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Biomedical subjects

T W Smith

Publications and source records attributed to T W Smith.

At least 145 records · Page 8Linked to original sources

Acadesine improves tolerance to ischemic injury in rat cardiac myocytes.

The ability of acadesine to modulate injury in a myocyte model of simulated ischemia was studied. When freshly isolated adult rat ventricular myocytes were subjected to 10 min of simulated ischemia and reperfusion, greater that 75% of myocytes developed hypercontracture and the amplitude of contraction of the remaining, potentially viable myocytes was markedly depressed. When cells were pretreated with 50 microM acadesine for 5 min and exposed to acadesine during simulated ischemia and during 2-10 min of reperfusion, followed by reperfusion with control buffer, up to 90% of myocytes maintained normal morphology and could be stimulated to contract. Acadesine alone had no significant effect on amplitude of contraction of the myocytes. Acadesine is known to alter adenosine metabolism and to increase coronary sinus [adenosine] in the ischemic heart. When cells were treated with the non-selective adenosine receptor antagonist 8-sulfonylphenyltheophylline, the protective effect of acadesine was abolished. Thus, in this adult rat cardiac myocyte model of simulated ischemia, acadesine protects partially against ischemia/reperfusion injury. The protective effect of acadesine is mediated, at least in part, by an adenosine receptor-dependent mechanism.

Aminoimidazole Carboxamide↗

Patient adherence and adjustment in renal dialysis: a person x treatment interactive approach.

We classified 52 in-center hemodialysis patients and 34 self-treated, continuous ambulatory peritoneal dialysis (CAPD) patients on two latent variable indices reflecting patient coping style (i.e., "Information Vigilance" and "Active Coping"). The concurrent and prospective interactive effects of Dialysis Type and Coping Style were examined on patient dietary and medication adherence and on patient depression. In cross-sectional analyses, higher Information Vigilance was associated with better dietary adherence for CAPD patients but poorer adherence for In-Center Hemodialysis patients. No significant effects were found on a measure of medication adherence. Information Vigilance exerted a concurrent main effect on depression, such that higher scores were associated with less depression irrespective of dialysis type. Higher Active Coping scores were associated with lower residualized change in depression for both types of dialysis.

Adaptation, Psychological↗

Cognitive distortion and depression in chronic pain: association with diagnosed disorders.

Previous studies have demonstrated that cognitive distortion is associated with increased levels of self-reported depression among chronic pain patients, suggesting that cognitive models of depression might be useful in this context. However, reliance on self-reports of depression hampers generalization of these results to clinically significant depressive disorders. To address this problem, we examined the association between depression diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised (DSM-III-R; American Psychiatric Association, 1987) (i.e., major depression and dysthymia) and scores on the Cognitive Errors Questionnaire (CEQ). Depressed chronic pain patients and depressed nonpain patients reported more cognitive distortion than did nondepressed pain patients and normal controls. These results support the relevance of cognitive theory in the explication of clinically significant depression among chronic pain patients.

Adult↗

Cognitive distortion, helplessness, and depressed mood in rheumatoid arthritis: a four-year longitudinal analysis.

Cognitive models of depression have been invoked to explain the development of depressive symptoms and disorders in patients with chronic pain. However, few long-term, prospective studies have examined A. T. Beck's (1967, 1987) model in this context. Seventy-two patients with rheumatoid arthritis completed the Beck Depression Inventory, the Cognitive Errors Questionnaire, and the Arthritis Helplessness Index during an initial assessment and again 4 years later. Initial levels of cognitive distortion were significantly related to follow-up levels of depressed mood, controlling for initial depression levels. This was also true for perceptions of helplessness. In contrast, initial depression levels did not predict changes in these cognitive processes. These results suggest that cognitive distortion and helplessness contribute to depressed mood among patients with arthritis.

Adult↗

Predictors of survival among hemodialysis patients: effect of perceived family support.

The authors examined the role of perceived family support and symptoms of depression as predictors of survival in a sample of 78 in-center hemodialysis patients. Cox regression analysis revealed significant effects for family support (p < .005), blood urea nitrogen (p < .01), and age (p < .005). The effect for depression was not significant. The Cox model indicated that a 1-point increase on the family support measure was associated with a 13% reduction in the hazard rate (i.e., mortality). Estimated 5-year mortality rates among low family support patients were approximately 3 times higher than estimated mortality for high support patients. Differences in patient adherence to the dietary and medication regimens failed to explain the significant effect of family support.

