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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 163 records · Page 9Linked to original sources

"Put yourself in the skin of the child," she said.

Two Native American children were adopted by a non-Indian family. Following a legal challenge under the provisions of the Indian Child Welfare Act, the case became before both the United States Supreme Court and an Indian Tribal Court. In this paper we analyze the procedure and outcome of this transcultural adoption case from the point of view of the children involved and compare it with the intracultural "Baby Richard" case. Anna Freud believed that continuity of care is vital for each child's healthy growth and development. Transcultural adoptions highlight questions that characterize contested placements, whether or not they cross cultural boundaries and whether or not they place children across lines of race, color, religion, or national origin.

Acculturation↗

Speed of onset of action of Tilarin.

Two studies have been carried out specifically to examine the speed of onset of action of intranasal nedocromil sodium 1% (Tilarin) for the relief of symptoms due to ragweed allergic rhinitis. One, a multicentre placebo-controlled comparative study using a QID regimen, 1 spray per nostril, was designed to assess the speed of onset of action of nedocromil sodium during the first week of treatment in patients with rhinitis symptoms, and to evaluate the efficacy and safety of nedocromil sodium during 6 weeks of treatment (1). A 1-week baseline, the start of which was timed to coincide with the start of the ragweed season, was followed by 6 weeks double-blind trial treatment; only patients (n = 166) who were symptomatic at the end of baseline were included in the double-blind phase. Non-parametric analyses of all variables including a summary score (stuffy nose, runny nose, itchy nose and sneezing) showed that the onset of action of nedocromil sodium occurred on the first day of treatment. Further, patients using nedocromil sodium had less symptoms during the 10 days of peak pollen, at which time physician assessment showed reduced mucosal oedema and nasal discharge, and both patient and clinician opinions favoured nedocromil sodium. No significant adverse events were reported during this 6-week study. In the second study (2), 104 patients were randomly allocated to receive either nedocromil sodium or placebo, QID. They then spent 10 hours per day for 2 consecutive days in Iowa City Park during the peak of the ragweed season. Only patients showing significant symptoms of seasonal allergic rhinitis (SAR) during 3 hourly baseline assessments were included. Over the 2-day period, symptom scores for stuffy nose, runny nose, itchy nose and sneezing, and global symptom summary scores, were recorded at 19 hourly time points. At home in the evening, patients recorded symptom scores for the post-exposure period. In comparison with placebo, nedocromil sodium significantly improved rhinitis symptoms within 2 hours, and this reduction in SAR symptoms was maintained throughout the 2-day exposure period. Post exposure symptom summary scores were also significantly lower in patients treated with nedocromil sodium than in those patients treated with placebo. Overall, very few adverse events were reported, none of them serious. In conclusion, nedocromil sodium 1% nasal spray acts rapidly, within 2 hours on the first day of treatment, to reduce ongoing symptoms of SAR. Relief of rhinitis symptoms is maintained throughout the peak pollen period with nedocromil sodium QID, which appears to be a safe and well tolerated treatment for ragweed SAR.

Adolescent↗

Tilarin in combination with astemizole.

This multicentre double-blind, placebo controlled study had a practical objective, based on the expectation that many patients with seasonal allergic rhinitis will be prescribed oral antihistamine monotherapy by their primary care physician, whereas allergy specialists are more likely to prescribe combination therapy including antiinflammatories. The specific question was, "Will the addition of nedocromil sodium 1% nasal spray to astemizole tablets improve control of symptoms of seasonal allergic rhinitis induced by ragweed pollen, as compared to astemizole therapy alone?'. Following a one-week baseline, planned to coincide with the start of the local ragweed pollen season, patients (aged 12-64) were randomly assigned to four weeks' double-blind test treatment with either nedocromil sodium 1% nasal spray four times daily (QID) + astemizole (n = 146) or placebo nasal spray + astemizole (n = 148) or double-dummy (nasal spray + capsules) placebo (n = 71). Patient diary cards were kept throughout the five weeks, and clinic visits were made before and after baseline and after one and four weeks' treatment. During the 10-day peak pollen period, the diary card rhinitis symptom summary score (0-4 severity scale) was significantly reduced in patients receiving either astemizole alone (p < 0.001) or the combination therapy (p < 0.001) as compared with placebo. Direct comparison of the active treatments further showed that symptoms were significantly less severe (p < 0.01) with the combined therapy than with astemizole alone, and this despite significantly greater reliance on permitted rescue medications (p < 0.05 for pseudoephedrine usage) in the astemizole group. Clinical assessments of rhinitis made during the peak pollen visit, after the first week of test treatment, were also significantly (p < 0.05 - p < 0.01) in favour of combined therapy with nedocromil sodium 1% nasal spray + astemizole rather than astemizole alone, and at the same time this preference was confirmed by physician (p = 0.011) and patient (p = 0.003) opinions of symptom control. In conclusion, this antiinflammatory + antihistamine treatment proved superior to antihistamine alone for effective management of allergic rhinitis. The combined therapy worked quickly and was well-tolerated, with no serious adverse events or untoward effects on blood or urine variables.

