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R Silverman

Publications and source records attributed to R Silverman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Research fundamentals: III. elements of a research protocol for clinical trials.

A clinical trial is a powerful technique for evaluating the effectiveness of an experimental intervention. The initial stages of planning a clinical trial involve choosing and refining a research question, selecting a study design, and deciding on appropriate statistical tests and sample sizes. The success of the study depends upon how well these issues are thought out in advance, and how they can be put into practice. The protocol is the written document that allows the investigator to communicate details of how the research question will be answered. In the following article, the basic components of the research protocol are described. Issues related to quality control, data entry, and pilot testing are discussed. This is the third in a series of research fundamental concept papers, written by members of the SAEM Research Committee.

Clinical Protocols↗
PubMed1998

Comparison of the Maxair Autohaler to wet nebulizer in patients with acute asthma.

STUDY OBJECTIVE: Patients with acute asthma often have difficulty using a conventional metered-dose inhaler. The Maxair Autohaler (3M Pharmaceuticals; St. Paul, MN) is a hand-held breath-actuated device developed to help patients coordinate drug administration. The study objective is to compare the efficacy of the Autohaler with inhaled beta-agonist administered by wet nebulizer in treating acute asthma exacerbations. DESIGN: Parallel, randomized, placebo-controlled clinical trial. SETTING: Emergency department (ED) of a university-affiliated hospital. PARTICIPANTS: Patients aged 18 to 55 years presenting to the ED with acute asthma and an FEV1 40 to 70% on hospital arrival. INTERVENTIONS AND MEASUREMENTS: Patients were given either six puffs of the Maxair Autohaler (1,200 microg pirbuterol) plus saline solution by nebulizer (active Autohaler group) or six puffs placebo by Autohaler plus 2,500 microg albuterol via nebulizer (active nebulizer group). Treatment was repeated at 30 and 60 min, with clinical evaluation performed before each treatment and again at 120 min. At 120 min, the protocol was completed. RESULTS: Twenty-four patients were enrolled, with 5 excluded because of protocol violations. Baseline FEV1 percent predicted values for the active Autohaler group were 53% vs 51% for the active nebulizer group (p=not significant [NS]). At time 120 min, values were 66% for Autohaler and 64% for nebulizer (p=NS). The average time to administer Autohaler was 2.9 min, vs 9.1 min for nebulizer. No patient was excluded because of the inability to use the Autohaler device adequately. CONCLUSION: In patients with moderate asthma exacerbations, similar improvements in pulmonary function are obtained when beta-agonists are given by either the Maxair Autohaler or a wet nebulizer device.

Acute Disease↗
PubMed1997

Low levels of serum ionized magnesium are found in patients early after stroke which result in rapid elevation in cytosolic free calcium and spasm in cerebral vascular muscle cells.

Ninety-eight patients admitted to the emergency rooms of three urban hospitals with a diagnosis of either ischemic stroke or hemorrhagic stroke exhibited early and significant deficits in serum ionized Mg2+ (IMg2+), but not total Mg, as measured with a unique Mg2+-sensitive ion-selective electrode. Twenty-five percent of these stroke patients exhibited >65% reductions in the mean serum IMg2+ found in normal healthy human volunteers or patients admitted for minor bruises, cuts or deep lacerations. The stroke patients also demonstrated significant elevation in the serum ionized Ca2+ (ICa2+)/IMg2+ ratio, a sign of increased vascular tone and cerebrovasospasm. Exposure of primary cultured canine cerebral vascular smooth muscle cells to the low concentrations of IMg2+ found in the stroke patients, e.g. 0.30-0.48 mM, resulted in rapid and marked elevations in cytosolic free calcium ions ([Ca2+]i) as measured with the fluorescent probe, fura-2, and digital image analysis. Coincident with the rise in [Ca2+]i, many of the cerebral vascular cells went into spasm. Reintroduction of normal extracellular Mg2+ ion concentrations failed to either lower the [Ca2+]i overload or reverse the rounding-up of the cerebral vascular cells. These results suggest that changes in Mg2+ metabolism play important roles in stroke syndromes and in the etiology of cerebrovasospasm associated with cerebral hemorrhage.

Adult↗
PubMed1997

Determination of size of aortic emboli and embolic load during coronary artery bypass grafting.

