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Biomedical subjects

R Smalling

Publications and source records attributed to R Smalling.

18 recordsLinked to original sources
PubMed2001

A double-blind, multicentered study comparing the accuracy of diagnostic markers to predict short- and long-term clinical events and their utility in patients presenting with chest pain.

BACKGROUND: Millions of patients present annually with chest pain, but only 10% have myocardial infarction (MI). We recently reported comparative sensitivity and specificity of available markers in the diagnosis of MI; however, optimum interpretation of marker results requires prognostic follow-up data. HYPOTHESIS: The study was undertaken to study the accuracy of CK-MB subforms, troponin I and T, myoglobin, and CK-MB in predicting clinical events at 30 days and 6 months. METHODS: In all, 955 consecutive patients with chest pain were enrolled in a prospective, multicenter, double-blind study to test the prognostic accuracy of these markers. RESULTS: Myocardial infarction was diagnosed in 119 by CK-MB mass criteria and unstable angina (UA) in 203 patients by clinical criteria. Follow-up at 30 days and 6 months was available in 824 and 724 patients, respectively, with mortalities of 2.8 and 4.14%, respectively. Cumulative 6-month mortality was 5.6% in MI, 4.4% in UA, and 3.0% in others. Revascularization was reported in 9.3% of patients by 6 months. A positive test on each of the markers except myoglobin was predictive of revascularization. The composite endpoint of death or revascularization occurred in 107 patients by 6 months and a positive result on each of the markers was predictive of this composite endpoint (p < 0.05). The relative risk of death or revascularization for patients who did not have MI but tested positive on each of the markers was > 1.0 but did not reach statistical significance. CONCLUSIONS: With the possible exception of myoglobin, each of the diagnostic markers displayed similar prognostic performance in patients with chest pain presenting to emergency departments. The most appropriate markers to triage patients with chest pain, which has both adequate early diagnostic sensitivity and prognostic accuracy, are the CK-MB subforms.

Adult↗
PubMed2000

Cardiogenic Shock.

In the setting of acute myocardial infarction, the timely recognition and treatment of cardiogenic shock are essential in reducing the incidence of death. Patients with cardiogenic shock should be treated aggressively with a combination of pharmacologic agents and mechanical support devices to achieve stabilization. Once stabilization has been achieved, the ultimate goal should be the restoration of flow in the infarct-related artery. This is best achieved with angioplasty or bypass surgery. In those centers not equipped for these procedures, thrombolysis should be performed, and the patient should then be transferred to a higher-level facility.

Journal Article↗
PubMed2000

Metastatic ocular melanoma to the left ventricle inducing near-syncope attacks in an 84-year-old woman.

Cardiac tumors may represent mechanical causes for syncope by limiting left ventricular filling and/or by obstructing the left ventricular outflow tract. Malignant melanoma is known to metastasize to the myocardium or pericardium, but there are only a very limited number of reports describing endocardial involvement by the tumor. We describe herein an 84-year-old woman who presented with daily near-syncope episodes, 9 years after treatment for a choroidal melanoma. The echocardiography and the pathologic examination revealed a metastatic melanoma. This is the first reported case of an ocular melanoma metastasizing to the heart and presenting as a left ventricular intracavitary pedunculated mass.

Aged↗
PubMed1999

Platelet function during and after thrombolytic therapy for acute myocardial infarction with reteplase, alteplase, or streptokinase.

BACKGROUND: Changes in platelet aggregation (PA) and platelet surface receptor expression induced by thrombolytic therapy for acute myocardial infarction may influence the rate of initial reperfusion and early reocclusion. METHODS AND RESULTS: In the RAPID-1 (Reteplase Angiographic Phase II International Dose-finding study), RAPID-2 (Reteplase vs Alteplase Patency Investigation During myocardial infarction), INJECT (INternational Joint Efficacy Comparison of Thrombolytics), and GUSTO-3 (Global Use of Strategies To Open occluded coronary arteries) trials, 126 patients were enrolled in a single center. Patients were treated with either conventional alteplase (100 mg/180 min; n=15), accelerated alteplase (100 mg/90 min; n=21), reteplase 10+10-U double bolus (n=50), reteplase 10+5-U double bolus (n=15), reteplase 15-U single bolus (n=15), or streptokinase (1.5 MU/60 min; n=10). PA (after stimulation with ADP), P-selectin expression and fibrinogen binding to glycoprotein (GP) IIb/IIIa (determined by flow cytometry with and without stimulation with ADP), and levels of soluble P-selectin, prothrombin fragments F1 and F2, thrombin-antithrombin complexes (TAT), and antithrombin III (ATIII) were determined. PA decreased significantly at 1 and 2 hours in patients treated by 10+10-U reteplase or by streptokinase. Fibrinogen binding to platelet GP IIb/IIIa followed a similar pattern. Significant thrombin generation and significantly elevated thrombin levels during thrombolysis were reflected by increased F1 and F2 fragments and TAT levels in all treatment groups. ATIII levels decreased significantly during thrombolytic therapy. CONCLUSIONS: A decrease in PA in patients treated by reteplase or streptokinase compared with alteplase could be observed in the early phase. Double bolus (10+10 U) reteplase and streptokinase resulted in lower PA at 1 and 2 hours than therapy with accelerated alteplase. Total fibrinogen and fibrinogen binding to GP IIb/IIIa tended to be lower during the first 2 hours after reteplase than after accelerated alteplase.

