Biomedical subjects

S Steinberg

Publications and source records attributed to S Steinberg.

At least 19 recordsLinked to original sources

PubMed2001

Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833.

PURPOSE: PSC 833 (valspodar) is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance. We conducted a phase I study of a 7-day oral administration of PSC 833 in combination with paclitaxel, administered as a 96-hour continuous infusion. PATIENTS AND METHODS: Fifty patients with advanced cancer were enrolled onto the trial. PSC 833 was administered orally for 7 days, beginning 72 hours before the start of the paclitaxel infusion. Paclitaxel dose reductions were planned because of the pharmacokinetic interactions known to occur with PSC 833. RESULTS: In combination with PSC 833, maximum-tolerated doses were defined as paclitaxel 13.1 mg/m(2)/d continuous intravenous infusion (CIVI) for 4 days without filgrastim, and paclitaxel 17.5 mg/m(2)/d CIVI for 4 days with filgrastim support. Dose-limiting toxicity for the combination was neutropenia. Statistical analysis of cohorts revealed similar mean steady-state concentrations (C(pss)) and areas under the concentration-versus-time curve (AUCs) when patients received paclitaxel doses of 13.1 or 17.5 mg/m(2)/d for 4 days with PSC 833, as when they received a paclitaxel dose of 35 mg/m(2)/d for 4 days without PSC 833. However, the effect of PSC 833 on paclitaxel pharmacokinetics varied greatly among individual patients, although a surrogate assay using CD56+ cells suggested inhibition of Pgp was complete or nearly complete at low concentrations of PSC 833. Responses occurred in three of four patients with non-small-cell lung cancer, and clinical benefit occurred in five of 10 patients with ovarian carcinoma. CONCLUSION: PSC 833 in combination with paclitaxel can be administered safely to patients provided the paclitaxel dose is reduced to compensate for the pharmacokinetic interaction. Surrogate studies with CD56+ cells indicate that the maximum-tolerated dose for PSC 833 gives serum levels much higher than those required to block Pgp. The variability in paclitaxel pharmacokinetics, despite complete inhibition of Pgp in the surrogate assay, suggests that other mechanisms, most likely related to P450, contribute to the pharmacokinetic interaction. Future development of combinations such as this should include strategies to predict pharmacokinetics of the chemotherapeutic agent. This in turn will facilitate dosing to achieve comparable CPss and AUCs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

[Automated image analysis of lateral roentgen images of the spine using anatomic models].

PURPOSE: Development of a software for fully automated image analysis of lateral lumbar spine X-rays. MATERIAL AND METHOD: Using the concept of active shape models, we developed a software that produces a form model of the lumbar spine from lateral lumbar spine radiographs and runs an automated image segmentation. This model is able to detect lumbar vertebrae automatically after the filtering of digitized X-ray images. The model was trained with 20 lateral lumbar spine radiographs with no pathological findings before we evaluated the software with 30 further X-ray images which were sorted by image quality ranging from one (best) to three (worst). There were 10 images for each quality. RESULTS: Image recognition strongly depended on image quality. In group one 52 and in group two 51 out of 60 vertebral bodies including the sacrum were recognized, but in group three only 18 vertebral bodies were properly identified. CONCLUSION: Fully automated and reliable recognition of vertebral bodies from lateral spine radiographs using the concept of active shape models is possible. The precision of this technique is limited by the superposition of different structures. Further improvements are necessary. Therefore standardized image quality and enlargement of the training data set are required.

Humans↗

PubMed2001

The efficacy of fluoxetine in improving physical symptoms associated with premenstrual dysphoric disorder.

