Search PubMed⌕ Search

Biomedical subjects

S Silberman

Publications and source records attributed to S Silberman.

At least 19 recordsLinked to original sources
PubMed2004

[Diagnosis of acute myocardial infarction using multislice computed tomography in emergency room].

Managing chest pain in emergency remains a diagnostic challenge because of the speediness and the accuracy that request. The authors report the case of a 40 years old patient admitted for chest pain with suspected aortic dissection. Multislice computed tomography (sixteen-slice CT) was performed at the patient's admission, initial diagnosis was rapidly corrected, showing both and accurately show both antero-septal defect perfusion and an acute occlusion of the proximal left anterior descending artery. Angioplasty was performed in emergency within the 6 first hours after onset of the symptoms. Multislice computed tomography was able to identify accurately not only the chest pain etiology but also to show the culprit artery, leading to quick and oriented percutaneous coronary intervention.

Adult↗
PubMed2004

Maternal alloanti-hrS--an absence of HDN.

A 24-year old female, gravida III, para III, delivered a full-term infant by cesarean section. A maternal blood sample at the time of admission showed antibody in her serum that had apparent anti-e specificity and that her RBCs were e+. Further studies determined that the antibody was anti-hrS. Cord RBCs had a negative DAT and a normal Hb level. There was no clinical evidence for increased hemolysis in the infant. We describe an hrS+ infant with no evidence of HDN due to anti-hrS.

Adult↗
PubMed2003

18FDG-Positron emission tomography for the early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec).

Imatinib mesylate (Glivec, formerly STI571) is the first effective systemic treatment for gastrointestinal stromal tumours (GISTs). Major changes in tumour volume, however, tend to occur late after the start of treatment. The aim of this study was to evaluate if [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) can be used for the early evaluation of response to imatinib mesylate treatment in soft-tissue sarcomas (STS). 21 patients (17 GIST, 4 other STS) underwent FDG-PET imaging prior to and 8 days after the start of treatment. PET response (European Organization for Research and Treatment (EORTC) guidelines) was observed in 13 GISTs (11 Complete Responders, 2 partial responders. Subsequent computerised tomography (CT) response Response Evaluation Criteria in Solid Tumours (RECIST) was observed in 10 of these patients after a median follow up of 8 weeks. Stable or progressive disease was observed on PET in 8 patients and none of them achieved a response on CT. PET response was also associated with a longer progression-free survival (PFS) (92% versus 12% at 1 year, P=0.00107). We conclude that FDG-PET is an early and sensitive method to evaluate an early response to imatinib treatment.

Adult↗
PubMed2001

Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are rare tumours of the gastrointestinal tract characterised by cell-surface expression of the tyrosine kinase KIT (CD117). No effective systemic treatment is available. Imatinib (STI571) inhibits a similar tyrosine kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown to inhibit KIT. We did a phase I study to identify the dose-limiting toxic effects of imatinib in patients with advanced soft tissue sarcomas including GISTs. METHODS: 40 patients (of whom 36 had GISTs) received imatinib at doses of 400 mg once daily, 300 mg twice daily, 400 mg twice daily, or 500 mg twice daily. Toxic effects and haematological, biochemical, and radiological measurements were assessed during 8 weeks of follow-up. 18Fluorodeoxy-glucose positron-emission tomography (PET) was used for response assessment in one centre. FINDINGS: Five patients on 500 mg imatinib twice daily had dose-limiting toxic effects (severe nausea, vomiting, oedema, or rash). Inhibition of tumour growth was seen in all but four patients with GISTs, resulting in 19 confirmed partial responses and six as yet unconfirmed partial responses or more than 20% regressions. 24 of 27 clinically symptomatic patients showed improvement, and 29 of 36 were still on treatment after more than 9 months. PET scan responses predicted subsequent computed tomography responses. INTERPRETATION: Imatinib at a dose of 400 mg twice daily is well tolerated during the first 8 weeks, side-effects diminish with continuing treatment, and it has significant activity in patients with advanced GISTs. Our results provide evidence of a role for KIT in GISTs, and show the potential for the development of anticancer drugs based on specific molecular abnormalities present in cancers.

Adult↗
PubMed2001

Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies.