Double-Blind Method↗
PubMed1999

Effectiveness of early coronary angioplasty and abciximab for failed thrombolysis (reteplase or alteplase) during acute myocardial infarction (results from the GUSTO-III trial). Global Use of Strategies To Open occluded coronary arteries.

We evaluated the effects of abciximab treatment during early angioplasty after clinically failed thrombolysis for acute myocardial infarction. In the Global Use of Strategies To Open occluded coronary arteries (GUSTO-III) trial of reteplase versus alteplase for acute infarction (n = 15,059), 392 patients underwent angioplasty a median of 3.5 hours after thrombolysis and had complete procedural data. We compared 30-day mortality and in-hospital outcomes between patients who received abciximab (n = 83) and those who did not (n = 309), and (among patients given abciximab) between those randomized to alteplase versus reteplase. Patients given abciximab had anterior infarction less often, but were more often in Killip classes III or IV. The 30-day mortality rate tended to be lower with abciximab (3.6% vs 9.7%, p = 0.076), more so after adjustment for baseline differences (p = 0.042). The composite of death, stroke, or reinfarction did not differ significantly with abciximab treatment (12% vs 14%, p = 0.7), but it occurred less often among abciximab-treated patients who had been randomized to reteplase (n = 55) versus alteplase (n = 28) (7% vs 21%, p = 0.08). Severe bleeding was increased among abciximab-treated patients (3.6% vs 1.0%, p = 0.08), despite less heparin use. No intracranial hemorrhages occurred with abciximab. The use of abciximab for early angioplasty after clinically failed thrombolysis resulted in trends toward lower 30-day mortality and increased bleeding.

Abciximab↗
PubMed1999

Diagnostic marker cooperative study for the diagnosis of myocardial infarction.

BACKGROUND: Millions of patients present annually with chest pain, but only 10% to 15% have myocardial infarction. Lack of diagnostic sensitivity and specificity of clinical and conventional markers prevents or delays treatment and leads to unnecessary costly admissions. Comparative data are lacking on the new markers, yet using all of them is inappropriate and expensive. METHODS AND RESULTS: The Diagnostic Marker Cooperative Study was a prospective, multicenter, double-blind study with consecutive enrollment of patients with chest pain presenting to the emergency department. Diagnostic sensitivity and specificity and frequency of increase in patients with unstable angina were determined for creatine kinase-MB (CK-MB) subforms, myoglobin, total CK-MB (activity and mass), and troponin T and I on the basis of frequent serial sampling for </=24 hours. Of 955 patients with chest pain, 119 (12.5%) had infarction identified by use of CK-MB mass, and 203 (21%) had unstable angina. CK-MB subforms were most sensitive and specific (91% and 89%) within 6 hours of onset, followed by myoglobin (78% and 89%). For late diagnosis, total CK-MB activity (derived from subforms) was the most sensitive and specific (96% and 98%) at 10 hours from onset, followed by troponin I (96% and 93%), but not until 18 hours, and troponin T (87% and 93% at 10 hours). In unstable angina, CK-MB subforms were increased in 29.5%, myoglobin in 23.7%, troponin I in 19.7%, and troponin T in 14.8%. All markers were increased in 99 patients. With each marker as the diagnostic standard, CK-MB subforms and myoglobin remained the most sensitive for early diagnosis. CONCLUSIONS: The CK-MB subform assay alone or in combination with a troponin reliably triages patients with chest pain and should lead to improved therapy and reduced cost.

Angina, Unstable↗
PubMed1998

Estrogen replacement therapy and outcome of coronary balloon angioplasty in postmenopausal women.