BACKGROUND: Embolic signals have been detected within both the aortic lumen and the intracranial vasculature during coronary artery bypass grafting. Total numbers of these emboli have been reported. The present study examined the size of individual emboli and the total volume of embolization. METHODS: Using transesophageal echocardiography, we continuously monitored the aortic lumen of 10 patients undergoing isolated coronary artery bypass grafting. We manually analyzed 720,000 individual echo frames over a 4-minute period after the release of aortic clamps to track and to calculate the volume of 657 individual particles. The embolic load for the entire procedure was calculated from mean volume based on analysis of 1,508 particles. We simultaneously monitored the middle cerebral artery using transcranial Doppler ultrasonography and compared numbers of emboli detected by the two techniques. RESULTS: Particle diameter ranged from 0.3 to 2.9 mm (mean, 0.8 mm), and particle volume from 0.01 to 12.5 mm3 (mean, 0.8 mm3). Twenty-eight percent of particles measured 1 mm or more, 44% measured 0.6 to 1.0 mm, and only 27% measured 0.6 mm or less in diameter. Aortic embolic load for the procedure ranged from 0.6 cm3 to 11.2 cm3 (mean, 3.7 cm3). Estimated cerebral embolic load for the procedure ranged from 60 to 510 mm3 (mean, 276 mm3). The fraction of aortic emboli entering the cerebral circulation was very variable (3.9% to 18.1%). Seventy-six percent of the embolic volume after the release of clamps occurred over a 20-second period. Only 1 patient was encephalopathic perioperatively. This patient had the largest estimated cerebral embolic load (510 mm3) and the second largest aortic embolic load (8.4 cm3). CONCLUSIONS: We determined the size of individual intraaortic embolic particles and the total volume of embolization during coronary artery bypass grafting, and found the proportion entering the cerebral circulation to be very variable. The constitution of these particles and the neurologic impairment resulting from such embolization remains to be determined.

Aged↗
PubMed1996

The effect of the menstrual cycle on asthma presentations in the emergency department.

BACKGROUND: Seventy-five percent of all adult hospital admissions for asthma are women. OBJECTIVE: To determine whether a relationship exists between phases of the menstrual cycle and asthma exacerbations in adult females. METHODS: Data were analyzed from 182 nonpregnant, adult females with asthma aged 13 years to menopause. Date of presentation, patient age, duration of asthma attack, date of last menstrual period, regular interval between menses, presenting peak expiratory flow rate, and admission and discharge decision were recorded prospectively. Treatment interventions abstracted retrospectively from patient charts included use of oxygen, xanthines, beta-adrenergic agonists, corticosteroids, and magnesium sulfate. The menstrual cycle was divided into 4 phases based on fluctuations in serum estradiol levels. The 4 intervals were preovulatory (days 5-11), periovulatory (days 12-18), postovulatory (days 19-25), and perimenstrual (days 26-4). RESULTS: Data were analyzed with a goodness-of-fit chi 2. Between June 1991 and May 1992, 182 females (mean +/- SD age, 28.5 +/- 8.0 years) were surveyed. No significant differences were noted for use of oxygen, beta-adrenergic agonists, xanthines, or magnesium among members of the 4 menstrual groups. Intervention with corticosteroids was least in the postovulatory interval (y:n) 0.5:1 and greatest in the preovulatory interval 3.0:1 (alpha = .03) Presentations by menstrual interval were as follows: preovulatory, 36 (20%); periovulatory, 43 (24%); postovulatory, 18 (10%); and perimenstrual, 85 (46%) (alpha < .01). CONCLUSIONS: Asthma presentations are least frequent when serum estradiol levels are at a sustained peak. We observed a 4-fold variation in asthma presentations during the perimenstrual interval, when serum estradiol levels decrease sharply after that prolonged peak. These findings suggest that monthly variations in serum estradiol levels may influence the severity of asthma in adult females.

Adolescent↗
PubMed1996

Positive and negative elements contribute to the cell-specific expression of the rat dopamine beta-hydroxylase gene.

