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S Weisberg

Publications and source records attributed to S Weisberg.

At least 19 recordsLinked to original sources
PubMed2001

Graphical model checking with correlated response data.

Correlated response data arise often in biomedical studies. The generalized estimation equation (GEE) approach is widely used in regression analysis for such data. However, there are few methods available to check the adequacy of regression models in GEE. In this paper, a graphical method is proposed based on Cook and Weisberg's marginal model plot. A bootstrap method is applied to obtain the reference band to assess statistical uncertainties in comparing two marginal mean functions. We also propose using the generalized additive model (GAM) in a similar fashion. The proposed two methods are easy to implement by taking advantage of existing smoothing and GAM softwares for independent data. The usefulness of the methodology is demonstrated through application to a correlated binary data set drawn from a clinical trial, the Lung Health Study.

Adult↗
PubMed2001

Anaplastic and atypical meningiomas express high levels of Fas and undergo apoptosis in response to Fas ligation.

In this study we characterized the expression of Fas and Fas ligand in different types of meningiomas and examined the effect of Fas ligation on the death of meningioma cells in culture. Using Western blot analysis, we found that extracts derived from anaplastic and atypical meningiomas expressed high levels of Fas, whereas benign meningiomas did not express detectable levels of this protein. All of the meningiomas examined expressed low levels of Fas ligand. Cultures of anaplastic meningiomas also expressed Fas and treatment of these cells with anti-Fas antibody induced cell death. The results of this study indicate that Fas is preferentially expressed in atypical and anaplastic meningiomas and suggest that it is involved in the increased apoptosis observed in these tumors.

Antibodies↗
PubMed2001

vFLIP protects PC-12 cells from apoptosis induced by Sindbis virus: implications for the role of TNF-alpha.

Sindbis virus (SV) is an alphavirus used as a model for studying the pathogenesis of viral encephalitis. In this study we examined the effects and the mechanisms involved in the apoptosis induced by SV in PC-12 cells, and the role of a vFLIP in this process. Infection of PC-12 cells with a neurovirulent strain of SV, SVNI, induced cell apoptosis. Overexpression of vFLIP encoded by the HHV-8 or treatment with a caspase-8 inhibitor inhibited cell apoptosis. SVNI induced an increase in the expression of tumor necrosis factor alpha (TNF-alpha), and pre-treatment of the cells with an anti-TNF-alpha blocking antibody or with soluble TNF-alpha receptor abrogated the apoptotic effect of SVNI. Moreover, TNF-alpha R1 knockout mice were more resistant to the cytopathic effects of the virus as compared to control animals. Our results indicate that the apoptosis induced by SVNI is mediated by activation of caspase-8, and that TNF-alpha plays an important role in the apoptotic response.

Animals↗
PubMed2000

In vivo efficacy of silver-coated fabric against Staphylococcus epidermidis.

BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE) is a serious complication of heart valve replacement. The use of silver-coated polyester fabric in sewing cuff fabrication is intended to reduce the incidence of PVE. In this study, three pathogenic strains of Staphylococcus epidermidis (two PVE and one peripheral vasculature pathogen) were used to evaluate infection of silver-coated and uncoated fabric. METHODS: Fabric was inoculated by preincubation for 30 min in bacterial suspensions containing 10(4), 10(5), 10(6), 10(7) or 10(8) CFU/ml, and implanted subdermally in mice for up to seven days. Bacteria adherent to fabric implanted for zero, one, three, or seven days were enumerated by sonicating the fabric and plating serial dilutions of the resulting suspension. Percent infection was assessed by implanting samples, subdermally, for seven days, then incubating explanted samples in growth media for three days and calculating the percent of fabric showing bacterial growth, for each concentration of inoculum. A logistic regression model was used to estimate curves relating percent infection to log concentration of the bacterial inoculum. These curves were used to estimate the concentration of inoculum required to produce 50% infection (ID50) for the three strains of S. epidermidis, for silver-coated and uncoated fabric. RESULTS: Direct enumeration showed no difference in bacteria adherent to silver-coated and uncoated fabric, and no bacteria present in either fabric type in samples implanted for seven days. Nevertheless, incubation of those samples in growth media showed that many of the samples were infected. The calculated ID50 was significantly lower for silver-coated fabric than for uncoated fabric, for all three strains of S. epidermidis tested. CONCLUSION: Silver-coated fabric increases resistance to infection by S. epidermidis in this direct-contamination, mouse subdermal model.

Animals↗
PubMed1999

Effects of fluticasone propionate, triamcinolone acetonide, prednisone, and placebo on the hypothalamic-pituitary-adrenal axis.