PURPOSE: To assess the feasibility of administering OSI-774, to recommend a dose on a protracted, continuous daily schedule, to characterize its pharmacokinetic behavior, and to acquire preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of OSI-774 in three study parts (A to C) to evaluate progressively longer treatment intervals. Part A patients received OSI-774 25 to 100 mg once daily, for 3 days each week, for 3 weeks every 4 weeks. Part B patients received OSI-774 doses ranging from 50 to 200 mg given once daily for 3 weeks every 4 weeks to establish the maximum tolerated dose (MTD). In part C, patients received this MTD on a continuous, uninterrupted schedule. The pharmacokinetics of OSI-774 and its O-demethylated metabolite, OSI-420, were characterized. RESULTS: Forty patients received a total of 123 28-day courses of OSI-774. No severe toxicities precluded dose escalation of OSI-774 from 25 to 100 mg/d in part A. In part B, the incidence of severe diarrhea and/or cutaneous toxicity was unacceptably high at OSI-774 doses exceeding 150 mg/d. Uninterrupted, daily administration of OSI-774 150 mg/d represented the MTD on a protracted daily schedule. The pharmacokinetics of OSI-774 were dose independent; repetitive daily treatment did not result in drug accumulation (at 150 mg/d [average]: minimum steady-state plasma concentration, 1.20 +/- 0.62 microg/mL; clearance rate, 6.33 +/- 6.41 L/h; elimination half-life, 24.4 +/- 14.6 hours; volume of distribution, 136. 4 +/- 93.1 L; area under the plasma concentration-time curve for OSI-420 relative to OSI-774, 0.12 +/- 0.12 microg/h/mL). CONCLUSION: The recommended dose for disease-directed studies of OSI-774 administered orally on a daily, continuous, uninterrupted schedule is 150 mg/d. OSI-774 was well tolerated, and several patients with epidermoid malignancies demonstrated either antitumor activity or relatively long periods of stable disease. The precise contribution of OSI-774 to these effects is not known.

Administration, Oral↗
PubMed2001

Exercise hemodynamics of aortic prostheses: comparison between stentless bioprostheses and mechanical valves.

BACKGROUND: Nonstented bioprostheses have been associated with lower resting gradients than stented bioprostheses or mechanical valves. We compared the hemodynamic performance of nonstented bioprostheses and mechanical valves with normal native aortic valves at rest and exercise. METHODS: Dobutamine echocardiography was used to assess gradients and effective orifice area index at rest and exercise in patients with the Toronto stentless porcine valve (TSPV; n = 13; mean implant size 25.7 mm), Medtronic Freestyle (FR; n = 11; mean implant size 23.9 mm), Sorin Bicarbon (SOR; n = 11; mean implant size 24.5 mm), St. Jude Medical (SJM; n = 10; mean implant size 21.3 mm), and normal native aortic valves (NOR; n = 10). RESULTS: All groups demonstrated a major rise in cardiac output at maximal dobutamine infusion. At rest and exercise, respectively, mean gradients were 5.48 +/- 1.1 mm Hg and 5.83 +/- 0.9 mm Hg for TSPV, 5.68 +/- 1.2 mm Hg and 7.50 +/- 1.7 mm Hg for FR, 10.29 +/- 1.4 mm Hg and 20.78 +/- 2.7 mm Hg for SJM, 5.26 +/- 0.8 mm Hg and 11.1 +/- 1.8 mm Hg for SOR, and 1.54 +/- 0.4 mm Hg and 2.18 +/- 0.7 mm Hg for NOR. In comparison with normal valves, both stentless groups showed no change in mean gradient at exercise, whereas both mechanical groups showed an increase in gradient at exercise (p < 0.04). CONCLUSIONS: Stentless valves behave similarly to normal aortic valves in that there is almost no increase in gradient at exercise. Both mechanical valve groups showed increased gradients at exercise, suggesting that these valves obstruct blood flow. Our data add further evidence that stentless valves are hemodynamically superior to mechanical valves in the aortic position.

Adult↗
PubMed2001

[Surgical repair of myxomatous mitral valve].

Myxomatous mitral valve disease is now the most common cause of mitral regurgitation in the western world. Repair of the leaking valve has become standard surgical procedure during the past 2 decades. Between 1993-1999 we performed 113 repairs of the mitral valve. In 25 patients the etiology was myxomatous degeneration (no mortality). Long-term clinical results depend on patients' functional class at surgery. Based on this fact, and the good surgical results, it is recommended to refer such patients even with severe mitral incompetence for surgery at an early stage, even if symptoms are minimal.

Adolescent↗
PubMed2000

[Mitral valve repair in ischemic cardiomyopathy with severe left ventricular dysfunction].

Patients with ischemic mitral insufficiency and poor left ventricular function are high operative risks. We present 101 patients who had mitral valve repair in our department: 21 had severely reduced left ventricular function, 19 were in NYHA functional Class IV, and 2 in Class III. All had concomitant coronary artery bypass. There was no early operative mortality, but there were 2 late deaths (9.6%). At follow-up (3-36 months) all valves were functioning normally, 9 patients (43%) were in NYHA functional Class I, and 4 (19%) in Class II. Our experience shows that repair of ischemic mitral insufficiency in the presence of severe left ventricular dysfunction can be performed with good results, and is preferable to mitral valve replacement. Late follow-up showed significant symptomatic improvement.

Aged↗
PubMed2000

Transradial catheterization: a word of caution.

The radial artery has been used as an access for transcatheter procedures as well as a source for arterial conduit during coronary bypass surgery. It has been reported that 5Eth 13% of radial arteries may be damaged during transradial catheterization. The damage can be irreversible, and may therefore prohibit the radial arteryOs subsequent utilization as a coronary conduit.

Cardiac Catheterization↗
PubMed1999

Role of mitogen-activated protein kinases and c-Jun/AP-1 trans-activating activity in the regulation of protease mRNAs and the malignant phenotype in NIH 3T3 fibroblasts.

