drift.

Adult↗

PubMed1999

Technical solution for an interactive functional MR imaging examination: application to a physiologic interview and the study of cerebral physiology.

Studies with functional magnetic resonance (MR) imaging produce large unprocessed raw data sets in minutes. The analysis usually requires transferring of the data to an off-line workstation, and this process frequently occurs after the subject has left the MR unit. The authors describe a hardware configuration and processing software that captures whole-brain raw data files as they are being produced from the MR unit. It then performs the reconstruction, registration, and statistical analysis, and displays the results in seconds after completion of the MR image acquisition.

Brain↗

PubMed1999

Responses of group III and IV muscle afferents to distension of the peripheral vascular bed.

This study was undertaken to test the hypothesis that group III and IV afferents with endings in skeletal muscle signal the distension of the peripheral vascular network. The responses of these slowly conducting afferents to pharmacologically induced vasodilation and to acute obstruction of the venous drainage of the hindlimbs were studied in barbiturate-anesthetized cats. Afferent impulses arising from endings in the triceps surae muscles were recorded from the L(7) and S(1) dorsal roots. Fifteen of the 48 group IV and 3 of the 19 group III afferents tested were stimulated by intra-aortic injections of papaverine (2-2.5 mg/kg). Sixty-two percent of the afferents that responded to papaverine also responded to isoproterenol (50 microg/kg). Seven of the 36 group IV and 2 of the 12 group III afferents tested were excited by acute distension of the hindlimb venous system. Four of the seven group IV afferents responding to venous distension also responded to papaverine (57 vs. 13% for the nonresponding). Finally, we observed that most of the group IV afferents that were excited by dynamic contractions of the triceps surae muscles also responded either to venous distension or to vasodilatory agents. These results are consistent with the histological findings that a large number of group IV endings have their receptive fields close to the venules and suggest that they can be stimulated by the deformation of these vascular structures when peripheral conductance increases. Moreover, such a mechanism offers the possibility of encoding both the effects of muscle contraction through intramuscular pressure changes and the distension of the venular system, thereby monitoring the activity of the veno-muscular pump.

Animals↗

PubMed1999

Characterization of differences between multiple sclerosis and normal brain: a global magnetization transfer application.

BACKGROUND AND PURPOSE: Although the exact nature of the physiological differences between normal and multiple sclerosis (MS) brains are unknown, it has been shown that their global magnetization transfer ratio (MTR) values are significantly different. To more fully understand these differences, we examined MTR values by using 30 distinct measures. We provide a unique illustration of these differences through a derived normal-to-MS transform. METHODS: Global MTR values for the group of normal subjects and for the group of MS subjects were characterized by 30 different measures involving simple statistics, histographic characteristics, MTR order information, and MTR range information. The measures that were significantly different with respect to these two groups were discovered. From the mean MTR histogram of the two groups, a transform was created to describe a conversion between the two brain states. Normal data were passed through this transform, creating a set of pseudo-MS data. The measures that were significantly different from the normal and pseudo-MS data were also obtained in order to verify the accuracy of the transform. RESULTS: Seventeen of the 30 measures were determined to be significantly different when comparing the sets of normal and MS data. The same set of 17 measures were found to be significantly different when comparing the normal and pseudo-MS data. CONCLUSION: The differences in the global MTR values of normal and MS subjects are statistically significant compared with a large number of measures (alpha = 0.05). A normal-to-MS transform is a novel method for illustrating these differences.

Adult↗

PubMed1998

Effect on airway caliber of stimulation of the hypothalamic locomotor region.

Airway dilation is one of the many autonomic responses to exercise. Two neural mechanisms are believed to evoke these responses: central command and the muscle reflex. Previously, we found that activation of central command, evoked by electrical and chemical stimulation of the mesencephalic locomotor region, constricted the airways rather than dilated them. In the present study we examined in decerebrate paralyzed cats the role played by the hypothalamic locomotor region, the activation of which also evokes central command, in causing the airway dilator response to exercise. We found that activation of the hypothalamic locomotor region by electrical and chemical stimuli evoked fictive locomotion and, for the most part, airway constriction. Fictive locomotion also occurred spontaneously, and this too, for the most part, was accompanied by airway constriction. We conclude that central command plays a minor role in the airway dilator response to exercise.

Airway Resistance↗

PubMed1998

Nutrient intake and the risk of pressure sore development in older patients.

This study explored the possibility of a link between diet prior to admission to hospital and the development of pressure sores in older patients. The intention was to use this information to develop a nutrient prediction score and nutrient risk indicator. Thirty patients over the age of 75, admitted with either a fractured neck of femur or for hip replacement surgery, formed the study population. A Waterlow assessment was completed on admission and each patient answered a specially developed food frequency questionnaire. Patients in both diagnostic groups had Waterlow scores which put them into the high-risk category. A total of 20 pressure sores developed in the two groups of patients during their stay in hospital. Patients admitted for hip replacement had higher nutrient intake values than patients with fractured neck of femur and they also had a higher occurrence of pressure sores. Overall diet for all patients appeared to be adequate; however, the diet of patients with fractured neck of femur was significantly lower in both iron and vitamin C than that of patients having hip replacement surgery. The nutritional assessment tool was not as sensitive as expected and further development and validation are needed. While no firm conclusions can be drawn from this small study, the results do emphasise the importance of adequate diet in elderly patients prior to admission, especially for planned admissions for hip replacement.