Administration, Intranasal↗

Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara.

The dynamics of plasma viremia were explored in a group of 12 simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta) that had received prior immunization with either nonrecombinant or trivalent (gag-pol, env) SIV-recombinant vaccinia viruses. Three distinct patterns of viral replication observed during and following primary viremia accounted for significant differences in survival times. High-level primary plasma viremia with subsequently increasing viremia was associated with rapid progression to AIDS (n = 2). A high-level primary plasma virus load with a transient decline and subsequent progressive increase in viremia in the post-acute phase of infection was associated with progression to AIDS within a year (n = 6). Low levels of primary plasma viremia followed by sustained restriction of virus replication were associated with maintenance of normal lymphocyte subsets and intact lymphoid architecture (n = 4), reminiscent of the profile observed in human immunodeficiency virus type 1-infected long-term nonprogressors. Three of four macaques that showed this pattern had been immunized with an SIV recombinant derived from the attenuated vaccinia virus, modified vaccinia virus Ankara. These data link the dynamics and extent of virus replication to disease course and suggest that sustained suppression of virus promotes long-term, asymptomatic survival of SIV-infected macaques. These findings also suggest that vaccine modulation of host immunity may have profound beneficial effects on the subsequent disease course, even if sterilizing immunity is not achieved.

Animals↗

Effects of ACE inhibition and beta-blockade on skeletal muscle fiber types in dogs with moderate heart failure.

The proportion of slow-twitch, fatigue-resistant type 1 skeletal muscle (SM) fibers is often reduced in heart failure (HF), while the proportion of fatigue-sensitive type-II fibers increases. This maladaptation may be partially responsible for the exercise intolerance that characterize HF. In this study, we examined the effects of early monotherapy with the angiotensin-converting enzyme inhibor, enalapril, and the beta-blocker, metoprolol, on SM fiber type composition in 18 dogs with moderate HF produced by intracoronary microembolizations. HF dogs were randomized to 3 mo therapy with enalapril (10 mg twice daily), metoprolol (25 mg twice daily), or no treatment. Triceps muscle biopsies were obtained at baseline, before randomization, and at the end of 30 mo of therapy. Type I and type II SM fibers were differentiated by myofibrillar adenosinetriphosphatase (pH 9.4). In untreated dogs, the proportion of type I fibers was 27 +/- 1% before randomization and decreased to 23 +/- 1% (P < 0.05) at the end of 3 mo of follow up. In dogs treated with enalapril or metoprolol, the proportion of type I fibers was 30 +/- 4 and 28 +/- 2% before randomization and 33 +/- 4 and 33 +/- 1%, respectively, after 3 mo of therapy. In conclusion, in dogs with moderate HF, early therapy with enalapril or metoprolol prevents the progressive decline in the proportion of type I SM fibers.

Adrenergic beta-Antagonists↗

Evidence of cardiocyte apoptosis in myocardium of dogs with chronic heart failure.