OBJECTIVE: To determine the effectiveness of fluoxetine in alleviating physical symptoms of premenstrual dysphoric disorder. DESIGN: Randomised, double-blind, placebo controlled, parallel study. SETTING: Canadian University based outpatient clinics. Participants Four hundred and five subjects, of whom 320 with prospectively determined premenstrual dysphoric disorder were randomised. METHODS: Randomised women were assigned to fluoxetine 20 or 60 mg/day or placebo. Common physical symptoms associated with premenstrual dysphoric disorder including breast tenderness, bloating, and headache were evaluated by visual analog scales and the self-rated and observer premenstrual tension syndrome scales. OUTCOME MEASURES: Luteal phase change from mean baseline scores to mean treatment scores for all scales. RESULTS: Fluoxetine treatment was statistically superior to placebo, with no significant differences between the two fluoxetine dosages in their effects on physical symptoms. CONCLUSION: Daily fluoxetine treatment is superior to placebo in improving the most common physical symptoms associated with premenstrual dysphoric disorder.

Adult↗

PubMed2001

Preparing for the future through genetics nursing education.

PURPOSE: To determine recommendations for curriculum change that are indicated by innovations in genetics. METHODS: Both quantitative and qualitative. The sample (n = 356) consisted of nurses identified as experts in genetics (n = 228) and nurses identified as potential users of genetics education (n = 128). Nurses' opinions of core components of a genetics curriculum were elicited via a mailed survey questionnaire. Participants also provided demographic information and completed the Jones Innovativeness Scale (1997). FINDINGS: Recommended content in genetics education for practicing nurses was identified by both groups of nurses. Innovativeness characterized 3% of the respondents. Ninety-eight percent of respondents said that adopting genetics education is important. In total, 398 items were identified as potential consequences of education that incorporates genetic information. CONCLUSIONS: Identified content provides a template for genetics education programs for nurses. Genetics nursing education was perceived to have positive outcomes for both nurses and clients.

Adult↗

PubMed2001

Disseminated vaccine strain varicella as the acquired immunodeficiency syndrome-defining illness in a previously undiagnosed child.

The Food and Drug Administration licensed a live-virus varicella vaccine (Varivax; Merck & Co Inc, West Point, PA) in March 1995. Prelicensure adverse events were minimal; however, since licensure and increased vaccine use, rare previously undetected risks have arisen. Presented here is the clinical course of a previously undiagnosed, human immunodeficiency virus-infected boy who developed dissemination of the vaccine strain of varicella zoster after immunization. chickenpox, human immunodeficiency virus, pneumonia, encephalopathy, varicella vaccine, adverse events, dissemination.

Chickenpox↗

PubMed2000

Effects of the renin-angiotensin system on the current I(to) in epicardial and endocardial ventricular myocytes from the canine heart.

The Ca(2+)-independent portion of transient outward K(+) current (I(to)) exhibits a transmural gradient in ventricle. To investigate control mechanisms for this gradient, we studied canine epicardial and endocardial ventricular myocytes with use of the whole-cell patch-clamp technique. I(to) was larger in amplitude, had a more negative voltage threshold for activation, and had a more negative midpoint of inactivation in epicardium. Recovery from inactivation was >10-fold slower in endocardium. Incubation of epicardial myocytes with angiotensin II for 2 to 52 hours altered I(to) to resemble unincubated endocardium and reduced the amplitude of the phase 1 notch of the action potential. In contrast, incubation of endocardial myocytes with losartan for 2 to 52 hours altered I(to) to resemble unincubated epicardium and induced a phase 1 notch in the action potential. With RNase protection assays, we determined that incubations with angiotensin II or losartan did not alter mRNA levels for either Kv4.3 or Kv1.4; thus, a change in the alpha subunit for I(to) is unlikely to be responsible. To test whether posttranslational modification produced the effects of angiotensin II, we coexpressed Kv4.3 and the angiotensin II type 1a receptor in Xenopus oocytes. Incubation with angiotensin II increased the time constant for recovery from inactivation of the expressed current by 2-fold with an incubation time constant of 3.7 hours. No effect on activation or inactivation voltage dependence was observed. These results demonstrate that the properties of I(to) in endocardium and epicardium are plastic and likely under the tonic-differing influence of the renin-angiotensin system.

Action Potentials↗

PubMed2000

Protein kinase C-beta and oxygen deprivation. A novel Egr-1-dependent pathway for fibrin deposition in hypoxemic vasculature.