Aged↗

PubMed1997

Early ambulation following 6 French diagnostic left heart catheterization: a prospective randomized trial.

Outpatient cardiac catheterization is frequently performed, but the optimal recovery time after sheath removal has not been defined. Left heart catheterization was performed via the femoral artery utilizing 6 French catheters on 323 outpatients. One hundred thirty-five patients were randomized to ambulate at a mean of 2.5 hr (group 1) after puncture site compression, whereas 188 patients were randomized to ambulate at a mean of 4.1 hr (group 2). Telephone follow-up occurred within 48 hr. A small hematoma (< 5 cm) occurred in 2 (1.6%) patients in group 1 and in 4 (2.4%) patients in group 2. These results indicate that it is safe to ambulate patients 2.5 hr following 6 French diagnostic heart catheterization.

Cardiac Catheterization↗

PubMed1994

Basal ganglia iron in tardive dyskinesia: an MRI study.

Alterations in brain iron could play an important role in the development of tardive dyskinesia in patients receiving neuroleptic medication. To test this hypothesis, magnetic resonance imaging scans of the brain were performed on 21 chronic schizophrenic patients. Ten patients met research diagnostic criteria for persistent tardive dyskinesia, and 11 were free of tardive dyskinesia. All patients had received long-term neuroleptic treatment and were on a stable neuroleptic dose for at least 3 months before scanning. The signal intensity of basal ganglia structures was obtained as a quantitative estimate of brain iron content. No difference was found in the signal intensity ratios between the two groups. This suggests that iron deposition in the basal ganglia, at least as assessed by this measure, does not play a role in the pathophysiology of tardive dyskinesia.

Adult↗

PubMed1994

Cholinesterase inhibitors do not prolong neuromuscular block produced by mivacurium.

Cholinesterase inhibitors antagonize neuromuscular block produced by mivacurium, but some may also decrease its metabolism by inhibiting pseudocholinesterase. These opposing interactions were examined in rats anaesthetized with pentobarbitone. After spontaneous recovery from an initial bolus dose of 0.03 mg kg-1, mivacurium was infused to produce 80-90% block of gastrocnemius muscle twitch. After 15 min, the infusion was discontinued and saline, edrophonium, pyridostigmine or neostigmine was administered. Fifteen minutes later, a second bolus dose of mivacurium was given. Edrophonium, pyridostigmine and neostigmine reduced the subsequent maximum block, compared with the change in saline control, by 3%, 19% and 35%, respectively. Correspondingly, the time to recovery of T1 to 50% was decreased by 20%, 58% and 62%. In rats, acetylcholinesterase-mediated antagonism of neuromuscular block predominated over decreased pseudocholinesterase-mediated metabolism, such that prior administration of a cholinesterase inhibitor did not prolong the neuromuscular blocking effects of mivacurium.

Animals↗

PubMed1994

Hypothermia minimally decreases nitrous oxide anesthetic requirements.

Over the 38-28 degrees C range, changes in minimum alveolar anesthetic concentration (MAC) parallel changes in lipid solubility of the anesthetics studied. We hypothesized that there would be minimal change in N2OMAC, since N2O lipid solubility is relatively unaltered by temperature changes. We determined N2OMAC in rats using a hyperbaric chamber. In Group N (normothermia, n = 10) rectal temperature was maintained at 37.5 +/- 1 degrees C (mean +/- SD). In Group H (hypothermia, n = 9) temperature was maintained at 29.7 +/- 1.8 degrees C. The hyperbaric chamber was pressurized with N2O and oxygen partial pressure was 0.4 +/- 0.1 atm. Chamber pressure was adjusted approximately 15% up or down, stabilized for approximately 15 min, and the noxious stimulus (electrical current) was applied. This process was continued until two N2O partial pressures were determined which just prevented and just permitted gross, purposeful movement. Nitrous oxide MAC for Group N and Group H were 1.9 +/- 0.2 atm and 1.6 +/- 0.2 atm, respectively, P < 0.01. Temperature and MAC correlated: r = 0.59, P < 0.01. We conclude that hypothermia minimally decreases N2OMAC, which is consistent with the effects of hypothermia on N2O solubility in lipid membranes.

Animals↗

PubMed1993

Acute effects of calcitonin gene-related peptide on the mechanical and electrical responses of the rat hemidiaphragm.

