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Biomedical subjects

S Steinberg

Publications and source records attributed to S Steinberg.

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

Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Acute Disease↗
PubMed1998

Compilation of tRNA sequences and sequences of tRNA genes.

Sequences of 3279 sequences of tRNA genes and tRNAs published up to December 1996 are included in the compilation. Alignment of the sequences, which is most compatible with the tRNA phylogeny and known three-dimensional structures of tRNA, is used. Sequences and references are available under http://www.uni-bayreuth. de/departments/biochemie/trna/

Animals↗
PubMed1998

A neutron reflectivity study of polymer-modified phospholipid monolayers at the solid-solution interface: polyethylene glycol-lipids on silane-modified substrates.

The structure of polymer-decorated phospholipid monolayers at the solid-solution interface was investigated using neutron reflectometry. The monolayers were composed of distearoylphosphatidylethanolamine (DSPE) matrixed with varying amounts of DSPE-PEG (DSPE with polyethylene glycol covalently grafted to its headgroup). Mixed lipid monolayers were Langmuir-Blodgett deposited onto hydrophobic quartz or silicon substrates, previously hydrophobized by chemically grafting a robust monolayer of octadecyltrichlorosilane (OTS). We show that this method results in homogeneous and continuous phospholipid monolayers on the silanated substrates and determine that the grafted PEG chains extend away from the monolayers into the solvent phase as a function of their density, as expected from scaling theories. In addition, ligands were coupled to the end of the PEG chains and selective binding was demonstrated using fluorescence microscopy. Our results demonstrate that these constructs are ideal for further characterization and studies with well-defined monomolecular films.

Adsorption↗
PubMed1998

Evidence of latent varicella-zoster virus in rat dorsal root ganglia.

Latent varicella-zoster virus (VZV) was studied in ganglia of rats that had been inoculated subcutaneously with either a high-passaged wild-type, a low-passaged wild-type, or the vaccine strain of virus using in situ hybridization. Nine of 11 rats injected with virus and no control rats developed serum VZV antibodies as demonstrated by fluorescent antibody membrane antigen. Polymerase chain reaction 2 weeks following inoculation did not detect viremia in the rats. VZV was detected by in situ hybridization in ganglia of 10 of the 11 infected rats but not in ganglia of the control rats. The distribution of VZV DNA is identical to that seen in humans; satellite cells and neurons contain VZV DNA. Although all animals received unilateral injections of virus, VZV DNA was in ipsilateral and contralateral ganglia in 6 animals, suggesting that virus replication and viremia had occurred.

Animals↗
PubMed1998

Polymerase chain reaction and restriction fragment length polymorphism analysis of varicella-zoster virus isolates from the United States and other parts of the world.

A polymerase chain reaction (PCR) assay that identifies and differentiates wild-type (wt) and vaccine strains of varicella-zoster virus (VZV) was used to determine if VZV strains with restriction fragment length polymorphisms resembling those of the Japanese Oka vaccine strain were present in the wt pool outside of Japan. Virus samples (n = 114) from patients with chickenpox and zoster from various parts of the United States and Australia were analyzed. The assay correctly identified 113 samples as wt strain. The 1 sample identified as Oka vaccine strain came from a child with leukemia who developed a vaccine-associated rash after receiving the live attenuated varicella vaccine. At this point, there is no evidence that wt strains resembling the vaccine are circulating outside of Japan. This indicates that this PCR assay can be utilized to distinguish rashes due to vaccine and wt VZV.

Australia↗
PubMed1998

Neither dopamine nor dobutamine corrects mesenteric blood flow depression caused by positive end-expiratory pressure in a rat model of acute lung injury.

