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T Steinberg

Publications and source records attributed to T Steinberg.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of interleukin-1beta-modulated mRNA gene transcription in human gingival keratinocytes by epithelia-specific cDNA microarrays.

BACKGROUND/OBJECTIVES: Proinflammatory cytokines such as interleukin-1beta are known to be synthesized in oral gingivitis and periodontitis and lead to the activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Although numerous effects of interleukin-1beta on mesenchymal cells are known, e.g. up-regulation of intercellular adhesion molecule-1 in endothelial cells, little is known of the effects of interleukin-1beta on oral keratinocytes. The purpose of the present study was to seek interleukin-1beta-mediated alterations in mRNA gene transcription and a putative activation of NF-kappaB in oral gingival keratinocytes. METHODS: As an in vitro model for gingivitis and periodontitis, immortalized human gingival keratinocytes (IHGK) were stimulated with the proinflammatory cytokine interleukin-1beta. An epithelia-specific cDNA microarray was used to analyze mRNA expression profiles from IHGK cells treated with 200 units interleukin-1beta/ml for 3, 6, 9, 12, and 24 h. Indirect immunofluorescence was carried out to detect NF-kappaB in IHGK following interleukin-1beta treatment. RESULTS: Detailed analysis revealed distinct patterns of time-dependent changes, including genes induced or repressed early (3-6 h) or late (12-24 h) after interleukin-1beta treatment. Differentially expressed genes were involved in (i) cell stress, (ii) DNA repair, (iii) cell cycle and proliferation, (iv) anti-pathogen response, (v) extracellular matrix turnover, and (vi) angiogenesis. A large number of genes were responsive to NF-kappaB and induction was concomitant with nuclear translocation of the p65 RelA subunit of NF-kappaB. Interestingly, many of these genes contain multiple NF-kappaB binding sites in their promoters. CONCLUSION: Analysis of altered gene expression allows identification of gene networks associated with inflammatory responses. In addition to a number of well-known genes involved in gingivitis and periodontitis, we identified novel candidates that might be associated with the onset and maintenance of an inflammatory disease.

Cell Cycle Proteins↗
PubMed2004

Comparison of beam characteristics of a gold x-ray target and a tungsten replacement target.

A new W-Cu target was designed to replace the existing Au target on a linear accelerator model in common use in radiotherapy. This work shows that targets of different material composition can be designed to produce beams with the same dosimetric character over a wide range of beam energies without adjusting the beam energy. The target design objective was to improve mechanical robustness, replacing water in the beam path with a Cu heat sink, without altering the beam properties for the nominal clinical energy range of 4-25 MV. The W-Cu could then be installed in place of the Au target without recommissioning. The effect of the target swap was measured in the test cells for 11 different beams ranging in nominal energy from 4 to 25 MV, with focus on open field dose distributions, including diagonal profiles taken for the largest (40x40 cm) field, measured at 4 different gantry angles. Depth dose curves agreed to 0.4% or better, profiles to 1.2% or better. Monte Carlo simulations of the treatment head were done for representative energies of 6 and 18 MV. Calculated and measured dose distributions generally matched within 1%, although dose measured in the build-up region of large fields was significantly more than in the simulations. Calculated spectral distributions on the central axis and angular distributions of energy fluence matched for the two targets, whereas angular distributions of fluence were significantly different. Matching energy fluence gave a more favorable match of dose profiles than matching fluence. The target was further tested on several machines operating in a radiotherapy clinic. Measurements were made for a wide range of open field sizes and with selected wedges and blocks. Dose distributions for the two targets agreed to 1.4% or better, including the dose in wedged fields. Wedge factors changed by no more than 0.5%, transmission through a 4.4 HVL block no more than 1.5%. The response of the monitor chamber was found to change, generally by 1%-2%. Therefore, when the W-Cu target was used to replace the Au target, the output of the machine was measured and adjusted appropriately, but there was no requirement for recommissioning.

Gold↗
PubMed2003

Low incidence of cytomegalovirus disease in liver transplant recipients receiving sirolimus primary immunosuppression with 3-day corticosteroid taper.

