Biomedical subjects

M Steinberg

Publications and source records attributed to M Steinberg.

At least 37 records · Page 2Linked to original sources

PubMed2000

Randomised study of anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women.

A total of 668 patients (340 anastrozole and 328 tamoxifen) were randomised in a double-blind, double-dummy multicentre study. Anastrozole was given in a dose of 1 mg once daily and compared with tamoxifen 20 mg daily in postmenopausal patients with tumours that were hormone-receptor positive or of unknown receptor status. The efficacy and tolerability of anastrozole was compared with that of tamoxifen as first-line therapy for advanced breast cancer. The median time to progression was similar for both treatments (8.2 months in anastrozole patients and 8.3 months in tamoxifen patients). Anastrozole was also as effective as tamoxifen in terms of objective response-rate with 33% in the anastrozole group and 32.6% in the tamoxifen group achieving a complete or partial response. Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen. In conclusion, these findings indicate that anastrozole can be considered as first-line therapy for postmenopausal women with advanced breast cancer.

Anastrozole↗

PubMed2000

Retrovirus-mediated transduction of primary ZAP-70-deficient human T cells results in the selective growth advantage of gene-corrected cells: implications for gene therapy.

Humans lacking the ZAP-70 protein tyrosine kinase present with an absence of CD8+ T cells and defective CD4+ T cells in the periphery. This severe combined immunodeficiency is fatal unless treated by allogeneic bone marrow transplantation. However, in the absence of suitable marrow donors, the development of alternative forms of therapy is desirable. Because lymphocytes are long-lived, it is possible that introduction of the wild-type ZAP-70 gene into CD4+ ZAP-70-deficient T cells will restore their immune function in vivo. Initial investigations evaluating the feasibility of gene therapy for ZAP-70 deficiency were performed using HTL V-I-transformed lymphocytes. Although transformation was useful in circumventing problems associated with the maintenance of ZAP-70-deficient T cells and low gene transfer levels, the presence of HTL V-I precluded any biological studies. Here, we investigated a retrovirus-mediated approach for the correction of primary T cells derived from two ZAP-70-deficient patients. Upon introduction of the wild-type ZAP-70 gene, TCR-induced MAPK activation, IL-2 secretion and proliferation were restored to approximately normal levels. Importantly, this gain-of-function was associated with a selective growth advantage of gene-corrected cells, thereby indicating the feasibility of a gene therapy-based strategy.

Cell Division↗

PubMed2000

Use of a screen log to audit patient recruitment into multiple randomized trials in the intensive care unit. Canadian Critical Care Trials Group.

OBJECTIVE: To develop and evaluate a screen log for monitoring enrollment in multiple randomized clinical trials conducted in a single center. SETTING: University-affiliated 20-bed tertiary care medical-surgical intensive care unit (ICU). PATIENTS: Consecutive ICU patients admitted between April 1995 and March 1997. METHODS: We developed a screen log for multicentered studies conducted in our ICU. Using a multiple-project, unicenter perspective, we evaluated the screen log as a tool for monitoring eligibility and enrollment of patients in four multicentered randomized trials focused on stress ulcer prophylaxis, blood transfusion thresholds, immunotherapy for sepsis and mechanical ventilation strategies. RESULTS: The screen log was used as an instrument to monitor trial execution. We recorded all aspects of study enrollment and created a taxonomy of reasons for nonenrollment into each trial. We calculated enrollment efficiency rates and used these data to develop strategies to maximize accrual. The screen log became a communication tool that fostered research-oriented continuous quality improvement initiatives for the management of concurrently conducted randomized trials in our ICU. CONCLUSIONS: Intensivists participating in several clinical trials may be interested in monitoring and maximizing enrollment when conducting multiple studies and understanding the influence of each trial on enrollment into the others. The unicenter, multiple-project screen log is one tool that may help to achieve these goals.

Canada↗

PubMed2000

Home safety assessment in the prevention of falls among older people.

OBJECTIVE: Home safety assessment was examined as part of a randomised trial of falls prevention interventions among older community dwellers. METHOD: Falls prevention strategies, including education and awareness-raising, exercise, home modifications and medical assessment, were trialed with 252 members of the National Seniors Association. Falls outcomes were monitored using a daily calendar diary during intervention and follow-up periods. RESULTS: The home assessment group was significantly more likely to modify their home environment than the controls (p < 0.0001). Participants, regardless of group allocation, reported a significant reduction in concern about falling (p < 0.0001). During the intervention, the home assessment group had lower incidence rates for falls and injuries than the control group, although differences were not significant. The lowered rates were sustained post-intervention. CONCLUSIONS: While the effect on falls incidence of a home safety intervention on its own could not be demonstrated, other benefits, including improved confidence attributable to awareness of such falls prevention measures, were recorded. IMPLICATIONS: The null effects of home modifications on falls prevention in this study may indicate that the program is more appropriate for the frail aged.