Age Factors↗

Prevalence of Borrelia burgdorferi in host-seeking ticks (Acari: Ixodidae) from a Lyme disease endemic area in northern Michigan.

The Lyme disease spirochete, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was recovered from the guts of questing Ixodes scapularis Say adults and nymphs and adult Dermacentor variabilis (Say), collected in Menominee County, Michigan, in 1992. Spirochetes were cultured successfully from guts placed in modified Barbour-Stoenner-Kelly II medium held in 5-ml cultures tubes or in 0.3-ml wells of microtiter plates. Most isolates were recovered within 2 wk of culturing at an incubation temperature of 34 degrees C. Spirochetes were recovered more rapidly in culture tubes than in microtiter plates. For determination of tick infection with B. burgdorferi, culturing was equivalent to examination of gut smears by immunofluorescence. We found the following infection rates: 57/179 I. scapularis females (31.8%), 62/204 I. scapularis males (30.4%), 9/54 I. scapularis nymphs (16.7%), and 5/383 D. variabilis adults (1.3%).

Animals↗

Continual electric field stimulation preserves contractile function of adult ventricular myocytes in primary culture.

To model with greater fidelity the electromechanical function of freshly isolated heart muscle cells in primary culture, we describe a technique for the continual electrical stimulation of adult myocytes at physiological frequencies for several days. A reusable plastic cover was constructed to fit standard, disposable 175-cm2 tissue culture flasks and to hold parallel graphite electrodes along the long axis of each flask, which treated a uniform electric field that resulted in a capture efficiency of ventricular myocytes of 75-80%. Computer-controlled amplifiers were designed to be capable of driving a number of flasks concurrently, each containing up to 4 x 10(6) myocytes, over a range of stimulation frequencies (from 0.1 to 7.0 Hz) with reversal of electrode polarity after each stimulus to prevent the development of pH gradients around each electrode. Unlike quiescent, unstimulated myocytes, the amplitude of contraction, and velocities of shortening and relaxation did not change in myocytes paced at 3-5 Hz for up to 72 h. The maintenance of normal contractile function in paced myocytes required mechanical contraction per se, since paced myocytes that remained quiescent due to the inclusion of 2.5 microM verapamil in the culture medium for 48 h also exhibited a decline in contractility when paced after verapamil removal. Similarly, pacing increased peak calcium current compared with quiescent cells that had not been paced. Thus myocyte contraction at physiological frequencies induced by continual uniform electric field stimulation in short-term primary culture in defining medium maintains some biophysical parameters of myocyte phenotype that are similar to those observed in freshly isolated adult ventricular myocytes.

Animals↗

T-type Ca2+ channels are abnormal in genetically determined cardiomyopathic hamster hearts.

Although there is substantial evidence of abnormal Ca2+ homeostasis in heart cells of the cardiomyopathic Syrian hamster (Bio 14.6 strain), the mechanism by which these myocytes become Ca(2+)-overloaded is not known. To elucidate the role of voltage-sensitive Ca2+ channels in the pathogenesis of myopathy, whole-cell Ca2+ currents were measured in myopathic and normal control cardiac myocytes. These studies demonstrate the presence of two voltage-sensitive Ca2+ channel types in ventricular myocytes isolated from 200- to 300-day-old cardiomyopathic and age-matched normal hamsters. The two Ca2+ channel types were identified by their unitary conductance properties and pharmacologic sensitivities. Both L-type and T-type Ca2+ channels were present in cardiomyopathic and normal cells. Current density through L-type Ca2+ channels was the same in cardiomyopathic and normal control myocytes. However, the mean current density of T-type Ca2+ channels in cardiomyopathic cells was significantly higher than in normal cells (myopathic, 12.3 +/- 1.8 pA/pF; normal, 5.8 +/- 1.1 pA/pF; n = 8; P < .01). The T-type Ca2+ current in cardiomyopathic myocytes was activated and inactivated at more negative potentials than in cells from normal hamster hearts. These findings demonstrate no abnormality of the dihydropyridine-sensitive voltage-dependent L-type Ca2+ channel. In contrast, the observed abnormalities in T-type Ca2+ channel function in cardiomyopathic hamster myocytes suggest that this alteration may be related to the pathogenesis of Ca2+ overload and the arrhythmias in this genetically determined form of cardiomyopathy.

Animals↗

Obsessive-compulsive disorders in Pick's disease.