Dopamine beta-hydroxylase catalyzes the final step in noradrenaline synthesis and is expressed exclusively in noradrenergic and adrenergic cells. In order to identify elements within the dopamine beta-hydroxylase (DBH) gene which contribute to the regulation of tissue-specific expression, we have analyzed the expression of the rat DBH promoter by transient transfection in both DBH-expressing and non-expressing cell lines. We have found that 1 kilobase of the DBH promoter can direct expression of the luciferase reporter gene in the DBH-expressing PC12, CATH.a, and SK-N-SH cell lines, but not in the non-DBH-expressing C6 glioma or CA77 cell lines. This activity was localized to a region between -133 and -173 upstream of the transcription start site. This element, however, also directed expression in non-DBH-expressing cell lines, but was inhibited when sequences between -212 and -388 were included. This inhibitory region contains sequences homologous to a silencer element recently identified in the human DBH gene, and shares homology with other previously identified silencer elements. Gel retardation experiments demonstrate that the rat DBH inhibitory region and the silencer elements found in the rat sodium type II channel and SCG10 genes bind a similar factor. The region between -133 and -173, which contains a consensus cyclic AMP response element (CRE), was also found to be responsive to cAMP in both DBH-expressing and non-expressing cells. Inclusion of sequences between -173 and -190 diminished the cAMP induction in PC12 cells, and nearly abolished the induction in C6 and CA77 cells, suggesting the presence of an additional negative element which inhibits cAMP induction in non-DBH expressing cells. DNA binding assays using antibodies to CRE binding protein-related transcription factors identified ATF-1 binding to the rat DBH-CRE, and further suggest that inhibition of cAMP regulation may be due to inhibition of ATF-1 binding by an additional factor, which binds to the DBH promoter immediately upstream of the CRE. These results demonstrate the importance of both positive and negative regulatory elements in the regulation of tissue-specific expression of the rat DBH gene.

Analysis of Variance↗
PubMed1996

Seroprevalence of tetanus antibodies among adults older than 65 years.

STUDY OBJECTIVE: To define the extent of immunity against tetanus among patients older than 65 years of age by measuring antitetanus antibody levels. METHODS: A convenience sample of 129 patients from an urban comprehensive care geriatric center was studied. Serum was obtained and enzyme-linked immunosorbent assay (ELISA) testing performed. Twenty health care providers, aged 25 to 40 years, were tested for comparison. RESULTS: In 64 (50%) of 129 study patients, antitetanus antibody levels did not reach protective levels. Fifty-four (59%) of 92 women and 10 (27%) of 37 men did not have adequate titers. All 20 health care workers had protective titers. CONCLUSION: Elderly patients are substantially less likely than young individuals to have adequate immunity against tetanus. Emergency physicians must take this into consideration when evaluating tetanus immunization status in injured elderly patients.

Adult↗
PubMed1996

Situational familiarity and feature recognition in schizophrenia.

Research has shown that schizophrenia patients are less able to identify a situation's abstract features (goals) than its concrete features (actions). However, it has been unclear whether this differential deficit represents a cognitive dysfunction or a lack of familiarity with many situations because of impoverished social experiences. Twenty-nine inpatients with DSM-III-R diagnosis of schizophrenia completed the Situational Feature Recognition Test, Version 2 (SFRT-2). The SFRT-2 included familiar and unfamiliar situations of which subjects were asked to identify characteristic goals and actions. A 2 x 2 x 2 analysis of variance (group by feature abstraction by situational familiarity) found a significant three-way interaction. Post-hoc analyses suggested that patients were better able to recognize concrete features in familiar situations. Differences in discriminating power of the four conditions of the SFRT-2 had been diminished on standardization and cross-validation groups. Therefore, the differential deficits shown by the patient sample probably do not represent psychometric confound. Implications for remediation of social cognitive deficits are discussed.

Adult↗
PubMed1996

Choroidal concentration of interferon after retrobulbar injection.

PURPOSE: To determine whether recombinant human interferon alpha-2a (IFN alpha-2a) would diffuse into the choroid in significant amounts from a retrobulbar depot. METHODS: One million international units of IFN alpha-2a were injected into the retrobulbar space of the eyes of 17 rabbits, and choroidal and serum concentrations were measured at 1, 2, 4, 8, 12, and 24 hours. The same dose of IFN alpha-2a was injected subcutaneously into 10 rabbits, and choroidal and serum concentrations were measured at the same intervals for comparison. Parabulbar and ocular tissues were studied by light microscopy for evidence of local toxicity. RESULTS: Peak concentration IFN alpha-2a in the choroid after retrobulbar injection occurred at 2 hours and averaged 32,000 IU/mg. Peak concentration in the serum occurred at 4 hours and averaged 227 IU/ml. Concentrations in choroid and serum fell rapidly, and IFN alpha-2a was not detectible at 24 hours. No IFN alpha-2a was detected in the choroid of the paired eye, and only a trace (< 50 IU/mg) was found in either eye after subcutaneous injection. Light microscopy revealed some lymphocytes in the fat adjacent to the retrobulbar depot after six daily injections of IFN alpha-2a or saline. Sclera, choroid, and retina appeared unaffected. CONCLUSIONS: IFN alpha-2a diffuses into the choroid from a retrobulbar depot in significant amounts. The serum concentration from a retrobulbar injection is < 1% of the choroidal concentration. The retrobulbar route to the choroid may be optimal for testing the effect of IFN alpha-2a on choroidal neovascularization.