BACKGROUND: Cytomegalovirus (CMV) disease is the most common infection following liver transplantation, occurring in approximately 20% of recipients. In liver transplant recipients, CMV is associated with a higher cost following transplantation, subsequent infections, and recurrent hepatitis C. Since we have initiated a prednisone-free immunosuppressive regimen in January 2000, we have noted an extremely low incidence of CMV disease in our cohort of liver transplant recipients. We report our findings here. METHODS: All 150 patients transplanted between January 2000 and December 2002 with tacrolimus (or cyclosporin A) and sirolimus, and 3-day corticosteroid taper were retrospectively analyzed. Recipients who were CMV IgG negative with a CMV IgG-positive donor ("CMV mismatch") received conventional prophylactic therapy with intravenous and oral ganciclovir. The incidence of CMV disease (defined as positive tissue culture or positive immunohistochemical stain of affected tissue or CMV-DNA >3000 associated with clinical symptoms) was recorded for each patient. RESULTS: The proportion of "CMV mismatches" (donor CMV IgG positive, recipient CMV IgG negative) was 15%. The mean total number of days of ganciclovir prophylaxis (intravenous and/or oral) administered to "CMV mismatch" patients was 45.6 days. The incidence of CMV disease in patients receiving sirolimus primary immunosuppression was 2%. The mean time to diagnosis of CMV disease was 139 days. CONCLUSIONS: (1) The incidence of CMV disease is very low using a prednisone-free, sirolimus immunosuppressive regimen. (2) Two possible explanations for this finding include appropriate prophylaxis with ganciclovir and low levels of immunosuppression including the absence of prednisone.

Adrenal Cortex Hormones↗
PubMed2002

Congenital insensitivity to pain. Orthopaedic manifestations.

We reviewed 13 patients with congenital insensitivity to pain. A quantitative sweat test was carried out in five and an intradermal histamine test in ten. DNA examination showed specific mutations in four patients. There were three clinical presentations: type A, in which multiple infections occurred (five patients); type B, with fractures, growth disturbances and avascular necrosis (three patients); and type C, with Charcot arthropathies and joint dislocations, as well as fractures and infections (five patients, four with mental retardation). Patient education, shoeware and periods of non-weight-bearing are important in the prevention and early treatment of decubitus ulcers. The differentiation between fractures and infections should be based on aspiration and cultures to prevent unnecessary surgery. Established infections should be treated by wide surgical debridement. Deformities can be managed by corrective osteotomies, and shortening by shoe raises or epiphysiodesis. Joint dislocations are best treated conservatively.

Adolescent↗
PubMed2001

Role of multileaf collimator in replacing shielding blocks in radiation therapy.

To facilitate the use of multileaf collimator (MLC) in field shaping, we tested the hypothesis that the changes in the penumbra due to MLC replacing a Cerrobend block can be related to a change in the margin of the block. We also investigated if it is possible to estimate the effect of MLC replacing a block in terms of a change in the block margin. Calculations were performed for a single field as well as a multiple field setup. For the single field setup, blocks with equal areas were drawn at the four corners of a 16 x 20 cm(2) field at angles of 20 degrees, 40 degrees, 60 degrees, and 80 degrees with the horizontal axis. The blocks were then replaced with MLC leaves. For 6 MV x-rays, dose profiles in the penumbra regions of the blocks at 5- and 10-cm depths were compared with those obtained with the corresponding MLC setup. For multiple fields, the same sets of blocks were set up on the anterio-posterior (AP-PA) pair of a four-field setup. The margins of the blocks were increased (i.e., block shaved) in 1 mm steps to a maximum of 6 mm. The similarity between MLC and the change in the block margin was examined by comparing the dose-volume histogram (DVH) of the normal tissues in the penumbral regions for the different setups. To correlate the effect of MLC with a change in the block margin, difference dose-volume histograms (DDVH) of the normal tissues relative to the original block were compared for the MLC setup with those for the changes in the block margin. The correlation obtained was used to predict the effect on the penumbra region of the MLC setup for the lateral fields of a patient irradiated with a four-field setup. The calculations were carried out with 15 MV x-rays. For the single field setup, dose undulation is largest for the 50% isodose line (IDL) as reflected in the largest increase in the 50% to 20% isodose region compared with the 90% to 10% and the 80% to 20% regions. The increase in the penumbral width is largest for the 20 degrees block when replaced by the MLC and is smaller as the angle increases. The increase in the penumbral width also increases with depth. The effect of replacing a Cerrobend block with an MLC is similar to an increase in the block margin. For 15 MV x-rays, the increase varies inversely with the angle of the blocks, from > 6 mm increase in block margin for the 20 degrees block to about 1 mm for the 80 degrees block. In the clinical example, replacing the blocks in the lateral fields of a four-field irradiation with MLC is similar to changing the margin of the blocks. For the posterior block, MLC is similar to a 1- to 2-mm increase in the margin of the block, whereas for the anterior block the effect is similar to 1 mm for the straight portion of the block to about 6 mm in the superior portion of the block. Characterization of an MLC setup replacing a Cerrobend block is necessary for adequate coverage of target volume. The effect of MLC replacing a Cerrobend block is similar to a change in the block margin. It is possible to estimate with reasonable accuracy the effect of MLC replacing a Cerrobend block.