The authors present a follow-up of a previously described patient with obsessive-compulsive disorder (OCD). Her condition continued to worsen, and she died 5 years after disease onset. Neuropathological findings were consistent with the diagnosis of Pick's disease. They revealed, in addition to the "knife-edge" frontotemporal atrophy, striking atrophy with extensive neuronal loss and gliosis involving the caudate nuclei and, to a lesser degree, the putamens and globus pallidus. Neuroimaging data had showed isolated atrophy of the caudate nuclei in the early stages of Pick's disease in this patient when OCD was the leading clinical manifestation. Relevant literature is reviewed, and the role of caudate nuclei atrophy in the development of OCD is discussed.

Adult↗

Diffuse axonal injury in craniocerebral trauma. A comparative histologic and immunohistochemical study.

Axonal swellings are the major histologic hallmark of diffuse axonal injury in craniocerebral trauma. In this study, we compared conventional histologic and immunohistochemical methods for demonstrating axonal swellings in 11 cases of head trauma. Brain regions known to be susceptible to diffuse axonal injury were examined with conventional hematoxylin-eosin and silver (Bodian) stains and immunohistochemical markers for neurofilaments, ubiquitin, and tau and beta/A4-amyloid. A quantitative assessment of the axonal swellings visualized with each stain was made. In all but one case, axonal swellings were identified with the hematoxylin-eosin stain. By contrast, both the silver and neurofilament stains demonstrated fewer axonal swellings and were often difficult to interpret due to staining of normal axons. In the majority of cases, the ubiquitin stain revealed the greatest number of axonal swellings. Axonal swellings were not visualized with the tau or beta/A4-amyloid antibodies. We conclude that the standard hematoxylin-eosin stain remains a reliable method for the detection of axonal swellings in craniocerebral trauma and is superior to the Bodian and neurofilament stains. Identification and quantitative assessment of diffuse axonal injury is aided by the use of immunocytochemical staining for ubiquitin.

Adolescent↗

Nitric oxide synthases and cardiovascular signaling.

Nitric oxide (NO) synthesized from L-arginine is a ubiquitous intercellular chemical messenger involved in signal transduction in diverse mammalian cells, including vascular endothelium and neuronal tissues. The recent isolation of molecular clones for NO synthases has permitted the characterization of several distinct enzyme isoforms and has allowed us to identify a family of related genes. NO synthesized in vascular endothelial cells appears to play an important role in the control of vascular tone and platelet aggregation, apparently through the activation of guanylate cyclase activity in target tissues mediated by NO. The role of the NO signaling pathway in the direct modulation of cardiac function is less well characterized. We have found that inhibitors of NO synthase can modulate the response of neonatal or adult rat ventricular myocytes exposed to muscarinic or adrenergic agonists. The effects of carbachol on the inhibition of the spontaneous beating rate of cultured neonatal rat cardiac myocytes are blocked by L-N-monomethylarginine, an L-arginine analog that inhibits NO synthase, and by methylene blue, an inhibitor of NO; these agents have no effect on the basal beating rate of these cells. The negative chronotropic effect of carbachol is also mimicked by analogs of cyclic guanosine monophosphate (cGMP), a second messenger implicated in mediating the action of NO in other cell types. Production of NO can be detected directly in carbachol-stimulated neonatal myocytes using a reporter cell bioassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Digoxin in heart failure.

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Angiotensin-Converting Enzyme Inhibitors↗

Control of cardiac muscle cell function by an endogenous nitric oxide signaling system.

Nitric oxide (NO) synthesized from L-arginine is a ubiquitous intracellular chemical messenger and is involved in signal transduction in diverse mammalian cells, including vascular endothelium and neuronal tissues. The role of the NO-signaling pathway in the direct modulation of cardiac function is less well characterized. In this report, the effects of inhibitors of NO synthase (NOS) were examined in isolated neonatal and adult rat ventricular myocytes exposed to either muscarinic or adrenergic agonists. Carbachol (10 microM) caused a 91% inhibition of the spontaneous beating rate of cultured neonatal rat cardiac myocytes. N omega-monomethyl-L-arginine, an L-arginine analog that inhibits NOS, and methylene blue, an inhibitor of NO, blocked the negative chronotropic effect of carbachol but had no effect on the basal beating rate of these cells. The inhibition by N omega-monomethyl-L-arginine of the negative chronotropic effect of carbachol was reversed by adding excess L-arginine. The negative chronotropic effect of carbachol was also mimicked by analogs of cGMP, a second messenger implicated in mediating the action of NO in other cell types. Production of NO could be detected directly in carbachol-stimulated neonatal myocytes by using a reporter cell bioassay. The regulation of adrenergic responsiveness by the NO signaling system was also documented in studies of adult cardiac myocyte contractility. The NOS inhibitor N omega-nitro-L-arginine significantly increased the inotropic effect of the beta-adrenergic agonist isoproterenol on electrically stimulated adult rat ventricular myocytes, whereas this inhibitor had no effect on basal contractility. Inhibition of NO production by N omega-monomethyl-L-arginine in these cells, as measured by reporter cell bioassay, was also reversible with excess L-arginine. Thus, the physiologic response of isolated neonatal and adult ventricular myocytes to both muscarinic cholinergic and beta-adrenergic stimulation is mediated, at least in part, by products of an endogenous NOS.