Fibrin deposition is a salient feature of hypoxemic vasculature and results from induction of tissue factor. Such tissue factor expression in an oxygen deficient environment is driven by the transcription factor Early Growth Response (Egr)-1. Using homozygous null mice for the protein kinase C beta-isoform gene (PKCbeta null), PKCbeta is shown to be upstream of Egr-1 in this oxygen deprivation-mediated pathway for triggering procoagulant events. Whereas wild-type mice exposed to hypoxia (6%) displayed a robust increase in tissue factor transcripts and antigen, and vascular fibrin deposition, PKCbeta null animals showed a markedly blunted response. Consistent with a central role for Egr-1 in hypoxia-induced expression of tissue factor, PKCbeta null mice subjected to oxygen deprivation displayed at most a minor elevation in Egr-1 transcripts, antigen, and intensity of the gel shift band by electrophoretic mobility shift assay, compared with normoxic animals. These data firmly establish PKCbeta as a trigger for events leading to induction of Egr-1 and tissue factor under hypoxic conditions, and provide insight into a biologic cascade whereby oxygen deprivation recruits targets of PKCbeta and Egr-1, thereby amplifying the cellular response.

Animals↗

PubMed2000

Epidemiology of HIV/AIDS in children.

HIV infection has been a major cause of morbidity and mortality since the first cases of AIDS among children were reported in 1982 in the United States. Considerable advances, especially in the past 5 years, in the understanding of the pathogenesis, diagnosis, treatment, monitoring, and prevention of HIV infection in children have changed the rate of pediatric HIV infection in the United States. Efforts to maximally decrease perinatal HIV transmission in the United States are ongoing. Physicians must try to prevent HIV infection among women, especially adolescents.

AIDS-Related Opportunistic Infections↗

PubMed2000

Reinventing fatherhood in Japan and Canada.

This article summarizes the findings of a transnational study of Japanese and Canadian families. Fathers' perceptions are presented for a critical developmental phase of life: pregnancy, labor, birth, the early and late postpartum periods. Using qualitative and quantitative research methods, 33 fathers and 194 mothers were interviewed: Japanese in Tokyo and Montreal, and English and French Canadians in Montreal. In addition, the study examines the impact of pregnancy and birth on the relationship of marriage. The results suggest that the social meaning of fatherhood has been transformed, legitimizing the presence of the father in the domestic sphere as a consequence of shifting extended family household structures, economic conditions and the empowerment of women. Other significant (p < 0.05) patterns were identified. (1) Canadian fathers participate in labor and delivery to a higher degree than Japanese fathers in Montreal and Tokyo do (mothers in Tokyo felt more isolated). (2) Canadian men (60%) are more likely to take time off from work during this phase than the Japanese. (3) Overall, the majority of fathers, in all four groups, cared for the child to a higher degree than expected and (4). Birth and early child rearing appears to have a significant impact on marriage in all four groups. Public policy issues are addressed and potential responses provided.

Adult↗

PubMed2000

8:45-9:00. Using PET 18F-FDG, 11CO, and 15O-water for Monitoring Prostate Cancer During a Phase II Anti-angiogenic Drug Trial with Thalidomide.

Assessing prostate metastases is difficult with conventional radiographic modalities as few patients have soft tissue involvement and most have only bone lesions. Even with FDG PET, problems due to decreased avidity compared to other tumor types can occur. We assessed PET's ability to monitor changes in such tumors during an anti-angiogenic therapy. We measured changes in tumor blood flow (15O), blood volume (11CO), 18F-FDG uptake and "metabolic volume" before and during thalidomide treatment, to see if these changes correlated with changes in PSA values.Six patients with androgen-independent prostate cancer were imaged with 18F-FDG, 11CO, and 15O water before and during (mean interval 63 days, range 55-76 days) thalidomide therapy (200-1200mg/day). Lesions were visually identified on FDG images (9 bone, 5 soft tissue lesions). VOI's were generated by 3D region growing, with a 50% maximum pixel threshold. These VOI's were registered with, and applied to, the 11CO and water studies. Correlations with PSA values were done using the Spearman rank test.The change in maximum (r = 0.77, p = 0.06) and mean FDG value (r = 0.83, p = 0.03), functional FDG volume (r = 0.66, p = 0.14), and 11-CO blood volume (r = 0.77, p = 0.06) all correlated with the change in PSA. Changes in blood flow values were smaller than the variance of the method for repeated measures, likely due to low flow values in bone.Changes in blood volume measured by 11CO, and the mean and peak activity and functional volume measured by 18F-FDG, correlate with changes in PSA and may be useful in monitoring anti-angiogenic therapy in prostate cancer.

