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Biomedical subjects

M A Silver

Publications and source records attributed to M A Silver.

At least 19 recordsLinked to original sources
PubMed2001

ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America.

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Adult↗
PubMed2001

TrkB-like immunoreactivity is present on geniculocortical afferents in layer IV of kitten primary visual cortex.

Exogenous administration of the neurotrophins brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/5), or blockade of their endogenous actions, have been reported to affect the anatomic organization and physiological responses of neurons in developing mammalian primary visual cortex. Experimental alteration of levels of these neurotrophic factors can also influence the morphology of the geniculocortical afferents that project from the lateral geniculate nucleus (LGN) to primary visual cortex. BDNF and NT-4/5 are ligands of the TrkB tyrosine kinase receptor. Although multiple populations of cortical neurons express TrkB, it is not known whether geniculocortical afferents express this receptor on their axon branches in visual cortex. We have anatomically labeled geniculocortical afferents of postnatal day 40 kittens with the anterograde neuronal tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and performed double-label immunofluorescence with a panel of anti-TrkB antibodies. Confocal microscopy and object-based colocalization analysis were used to measure levels of TrkB-like immunoreactivity (IR) on geniculocortical afferents in layer IV of primary visual cortex. By using a conservative analysis involving a comparison of measured colocalization with the amount of colocalization expected based on random overlap of TrkB puncta and PHA-L--labeled afferents, 3 of 5 anti-TrkB antibodies tested showed significant colocalization with the geniculocortical axons. Results for the other two antibodies were indeterminate. The indices obtained for colocalization of TrkB and geniculocortical afferents were also compared with the equivalent index obtained for GAD65, a protein that has a similar overall expression pattern to that of TrkB but is not expressed on geniculocortical axons. This analysis indicated that TrkB was present on geniculocortical axons for all five TrkB antibodies tested. TrkB-like IR was also observed on neuronal somata in the LGN. These results indicate that TrkB receptors on geniculocortical afferents are potential mediators of the actions of BDNF and NT-4/5 in developing visual cortex.

Animals↗
PubMed2001

A new method of monitoring recovery and weaning the Thoratec left ventricular assist device.

BACKGROUND: Recent scientific and clinical data suggest that chronic mechanical ventricular unloading may lead to myocardial recovery. Evaluating and monitoring patients for myocardial recovery and the optimal methods of weaning the left ventricular assist device are not well defined. METHODS: Six patients with advanced heart failure and severe mitral regurgitation have undergone successful bridge to recovery using a Thoratec left ventricular assist device. Data that details their monitoring for myocardial recovery and weaning from the left ventricular assist device were prospectively collected. RESULTS: Clinical data collected during the recovery phase included chest roentgenogram, echocardiography, plasma norepinephrine, tumor necrosis factor-alpha, bioimpedance, and cardiopulmonary exercise testing (peak oxygen consumption). Normalization of these variables with a 10% increase in the peak oxygen consumption was obtained before weaning. The Thoratec device rate and percent systole were manipulated to allow gradual reloading of the ventricle. The weaning process occurred for more than 5 to 10 days to allow time for observation of the ventricle and its response to the increasing workload. CONCLUSIONS: Select patients with advanced congestive heart failure and severe mitral insufficiency can benefit from mechanical device support. We describe our technique of monitoring for myocardial recovery using clinical variables. Our technique of weaning allows for gradual reloading of the ventricle and a longer period of observation before device removal. Additional research is needed to determine which variables will accurately predict long-term myocardial recovery and the optimal weaning method.

Adult↗
PubMed2001

Infusion of nerve growth factor (NGF) into kitten visual cortex increases immunoreactivity for NGF, NGF receptors, and choline acetyltransferase in basal forebrain without affecting ocular dominance plasticity or column development.

Intracerebroventricular or intracortical administration of nerve growth factor (NGF) has been shown to block or attenuate visual cortical plasticity in the rat. In cats and ferrets, the effects of exogenous NGF on development and plasticity of visual cortex have been reported to be small or nonexistent. To determine whether locally delivered NGF affects ocular dominance column formation or the plasticity produced by monocular deprivation in cats at the height of the critical period, we infused recombinant human NGF into the primary visual cortex of kittens using an implanted cannula minipump. NGF had no effect on the normal developmental segregation of geniculocortical afferents into ocular dominance columns as determined both physiologically and anatomically. The plasticity of binocular visual cortical responses induced by monocular deprivation was also normal in regions of immunohistochemically detectable NGF infusion, as measured using intrinsic signal optical imaging and single-unit electrophysiology. Immunohistochemical analysis of the basal forebrain regions of the same animals demonstrated that the NGF infused into cortex was biologically active, producing an increase in the number of NGF-, TrkA-, p75(NTR)-, and choline acetyltransferase-positive neurons in basal forebrain nuclei in the hemisphere ipsilateral to the NGF minipump compared to the contralateral basal forebrain neurons. We conclude that NGF delivered locally to axon terminals of cholinergic basal forebrain neurons resulted in increases in protein expression at the cell body through retrograde signaling.

