Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 91 records · Page 5Linked to original sources

PubMed1999

Porous balloon delivery of S-dC28 does not prevent restenosis in the porcine coronary artery model of balloon injury.

Phosphorothioate (PS) oligodeoxynucleotides (ODN) inhibit vascular smooth muscle cell proliferation through antisense and G-quartet aptameric mechanisms. PS-ODN such as the cytidine homopolymers, have been demonstrated to have non-G-quartet, nonsequence-specific inhibitory effects in a rat carotid balloon injury model of neointimal proliferation. We sought to test the efficacy of S-dC28, a cytidine homopolymer lacking G-quartets, on neointimal proliferation in the porcine coronary artery model of balloon injury. A total of 23 animals (11 controls, 12 treated) were subjected to balloon injury in a coronary artery, followed by infusion of control solution or S-dC28 via porous balloon, the Scimed Dispatch Coronary Infusion Catheter. After a mean interval of 49 days, the animals were killed, and the target coronary segments were examined histologically. S-dC28 did not significantly inhibit neointimal formation. Fluorescein isothiocyanate (FITC)-labeled S-dC28 was present in the intima and media immediately after administration but was present mainly within the adventitia 3 hours after administration. S-dC28, when delivered by a Scimed Dispatch Coronary Infusion Catheter (Maple Grove, MN), did not significantly affect neointimal proliferation after balloon injury in a porcine coronary artery model.

Angioplasty, Balloon, Coronary↗

PubMed1999

Primary dural leiomyosarcoma in a patient infected with human immunodeficiency virus: case report.

INTRODUCTION: We report the magnetic resonance imaging, angiographic, and immunohistochemical characteristics of a dural leiomyosarcoma in a patient infected with human immunodeficiency virus. METHODS AND RESULTS: A 38-year-old homosexual man presented with a recent history of headaches. Magnetic resonance imaging of the brain revealed an enhancing dural based right lateral wing mass that was thought to be a meningioma. The tumor had a signal intensity similar to the adjacent gray matter on T1-, T2-, and proton-weighted images. Angiography revealed that the tumor was vascular, supplied by the middle meningeal artery, but with contrast puddling as if there were small vascular lakes within the tumor. This evoked the possibility of a cavernous hemangioma. A craniotomy was performed, and the mass was resected. The pathological finding was consistent with a leiomyosarcoma. Immunohistochemistry revealed that the tumor was positive for alpha smooth muscle actin. Repeat testing for human immunodeficiency virus 2 months postoperatively was positive. Dural leiomyosarcomas are thought to take origin from the smooth muscles of the blood vessel walls. Another possible source is pluripotential mesenchymal cells. There may be an association with immunosuppression. CONCLUSION: Primary dural leiomyosarcomas simulate meningiomas on preoperative magnetic resonance images. They should be included in the differential diagnosis of dural based enhancing lesions.

Adult↗

PubMed1999

Establishing oral preference for quinine, phencyclidine and caffeine solutions in rats.

Rats were given fixed-time, 1-min food-pellet delivery sessions, for 3 h every day, which resulted in over drinking (schedule-induced polydipsia). In previous research, groups of animals came to prefer solutions of cocaine or lidocaine to concurrently presented water, if the drugs were first offered in a glucose/saccharin vehicle, which was then gradually eliminated, so that the choice became a drug solution in water vehicle versus water. In the present experiment, the same procedure produced a preference for 0.025 mg/ml quinine solution to water, indicating that a bitter solution that was not a topical anesthetic agent could come to be preferred. After establishing preference for quinine solution, it was possible to gradually remove quinine while increasing phencyclidine (PCP) concentration to produce preference for 0.075 mg/ml PCP solution, and similarly to produce subsequent preference for 0.1 mg/ml caffeine solution, although not for all animals. For additional groups, drinking either 0.15 mg/ml PCP or 0.1 mg/ml caffeine, while gradually reducing the glucose/saccharin vehicle to water vehicle was a less successful procedure for establishing the respective drug preferences. The latter result suggests that first instituting a preference for quinine solution to water facilitated the later establishment of preferences for PCP and caffeine solutions.

Animals↗

PubMed1999

Developmental changes in response to subatmospheric pressure loading of the upper airway.