BACKGROUND: Many clinicians are reluctant to prescribe inhaled corticosteroids because of concerns over potential effects on the hypothalamic-pituitary-adrenal axis. OBJECTIVE: The purpose of this study was to compare the adrenal responses to 6-hour cosyntropin infusion after treatment with fluticasone propionate aerosol, triamcinolone acetonide aerosol, prednisone, and placebo for 4 weeks, a sufficient time interval to assess any effects on the adrenal response to stress. METHODS: This double-blind, triple-dummy, randomized, placebo-controlled study was conducted in 128 patients to evaluate adrenal response to 6-hour cosyntropin infusion (a clinically relevant method for evaluating adrenal function) after 28 days of treatment with fluticasone propionate aerosol 88 microg or 220 microg twice daily, triamcinolone acetonide aerosol 200 microg 4 times daily or 400 microg twice daily, prednisone 10 mg once daily, and placebo. RESULTS: After 28 days of treatment, mean plasma cortisol response to cosyntropin over 12 hours after initiation of the 6-hour infusion was similar among fluticasone, triamcinolone, and placebo groups; cortisol response was significantly (P <.05) reduced after treatment with prednisone compared with the other treatment groups. Mean 8-hour area under the plasma cortisol concentration-time curves and peak plasma cortisol concentrations were significantly (P </=.003) lower with prednisone than any other treatment; no significant differences were noted between placebo and either of the fluticasone groups in any assessment. Mean reductions from baseline in area under the plasma cortisol concentration time curves and peak cortisol concentrations were significantly (P <.05) greater with triamcinolone 400 microg twice daily compared with placebo. CONCLUSION: These results suggest that fluticasone propionate at therapeutic doses has effects on the hypothalamic-pituitary-adrenal axis comparable to that of placebo and has significantly less effect than prednisone as measured by 6-hour cosyntropin infusion after 28 days of treatment.

Administration, Inhalation↗
PubMed1997

Phenylketonuria: current dietary treatment practices in the United States and Canada.

OBJECTIVE: A survey of treatment centers for phenylketonuria (PKU) in the United States and Canada was undertaken regarding current practices of dietary treatment of PKU. METHODS: A total of 111 centers, who follow more than 6,950 patients with PKU responded to the survey. RESULTS: The majority of the centers, 87%, favor life-long dietary control of phenylalanine intake. The survey found lack of uniformity regarding acceptable range of blood phenylalanine levels. The frequency of clinic visits varied and became less frequent as patients got older. Although most of the clinics recommend diet for life, only one-third of the clinics follow patients beyond the age of 18 years, therefore, it is unclear who manages these patients beyond that age. The survey also showed a high number of families with children who were reported for medical neglect (3.0% compared to < 0.06% in the general population). Because of dietary noncompliance, 1% of the children were removed from the home. DISCUSSION: The survey points to the common treatment goal of diet for life for patients with PKU and underscores the need for uniform guidelines for achieving this goal.

Adolescent↗
PubMed1997

Cardioprotection with dexrazoxane for doxorubicin-containing therapy in advanced breast cancer.

PURPOSE: To determine the cardioprotective effect of dexrazoxane (DZR) used in a doxorubicin-based combination therapy in advanced breast cancer. PATIENTS AND METHODS: Between November 1988 and January 1991, 534 patients with advanced breast cancer were randomized to two multicenter, double-blind studies (088001 and 088006). Patients received fluorouracil, doxorubicin, and cyclophosphamide (FAC) with either DZR (DZR-to-doxorubicin ratio, 10:1) or placebo (PLA) every 3 weeks and were monitored with serial multiplegated acquisition (MUGA) scans. RESULTS: The hazards ratio (HR) of PLA to DZR for a cardiac event, which was predefined ejection fraction changes or congestive heart failure (CHF), was 2.63 (95% confidence interval [CI], 1.61 to 4.27; P < .001) for 088001 and 2.00 (95% CI, 1.01 to 3.96; P = .038) for 088006. The objective response rates for 088001 were 46.8% for DZR and 60.5% for PLA, a difference of 14% (95% CI, -25% to -2%; P = .019), and for 088006 were 53.7% for DZR and 49.3% for PLA, a difference of 4% (95% CI, -13% to 22%; P = .63). Time to progression and survival were not significantly different between treatment arms in either study. Toxicities on the DZR arms included lower granulocyte and platelet counts at nadir (P = .009 and P = .004, respectively) and more pain on injection (P = .001), with no difference in the rates of fever, infection, or hemorrhage. CONCLUSION: DZR had a significant cardioprotective effect as measured by noninvasive testing and clinical CHF. One of the two studies (088001) showed a lower response rate with DZR, but time to progression and survival were not significantly different. DZR is the first agent shown to reduce cardiotoxicity from doxorubicin.

Aged↗
PubMed1996

Increasing the effectiveness of frontline workers through a model mental health training program.

The Ontario Ministry of Housing provides permanent, affordable, independent housing for mental health consumers. This approach, not contingent on consumer participation in support service programs, is part of a continuum of housing options. To help integrate consumers into social housing communities, the ministry engaged a Senior Advisor, Mental Health, to develop alternate ways to maintain housing for this group. A province-wide mental health training initiative aimed at frontline housing staff, which uses unique techniques such as popular theatre, experiential exercises and partnership building/strategic alliance development will be described in this paper.