It is often speculated that progressive deterioration of left ventricular function in heart failure is due to ongoing loss of viable cardiocytes. In this study, we examined the possibility that cardiocyte loss in heart failure may be due, in part, to apoptosis, an active process of gene-directed cellular self-destruction. Studies were performed in left ventricular tissue obtained from 10 dogs with chronic heart failure produced by multiple intracoronary microembolizations (left ventricular ejection fraction 27 +/- 1%) and from 5 normal dogs. Evidence for cardiocyte apoptosis was based on transmission electron microscopy criteria and on in situ immunohistochemical labeling of nuclear DNA fragmentation. There was no evidence of apoptotic cardiocytes in normal dogs. Features of cardiocyte apoptosis were observed in dogs with heart failure primarily in regions bordering old infarcts. Electron microscopic features of cardiocyte apoptosis included (1) intact sarcolemma and inner organelles in the presence of compaction and segregation of nuclear chromatin into sharply delineated masses that about the nuclear envelope, (2) intact sarcolemma in the presence of cytoplasm shrinkage, blebbing, and nuclear fragmentation, and (3) intact sarcolemma in the presence of complete disorganization of inner organelles and disappearance of nucleolemma. A count of all of the apoptotic bodies positively labeled for nuclear DNA fragments showed that 11% were of cardiocyte origin confirmed by positive labeling with striated muscle antimyosin antibody. We conclude that morphological and biochemical features of cardiocyte apoptosis exist in the left ventricular myocardium of dogs with chronic heart failure.

Animals↗

Load dependence of left atrial and left ventricular filling dynamics by transthoracic and transesophageal Doppler echocardiography.

This article evaluates the pattern and effect of varying loading conditions on pulmonary venous flow and transmitral flow obtained by transthoracic and transesophageal echocardiography. We have conducted a two-stage study. A transthoracic echocardiographic study was performed in 15 patients with coronary artery disease and preserved left ventricular function. The transesophageal approach was used before open heart surgery where hemodynamic conditions were invasively monitored. Sublingual nitroglycerin (NTG) was administered to lower systolic blood pressure (mean 18 mm Hg) and resulted in a significant decrease in the peak passive left ventricular diastolic filling velocity (E wave) from 72 +/- 23 to 49 +/- 16 cm/s without marked changes in pulmonary venous flow pattern. In the transesophageal part of the study, Doppler-derived systolic (J), diastolic (K), and retrograde (R) phases of pulmonary venous flow, and passive (E) and active (A) phases of mitral flow were measured. Hemodynamic data were obtained invasively. Loading conditions were increased by infusion of saline and phenylephrine and reduced by NTG. Increased preload resulted in an augmented mitral E wave, an increased J wave, and an increased retrograde flow wave from the pulmonary veins. These changes were reversed by reduction of preload with NTG. Monitoring mitral and pulmonary venous flow may provide a relatively noninvasive means to assess directional changes in left ventricular preload.

Aged↗

Reversal of end-stage heart failure is predicted by long-term therapeutic response rather than initial hemodynamic and neurohormonal profile.

BACKGROUND: Long waiting list periods for heart transplantation have led to clinical improvements for some patients resulting in their removal from the waiting list. This study sought to determine what characteristics differentiated those patients with a good clinical outcome from those who continued to need a transplant. METHODS: The initial and final serial (every 3 months) right heart catheterization data of 60 patients awaiting transplantation were retrospectively analyzed, and the patients were divided into two groups: group A, patients who were taken off the list in follow-up because of improvement (n = 18 of 60), and group B who continued to require transplantation or died (n = 42 of 60). RESULTS: For Group A, there were significant declines in right atrial pressure (9 +/- 4 to 4 +/- 3 mm Hg, initial versus final, p = 0.001), systolic pulmonary arterial pressure (51 +/- 17 to 34 +/- 6 mm Hg, p = 0.0001), with an increase in electron in ejection fraction (20% +/- 4% to 34% +/- 10%, p = 0.005). The change in cardiac output and norepinephrine level was not statistically significant. For Group B, there were no changes in the initial and final values of right atrial pressure, systolic pulmonary arterial pressure, pulmonary capillary wedge pressure, or norepinephrine levels. A significant rise in ejection fraction from 17% +/- 22% +/- 8%, p = 0.003 did occur. The majority of patients in group A (12 of 18) had idiopathic dilated cardiomyopathy. In contrast, an ischemic etiology was found in the majority of group B patients (25 of 42). CONCLUSIONS: This study shows that transplant waiting list outcome cannot be predicted from a patient's initial hemodynamic or neurohormonal presentation. Rather, those patients capable of reversing their hemodynamic derangements with therapy over time are most likely to sustain a favorable clinical outcome. It appears that patients with idiopathic rather than ischemic cardiomyopathy respond more favorably to medical interventions with improved prognosis.