Estrogen replacement therapy (ERT) in women after menopause is associated with prevention of clinical coronary artery disease. However, few studies have investigated possible benefits from ERT in postmenopausal women undergoing treatment for established coronary disease. We therefore retrospectively reviewed the clinical outcomes of 428 postmenopausal women undergoing percutaneous transluminal coronary balloon angioplasty (PTCA) to test the hypothesis that ERT has a beneficial effect in this setting. The women were divided into 2 groups based on ERT status at the time of the procedure. Estrogen users were younger (60 +/- 10 vs 68 +/- 9 years, p <0.001), more commonly had family histories of coronary heart disease (54% vs 41%, p = 0.04), had less incidence of hypertension (63% vs 76%, p = 0.02), and had slightly fewer diseased vessels per patient (1.3 +/- 0.5 vs 1.5 +/- 0.7, p = 0.03) compared with nonusers. No in-hospital deaths occurred in estrogen users compared with 5% hospital mortality in nonusers (p = 0.01). The combined outcome of death or myocardial infarction (MI) also was lower in estrogen users (4% vs 12%, p = 0.04). Of 348 women discharged after successful PTCA, 336 (97%) were able to be contacted at an average follow-up interval of 22 +/- 17 months (range 5 to 82). Estrogen users had superior event-free survival both for death as well as for death or nonfatal MI. Repeat revascularizations were similar in both groups (32% vs 24%, p = 0.15). In a Cox proportional-hazards model, nonusers had 4 times the likelihood of death after angioplasty compared with estrogen users (OR = 4.025, 95% CI = 1.3 to 13.4, p = 0.02). We conclude that estrogen replacement may offer protection against clinical coronary events in postmenopausal women who already have established coronary disease and are undergoing balloon angioplasty. The benefit was independent of age, smoking, presence of diabetes mellitus, or the number of diseased coronary vessels. However, it did not include a reduction in repeat revascularization procedures, suggesting no reduction in restenosis.

Adult↗
PubMed1994

Percutaneous double balloon valvotomy for bioprosthetic tricuspid stenosis.

We report two cases of percutaneous balloon valvotomy of porcine tricuspid valves and review the brief literature. Both procedures were successful, but "restenosis" resulted in tricuspid valve replacement in patient 2. The explanted valve showed leaflet thickening and calcified cuspal nodules. Patient 1 is improved 10 months later.

Adult↗
PubMed1993

Granulocyte colony stimulating factor: animal studies for risk assessment.

In mice, rats, hamsters, dogs, and monkeys, doses of > or = 1.1 microgram/kg/day of r-metHuG-CSF stimulated neutrophil production in bone marrow. There was a resulting rapid release of mature neutrophils from the marrow storage pool into circulation and a distinct neutrophilia maintained for the dosing period in each study. R-metHuG-CSF corrected cyclic hemopoiesis in dogs, established sustained endogenous recovery after lethal bone marrow suppression, and elicited differention and maturation induction and enhanced functional activity of mature neutrophils. Reversible side effects due to an exaggerated pharmacological activity of the growth factor were observed at doses of > or = 115 micrograms/kg/day, with the exception of a rodent-specific osteopathy, which occurred in some animals after 3 months at > or = 5.7 micrograms/kg/day. The only irreversible adverse effect was seen in monkeys at doses of 1150 micrograms/kg/day (equivalent to 200 times the recommended human dose) when leukocyte counts exceeded 100 x 10(9)/liter. It consisted of hyperleukocytosis, leukostasis in terminal capillaries of the brain, followed by tissue hypoxia and intracerebral hemorrhage. Local tolerance of r-metHuG-CSF was good and no hypersensitivity reactions were observed. Antibody formation was minimal in monkeys but occasionally marked in dogs, which is not suprising due to the species difference in the amino acid sequence of the factor. The use of recombinant canine G-CSF, however, did not elicit formation of neutralizing antibodies in dogs. Moreover, relatively few untoward effects were seen in reproductive toxicology except when maternal toxicity or weight loss of dams occurred. In addition, negative results were obtained in all genotoxicity studies performed.

Animals↗
PubMed1986

Monkey erythropoietin gene: cloning, expression and comparison with the human erythropoietin gene.