Humans↗
PubMed2001

Adult-to-adult living donor liver transplantation using right-lobe grafts: results and lessons learned from a single-center experience.

Living donor liver transplantation (LDLT) for adults is now a practical alternative to cadaveric liver transplantation. Use of right-lobe grafts has become the preferred donor procedure. Because of the complexity of this operation, a learning curve is to be expected. We report the outcome of our first 41 LDLTs at the University of Colorado Health Sciences Center (Denver, CO). We also discuss the lessons learned and the resultant modifications in the procedure that evolved during our series. Patient records were retrospectively reviewed between August 1997 and February 2001 for the following end points: recipient survival, graft survival, and donor and recipient complications. Thirty-eight of 41 living donor liver transplant recipients (93%) are alive and well postoperatively with a mean follow-up of 9.6 months. Four patients required retransplantation secondary to technical problems (9.8%); all 4 patients were in our initial 11 cases. Modification of the donor liver plane of transection resulted in venous outflow improvement. Also, biliary management was modified during the series. Donor complications are listed; all 41 donors have returned to normal pretransplantation activity. Our results indicate that LDLT can be performed safely with excellent donor and recipient outcomes. Dissemination of our experience can help shorten the learning curve for other institutions.

Adult↗
PubMed2000

Evaluation of 100 patients for living donor liver transplantation.

The initial success of living donor liver transplantation (LDLT) in the United States has resulted in a growing interest in this procedure. The impact of LDLT on liver transplantation will depend in part on the proportion of patients considered medically suitable for LDLT and the identification of suitable donors. We report the outcome of our evaluation of the first 100 potential transplant recipients for LDLT at the University of Colorado Health Sciences Center (Denver, CO). All patients considered for LDLT had first been approved for conventional liver transplantation by the Liver Transplant Selection Committee and met the listing criteria of United Network for Organ Sharing status 1, 2A, or 2B. Once listed, those patients deemed suitable for LDLT were given the option to consider LDLT and approach potential donors. Donors were evaluated with a preliminary screening questionnaire, followed by formal evaluation. Of the 100 potential transplant recipients evaluated, 51 were initially rejected based on recipient characteristics that included imminent cadaveric transplantation (8 patients), refusal of evaluation (4 patients), lack of financial approval (6 patients), and medical, psychosocial, or surgical problems (33 patients). Of the remaining 49 patients, considered ideal candidates for LDLT, 24 patients were unable to identify a suitable donor for evaluation. Twenty-six donors were evaluated for the remaining 25 potential transplant recipients. Eleven donors were rejected: 9 donors for medical reasons and 2 donors who refused donation after being medically approved. The remaining 15 donor-recipient pairs underwent LDLT. Using our criteria for the selection of recipients and donors for LDLT gave the following results: (1) 51 of 100 potential transplant recipients (51%) were rejected for recipient issues, (2) only 15 of the remaining 49 potential transplant recipients (30%) were able to identify an acceptable donor, and (3) 15 of 100 potential living donor transplant recipients (15%) were able to identify a suitable donor and undergo LDLT. Recipient characteristics and donor availability may limit the widespread use of LDLT. However, careful application of LDLT to patients at greatest risk for dying on the waiting list may significantly reduce waiting list mortality.

Adult↗
PubMed1999

Early steroid withdrawal in liver transplantation is safe and beneficial.

This report reviews the literature and discusses steroid withdrawal after hepatic transplantation. Our experience with steroid withdrawal is highlighted. The hypothesis is that steroid withdrawal from liver transplant recipients is safe and beneficial. A review of the English literature yielded 16 reports with a total of 901 patients (749 adults and 152 children). Most reports were nonrandomized and uncontrolled. Only two reports were randomized, controlled trials; three reports featured early steroid withdrawal (</= 3 months); and one report featured very early steroid withdrawal (14 days). Steroid withdrawal was achieved in approximately 85% of the patients. Acute rejection was not significantly increased by steroid withdrawal; rates were 5% to 14% in uncontrolled trials and 7% versus 7% (late steroid withdrawal v control; P = not significant [NS]) and 4% versus 8% (early steroid withdrawal v control; P = NS) in controlled trials. Acute rejection rates after very early steroid withdrawal (14 days posttransplantation) were 42% to 46%, similar to or less than the 40% to 70% reported for steroid-containing regimens. Chronic rejection was not increased by steroid withdrawal; the rate was 3.9% in one uncontrolled trial and 0% versus 3% (early steroid withdrawal v control; P = NS) in one controlled trial. Patient and graft survival were not adversely affected. Steroid withdrawal was associated with reduced rates and better control of hypertension, reduced total cholesterol levels, reduced rate of posttransplantation diabetes mellitus, improved control of diabetes, and reduced rate of obesity. The aggregate experience with steroid withdrawal suggests it is safe, associated with improvement in several posttransplantation complications, and deserves broader clinical application.