Accidental Falls↗

PubMed2000

A sustainable programme to prevent falls and near falls in community dwelling older people: results of a randomised trial.

STUDY OBJECTIVE: In the causative mechanism of falls among older community dwellers, slips and trips have been found to be significant precursors. The purpose of the two year trial was to assess the effectiveness of multi-component interventions targeting major risk factors for falls in reducing the incidence of slips, trips and falls among the well, older community. DESIGN: Four groups with approximately equal numbers of participants were randomly allocated to interventions. The prevention strategies included education and awareness raising of falls risk factors, exercise sessions to improve strength and balance, home safety advice to modify environmental hazards, and medical assessment to optimise health. The interventions combined the strategies in an add on approach. The first intervention group receiving the information session only was regarded as the control. The outcome of interest was the occurrence of a slip, trip or fall, monitored prospectively using a daily calendar diary. PARTICIPANTS AND SETTING: Two hundred and fifty two members of the National Seniors Association in the Brisbane district agreed to participate. National Seniors clubs provide a forum for active, community dwelling Australians aged 50 and over to participate in policy, personal development and recreation. MAIN RESULTS: Using Cox's proportional hazards regression model, adjusted hazard ratios comparing intervention groups with the control ranged from 0.35 (95% CI 0.17, 0.73) to 0.48 (0.25, 0.91) for slips; 0.29 (0.16, 0.51) to 0.45 (0.27, 0.74) for trips; and 0.60 (0.36, 1.01) to 0.82 (0.51, 1.31) for falls. While calendar monitoring recorded outcome, it was also assessed as a prevention strategy by comparing the intervention groups with a hypothetical nonintervened group. At one year after intervention, reductions in the probability of slips, trips and falls (61 (95% CI 54, 66)%; 56 (49, 63)%; 29 (22, 36)% respectively) were demonstrated. CONCLUSIONS: This study makes an important contribution to the priority community health issue of falls prevention by showing that effective, sustainable, low cost programmes can be introduced through community-based organisations to reduce the incidence of slips, trips and falls in well older people.

Accidental Falls↗

PubMed2000

Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study.

OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD: Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.

Aged↗

PubMed2000

Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging.

OBJECTIVE: The authors report findings from a study of 5,092 community residents who constituted 90% of the elderly resident population of Cache County, Utah. METHOD: The 5,092 participants, who were 65 years old or older, were screened for dementia. Based on the results of this screen, 1,002 participants (329 with dementia and 673 without dementia) underwent comprehensive neuropsychiatric examinations and were rated on the Neuropsychiatric Inventory, a widely used method for ascertainment and classification of dementia-associated mental and behavioral disturbances. RESULTS: Of the 329 participants with dementia, 214 (65%) had Alzheimer's disease, 62 (19%) had vascular dementia, and 53 (16%) had another DSM-IV dementia diagnosis; 201 (61%) had exhibited one or more mental or behavioral disturbances in the past month. Apathy (27%), depression (24%), and agitation/aggression (24%) were the most common in participants with dementia. These disturbances were almost four times more common in participants with dementia than in those without. Only modest differences were observed in the prevalence of mental or behavioral disturbances in different types of dementia or at different stages of illness: participants with Alzheimer's disease were more likely to have delusions and less likely to have depression. Agitation/aggression and aberrant motor behavior were more common in participants with advanced dementia. CONCLUSIONS: On the basis of their findings in this large community population of elderly people, the authors conclude that a wide range of dementia-associated mental and behavioral disturbances afflict the majority of individuals with dementia. Because of their frequency and their adverse effects on patients and their caregivers, these disturbances should be ascertained and treated in all cases of dementia.

Aged↗

PubMed2000

Vascular dementia and Alzheimer's disease: is there a difference? A comparison of symptoms by disease duration.