Journal Article↗

PubMed2000

The geographic distribution of AIDS in the United States: is there a rural epidemic?

The goal of this study was to examine where people with acquired immune deficiency syndrome (AIDS) in the United States live and the degree to which AIDS is present in rural areas. AIDS cases reported to the Centers for Disease Control and Prevention (CDC) in 1996 were categorized by metropolitan statistical area (MSA) size and compared to the general population. Data were analyzed by region, race/ethnicity and risk exposure; AIDS incidence rates were compared over time by MSA size. Relative to the U.S. population, AIDS cases were disproportionately black (43 percent vs. 11 percent), male (80 percent vs. 48 percent), and from the Northeast (32 percent vs. 20 percent). In all regions, a greater proportion of AIDS cases reside in large MSAs compared with the general population. Risk exposures differ little by MSA size, except in the Northeast. The proportion of people with AIDS who reside in large MSAs exceeds the proportion of the population in those areas, especially when race/ethnicity is considered. AIDS rates have increased in non-MSAs relative to large MSAs, yet do not indicate that the epidemic is increasing rapidly in rural areas. Fewer AIDS cases are reported from smaller communities, yet require medical and social services that may burden the rural health care system.

Acquired Immunodeficiency Syndrome↗

PubMed1999

A placebo-controlled clinical trial of L-tryptophan in premenstrual dysphoria.

BACKGROUND: Antidepressant drugs, including specific serotonin reuptake inhibitors, have been shown to be beneficial in the treatment of premenstrual dysphoric disorders. The present study tests the efficacy of L-tryptophan, which acts specifically on serotonergic neurons, in this disorder. METHODS: In a randomized controlled clinical trial, 37 patients with premenstrual dysphoric disorder were treated with L-tryptophan 6 g per day, and 34 were given placebo. The treatments were administered under double-blind conditions for 17 days, from the time of ovulation to the third day of menstruation, during three consecutive menstrual cycles. RESULTS: The Visual Analogue Scales (VAS) revealed a significant (p = .004) therapeutic effect of L-tryptophan relative to placebo for the cluster of mood symptoms comprising the items of dysphoria, mood swings, tension, and irritability. The magnitude of the reduction from baseline in maximum luteal phase VAS-mood scores was 34.5% with L-tryptophan compared to 10.4% with placebo. CONCLUSIONS: These results suggest that increasing serotonin synthesis during the late luteal phase of the menstrual cycle has a beneficial effect in patients with premenstrual dysphoric disorder.

Adult↗

PubMed1999

A placebo-controlled study of the effects of L-tryptophan in patients with premenstrual dysphoria.

In a randomized controlled clinical trial, 37 patients with premenstrual dysphoric disorder were treated with L-tryptophan 6 g per day and 34 were given placebo. The treatments were given under double-blind conditions for 17 days, from the time of ovulation to the third day of menstruation, during three consecutive cycles. Visual Analog Mood Scales revealed a significant (p = 0.004) therapeutic effect of L-tryptophan relative to placebo for the cluster of mood symptoms comprising the items dysphoria, mood swings, tension and irritability. These results suggest that increasing serotonin synthesis during the late luteal phase of the menstrual cycle is therapeutic in patients with premenstrual dysphoric disorder.

Adult↗

PubMed1999

The measurement of premenstrual mood symptoms.