Children snore less than adults and have fewer obstructive apneas, suggesting a less collapsible upper airway. We therefore hypothesized that the compensatory upper airway responses to subatmospheric pressure loading decrease with age because of changes in upper airway structure and ventilatory drive. We measured upper airway upstream pressure-flow relationships during sleep in 20 nonsnoring, nonobese children and adults. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. The slope of the upstream pressure-flow curve (S(PF)) was used to characterize upper airway function. We found that S(PF) was flatter in children than in adults (8 +/- 5 vs. 30 +/- 18 ml x s(-1). cmH(2)O(-1), P < 0.002) and that S(PF) correlated with age (r = 0.62, P < 0.01) and body mass index (r = 0. 63, P < 0.01). The occlusion pressure in 100 ms during sleep was measured in six children and two adults; it correlated inversely with S(PF) (r = -0.80, P < 0.02). We conclude that the upper airway compensatory responses to subatmospheric pressure loading decrease with age. This is associated with increased body mass index, even in nonsnoring, nonobese subjects. Ventilatory drive during sleep plays a role in modulating upper airway responses.

Adolescent↗

PubMed1999

Lack of evidence of acute ischemic tissue change in transient global amnesia on single-shot echo-planar diffusion-weighted MRI.

BACKGROUND AND PURPOSE: There is uncertainty concerning the etiology of transient global amnesia (TGA). Previous CT and MRI studies have indicated that permanent structural abnormality is rare in TGA. Diffusion-weighted (DW) MRI is very sensitive to early ischemic parenchymal changes and has recently demonstrated embolic infarction in the posterior cerebral artery territory in 2 TGA patients. We report the findings of DW MRI in 8 patients in acute stages of TGA. METHODS: Conventional and echo-planar DW MRI was performed in 2 patients in the active phase and 6 patients in the recovery phase (1 to 8 hours after cessation of anterograde memory dysfunction) of spontaneously occurring TGA. RESULTS: None of the patients showed signs of hyperintensity on DW images or hypointensity on quantitative apparent diffusion coefficient (ADC) maps to suggest regional decreases of water mobility or acute T2 changes on transverse or coronal slices. CONCLUSIONS: We were unable to detect ADC or acute T2 changes with echo-planar DW MRI in patients with TGA, which suggests that mechanisms other than ischemic infarction may cause TGA. We did not identify spreading depression-associated changes of the ADC. Further refinement of MRI sequences may be necessary to detect subtle or transient signal change in brain parenchyma.

Aged↗

PubMed1999

Preschoolers' characterizations of multiple family relationships during family doll play.

Investigated 4-year-olds' depictions of family relationships during a semistructured doll play task. Examined developmental and family correlates of these depictions, and their relative stability over a 1-month period. Forty-nine children related stories about happy, sad, mad, and worried families using dolls reflecting their own family configuration. For each story, coders recorded (a) proportion of total story time devoted to each family dyad and (b) number of conflictive, aggressive, and affectionate acts per dyad. Children divided their focus during stories evenly between father-child, mother-child, and father-mother relationships with child-sibling interactions occurring regularly among participants with siblings. Depictions of affection and aggression among family figures were relatively commonplace, related to mothers' reports of family climate, and stable across a 1-month period. Results substantiated preschoolers' awareness and discrimination of intrafamily relationship dynamics and provided some guidelines and cautions to practitioners who employ doll family assessments in their clinical work.

Aggression↗

PubMed1999

Additional construct validity of the Schwartz Cancer Fatigue Scale.

The purpose of this article is to report the results of additional construct validity testing of the Schwartz Cancer Fatigue Scale. Latent variable modeling was used to determine the best fit of the data to the model. Testing with a heterogeneous sample (n = 303) did not support the proposed model. Using exploratory techniques a six-item, two-factor scale was formed which demonstrated that all measures of fit were consistently strong, and that the standardized solution factors loaded strongly. Reliabilities for the total scale and subscales were all greater than 0.80. These results provide preliminary support for the reliability and validity of the two-factor model of the six-item Schwartz Cancer Fatigue Scale.

Adult↗

PubMed1999

Changes in coagulation and fibrinolysis markers in acute ischemic stroke treated with recombinant tissue plasminogen activator.