Animals↗
PubMed1995

Time to equilibration of oxygen saturation using pulse oximetry.

OBJECTIVE: To determine the time it takes for O2 saturation measured by pulse oximetry to equilibrate after a change is made in supplemental O2 administered by nasal cannula in patients with cardiac and pulmonary disease. METHODS: A prospective, observational study of a convenience sample of 51 patients treated in a university-affiliated ED with nasal cannula O2. Patients were placed on and/or subsequently taken off O2 via nasal cannula set at 2 or 4 L/min based on clinical indications. Oxygen saturation was measured at 1-minute intervals over a 30-minute period using finger-probe pulse oximetry. Of the 51 patients in the study, 43 were monitored while O2 treatment was initiated and 18 were monitored when it was discontinued. RESULTS: Most (95%) of the patients placed on O2 attained equilibration of O2 saturation within 3.5 minutes. Most (95%) of the patients taken off supplemental O2 attained equilibration of O2 saturation within 4.5 minutes. CONCLUSION: The interval to equilibration of O2 saturation in patients receiving O2 by nasal cannula is considerably shorter than the 20-30 minutes generally suggested. Adequacy of O2 supplementation should be assessable much sooner than was previously taught.

Adult↗
PubMed1995

Intravenous magnesium sulfate as an adjunct in the treatment of acute asthma.

STUDY OBJECTIVE: This study was conducted to determine whether intravenous magnesium sulfate (MgSO4), when used as part of a standardized treatment protocol, can improve pulmonary function and decrease admission rate in patients presenting to the emergency department with exacerbations of asthma. DESIGN: In this randomized double-blind placebo-controlled study, patients with acute asthma were treated with inhaled beta-agonists at regular intervals and intravenous (IV) steroids. At 30 min after entry, patients received either 2 g IV MgSO4 or IV placebo. Patients were monitored for up to 4 h with regular measurements of pulmonary function. Patients who were discharged from the emergency department were contacted at 1 day and 7 days for follow-up. SETTING: Emergency departments of a university-affiliated, voluntary hospital and municipal hospital. PARTICIPANTS: Asthmatics aged 18 to 65 years during acute exacerbation with FEV1 less than 75% predicted both before and after a single albuterol treatment. INTERVENTIONS: Patients were given 2 g of MgSO4 or placebo as an adjunct to standardized emergency department procedure for acute asthma. MEASUREMENTS AND RESULTS: One hundred thirty-five patients were studied. Hospital admission rates were 35.3% for placebo-treated group and 25.4% for the magnesium-treated group (p = 0.21). FEV1 measured at 120 min was 56% predicted for the placebo-treated group and 55% predicted for the magnesium-treated group. (p = 0.92) For subgroup analysis, patients were divided into "severe" (baseline FEV1 < 25% predicted on presentation) or "moderate" (baseline FEV1, 25 to 75% predicted on presentation). For the severe group, admission rates were 78.6% (11/14) for the placebo-treated group and 33.3% (7/21) for the magnesium-treated group (p = 0.009). For the moderate patients, admission rates were 22.4% (11/49) for the placebo-treated group and 22.2% (10/25) for the magnesium-treated group (p = 0.98). There was no significant improvement in FEV1 in the moderate group for magnesium-treated patients. However, in the severe group, there was a significant improvement in FEV1 at 120 min and 240 min (p = 0.014 and 0.026, respectively). CONCLUSION: Intravenous MgSO4 decreased admission rate and improved FEV1 in patients with acute severe asthma but did not cause significant improvement in patients with moderate asthma.

Acute Disease↗
PubMed1994

Regulation of interferon-alpha-inducible cellular genes in human immunodeficiency virus-infected monocytes.

Cellular mechanisms that control susceptibility to opportunistic infection in human immunodeficiency virus (HIV)-infected individuals remain poorly understood. HIV may induce certain cellular genes that restrict HIV replication and protect cells against other superinfecting viral pathogens. Indeed, HIV-infected monocytes resist infection by vesicular stomatitis virus (VSV). HIV-induced VSV interference in monocytes increases with time after HIV infection. Such interference was evident 6 h after HIV infection and reached maximal levels at 14 days. Monocytotropic but not T cell-tropic HIV strains elicited these effects, signaling a requirement for viral entry and/or replication. Viral interference was independent of interferon (IFN) and was unaffected by addition of neutralizing IFN-alpha and -beta antibodies. The well-described IFN-alpha-inducible antiviral pathways were examined to determine their relationship to the cellular mechanism(s) underlying VSV interference. HIV and IFN-alpha both induced the expression of 2-5A synthetase and Mx gene. In contrast, the guanylate-binding protein (GBP), 6-16, and 9-27 cellular genes were up-regulated by IFN-alpha but not HIV. MxA was detected in HIV-infected monocytes but not in uninfected monocytes. The association between Mx expression and resistance to VSV, coupled with previously described anti-VSV activities by human MxA, suggested that Mx may be an effector molecule for the HIV-induced anti-VSV activities. These results, taken together, suggest that HIV can induce antiviral cellular gene expression, independent of IFN.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