INTRODUCTION: To aid in the diagnosis and management of premenstrual syndromes, dozens of symptom measurement instruments have been created and several methods for classifying clinically important change in symptoms have been defined. While the diagnosis of premenstrual dysphoric disorder (PMDD) has become standardized through the application of research criteria, consensus amongst investigators as to the instruments best able to confirm the diagnosis and measure treatment effects has yet to be reached. OBJECTIVE: To determine the performance and inter-correlations of three prospective symptom rating scales used to establish severity of premenstrual mood symptoms and measure efficacy during a treatment trial for premenstrual dysphoria. METHODS: Single item visual analogue scales (VASs) for irritability, tension, depression and mood swings were used in combination with the Premenstrual Tension Syndrome Observer (PMTS-O) and Self-Rating (PMTS-SR) scales to measure the severity of premenstrual mood symptoms at baseline and during treatment. RESULTS: Premenstrual mood symptoms as measured by VASs significantly correlated with PMTS-0 and PMTS-SR scale scores (range 0.70 to 0.82, P < 0.001). All scales were sensitive to premenstrual symptom worsening (which is a required characteristic of this disorder) and revealed differences in effects of treatment on premenstrual mood symptoms (P < 0.001). CONCLUSIONS: VASs in combination with the PMTS-O are low in burden to the client, reliable, valid and sensitive to change. In light of the current debates regarding instruments most appropriate for the classification and measurement of treatment effects in women diagnosed with premenstrual dysphoria, further refinement of these scales is warranted.

Double-Blind Method↗

PubMed1999

Sensitivity to CCK-4 in women with and without premenstrual dysphoric disorder (PMDD) during their follicular and luteal phases.

The authors determined whether women with premenstrual dysphoric disorder (PMDD) exhibit a heightened sensitivity to the panicogenic effects of CCK-4 administration and whether this enhanced sensitivity to CCK-4 would vary with the phase of the menstrual cycle at the time of CCK-4 injection. Twenty-one normal controls and 18 PMDD women were randomly assigned to receive the first and second CCK-4 injection during the follicular phase and the luteal phase or vice versa. PMDD women showed a greater anxiety and panic response to CCK-4. These preliminary results suggest that the CCK-B system may play a role in the pathophysiology of PMDD.

Adult↗

PubMed1999

Paclitaxel chemotherapy after autologous stem-cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients.

The MDR1 multidrug resistance gene confers resistance to natural-product anticancer drugs including paclitaxel. We conducted a clinical gene therapy study to determine whether retroviral-mediated transfer of MDR1 in human hematopoietic cells would result in stable engraftment, and possibly expansion, of cells containing this gene after treatment with myelosuppressive doses of paclitaxel. Patients with metastatic breast cancer who achieved a complete or partial remission after standard chemotherapy were eligible for the study. Hematopoietic stem cells (HSCs) were collected by both peripheral blood apheresis and bone marrow harvest after mobilization with a single dose of cyclophosphamide (4 g/m2) and daily filgrastim therapy (10 microg/kg/day). After enrichment for CD34+ cells, one-third of each collection was incubated ex vivo for 72 h with a replication-incompetent retrovirus containing the MDR1 gene (G1MD) in the presence of stem-cell factor, interleukin 3, and interleukin 6. The remaining CD34+ cells were stored without further manipulation. All of the CD34+ cells were reinfused for hematopoietic rescue after conditioning chemotherapy with ifosfamide, carboplatin, and etoposide regimen. After hematopoietic recovery, patients received six cycles of paclitaxel (175 mg/m2 every 3 weeks). Bone marrow and serial peripheral blood samples were obtained and tested for the presence of the MDR1 transgene using a PCR assay. Six patients were enrolled in the study and four patients received infusion of genetically altered cells. The ex vivo transduction efficiency, estimated by the PCR assay, ranged from 0.1 to 0.5%. Three of the four patients demonstrated engraftment of cells containing the MDR1 transgene. The estimated percentage of granulocytes containing the MDR1 transgene ranged from a maximum of 9% of circulating nucleated cells down to the limit of detection of 0.01%. One patient remained positive for the MDR1 transgene throughout all six cycles of paclitaxel therapy, whereas the other 2 patients showed a decrease in the number of cells containing the transgene to undetectable levels. Despite the low level of engraftment of MDR1-marked cells, a correlation was observed between the relative number of granulocytes containing the MDR1 transgene and the granulocyte nadir after paclitaxel therapy. No adverse reactions to the genetic manipulation procedures were detected. Therefore, engraftment of human HSCs transduced with the MDR1 gene can be achieved. However, the overall transduction efficiency and stable engraftment of gene-modified HSCs must be improved before MDR1 gene therapy and in vivo selection with anticancer drugs can be reliably used to protect cancer patients from drug-related myelosuppression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Immune selection after antigen-specific immunotherapy of melanoma.