Adult↗

[Acute promyelocytic leukemia: experience with trans-retinoic acid in Argentina].

From February 1992 to February 1995, 77 patients with APL were treated with ATRA in induction (59 patients de novo, 6 in first relapse, 1 with APL secondary to a mielodisplastic syndrome). The dose used was 45 mg/k/day-30 mg/k/day until complete remission (CR) was achieved; of the 66 evaluable patients, 50 achieved complete remission (78%). Among the 14 patients who did not attain CR, 13 died, 10 of bleeding episodes and 3 of retinoic syndrome; one was rescued with chemotherapy. We proposed consolidation treatment with high dose Ara-C and Idarubicin to the 49 patients in complete remission; 6 could not receive it and 5 died; the disease free survival period of the other patients was 81% (CI95 90%-66%) at one year and 74% (CI95 91%-52%) at two years. We consider that our results are similar to those of other groups and we are inclined to continue with this treatment protocol.

Adolescent↗

Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors.

BACKGROUND: Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied. METHODS AND RESULTS: We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20 +/- 0.07 to 0.39 +/- 0.11 mg/day corresponding to an increase in the serum digoxin concentration from 0.67 +/- 0.22 to 1.22 +/- 0.35 ng/mL. Radionuclide and echocardiographic left ventricular ejection fraction; maximal treadmill time; heart failure score; serum concentrations of norepinephrine, aldosterone, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity were obtained before and after the increase in digoxin dose. Subsequently, 9 patients were randomized to receive digoxin and 9 to receive placebo and radionuclide ejection fraction measured after 12 weeks. With the higher dose of digoxin compared with the lower dose, there was a significant increase in radionuclide ejection fraction from 23.7 +/- 9.6% to 27.1 +/- 11.8% (P = .007). No significant changes were noted in heart failure score; exercise tolerance; serum concentrations of norepinephrine, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, there was a significant decrease in ejection fraction (from 29.4 +/- 10.4% to 23.7 +/- 8.9%) in the placebo group but not in patients who continued to receive digoxin (P = .002). CONCLUSIONS: The increase in maintenance digoxin dose, while maintaining serum concentrations within therapeutic range, resulted in a significant increase in left ventricular ejection fraction that was not associated with significant changes in heart failure score, exercise tolerance, and neurohumoral profile.

Aldosterone↗

Abnormalities of skeletal muscle metabolism during nerve stimulation determined by 31P nuclear magnetic resonance spectroscopy in severe congestive heart failure.

These data confirm the presence of abnormal skeletal muscle metabolic function in patients with chronic heart failure. These changes are independent of patient compliance and central hemodynamic response to conventional exercise, and may explain, in part, the marked decrease in exercise tolerance often observed in patients with chronic severe heart failure. The etiology of these abnormalities of metabolic function and nutritive flow remains uncertain. TNS may prove useful in further elucidation of the peripheral metabolic consequences of chronic heart failure.

Acute Disease↗

Effects of long-term therapy with enalapril on severity of functional mitral regurgitation in dogs with moderate heart failure.

OBJECTIVES: This study examined the effects of early long-term monotherapy with enalapril on the severity of functional mitral regurgitation in dogs with moderate heart failure. BACKGROUND: Functional mitral regurgitation often develops in patients with heart failure and, depending on its severity, can have a marked adverse impact on the stroke output of the failing left ventricle and contribute to progressive deterioration of the heart failure state. METHODS: Left ventricular dysfunction (ejection fraction 30% to 40%) was produced in 14 dogs by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months of therapy with enalapril (10 mg twice daily, n = 7) or no therapy at all (control, n = 7). The severity of functional mitral regurgitation was quantified by Doppler color flow mapping in seven control and six enalapril-treated dogs. Mitral annular diameter was assessed by echocardiography and left ventricular volumes and shape by ventriculography. Measurements were made before initiation and after completion of therapy. RESULTS: In control dogs, the severity of mitral regurgitation increased during the follow-up period ([mean +/- SEM] 14 +/- 4 vs. 23 +/- 4%, p < 0.001) and was associated with increased left ventricular end-systolic and end-diastolic volumes. In contrast, the severity of regurgitation was not significantly changed in dogs treated with enalapril (18 +/- 3 vs. 16 +/- 6%, p < 0.59) and was associated with preservation of left ventricular volumes. CONCLUSIONS: In dogs with moderate heart failure, early long-term therapy with enalapril prevents progressive worsening of functional mitral regurgitation. This beneficial effect is most likely achieved by prevention of progressive left ventricular dilation.