Calcitonin gene-related peptide (CGRP) acutely augments the contractile response of skeletal muscle to both direct and indirect stimulation. However, studies in whole muscle tissues have produced extremely variable results. To determine if differences in stimulation parameters are the source of this variation, the effects of increasing stimulus duration were evaluated in the isolated perfused rat hemidiaphragm. The effect of CGRP on the maximum force of contraction (Fc) was dependent upon the stimulus duration. CGRP (10(-6) M) produced an 11% increase in Fc with a 0.1-msec duration stimulus and a 32% increase with a 1.0-msec stimulus. In contrast, CGRP decreased the time for twitch relaxation and this effect was independent of stimulus duration. Additional studies demonstrated that CGRP shortened the relative refractory period. Compound muscle action potential recordings revealed that stimulus durations greater than 0.5 msec produced a second peak of electrical activity with an associated increased Fc. The effects of CGRP on Fc corresponded to the effects of CGRP on this second peak of compound muscle action potential activity. We conclude that, by decreasing the relative refractory period of the muscle tissue, CGRP enhances the potential for repetitive stimulation with commonly used experimental parameters.

Action Potentials↗

PubMed1990

Are postsynaptic nicotinic end-plate receptors involved in lead toxicity?

The effects of Pb2+ on the postsynaptic nicotinic end-plate receptor were examined in the perfused mouse hemidiaphragm preparation. Postsynaptic nicotinic responses, evoked by pressure ejection of ACh, were blocked by Pb2+ in a transient way. After 9-12 min of exposure to 1 microM Pb2+ the amplitude of the depolarization induced by 1 mM ACh was reduced to 39.5 +/- 11% of the control value. During continued exposure to Pb2+ this blocking effect was reversed and after 30 min of exposure to 1 microM Pb2+ the amplitude of the ACh-induced depolarization had returned to the control value. The amplitude and the frequency of miniature end-plate potentials were not altered in the presence of 1 microM Pb2+. Under voltage clamp conditions the effects of Pb2+ on the ACh-induced inward current were similar to those of Pb2+ on the ACh-induced depolarization. After 12 min of exposure to 1 microM Pb2+ the inward current induced by 1 mM ACh was reduced to 44% of the control value and after 30 min the ACh-induced inward current had recovered to 94% of the control value. It is concluded that, in addition to the generally established mechanism of action of Pb2+ at the muscle end-plate, Pb2+ blocks the postsynaptic nicotinic receptor-mediated response at a relative low concentration. The contribution of these postsynaptic effects to the neurotoxic symptoms of Pb2+ remains to be established.

Acetylcholine↗

PubMed1975

Serum insulin changes in arteriosclerotic breeder female rats versus non-arteriosclerotic virgin rats.

Immunoreactive serum insulin (IRI), glucose, free fatty acids (FFA), and corticosterone (Cmpd. B) were measured in non-arteriosclerotic virgin versus arteriosclerotic, breeder female rats exhibiting normal 4-day cycles. In the arteriosclerotic breeder females, the normal increase in IRI during proestrus and estrus did not occur. The IRI levels during these times were comparable to the minimal levels found during metestrus in the non-arteriosclerotic virgin rats and were even lower than the IRI levels or ovariectomized rats. Since both young and old non-arteriosclerotic virgin rats had similar IRI patterns, the lack of cyclic insulin change in the arteriosclerotic breeder rats is not considered to be age-related. Instead, these changes are ascribed to hypothalamic-pituitary-adrenal hyperactivity associated with repeated reproductive activity and the development of arteriosclerosis.

Animals↗

PubMed1975

Metabolic response after isoproterenol-induced myocardial infarction in arteriosclerotic breeder vs nonarteriosclerotic virgin intact and gonadectomized male rats.

Male, nonarteriosclerotic (virgin) intact and castrated, Sprague-Dawley rats and male, arteriosclerotic (breeder) rats were subjected to an acute and massive myocardial infarct, by treating them with two large, subcutaneous doses of isoproterenol, spaced 24 hr apart. Serum insulin and glucose rose abruptly after the first injection of isoproterenol, but not after the second injection. Free fatty acids rose, most markedly, in the intact, nonarteriosclerotic rats, less in the arteriosclerotic breeders, and least in the castrates. These changes in free fatty acids coincided with numerical survival, i.e., greatest number of survivors in castrates. The castrated males also manifested the least amount of congestive heart failure and showed the greatest capacity to affect myocardial repair. It is suggested that reduced androgen levels may have an ameliorative effect on the usual pathogenesis of isoproterenol-induced myocardial infarction in rats.

Animals↗

PubMed1975

Serum prolactin levels in rats following isoproterenol-induced myocardial infarction.

Circulating prolactin levels were monitored in nonarteriosclerotic, arteriosclerotic, and hormonally sterilized male and female Sprague-Dawley rats during the acute necrosis and repair phases of myocardial infarction induced by isoproterenol. Male rats are particularly prone to succumb to acute myocardial ischemia but reduction of androgen levels by neonatal sterilization improved survival considerably. Circulating prolactin levels are greatly increased, particularly in females, during acute myocardial ischemia. Since androgens suppress the hypothalamic center for prolactin release, prolactin levels were delayed and transitory in males. It is suggested that the superior survival of female rats may be related to their greater production of prolactin during acute stages of myocardial ischemia, which would dampen the tachycardia-inducing effects of the potent beta-adrenergic stimulating agent, isoproterenol.

Androgens↗