OBJECTIVE: To determine if either dopamine or dobutamine would counteract the deleterious effect that positive end-expiratory pressure (PEEP) has on cardiac output and mesenteric blood flow in a rat model of acute lung injury. DESIGN: Prospective, randomized, controlled trial in a clinically relevant model of acute lung injury. SETTING: Microcirculation research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals were anesthetized with pentobarbital (30 mg/kg) by intraperitoneal injection. They underwent tracheostomy, jugular and femoral vein cannulation, femoral artery cannulation, carotid artery thermistor placement, and bowel preparation for in vivo video microscopy. Acute lung injury was created by administering 0.1 N hydrochloric acid (1 mL/kg) via the tracheostomy. Dopamine or dobutamine (2.5 or 12.5 microg/kg/min), followed by two intravenous fluid boluses, was administered to rats ventilated with 5, 10, 15, and 20 cm H2O of PEEP. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, thermodilution cardiac output, mesenteric arteriolar diameter, and red blood cell velocity were measured and mesenteric blood flow was calculated. Cardiac output was depressed in rats exposed to 20 cm H2O of PEEP by 32+/-2%. The corresponding values for cardiac output depression at 20 cm H2O of PEEP in rats receiving 2.5 and 12.5 microg/kg/min of dopamine and 2.5 and 12.5 microg/kg/min of dobutamine were 31+/-1%, 21+/-1%, 29+/-0%, and 24+/-2%, respectively. Mesenteric blood flow was depressed in rats ventilated with 20 cm H2O of PEEP by 74+/-3%, while the corresponding values in rats exposed to 20 cm H2O of PEEP and receiving 2.5 or 12.5 microg/kg/min of dopamine or 2.5 or 12.5 microg/kg/min of dobutamine were 86+/-3%, 77+/-3%, 73+/-3%, and 66+/-3%, respectively. Fluid boluses did not correct the deficits in cardiac output or mesenteric blood flow caused by the combination of acute lung injury and PEEP. CONCLUSIONS: The higher doses of dopamine and dobutamine partially, but insignificantly, corrected the cardiac output depression caused by PEEP in a model of acute lung injury. Neither dose of dopamine nor dobutamine was able to improve PEEP-induced mesenteric blood flow depression.

Animals↗
PubMed1998

Psychosocial outcome after ICD implantation: a current perspective.

Depression and reduced sexual functioning have been identified as problems following ICD placement. We examined these issues, and multiple other quality-of-life measures, and their relationship to ICD and ICD discharge. Patients were 64 +/- 11 years old, 72% male, and had undergone ICD 20 +/- 14 months previously. Fifty-eight patients responded to a confidential biopsychosocial questionnaire. Positive attitudes toward the procedure increased from 52% before to 76% after implantation. Satisfaction correlated most strongly with less anger (P = 0.002, r = 0.45), less worry about ICD size (P = 0.007, r = 0.38), less sadness (P = 0.01, r = 0.37), and perceived better health (P = 0.01, r = 0.35). Of these ICD patients, 20%-58% reported measures of depression, and sexual frequency was reduced in 45%. Despite successful ICD placement, health concern increased in 62% of the respondents. Thirty-nine percent attended support groups; 96% found them very helpful. Mean number of ICD discharges described by responders was 5 +/- 11. Fifty percent of our sample reported > or = 1 shock; equal numbers had 1, 2-5, 6-10, and more than 10 shocks. Sixty-two percent of men had at least one discharge compared to 13% of women. After controlling for cardiac clinical variables, experiencing > or = 1 ICD shock was strongly associated with anxiety about family (odds ratio = 7.3), reduced new activities (odds ratio = 6.9), increased sadness (odds ratio = 6.2), and health worry (odds ratio = 5.8). Experiencing > or = 5 ICD shocks was strongly associated with increased health concern (odds ratio = 13.6), increased sadness (odds ratio = 12.5), increased fatigue (odds ratio = 6.1), current sadness (odds ratio = 5.8), and increased nervousness (odds ratio = 5.3). ICD implantation powerfully affects quality-of-life. Postimplantation health concern is paradoxically increased despite improvement in actual health. Negative emotions are associated with defibrillator discharge.

Attitude to Health↗
PubMed1997

Structural rules and conformational compensations in the tRNA L-form.

The mitochondrial tRNAs (mtRNA) of five distinct, secondary structure types have been identified in the tRNA sequence compilation, and the three-dimensional modeling for representative sequences of these types has been carried out using a new criterion for the lengths of the helical domains and connector regions in a full-sized tRNA conformation. This criterion has been derived from the analysis of the known structures of cytosolic tRNAs and states that in the tRNA structure nucleotide 59 of the T-loop should stack onto Domain 1. To ensure this, Domain 1 must have 12 layers of stacked nucleotides, and in the case of a deletion of a base-pair in the T-stem, an additional 13th layer is required. Although a number of mitochondrial tRNAs harbored deficiencies in this criterion and, therefore, could not be modeled directly, this disability could be corrected and modeling accomplished by invoking structural compensations derived from one of two unusual aspects of these tRNAs. One class of these tRNAs contained an unpaired nucleotide in their anticodon stem, and their three-dimensional structure was successfully modeled when the unpaired nucleotide was intercalated into the helical domain of the stem. The second class contained more than the required number of nucleotides connecting the tRNA helical domains; the conformational flexibility of these nucleotides allowed them to take the place of the absent layers. The conformational compensation that we report rationalizes disparate features of these tRNAs and suggests that the stacking of nucleotide 59 on Domain 1 is an essential feature of the three-dimensional L-form of tRNA.