Animals↗

Association between ease of suppression of ventricular arrhythmia and survival.

BACKGROUND: We tested the hypothesis that patients whose ventricular arrhythmias are easy to suppress have a lower rate of arrhythmic death, defined as arrhythmic death and nonfatal cardiac arrest, the primary end point in the Cardiac Arrhythmia Suppression Trials (CAST-I and CAST-II), than patients whose ventricular arrhythmias are hard to suppress. In addition, we evaluated the association between ease of suppression of ventricular arrhythmias and mortality of all causes. METHODS AND RESULTS: CAST-I investigated the effect on arrhythmic death of ventricular premature depolarization (VPD) suppression achieved by three drugs, encainide, flecainide, and moricizine, at two different dose levels; CAST-II investigated the same effect, using moricizine alone at three dose levels. If suppression was achieved, patients were randomized to the effective active drug or corresponding placebo. To examine the independence of easily suppressed ventricular arrhythmias as a predictor of arrhythmic death, we adjusted statistically for other variables that were related both to ease of suppression and arrhythmic death. Patients with ventricular arrhythmias (n = 1778) that were easy to suppress had fewer arrhythmic deaths during follow-up than those with ventricular arrhythmias that were hard to suppress (n = 1173) (relative risk, .59; P = .003). Patients whose VPDs were easily suppressed were older and had a lower frequency of prior history of heart failure and myocardial infarction. They also had a higher incidence of anterior myocardial infarction, VPD frequency, and average ejection fraction. After adjusting for these variables, we found that easily suppressed ventricular arrhythmias were still significant predictors of arrhythmic death (relative risk, .66; P = .013). CONCLUSIONS: This study shows that the ease of VPD suppression identifies a subgroup of postmyocardial infarction patients who have low risk of arrhythmic death.

Aged↗

Thymoma with pericardial tamponade.

Thymomas are tumors of the anterior mediastinum. They are most often seen in adults aged 45 to 50 years. These tumors are routinely asymptomatic for prolonged periods of time. The most common presentation is discovery on routine chest x-ray. We therefore present a case report of an elderly woman who presented with symptoms of dyspnea caused by a malignant thymoma. To our knowledge, symptomatic pericardial tamponade due to a thymoma with a massive pericardial effusion has not been described previously.

Aged↗

Overexpression of insulin-like growth factor binding protein-3 by senescent human fibroblasts: attenuation of the mitogenic response to IGF-I.

We have previously demonstrated that senescent human diploid fibroblasts (HDF) produce large amounts of IGF-binding protein-3 (IGFBP-3) in comparison to early-passage vigorously proliferative HDF. In order to determine whether this excess IGFBP-3 accumulation plays a role in the observed attenuation of DNA synthesis in senescent HDF, we examined the response of these cells to IGF-I and two IGF-I functional analogs, [QAYL]IGF-I and insulin, both of which have extremely low binding affinity for IGFBP-3 but which exert their mitogenic effect via the IGF-I plasma membrane receptor. Senescent HDF showed an increased sensitivity of DNA synthetic response to [QAYL]IGF-I and insulin compared to IGF-I. IGF binding activity was significantly higher in conditioned medium of senescent HDF than the medium of young HDF, and virtually all of this enhanced binding capacity could be accounted for by IGFBP-3. Addition of recombinant IGFBP-3 to young cells at a constant molar ratio of 1:1 with respect to IGF-I significantly attenuated the response to IGF-I and abolished the response at a 2:1 molar ratio. These data indicate that IGFBP-3 accumulated in medium of senescent HDF can bind and sequester IGFs when present in molar excess and thereby account for a significant part of the attenuated response of senescent HDF to IGF-I.

Carrier Proteins↗