Acute Disease↗
PubMed1997

Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus.

BACKGROUND: The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications. METHODS: A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia. RESULTS: The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months). CONCLUSIONS: MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.

Acute Disease↗
PubMed1997

Penicillin-resistant pneumococcal meningitis in Israel.

Penicillin-resistant Streptococcus pneumoniae (PRP) is of worldwide concern. Treatment failures and fatalities of meningitis caused by PRP have been reported in other locations but not yet in Israel. We describe an 11-month-old infant with meningitis caused by PRP who failed to respond to initial treatment with cefotaxime. Vancomycin treatment caused a prompt cure. The minimal inhibitory concentrations of the isolate to penicillin, cefuroxime and cefotaxime were 1.0, 4.0 and 1.0 micrograms/ml, respectively. New guidelines for the treatment of meningitis in Israel are suggested.

Anti-Bacterial Agents↗
PubMed1990

Histo- and immunomorphometry of megakaryopoiesis in chronic myeloid leukemia with myelofibrosis and so-called primary (idiopathic) osteo-myelofibrosis/-sclerosis.

A morphometric study was performed on trephine biopsies of bone marrow in patients with chronic myeloid leukemia (CML) accompanied by myelofibrosis and in so-called primary (idiopathic) osteomyelofibrosis/-sclerosis (OMF) to evaluate distinctive features of megakaryopoiesis. The periodic acid Schiff reaction (PAS) and a monoclonal antibody against glycoprotein IIIa were employed for the identification of megakaryocytes including precursor cells and Gomori's silver impregnation to determine the density of argyrophilic fibers. All patients with CML revealed a slight to moderate degree of medullary fibrosis and were compared with early hyperplastic stages of OMF showing an identical fiber count. Statistical analysis disclosed that distinctive features existed between these two subgroups. Amongst these variables were sizes of megakaryocytes and corresponding nuclei, frequency of bare nuclei, emperipolesis and numbers of isolated nuclear fragments as well as the circular deviation of cell and nuclear perimeters. Immunomorphometry also included immature elements (pro- and megakaryoblasts) of the megakaryocyte series. Consequently higher cell counts were calculable in both groups combined with smaller sizes and a more rounded aspect of nuclei. However, following immunostaining, significant differences in several megakaryocytic parameters (frequency, size, shape of nuclei) were still demonstrable between CML and OMF cases.

Adult↗
PubMed1989

Primary (essential) thrombocythemia versus initial (hyperplastic) stages of agnogenic myeloid metaplasia with thrombocytosis--a critical evaluation of clinical and histomorphological data.

In 40 patients (17 male, 23 female, median age 57 years) with the presumptive diagnosis of primary (essential) thrombocythemia (PTH) according to the diagnostic requirements of the Polycythemia-Vera-Study-Group (PVSG) a follow-up study and a histological evaluation of initial trephine biopsies of the bone marrow were performed. Thorough review of the hematological data during the lengthy course of disease (observation time ranging from 1.5-10.5 years) and the histomorphology of the bone marrow implied a discrimination into two groups of patients. Group I patients (n = 26; 10 male, 16 female) were compatible with PTH according to our follow-up studies. Group II patients consisted of 14 cases (7 male, 7 female) which suggested retrospectively early hyperplastic stages of agnogenic myeloid metaplasia (AMM) with concomitant thrombocytosis. In PTH (group I patients) there was a sustained elevation of the platelet count lasting for several years accompanied by stable other blood values. Early AMM (group II patients) was characterized by an insidious decline of the initially elevated thrombocyte count, starting in a few patients already 4-6 months after admission. In AMM there was further an increase in hepatosplenomegaly observable together with the level of LDH and the score of the leukocyte alkaline phosphatase, and finally an evolution of a leukoerythroblastic blood picture could be noticed. Initial histopathology of the bone marrow revealed a profound proliferation of a not severely dysplastic megakaryopoiesis in group I patients (PTH) and a normal content of reticulin fibers. In early thrombocythemic AMM (group II patients) conspicuous abnormalities of megakaryocytes were accompanied by a slight to moderate increase in argyrophilic fibers and a left-shifted neutrophilic granulocyto- as well as erythropoiesis. These differences of certain histomorphological features could be substantiated by morphometric analysis. Our findings suggest that even the rigid requirements for the diagnosis of PTH as proposed by the PVSG may not be sufficiently restrictive to exclude patients with early hyperplastic stages of thrombocythemic AMM.

Biopsy, Needle↗