Base Composition↗
PubMed1997

Transmission of varicella-vaccine virus from a healthy 12-month-old child to his pregnant mother.

A 12-month-old healthy boy had approximately 30 vesicular skin lesions 24 days after receiving varicella vaccine. Sixteen days later his pregnant mother had 100 lesions. Varicella-vaccine virus was identified by polymerase chain reaction in the vesicular lesions of the mother. After an elective abortion, no virus was detected in the fetal tissue. This case documents transmission of varicella-vaccine virus from a healthy 12-month-old infant to his pregnant mother.

Abortion, Induced↗
PubMed1997

Effect of fluoxetine on menstrual cycle length in women with premenstrual dysphoria.

OBJECTIVE: To examine whether changes in menstrual cycle length occurred in women who received 20 mg of fluoxetine per day and women who received 60 mg of fluoxetine per day as compared with women who received placebo. METHODS: A two-cycle, single-blind placebo phase was followed by a six-cycle double-blind phase. Only placebo nonresponders were randomized to one of three treatment arms: placebo, fluoxetine 20 mg/day, or fluoxetine 60 mg/day. Cycle length was established using a prospective daily calendar. Cycle-length data from women who completed at least three treatment cycles were used in this analysis. Cycle-length change was defined a priori as cycle lengthening or shortening of 4 days or more (1 or more standard deviations from the mean change between baseline cycles). RESULTS: Eleven of the 62 women receiving 60 mg of fluoxetine per day and seven of the 70 women receiving 20 mg of fluoxetine per day but only one of the 61 women in the placebo group demonstrated cycle-length change at the end of the first treatment cycle (P = .011). In total, 15% of the women in the fluoxetine 60 mg/day group demonstrated a cycle-length change during two of the three observed cycles compared with 6% of the women in the fluoxetine 20 mg/day group and 3% of the women in the placebo group (P = .048). Women with cycle-length changes demonstrated either shortening or lengthening only. There were no differences between the number of women with changes in either direction. CONCLUSION: Cycle-length change occurred more frequently in the fluoxetine 60 mg/day group than in the fluoxetine 20 mg/day or placebo groups. The effects of selective serotonin reuptake inhibitors on menstrual cycle length are mostly unknown and warrant careful monitoring in women of reproductive age, who are the prime consumers of these medications.

Adult↗
PubMed1997

Varicella-zoster virus infection in children with underlying human immunodeficiency virus infection.

This article describes a prospective longitudinal study of varicella-zoster virus (VZV) infections in human immunodeficiency virus (HIV)-infected children, designed to determine their natural history of VZV infection and possible effects of VZV on the progression of HIV infection. Varicella was usually not a serious acute problem, and it did not seem to precede clinical deterioration. The rate of zoster was high: 70% in children with low levels of CD4+ lymphocytes at the time of development of varicella. It is predicted that immunization with live attenuated varicella vaccine is unlikely to be deleterious to HIV-infected children. Moreover, if they are immunized when they still have relatively normal levels of CD4+ lymphocytes, they may have a lower rate of reactivation of VZV than if they were allowed to develop natural varicella when their CD4+ cell counts have fallen to low levels as a result of progressive HIV infection.

Antibodies, Viral↗
PubMed1997

Transmission of vaccine strain varicella-zoster virus from a healthy adult with vaccine-associated rash to susceptible household contacts.

Twelve days after receiving an investigational Oka strain live attenuated varicella vaccine, a 38-year-old healthy white woman developed a rash consisting of 30 scattered lesions. Sixteen days later, her 2 children also developed rash. Swabs obtained from the skin lesions of the vaccinee and her children demonstrated the presence of varicella-zoster virus (VZV) DNA by a polymerase chain reaction (PCR) assay. Restriction endonuclease polymorphisms present in wild and vaccine type VZV were examined, and the amplified VZV DNA was determined to be vaccine type. This case documents transmission of varicella vaccine type virus from a healthy vaccinee to susceptible household contacts. Since vaccine-associated rashes are uncommon and mild, it is likely that transmission of vaccine virus will also be uncommon. With widespread immunization beginning in the United States, ongoing studies will define the frequency of this transmission.

Adult↗