BACKGROUND: Melanoma antigen (MA)-specific vaccination strongly enhances antitumor reactivity in vivo and is capable of producing strong cytotoxic T lymphocyte responses in vitro. Furthermore, specific human leukocyte antigen-restricted T cell activation is hypothesized to occur in response to peptide-based immunotherapy, which may lead to the preferential killing of tumor cells bearing the relevant MA. The development of melanoma antigen-loss variants may subsequently occur in vivo. METHODS: Analysis of 532 melanoma lesions from 204 patients was performed on fine-needle aspiration biopsy specimens. Lesions were graded for the expression of the MAs gp100 and MART-1 with use of immunocytochemistry. A total of 351 melanoma lesions were divided into cohorts on the basis of the treatment received. The pretreatment group (n = 175) consisted of lesions obtained before any form of gp100 immunotherapy, with the posttreatment group (n = 176) consisting of lesions obtained after vaccination with a modified gp100 epitope, gp209-2M +/- interleukin 2 (IL-2). RESULTS: The percentage of lesions not expressing the gp100 antigen is greater than the percentage not expressing MART-1 (26% vs 14%). The frequency of lesions with high expression (> 75%) of gp100 significantly decreased with therapy (47% vs 34%) and conversely negative lesions increased (18% vs 29%). Treatment of lesions with peptide alone (no IL-2) revealed a significant decrease in gp100 expression (47% vs 32%), enhanced with the addition of IL-2 to therapy (47% vs 35%). The expression of MART-1 remained essentially unchanged unless IL-2 was added (54% vs 54%, MART-1 peptide alone, 54% vs 43%, MART-1 peptide + IL-2). Of 94 patients (181 lesions) assessed for gp100 expression before treatment, 10 patients responded to therapy. Pretreatment lesions in responding patients expressed some level of gp100 in all cases compared with 27% of nonresponding lesions, which were negative for gp100 expression. CONCLUSIONS. This study indirectly demonstrates that vaccination with an MA-derived peptide can result in immune selection in vivo. Furthermore, it provides strong immunologic evidence for the specificity of MA vaccines and to the relevance of MA expression in predicting the response to vaccination.

Antigens, Neoplasm↗

PubMed1998

Trends in HIV prevalence among childbearing women in the United States, 1989-1994.

We used data from a national serosurvey to describe national and regional trends in the prevalence of HIV among women giving birth in the United States from 1989 through 1994, and to estimate the number of women between 15 and 44 years old with HIV infection who had not yet developed opportunistic infections defining AIDS. We compared these estimates with AIDS prevalence and mortality estimates from the national AIDS case surveillance system. HIV seroprevalence among childbearing women remained stable nationwide from 1989 through 1994, ranging from 1.5 to 1.7/1000 women. In the Northeast, seroprevalence declined significantly after 1989. Seroprevalence increased significantly in the South through 1991 and then stabilized, although seroprevalence among black women continued to increase through 1994 in some southern states. Although AIDS prevalence and mortality increased nationwide each year from 1989 through 1994, the number of women infected with HIV who had not yet developed AIDS changed little and was approximately 86,000 in 1994. Our data suggest that new HIV infections among women of reproductive age are occurring at a rate that offsets losses from this population due to aging, disease progression, and death.

Acquired Immunodeficiency Syndrome↗