Comparison of magnetic resonance imaging and endoscopy in distinguishing the type and severity of inflammatory bowel disease.

Twenty consecutive patients with first-time presentation of suspected inflammatory bowel disease underwent both endoscopy with biopsy and magnetic resonance imaging (MRI) within a 3-day period; the relative abilities of endoscopy and MRI to distinguish ulcerative colitis (UC) from Crohn's disease (CD) and to determine the severity of the disease process were compared. In 18 of 20 patients, a diagnosis of UC or CD could be made on histological specimens. MRI correctly diagnosed 17 of these 18 patients using T1-weighted fat-suppressed spin echo and gadolinium enhancement. Endoscopy correctly diagnosed 15 patients. Overall, MRI was not significantly better (p > 0.05) than endoscopy in distinguishing UC from CD. MRI correctly graded the severity of inflammatory changes in 13 of 20 patients, and endoscopy did so in 11 of 20. MRI and endoscopy findings were within one grade of histology findings in seven patients each. No significant difference (p > 0.05) was found between MRI and endoscopy in the ability to estimate the severity of the disease (as determined from biopsies). Bowel wall thickness measured on MR images demonstrated good correlation with percentage of contrast enhancement: r = 0.61; p = 0.003. In sum, magnetic resonance imaging was shown to be comparable with endoscopy in differentiating UC from CD and in gauging the severity of disease. Transmural assessment, sagittal imaging, and the lack of invasiveness were attractive features of MRI.

Adult↗
PubMed1994

Immunomodulation in choroidal melanoma: reversal of inverted CD4/CD8 ratios following treatment with ultrasonic hyperthermia.

It has long been suggested that malignant melanomas, cutaneous as well as uveal, are responsive to human immune-mediated host defenses. We report here 5 consecutive cases of posterior choroidal melanomas which were treated with hyperthermia generated by high-intensity focused ultrasound. Patient immune function was monitored by determination of T-cell helper/suppressor (CD4/CD8) ratios immediately before and approximately 1 week following hyperthermia treatment. All 5 patients had normal total T-cell counts as measured by the pan-T-cell marker CD3. Two patients were noted to have inverted CD4/CD8 ratios (< 1:1) before hyperthermia. In both these cases, the ratio reverted to normal (> 1:1) 1 week following treatment. One patient whose CD4/CD8 ratio was not inverted was noted to have a further increase in his CD4 T cells relative to his CD8 (37% increase). Two patients with initially normal CD4/CD8 demonstrated no significant change following hyperthermia. It appears that ultrasonic hyperthermia may induce a systemic immunomodulatory effect in patients with posterior choroidal melanoma and inverted T-cell helper/suppressor resulting in a normalization of T-cell subset ratios.

Aged↗
PubMed1993

Safety of lumbar puncture in patients with hemophilia.

STUDY OBJECTIVE: To determine the safety of lumbar puncture in patients with hemophilia who are pretreated with clotting factor. DESIGN: Retrospective analysis of medical records between 1980 and 1990. SETTING: Three hospitals, each serving as a regional hemophilia center. PARTICIPANTS: Thirty-three patients with hemophilia A or B who received one or more lumbar puncture. INTERVENTION: All patients received replacement of deficient factor before the lumbar puncture. Serious post-lumbar puncture complications were defined as motor or sensory deficits, incontinence, or documented intraspinal hemorrhage. RESULTS: Thirty-three patients with hemophilia A or B received a total of 52 lumbar punctures during the study period. Thirty of 33 patients (91%) had severe baseline factor deficiency, two (6%) had moderate deficiency, and one (3%) had mild deficiency. There were no serious complications reported as a result of the lumbar puncture. The 95% confidence interval for the risk of a serious complication was 0% to 5.8%. CONCLUSION: With adequate factor replacement, a lumbar puncture can be done safely in patients with hemophilia.

Adolescent↗