Animals↗
PubMed2000

Distributions of synaptic vesicle proteins and GAD65 in deprived and nondeprived ocular dominance columns in layer IV of kitten primary visual cortex are unaffected by monocular deprivation.

Two days of monocular deprivation (MD) of kittens during a critical period of development is known to produce a loss of visual responses in the primary visual cortex to stimulation of the nondeprived eye, and 7 days of deprivation results in retraction of axon branches and loss of presynaptic sites from deprived-eye geniculocortical arbors. The rapid loss of responsiveness to deprived-eye visual stimulation could be due to a decrease in intracortical excitatory input to deprived-eye ocular dominance columns (ODCs) relative to nondeprived-eye columns. Alternatively, deprived-eye visual responses could be suppressed by an increase in intracortical inhibition in deprived columns relative to nondeprived columns. We tested these hypotheses in critical period kittens by labeling ODCs in layer IV of primary visual cortex with injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into lamina A of the lateral geniculate nucleus (LGN). After either 2 or 7 days of MD, densities of intracortical excitatory presynaptic sites within deprived relative to nondeprived ODCs were estimated by measuring synaptic vesicle protein (SVP) immunoreactivity (IR). Because most of the synapses within layer IV of primary visual cortex are excitatory inputs from other cortical neurons, levels of SVP-IR provide an estimate of the amount of intracortical excitatory input. We also measured levels of immunoreactivity of the inhibitory presynaptic terminal marker glutamic acid decarboxylase (GAD)65 in deprived relative to nondeprived ODCs. Monocular deprivation (either 2 or 7 days) had no effect on the distributions of either SVP- or GAD65-IR in deprived and nondeprived columns. Therefore, the rapid loss of deprived-eye visual responsiveness following MD is due neither to a decrease in intracortical excitatory presynaptic sites nor to an increase in intracortical inhibitory presynaptic sites in layer IV of deprived-eye ODCs relative to nondeprived columns.

Animals↗
PubMed2000

A method for measuring colocalization of presynaptic markers with anatomically labeled axons using double label immunofluorescence and confocal microscopy.

Information concerning the location and distribution of presynaptic neurotransmitter release sites within anatomically labeled axons would be of value for a large number of studies in functional anatomy, development, and plasticity. Here we report a method for localizing presynaptic sites within identified arbors of interest using anterograde anatomical tracer injections to label axonal projections and synaptic vesicle protein (SVP) antibodies to label presumptive presynaptic terminals. The axons and presynaptic sites are independently visualized with double label immunofluorescence and confocal microscopy. Stacks of images representing adjacent focal planes are collected, and image processing techniques are applied to identify the location of each axonal branch segment and each cluster of SVP label in three-dimensional space. Segmentation of the SVP label into distinct pixel clusters in three-dimensional space, followed by colocalization of these clusters with the labeled axons (object-based analysis), yields much more reliable and sensitive measures of colocalization than a simple determination of the number (or summed intensities) of colocalized pixels in a single optical section (pixel-based analysis). The method has been extended to measure the colocalization of antigens that are not located at the presynaptic terminal with a labeled population of axons.

Animals↗
PubMed1999

Synaptic density in geniculocortical afferents remains constant after monocular deprivation in the cat.

Monocular eyelid closure in cats during a critical period in development produces both physiological plasticity, as indicated by a loss of responsiveness of primary visual cortical neurons to deprived eye stimulation, and morphological plasticity, as demonstrated by a decrease in the total length of individual geniculocortical arbors representing the deprived eye. Although the physiological plasticity appears maximal after 2 d of monocular deprivation (MD), the shrinkage of deprived-eye geniculocortical arbors is less than half-maximal at 4 d and is not maximal until 7 d of deprivation, at which time the deprived arbors are approximately half their previous size. To study this form of plasticity at the level of individual thalamocortical synapses rather than arbors, we developed a new double-label colocalization technique. First, geniculocortical afferent arbors serving either the deprived or nondeprived eye were labeled by injection of the anterograde tracer Phaseolus vulgaris leucoagglutinin into lamina A of the lateral geniculate nucleus. Then, using antibodies to synaptic vesicle proteins, we identified presynaptic terminals within the labeled arbors in layer IV of the primary visual cortex. Analysis of serial optical sections obtained using confocal microscopy allowed measurement of the numerical density of presynaptic sites and the relative amounts of synaptic vesicle protein in geniculocortical afferents after both 2 and 7 d of MD. We found that the density of synapses in geniculocortical axons was similar for deprived and nondeprived afferents, suggesting that this feature of the afferents is conserved even during periods in which synapse number is reduced by half in deprived-eye arbors. These results are not consistent with the hypothesis that a rapid loss of deprived-eye geniculocortical presynaptic sites is responsible for the prompt physiological effects of MD.