This study examined differences between vascular dementia (VaD) by the NINDS/AIRENS criteria and Alzheimer's disease (AD) on clinical grounds. A consecutive series of 517 patients with probable and possible VaD or AD were evaluated for cognitive, functional, and behavioral symptoms and separated into three subgroups by duration of dementia. These AD and VaD subgroups were then compared on a series of standardized clinical measures. The only consistent trends were for VaD patients to be more depressed, more functionally impaired, and less cognitively impaired within each disease duration subgroup. The authors conclude that there are few differences between clinically diagnosed VaD and AD. Subclassification of VaD into subgroups will improve the clinical utility of this nosologic entity.

Aged↗

PubMed2000

Advances in the clinical assessment of dissociation: the SCID-D-R.

A comprehensive assessment of dissociative symptoms is recommended for effective treatment of trauma survivors. The author reviews the systematic detection of dissociative symptoms and disorders using the Structured Clinical Interview for DSM-IV Dissociative Disorders--Revised (SCID-D-R) in adolescents and adults (Steinberg, 1994b). Numerous investigations have reported good-to-excellent reliability and validity of the SCID-D-R, both in the United States and abroad. Clinical applications, including the SCID-D-R's utility for psychological and forensic evaluations, treatment planning, differential diagnosis, and evaluation of malingering, are reviewed.

Adult↗

PubMed1999

Effect of metal reconstruction plates on cobalt-60 dose distribution: a predictive formula and clinical implications.

PURPOSE: We sought to create a predictive formula for the dose perturbations caused by head and neck reconstruction plates in the delivery of postoperative radiotherapy with 60Co beams. MATERIALS AND METHODS: The dose perturbation effects of Vitallium and Titanium reconstruction plates and flat metal plates of aluminum (13Al), stainless steel (26Fe), tin (50Sn) and lead (82Pb) irradiated with a 60Co beam were measured in polystyrene phantoms using a film dosimetry system. We then used these results to create formulas to predict the effect of a metal reconstruction plate dependent upon its effective atomic number. RESULTS: Percentage dose increases secondary to back scattering were 10% at 1 mm in front of the Vitallium plate and 40% at the plate while the percentage dose decrease was 29% at the plate and 10% 1 mm behind the plate. For the Titanium plate, the percentage dose increase was 5% at 1 mm in front the plate and 25% at the plate while the percentage dose decrease was 20% at the plate and 5% 1 mm behind the plate. For flat plates the percentage dose increases and decreases, respectively, at the plate surfaces were: 13Al (8%, 6%), 26Fe (35%, 16%), 50Sn (60%, 24%), and 82Pb (85%, 13%). A second order polynomial predicting the back scatter and shadowing effects was created, Y = a + bZ + cZ2, where Z is the effective atomic number of the plate while a, b, and c are the following constants: for back scatter a = 0.854 +/- 0.082, b = 0.0212 +/- 0.0044, c = -0.00011 +/- 0.00004 and for shadowing a = 1.108 +/- 0.021, b = -0.0141 +/- 0.0011, c = 0.00014 +/- 0.00001. CONCLUSIONS: It is possible to predict the effect of a metal reconstruction plate upon the delivered postoperative radiotherapy dose. The dose perturbations around the plate only exist for a few millimeters, but this is substantially greater than the thickness of a normal tissue or tumor cell. Perhaps a coating of a low effective atomic number, biologically inert, substance might allow for greater dose homogeneity and decrease the risks of plate failure or tumor recurrence.

Bone Plates↗

PubMed1999

The effect of different solvents on the ATP/ADP content and growth properties of HeLa cells.

Testing of the effects of xenobiotics in cultured cells often requires the use of organic solvents to effect suspension of the test agents in cell culture media. However, the toxic effects of the solvents themselves may introduce artifacts, which obscure interpretation of the experimental results. In this article, the toxicity of different solvents commonly used for solvation of a variety of xenobiotic agents was studied. We show that ethanol, acetone, isooctane, methanol, and hexane were considerably less toxic than the more commonly used solvent, DMSO, when ATP content and growth rates of HeLa cells exposed to these solvents was measured.

Acetone↗

PubMed1999

Wandering behaviour in community-residing persons with dementia.