BACKGROUND AND PURPOSE: Shifts of the balance between coagulation and fibrinolysis play a crucial role in pathogenesis and treatment of cerebral ischemia. In this study, we characterized the kinetics of hemostatic abnormalities induced by acute ischemic stroke and its thrombolytic (recombinant tissue plasminogen activator [rtPA]) or anticoagulant (heparin) treatment. METHODS: Systemic generation of molecular markers of hemostasis (fibrin monomer, D-dimer, thrombin-antithrombin complex, and fibrinopeptide 1.2) was monitored in acute ischemic stroke, and the effects of thrombolytic and anticoagulant treatments were analyzed. RESULTS: Thrombolysis with rtPA induced a massive response of markers of coagulation activation and fibrin formation that peaked after 1 to 3 hours and persisted for up to 72 hours. In contrast, only minor hemostatic changes were induced by acute ischemic stroke itself. Administration of heparin did not significantly affect these hemostatic abnormalities. CONCLUSIONS: This first characterization of the coagulation activation induced by rtPA treatment for acute ischemic stroke and the failure to abolish such hemostatic abnormalities by heparin may be of value for further refinement of the currently discussed thrombolytic therapy and the controversial adjunctive anticoagulant prophylaxis in stroke patients.

Aged↗

PubMed1998

Photochemical localization of the semotiadil binding region within the cardiac Ca2+ channel alpha1 subunit. Comparison with the skeletal muscle counterpart.

We have previously identified the binding region of a new Ca2+ antagonist semotiadil in the skeletal muscle Ca2+ channel. To the same semotiadil derivatives, the cardiac counterpart showed distinct and different binding characteristics: semotiadil and its photoaffinity analog D51-4700 inhibited [3H]PN200-110 binding to cardiac membrane preparations with IC50 values of 13-20 microM, which are 10 times higher than those in skeletal muscle. Hill slopes of the binding inhibition were 0.94-1.0 for the cardiac channels compared to 0.63-0.67 for the skeletal muscle channels. A possible explanation for the difference is that the semotiadil binding site is differently conferred in cardiac and skeletal muscle Ca2+ channels. To reveal this within the primary structure, photoaffinity labeling of cardiac membranes was employed. [3H]D51-4700 was photo-incorporated in several polypeptides but only the alpha1 subunit of the Ca2+ channel was photolabeled in a specific manner. Antibody mapping of the [3H]D51-4700-labeled alpha1 subunit with several anti-peptide antibodies revealed that the labeled site was located solely in a peptide fragment between Cys1461 and Lys1529. This region encompasses the labeled site of skeletal muscle, but contains several non-identical amino acid residues, which may participate in expressing different binding characteristics between the two muscle type Ca2+ channels.

Amino Acid Sequence↗

PubMed1998

Quantitative flow cytometry: inter-laboratory variation.

Quantitative flow cytometry (QFCM) offers a means of standardization within and between flow cytometers. QFCM parameters were set by determining the antibody-binding capacity (ABC) of CD4, CD8, and CD3 cells from 10 normal donors with the use of eight FACScan flow cytometers. QC3 beads and a certified blank bead were used to set up the instruments. Fluorescein isothiocyanate (FITC) conjugated to molecular equivalents of soluble fluorochrome (MESF) microbead standards was used before and after the donor samples were run to ensure that the machines were operating consistently. Lyophilized cells (Cytotrol) were used as a target, to control for antigen expression in the cell preparation. Quantitative Simply Cellular (QSC) beads were used to establish a standard calibration curve for each of the FITC and phycoerythrin antibody conjugates on each of the instruments. Single-parameter fluorescent histograms derived from list-mode files were used to calculate the slope (coefficient of response), intercept (zero channel), number of channels per decade, and ABC or MESF threshold (blank bead). The fluorescence intensity (geometric mean) of the positive and negative donor cell populations was compared with the standard curves, and the ABCs were calculated. The results show consistent instrument performance between laboratories. However, after standardization of CD3, CD4, and CD8 ABCs to microbeads, large variations were noted between donors and laboratories. The source of this variation does not appear to be in the instrumentation but may be due to the lack of an unified set-up protocol, introducing issues of antibody saturation, methods for whole blood lysis and fixation, and the behavior of the microbead standards.

Flow Cytometry↗

PubMed1998

Standardizing flow cytometry: a classification system of fluorescence standards used for flow cytometry.

The growing number of standards commercially available in the field of flow cytometry makes it difficult to know which standards to use to obtain a desired level of quality assurance. A classification system of fluorescence standards has been developed on the basis of their physical characteristics. In turn, these physical characteristics determine the ability of the specific standards to perform selected functions, such as alignment, target referencing, compensation, and calibration. Knowing the properties and limitations of specific standards will help flow cytometer users to select the appropriate standard for the application that they will be performing, especially in regard to intra- and interlaboratory quality assurance. Common protocols used in conjunction with specific classifications of reference standards can provide unified analysis regions or window of analysis across different instruments and/or laboratories. In addition, specific classifications of calibration standards can help select those standards that will provide independent and direct comparison of instrument performance parameters, especially in studies involving multiple laboratories. Knowledge and understanding of the classification system can guide flow cytometer users in more efficient and accurate instrument setup and quality control when conducting research, as well as clinical applications.