The erythropoietin (Epo) gene from Cynomolgus monkeys has been isolated from a kidney cDNA library using mixed 20-mer oligodeoxynucleotide probes. The gene encodes a 168 amino acid (aa) mature protein with a calculated Mr of 18,490 and a presumptive signal peptide of 24 aa. The Epo gene, when transfected into Chinese hamster ovary (CHO) cells, produces a glycosylated protein with an apparent Mr of 34,000. The expressed product is biologically active in vivo. The monkey gene exhibits 92% and 94% homology to the human gene at the aa and nucleotide sequence levels, respectively. When compared with the human Epo, monkey Epo has an additional 3-aa residue at the N terminus of the mature protein and a deletion of an internal lysine residue.

Amino Acid Sequence↗
PubMed1986

Characterization and biological effects of recombinant human erythropoietin.

Human recombinant erythropoietin (rHuEPO) has been purified to apparent homogeneity and compared to purified human urinary erythropoietin (EPO). Both the purified natural and recombinant EPO preparations were characterized in a competition radioimmunoassay (RIA), the exhypoxic polycythemic mouse bioassay, in vitro tissue culture bioassays using bone marrow cells, and by Western analysis. In the immunological and biological activity assays, the rHuEPO shows a dose response which parallels that of the natural hormone. By Western analysis, the recombinant and human urinary EPO migrate identically. Administration of rHuEPO increases the hematocrit of normal mice in a dose-dependent manner. Additionally, the rHuEPO is able to increase the hematocrit of rats made uremic as a result of subtotal nephrectomy. In summary, by all criteria examined, the rHuEPO is biologically active and equivalent to the natural hormone.

Animals↗
PubMed1985

Studies of TGEV spike protein gp195 expressed in E. coli and by a TGE-vaccinia virus recombinant.

The gene coding for the surface spike protein gp195 of TGEV has been cloned and expressed in E. coli in the form of fusion proteins. These proteins were isolated and used to immunize laboratory animals. All animals developed antibodies cross-reacting with the TGEV virion but failed to neutralize the virus. The entire gp195 gene was also inserted into vaccinia to generate a TGEV-vaccinia recombinant virus (vTGE) that expressed TGEV gp195. Animals vaccinated with vTGE produced neutralizing antibodies against both TGEV and vaccinia. These results suggest the potential use of the recombinant vTGE as a vaccine against TGEV infection.

Animals↗
PubMed1985

Cloning and expression of the human erythropoietin gene.

The human erythropoietin gene has been isolated from a genomic phage library by using mixed 20-mer and 17-mer oligonucleotide probes. The entire coding region of the gene is contained in a 5.4-kilobase HindIII-BamHI fragment. The gene contains four intervening sequences (1562 base pairs) and five exons (582 base pairs). It encodes a 27-amino acid signal peptide and a 166-amino acid mature protein with a calculated Mr of 18,399. The erythropoietin gene, when introduced into Chinese hamster ovary cells, produces erythropoietin that is biologically active in vitro and in vivo.

Amino Acid Sequence↗
PubMed1979

Comparison of digital boundary detection and semi-automated analysis of left ventricular cine angiograms.

A technique has been developed to analyze automatically 35 mm left ventricular cine angiograms with an image dissector and digital computer. The analysis procedure detected the ventricular boundary and aortic valve position, then calculated the projected left ventricular area and estimated volume, and performed a polar wall motion analysis as a function of time. The automated method was compared to a semi-automated method using a technician-operated electronic cursor linked to a mini-computer. The two methods were used to analyze a set of idealized ventricular models as well as normal and abnormal angiographic data. The volumetric and wall motion data for the idealized models calculated by the two methods were equivalent (r greater than 0.99). Volumetric analysis of the patients' ventriculograms produced correlation coefficients of 0.88-0.99. Corresponding wall motion data produced correlation coefficients of 0.72-0.94. The time necessary to analyze 30 frames of cine ventriculogram was approximately 30 minutes for each method.

Aged↗
PubMed1976

Cardiac amyloidosis, contrictive pericarditis and restrictive cardiomyopathy.

Cardiac amyloidosis is not characterized by a single hemodynamic pattern. Some of the cases present the clinical findings of restrictive cardiomyopathy and in these differentiation from constrictive pericarditis remains difficult in spite of the introduction of techniques designed to assess myocardial contractility and ventricular diastolic compliance. The clinical features and the demonstration of left ventricular diastolic pressure greater than right remain the most useful means of distinguishing restrictive cardiomyopathy from constrictive pericarditis. In other cases of cardiac amyloidosis the diastolic pressure is elevated throughout diastole and ventricular ejectile ability is lost. These cases do not simulate constrictive pericarditis and should not be classified as restrictive cardiomyopathy.

Amyloidosis↗