OBJECTIVES: To examine wandering behaviour in elderly demented persons in the community setting with respect to dementia characteristics and other factors that might influence wandering behaviour; to generate a statistical model to assess the relative importance of these various factors in predicting wandering behaviour. DESIGN: Cross-sectional, case-control investigation. SETTING: University-affiliated outpatient neuropsychiatric assessment center. PARTICIPANTS: Six hundred and thirty-eight consecutive community-residing new patients with dementia referred for evaluation. MEASUREMENTS: Comprehensive neuropsychiatric evaluation, including rating with Mini-Mental State Examination; General Medical Health Rating; Comell Scale of Depression in Dementia and caregiver interview. RESULTS: Wandering behaviour occurred in 17.4% of participants. It was significantly more prevalent in patients with Alzheimer Dementia (AD), patients with dementia of longer duration, and patients with more severe dementia. Wandering behaviour was associated with moderate to severe depression, delusions, hallucinations, and sleep disorder. Other significant associations of wandering behaviour included use of neuroleptic medication and male gender. After statistical adjustment for other variables, duration of dementia, severity of dementia and presence of sleep disorder retained significant statistical association with wandering behaviour. CONCLUSIONS: Wandering behaviour among community-residing elderly dementia patients is associated with a number of factors, some of which may be subject to modification. It is possible that management of coexistent psychopathology, particularly of sleep disorder, and of the underlying disease process of AD would help to ameliorate this problematic behavioural disorder. Further investigation is warranted into the relationship between neuroleptic medication and wandering behaviour and into possible alternative measures to control agitation in elderly dementia patients.

Age Distribution↗

PubMed1999

Consistency in the ratings of behaviors of communicatively impaired autistic and non-autistic preschool children.

Typically, children with disabilities are evaluated clinically by a number of professionals with different backgrounds whose task is to provide a diagnosis and an intervention plan. This study was carried out to describe interrater agreement for pairs of independent observers rating with different instruments the behaviors of 505 communicatively impaired autistic and nonautistic preschool children. Observers were parents, teachers, neurologists, and psychiatrists. Parents and teachers responded to behavioral questionnaires, neurologists filled out the mental status part of a standardized neurologic evaluation, and psychiatrists an observational questionnaire. All four types of observers rated sociability, language, play, attention, stereotyped, and other aberrant behaviors. Agreement between pairs of raters was significant but moderate. Owing to range restriction with smaller numbers of subjects, agreement decreased for ratings of subsamples divided according to diagnosis, cognitive level, or age. There were some differences among observers' ratings of the severity of particular categories of behaviors, with physicians generally viewing the children as more severely impaired and teachers as least impaired. Interrater agreement was not enhanced when parents and teachers rated similarly worded behavioral items. Modest interrater agreement in this study, like agreement among disparate raters of children's behaviors in other studies, suggests that observers are sensitive to different aspects of behavior and that their ratings are more likely to be complementary than unreliable.

Autistic Disorder↗

PubMed1999

Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine.

Mixed drug reactions are frequently encountered in emergency department overdose cases and also in fatal intoxications. Assessment of the relative contribution of each drug in producing adverse effects is often compounded by lack of case history and the paucity of cases reported in the literature. This report describes a fatal intoxication with three common over-the-counter medications: guaifenesin, diphenhydramine, and chlorpheniramine. A 48-year-old woman was found dead in the attic bedroom of her residence. Specimens obtained at autopsy for toxicologic analysis included heart blood, urine, bile, gastric contents, vitreous humor, and cerebrospinal fluid. The over-the-counter drugs were identified and quantitated by acid/neutral or basic liquid-liquid extraction followed by gas chromatographic analysis with nitrogen phosphorus detection. Concentrations of guaifenesin, diphenhydramine, and chlorpheniramine detected in the heart blood were 27.4, 8.8, and 0.2 mg/L, respectively. The cause of death was determined to be acute intoxication by the combined effects of guaifenesin, diphenhydramine, and chlorpheniramine, and the manner of death was determined to be suicide. To our knowledge, the blood guaifenesin concentration in this case is the highest reported concentration to date associated with an acute intoxication.

Chlorpheniramine↗

PubMed1999

The General Medical Health Rating: a bedside global rating of medical comorbidity in patients with dementia.

OBJECTIVE: Dementia is a serious public health problem. General medical comorbidity is common in dementia patients and critical to their care. However, little is known about medical comorbidity in these patients, and there are no straightforward bedside global rating scales for the seriousness of comorbid medical illness. This paper describes the development and measurement properties of the General Medical Health Rating (GHMR), a rapid global rating scale of medical comorbidity in dementia patients. DESIGN: Interrater reliability, concurrent validity, and predictive validity of the GMHR are reported. SETTING: An outpatient dementia clinic, assisted living, and nursing home. PARTICIPANTS: A total of 819 consecutive dementia clinic outpatients and 180 consecutive admissions to Copper Ridge, a long-term care residence for people with dementia, were included in the study. RESULTS: GMHR was found to be highly reliable (weighted kappa = .91). Across all stages and types of dementia, GMHR ratings were correlated with number of comorbid medical conditions, number of medications being taken for comorbid conditions, and with activity of daily living impairment, even after adjustment for severity of dementia. GMHR ratings were also a strong predictor of falls and of mortality in long-term care residents after adjustment for age and severity of dementia. CONCLUSION: GMHR is a reliable, valid, global bedside measure of severity of general medical comorbidity for patients with dementia that can be used for clinical and research purposes.