Calibration↗

PubMed1998

Multiple modulation pathways of calcium channel activity by a beta subunit. Direct evidence of beta subunit participation in membrane trafficking of the alpha1C subunit.

In order to study the precise mechanisms of alpha1 subunit modulation by an auxiliary beta subunit of voltage-dependent calcium channels, a recombinant beta3 subunit fusion protein was produced and introduced into oocytes that express the human alpha1C subunit. Injection of the beta3 subunit protein rapidly modulated the current kinetics and voltage dependence of activation, whereas massive augmentation of peak current amplitude occurred over a longer time scale. Consistent with the latter, a severalfold increase in the amount of the alpha1C subunit in the plasma membrane was detected by quantitative confocal laser-scanning microscopy after beta3 subunit injection. Pretreatment of oocytes with bafilomycin A1, a vacuolar type H+-ATPase inhibitor, abolished the increase of the alpha1C subunit in the plasma membrane, attenuated current increase, but did not affect the modulation of current kinetics and voltage dependence by the beta3 subunit. These results provide clear evidence that the beta subunit modifies the calcium channel complex in a binary fashion; one is an allosteric modulation of the alpha1 subunit function and the other is a chaperoning of the alpha1 subunit to the plasma membrane.

Animals↗

PubMed1998

Photochemical identification of transmembrane segment IVS6 as the binding region of semotiadil, a new modulator for the L-type voltage-dependent Ca2+ channel.

To identify the binding domain of a new Ca2+ antagonist semotiadil on L-type Ca2+ channels from skeletal muscle, photolabeling was carried out by using an azidophenyl derivative of [3H]semotiadil. Photoincorporation was observed in several polypeptides of membrane triad preparations; the only specific photoincorporation was in the alpha1 subunit of the Ca2+ channel. After solubilization and purification, the photolabeled alpha1 subunit was subjected to proteolytic and CNBr cleavage followed by antibody mapping. Specific labeling was associated solely with the region of transmembrane segment S6 in repeat IV. Quantitative immunoprecipitation was found in the tryptic and the Lys-C/Glu-C fragments of 6.6 and 6.1 kDa, respectively. Further CNBr cleavage of the Lys-C digests produced two smaller fragments of 3.4 and 1.8 kDa that were included in the tryptic and Lys-C/Glu-C fragments. The smallest labeled fragments were: Tyr1350-Met1366 and Leu1367-Met1381 containing IVS6, a possible pore-forming region. The data suggest that semotiadil binds to a region that is overlapped with but not identical to those for phenylalkylamines, dihydropyridines and benzothiazepines. The present study also provides evidence that region IV represents an important component of a binding pocket for Ca2+ antagonists.

Animals↗

PubMed1998

Mood disorders and dysfunction of the hypothalamic-pituitary-adrenal axis in multiple sclerosis: association with cerebral inflammation.

OBJECTIVE: To investigate the association between affective and neuroendocrine abnormalities, commonly observed in multiple sclerosis, with inflammatory disease activity. DESIGN: Cross-sectional design. Twenty-three patients with definite relapsing-remitting multiple sclerosis and age- and sex-matched control subjects were investigated. Depression and anxiety were assessed using structured interviews, self-report measures, and Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised criteria. Neurologic impairment was assessed by the Kurtzke Expanded Disability Status Scale and function of hypothalamic-adrenal-pituitary axis was analyzed using a corticotropin-releasing hormone stimulation test after dexamethasone suppression. Inflammatory disease activity was evaluated first by routine and experimental laboratory tests, and second by magnetic resonance assessment of gadolinium uptake of multiple sclerotic plaques. SETTING: University hospital, a major provider of acute neurologic care. RESULTS: Compared with controls, patients with multiple sclerosis had higher scores on depression and anxiety scales and exhibited a failure of suppression of cortisol release after dexamethasone pretreatment. Both affective symptoms and neuroendocrine abnormalities were correlated with cerebrospinal fluid white blood cell counts and presence of gadolinium-enhancing lesions on magnetic resonance images; however, no association with the degree of neurologic impairment was observed. CONCLUSION: Affective and neuroendocrine disorders were related to inflammatory disease activity but not to degree of disability, supporting the hypothesis that these symptoms are causally associated with brain injury.