Activities of Daily Living↗
PubMed1995

Phenylketonuric patients decades after diet.

Nineteen early-treated phenylketonuric patients, whose diet was discontinued between 4.5 and 13 years of age, and who have been off the diet for 12-28 years, were reassessed in 1992-93. There was little change in mean IQ between end of diet and follow-up, less than one IQ point on the average, with no change for any individual exceeding 12 IQ points. Both prior and current IQ correlated slightly negatively with mean phenylalanine (Phe) concentration, and positively with parents' education. The phenylalanine level at follow-up was significantly lower on average by about 900 mumol/L. Five of the subjects (26%) have evidence of mental disease. However, the data suggest that the discontinuation of the diet did not cause intellectual deterioration. Nonetheless, the patients' intellect cannot be the only consideration for maintenance of diet. The occurrence of psychopathology among phenylketonuric patients and the possible unknown effects of toxic elevation of phenylalanine during their lifetime suggest the need to maintain the diet. The use of DNA for diagnostic and prognostic purposes might assist in decisions about dietary quality and duration, and in anticipation of psychopathology.

Adult↗
PubMed1991

Bony changes of PKU neonates unrelated to phenylalanine levels.

In 1962 bone abnormalities were described radiographically in phenylketonuria patients. Later, observations were made on PKU infants during the neonatal period, which allowed differentiation between inherited alterations in bone development from those changes due to dietary restriction. Similar changes have been described in other aminoacidurias. Wrist radiographs and serum phenylalanine levels were obtained on 73 patients first seen between 1965 and 1990. All radiographs were taken on the day of referral, when the patient was between 6 and 57 days old. Forty-nine patients were less than 28 days old. Bone abnormalities were present in 56 of 73 (77%) of the children, as compared to 0 of 16 in a control group. The presence or absence of bone abnormality is unrelated to serum phenylalanine level, and to the age of the children at referral. This finding suggests that the cause of these mesodermal changes is not a deviation of a single amino acid in the infant, but that they are caused by an intrauterine amino acid imbalance.

Bone and Bones↗
PubMed1990

Families as educational consumers: what do they want? What do they receive?

In this study of 100 families of patients diagnosed with psychiatric disorders, the authors sought to discover what kinds of help families as educational consumers wanted, whether the desired help was received, and where they got (or hoped to get) help. One-half of the families wished they had received more assistance. Most wanted information from psychiatrists, and their level of education was an important factor in determining whether they actually saw psychiatrists. The families felt a need for professionally run information and support groups, but few actually received such help. Professionals did not satisfy the educational needs of families of patients suffering from psychiatric disorders.

Adult↗
PubMed1985

Relationship between phenylalanine tolerance and psychological characteristics of phenylketonuric families.

The purpose of this study was to find out how genetic and biochemical limitations influence psycho-social performance and to partially test the validity of justification theory. The ability to convert phenylalanine to tyrosine was compared with intellectual and personality characteristics in PKU family members. Each of the tested persons was given an oral dose of phenylalanine, the Shipley-Hartford Intelligence Test, and the Minnesota Multiphasic Personality Inventory (MMPI). Only those persons with reading ability at the sixth grade level or higher were tested. Eighty-six persons were tested: fifteen PKUs, forty-three siblings, and twenty-eight parents. A comparison was made among parents, PKUs, and the siblings. Siblings with the higher 2/3's of P2/T ratios were contrasted with those with the lowest 1/3 of ratios on measures of intelligence and psychopathology. Statistical analyses of the data reflected a trend in support of the justification theory. PKUs had significantly lower intelligence than their sibs and parents. The PKUs' mean IQ was 95 (homozygotes born of heterozygotes), followed by the upper 2/3's sibling mean IQ of 105 (heterozygotes born of nonheterozygote mothers). The lower 1/3 siblings' mean IQ was 107 (nonheterozygotes born from heterozygote mothers), and finally, the parents' mean IQ was 109 (heterozygotes, among them 50% were born from nonheterozygote mothers). The latter three mean IQs are not significantly different from each other. The personality tests revealed a trend toward more abnormality in PKUs than in their heterozygote siblings. The lowest rate of abnormality occurred in the nonheterozygote sibling group; that rate was significantly lower than in all other groups. The parents had the highest absolute rate of personality abnormality, but statistically so compared to the low-ratio siblings.

Adolescent↗
PubMed1984

Growth development and its relationship to intellectual functioning of children with phenylketonuria.

Growth measurements, including weight, height, and head circumference, of 67 early treated children with phenylketonuria (PKU) were compared to normal standards from infancy up to six years of age. Children with PKU, both girls and boys, achieved growth parameters that were similar to those of normals. Head circumference of the boys at six years of age and of the girls at three and four years of age correlated positively with IQ scores. Weight/height (W/H) ratios at one year of age correlated positively with IQ scores for boys. Similar correlations between IQs and weight/height ratios were found for girls at one, two, and three years of age.

Body Height↗