Accidental Falls↗

PubMed1999

Physical aggression in dementia patients and its relationship to depression.

OBJECTIVE: The goal of this study was to determine the frequency of physically aggressive behavior in community-residing patients with dementia and its relationship to depression. METHOD: A consecutive series of 541 patients with DSM-IV-defined dementia underwent comprehensive neuropsychiatric evaluation and were rated on the Cornell Scale for Depression in Dementia, the Mini-Mental State, the Psychogeriatric Dependency Rating Scale, and the General Medical Health Rating. RESULTS: Physically aggressive behavior was exhibited by 79 patients in the 2 weeks before evaluation. Aggressive behavior was closely associated with moderate to severe depression, male gender, and greater impairment in activities of daily living, even after adjustment for delusions, hallucinations, sleep disturbance, and severity of cognitive impairment. After adjustment for depression, gender, and impairment in activities of daily living, there was no association between physically aggressive behavior and the presence of either delusions or hallucinations. CONCLUSIONS: A substantial minority of patients with dementia exhibit physically aggressive behavior, and this aggression is strongly linked with the presence of depressive symptoms. It is possible that the identification and treatment of depression in dementia may be a means of preventing and managing physically aggressive behavior.

Activities of Daily Living↗

PubMed1998

Anastrozole versus megestrol acetate in the treatment of postmenopausal women with advanced breast carcinoma: results of a survival update based on a combined analysis of data from two mature phase III trials. Arimidex Study Group.

BACKGROUND: This report presents the results of a survival update based on the combined data from two studies that compared the efficacy and tolerability of anastrozole (1 or 10 mg once daily), a selective, nonsteroidal aromatase inhibitor administered orally, and megestrol acetate (40 mg 4 times daily) in the treatment of postmenopausal women with advanced breast carcinoma whose disease had progressed after treatment with tamoxifen. METHODS: Two randomized, parallel-group, multicenter trials were conducted, involving a total of 764 patients. The two trials were identical in design; both were double blind for anastrozole and open label for megestrol acetate. Overview analyses were conducted with the intent of strengthening the interpretation of results from each trial. The median follow-up duration for this survival update was 31 months. RESULTS: At the clinical dose of 1 mg daily, anastrozole demonstrated a statistically significant survival advantage over megestrol acetate, with a hazard ratio of 0.78 (P < 0.025)(0.60 < 97.5% confidence interval [CI] <1.0). The 1 mg anastrozole group also had a longer median time to death (26.7 months) compared with 22.5 months for the megestrol acetate group. The 10 mg anastrozole group also had a survival benefit over the megestrol acetate group, with a hazard ratio of 0.83 (P=0.09, not significant)(0.64 < 97.5% CI < 1.1). Higher 2-year survival rates were observed for both anastrozole treatment groups than for the megestrol acetate group (56.1%, 54.6%, and 46.3% for the groups given 1 mg anastrozole, 10 mg anastrozole, and megestrol acetate, respectively). CONCLUSIONS: This combined analysis of two trials of postmenopausal patients with advanced breast carcinoma has clearly demonstrated that, after disease progression with tamoxifen, treatment with anastrozole 1 mg once daily results in a statistically and clinically significant advantage over a standard treatment, megestrol acetate. This important benefit, in addition to the good tolerability profile of anastrozole, supports the use of this drug as a valuable new treatment option for this patient population.

Aged↗

PubMed1998

Relationship of cognitive and functional impairment to depressive features in Alzheimer's disease and other dementias.

Patients with clinical diagnoses of Alzheimer's disease, vascular dementia, or undifferentiated dementia were rated on standardized measures of depression, cognitive impairment, and functional impairment. Logistic regression was used to evaluate the relationship between functional or cognitive impairment, as well as their interaction, and depressive features in each group. This analysis revealed notable differences by type of dementia. The results imply that the mechanisms underlying depression in Alzheimer's disease may be different from those in vascular and other types of dementia. These results also provide indicators to the clinician for further evaluation of depression in different dementia subtypes.

Aged↗