Aging↗
PubMed1999

Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.

OBJECTIVES: The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo. BACKGROUND: Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction < or =35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion. RESULTS: One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion. CONCLUSIONS: The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.

Atrial Natriuretic Factor↗
PubMed1999

Plasmapheresis with intravenous immunoglobulin G is effective in patients with elevated panel reactive antibody prior to cardiac transplantation.

BACKGROUND: Patients with a PRA >10% are considered to be at greater risk for the development of not only acute cellular and humoral rejection but also increased mortality when compared to nonsensitized patients following transplantation. All patients with a PRA >10% at our institution are treated with plasmapheresis and intravenous immunoglobulin G immediately prior to cardiac transplantation. METHODS: Sixteen (Group 1) of 118 patients awaiting cardiac transplantation were found to be sensitized. These patients underwent plasmapheresis followed by 20 gm of intravenous immunoglobulin G (IVIG) immediately prior to cardiac transplantation. Group 1 was compared to the remaining 102 patients with a PRA <10% (Group 2). RESULTS: Despite more patients in Group 1 having a positive crossmatch, pulmonary hypertension, and requiring mechanical circulatory support, there was no statistically significant difference in length of stay or mortality at a mean follow-up of 21.6+/-15.0 months. There was no difference in the occurrence of mild, moderate or severe cellular rejection or humoral rejection in these sensitized patients when compared to Group 2. CONCLUSIONS: Pretransplant plasmapheresis followed by intravenous immunoglobulin G may be an effective therapy that obviates the need for a prospective crossmatch and allows sensitized patients to undergo cardiac transplantation. There is no increase in the post transplant length of stay, occurrence of rejection or short term mortality. Long term follow up is necessary to evaluate whether there is a difference in the development of late rejection, transplant vasculopathy and survival.

Adult↗
PubMed1998

Effective oral ganciclovir prophylaxis against cytomegalovirus disease in heart transplant recipients.

The presented data show the combined sequential use of i.v. G for 14 days followed by PO G for 90 days is a much more effective prophylaxis for CMVD after heart transplantation than use of i.v. G for 14 days followed by PO A for 90 days. A need for hospitalization due to CMVD is significantly reduced by this new strategy. The follow-up in group II is shorter than in group I but is now at least 6 months in group II, without any new cases in the first 6 months after cardiac transplantation. Some currently unknown adverse effect of prolonged PO G, which may be present, is not identified in this analysis.

Administration, Oral↗
PubMed1995

Use of the Living With Heart Failure questionnaire to ascertain patients' perspectives on improvement in quality of life versus risk of drug-induced death.

Treatments for heart failure, such as flosequinan, may have opposite effects on survival and quality of life. The Living With Heart Failure questionnaire was used to examine patients' willingness to risk drug-induced death for improved quality of life. In addition, patients' opinions concerning worthwhile improvements in the Living With Heart Failure score were described to provide a perspective for interpreting the results of clinical trials. A sample of 101 patients with heart failure were interviewed in cardiology clinics. Median (interquartile range) Living With Heart Failure questionnaire score were 54 (interquartile range, 34-74). Forty-nine percent of the patients would accept a1 in 100 risk of drug-induced death if the corresponding improvements in the Living With Heart Failure score were 20 (interquartile range, 10-25). In contrast, 40% were willing to accept a risk of drug-induced death equal to or greater than 5 in 100 for significantly (P < .001) smaller score improvements of 5 (interquartile range, 5-10). Living With Heart Failure scores that increase with perceived limitations secondary to heart failure tended to be higher, although not significantly (P = .22), in the subgroup that accepted greater risk of drug-induced death: 45 (interquartile range, 34-73) versus 58 (interquartile range, 42-77). A score improvement of 5, which has been commonly observed in clinical trials, would be sufficient reason for 72% of patients to take a medication that did not have side effects or significant costs. A 5-point improvement was less acceptable when costs or risks were associated with therapy: 52% would pay $60 per month and 38% would risk drug-induced death. These data suggest that many patients with heart failure would accept some risk of drug-induced death for improved quality of life. A 5-point improvement in the Living With Heart Failure score may be clinically significant depending on costs and adverse effects. The Living With Heart Failure questionnaire can be used to help patients evaluate the benefits versus risks of medical interventions.

Aged↗
PubMed1994

Finding alternatives to the streets for the homeless mentally ill: efficacy at a state hospital intensive placement unit.

The authors describe a sample of homeless mentally ill patients receiving extended psychiatric care on an intensive placement unit. Summaries of 246 discharges were reviewed to examine demographic and clinical factors associated with extended psychiatric care and postdischarge placement. It was found that homeless patients requiring extended care were often medically ill and substance abusing. Residential placements were accepted by most patients on discharge. It was determined that homeless psychiatric patients benefited from extended care on an inpatient unit designed to alleviate anxieties regarding living arrangements and psychiatric treatment systems historically rejected by this population.

Adult↗