Aging↗

Vascular amyloid deposition in Alzheimer's disease. Neither necessary nor sufficient for the local formation of plaques or tangles.

OBJECTIVE: To determine the relationship between vascular beta-amyloid (beta A4) and senile plaques (SPs) and neurofibrillary tangles (NFTs). DESIGN: We counted vascular amyloid deposition with SP and NFT density in the medial temporal lobe (CA1 plus the subiculum) and the cerebellum. PATIENTS: The brains of seven patients with Alzheimer's disease and of three age-matched nondemented control subjects were studied. RESULTS: In Alzheimer's disease, the density of beta A4-laden blood vessels was significantly higher in the cerebellum than in CA1 plus the subiculum. Conversely, the densities of SPs and NFTs were much greater in the CA1 plus the subiculum than in the cerebellum. CONCLUSIONS: This study indicates that local vascular beta A4 deposition is not directly correlated with SP and NFT densities. Deposition of beta A4 in blood vessel walls may not be instrumental in the formation of SPs and/or NFTs in the brain.

Aged↗

Impact of anomalous vertebral segmentation on measurements of bone mineral density.

In anteroposterior (AP) bone mineral density (BMD) measurements of the lumbar spine (LS), the presence of ribs is used to identify vertebra T12. Similarly, in lateral LS-BMD measurements, the position of the iliac crest is used to identify the lumbar vertebrae. The aim of this study was to determine the impact of variations in spinal segmentation and iliac crest position on BMD measurements. In 375 women (ages 50-85 years) radiographs were taken of the thoracic and lumbar spine, as well as AP measurement of LS-BMD, by dual-energy x-ray absorptiometry (DXA). In 121 subjects lateral decubitus LS-BMD was also measured. Anomalous spinal segmentation was found in 16.5%, and L1 would have been incorrectly identified on the AP-DXA image in 13%. The change in BMC and BMD between adjacent vertebrae was greater in the upper than the lower lumbar spine. Misidentification of L1 for T12 resulted in underestimation of the bone mineral content in grams (BMC) of L1 by a mean of 11.5 +/- 14.4% (SD; range -33.5 to 33.5%). For the usual region of interest, L2-4, the BMC (g) was underestimated by 8.4 +/- 8.7% (range -1.5 to 29.2%), with the BMD (g/cm2) underestimated by 3.6 +/- 4.8% (range -5.4 to 11.6%). The position of the iliac crest on the lateral decubitus DXA scans would have led to misidentification of either L2 or L4 for L3 in 15 cases (12%). This resulted in the BMD of L3 being underestimated by 2.7 +/- 19.4% (range -242.4 to 34.6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Acute myopathy and neuropathy in status asthmaticus: case report and literature review.

A 38-year-old woman developed acute, severe weakness during the treatment of status asthmaticus that included high-dose intravenous corticosteroids. A muscle biopsy and EMG indicated a myopathy, and nerve conduction studies disclosed a neuropathic component. In association with corticosteroid tapering, the clinical, EMG, and nerve conduction abnormalities resolved. In some patients, intensive treatment of status asthmaticus may cause a reversible, toxic disorder of muscle and nerve.

Acute Disease↗

Cortical tubers demonstrate reduced immunoreactivity for synapsin I.

To evaluate the effects of tuberous sclerosis (TS) on cortical synaptic organization, we analyzed synaptic densities within cortical tubers from the brains of two TS patients using a polyclonal antibody directed against synapsin I, a synaptic terminal-specific protein. The synaptic densities of the tubers and adjacent histologically normal cortex were obtained by determining optical densities using an IBAS (Zeiss) image analysis system. The tubers showed abnormally low levels of synapsin I compared with the normal cortex. The data suggest that cortical tubers do not contain a normal complement of synapses. This may reflect focal underdevelopment of normal cortical-cortical connections. Altered afferent cortical projections may also contribute to synaptic loss in cortical tubers.

Cerebral Cortex↗