Adult↗

PubMed1998

Spontaneous healing of cervical pseudoaneurysm in vertebral artery dissection under anticoagulant therapy.

We report a 41-year-old woman with embolic stroke of the mid-pons attributed to embolism from vertebral artery dissection. Angiography revealed an occluded artery on one side and an incidental pseudoaneurysm of the midcervical portion of the vertebral artery on the other. After 3 months of warfare in therapy control angiography showed complete occlusion of the pseudoaneurysm. We discuss therapeutic choices and review the literature.

Adult↗

PubMed1998

Assessment of T2- and T1-weighted MRI brain lesion load in patients with subcortical vascular encephalopathy.

Previous cross-sectional studies in patients with subcortical vascular encephalopathy (SVE) have shown little or no correlation between brain lesion load and clinical disability, which could be due to the low specificity of T2-weighted MRI. Recent studies have indicated that T1-weighted MRI may be more specific than T2-weighted MRI for severe tissue destruction. We studied 37 patients with a diagnosis of SVE and 11 normal controls with standardised T1- and T2-weighted MRI. All patients underwent detailed clinical assessment including a neuropsychological test battery and computerised gait analysis. Both the T2- and T1-weighted total MRI lesion loads different between patients and controls different, particularly T1. The ratio of T2-/T1-weighted lesion load was lower in controls than in patients. There was no overall correlation of T1- or T2-weighted lesion load with clinical disability, but group comparison of patients with severe and mild clinical deficits showed different lesion loads. We suggest that T1- and T2-weighted MRI lesion loads demonstrate relevant structural abnormality in patients with SVE.

Aged↗

PubMed1998

Prevalence of hypophosphatemia in sepsis and infection: the role of cytokines.

BACKGROUND: Sepsis occurs following the presence of bacteria in the circulation and is associated with fever, hyperthermia, and hypotension. Hypophosphatemia develops in the early stages of sepsis. High levels of inflammatory cytokines also characterize early sepsis. AIM: The aim of the present study was to correlate hypophosphatemia with cytokines and cytokine receptor levels during early sepsis. We aimed to reestablish the results obtained from patients in an in vivo experimental model, in order to understand the mechanism of hypophosphatemia induction in early sepsis. METHODS: Ninety-nine patients were enrolled in this study and their clinical condition was classified as the presence of infection, sepsis, and bacterial growth in blood cultures. Phosphate levels and cytokine levels were recorded. In order to determine whether hypophosphatemia is correlated to the increased inflammatory cytokines, we injected normal mice with recombinant cytokines and studied their effect on phosphate levels. RESULTS: Our results revealed that 80% of the septic patients had hypophosphatemia associated with very high levels of tumor necrosis factor (TNF)alpha and interleukin (IL)-6 and of soluble IL receptor (sIL)-2R and IL-6R, especially in those patients with positive blood cultures. Injection of IL-6, TNFalpha and IL-1beta in mice markedly decreased the phosphate serum levels. CONCLUSIONS: Significant associations were demonstrated between high levels of inflammatory cytokines and their receptors and between serum phosphate levels, especially in patients with positive blood culture. Our results point to a correlation between the high inflammatory cytokines levels and hypophosphatemia during early sepsis. Cytokine levels and hypophosphatemia may be included in sepsis evaluation and prognosis. Anticytokine strategies might, therefore, reverse hypophosphatemia and other parameters of sepsis.

Cytokines↗

PubMed1998

Functional magnetic resonance imaging of category-specific cortical activation: evidence for semantic maps.

Functional magnetic resonance imaging (fMRI) was used to examine the pattern of cortical activity during a picture naming task. Subjects (n=12) had to covertly name either animals or furniture items. Functional scanning was performed using a conventional 1.5-Tesla whole-body MRI system. Images obtained during naming the two categories were compared using a non-parametric test. The study revealed evidence for domain-specific lexical regions in left middle, right middle and inferior frontal areas, as well as in superior and middle temporal areas. The results corroborate neuropsychological data and demonstrate directly and non-invasively in human volunteers that semantic representations in frontal and temporal areas are, to some degree, localized and possibly implemented as multiple maps. A completely distributed storage of semantic information is rendered unlikely.

Adult↗