Ras activates a multitude of downstream activities with roles in cellular proliferation, invasion and metastasis, differentiation, and programmed cell death. In this work we have evaluated the requirement of extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase kinase (JNKK), and c-Jun/AP-1 activities in transformation and extracellular matrix invasion of ras oncogene expressing NIH 3T3 fibroblasts by expressing stable mutant genes that constitutively inhibit these activities. Whereas the inhibition of ERK activity reverts the transformed and invasive phenotype, the inhibition of the JNK pathway and AP-1 trans-activating activities by JNKK[K129R] and c-Jun(TAM67) had no effect on the ability of the ras oncogene-expressing cells to grow in soft agar or invade Matrigel basement membrane. Thus an elevated JNK activity and/or c-Jun/AP-1 trans-activating activity are not absolute requirements for ras transformation or invasion through basement membrane, and the dependence on AP-1 activity for transformation is cell-specific. However, inhibition of JNK kinase (JNKK) in ras-transformed cells with normally elevated JNK activity switches the protease-dependent invasive phenotype from a urokinase plasminogen activator (uPA)-dependent to a cathepsin L (CL)-dependent invasive phenotype. Conversely, treatment of ras-transformed cells of low constitutive JNK activity with the JNK stimulator, anisomycin, converts the protease mRNA levels from those characteristic of a CL-dependent to a uPA-dependent phenotype. These protease phenotypes can be duplicated in untransformed NIH 3T3 cells that express platelet-derived growth factor receptors and m1 muscarinic receptors that selectively stimulate the ERK or JNK pathways, respectively. It is concluded that high ERK activity is required for both protease phenotypes, whereas the JNK pathway and c-Jun/AP-1 activity are not required for transformation but regulate a switch between uPA and CL protease phenotypes in both transformed and untransformed cells. In ras-transformed NIH 3T3 fibroblasts, the uPA- and CL-dependent protease phenotypes are redundant in their ability to invade through basement membrane.

3T3 Cells↗
PubMed1999

Platelets: preparations, transfusion, modifications, and substitutes.

OBJECTIVE: To summarize current knowledge and recent progress pertaining to platelet concentrate preparations, modifications, and future prospects for platelet substitutes. METHODS: Current publications identified through a search of an electronic literature database were evaluated and reviewed. Relevant data were abstracted into this article. Abstractions of the data were made depending on their relevance. This review starts with standard methods of platelet preparation and goes on to describe different modifications intended to optimize the product and increase its safety. The article concludes with a discussion of the use of hematopoietic growth factors and novel kinds of platelet components for future use. CONCLUSIONS: Many modifications in the preparation of platelet transfusions have occurred in recent years. Platelets prepared by standard techniques contain significant numbers of donor leukocytes, which are responsible for several adverse effects. Awareness of this problem has lead to the development of effective means for their removal. Several methods to reduce the risk of viral and bacterial transmission through platelet transfusions are emerging. New technologies in the use of platelet substitutes have attempted to prolong the platelet storage potential and prevent the development of recipient alloimmunization. As the biological activities of growth factors become better understood, the clinical applications of novel recombinant products may redefine the concept of future platelet transfusions. It is important that research continues into the optimal methods for the preparation and use of platelet transfusions to provide maximal clinical benefits with minimal risk of complications.

Blood Platelets↗
PubMed1998

Femoro-femoral bypass for repeat open-heart surgery.

Repeat open-heart operations are becoming more frequent with a patient population at higher risk. Sternal re-entry poses the risk of possible damage to vital structures. These include laceration of the myocardium, especially the right ventricle, tearing of patent grafts and internal mammary grafts in particular, or dislodgement of emboli from patent vein grafts. To minimize the risk associated with sternal re-entry, we adopted the method of establishing femoral artery-femoral vein cardiopulmonary bypass (CPB) in order to achieve cardiac decompression prior to sternotomy. Between June 1994 and October 1997, 94 patients underwent repeat open-heart operations at our institution. Of these, seven were a second time reoperation. Mean age was 62 years (range 31-80 years), and 65 were male. Fifty-nine patients had coronary bypass, 27 had aortic valve replacement, 45 had mitral valve replacement, and nine had other procedures (these numbers include patients having combined procedures). In patients with no known vascular disease, the femoral vessels were exposed, and if found suitable, were cannulated, and the patients connected to CPB. The sternum was opened with an oscillating saw, and on penetration through the posterior table, the heart was drained to allow for decompression. If the femoral vein cannula did not allow full bypass, ventilation was maintained until the right atrium was exposed and cannulated and full bypass was achieved. Femoro-femoral bypass was established in 75 patients. In 19 patients it was not done for the following reasons: eight patients had a diseased femoral artery, in one patient the femoral vein could not be cannulated, nonuse of CPB altogether occurred in three patients, and it was because of surgeon's preference in seven patients. In one patient a high pressure developed in the arterial line, requiring conversion to aortic cannulation during the course of CPB, without any negative consequences. There were no problems associated with sternal re-entry, no patient had limb ischemia or venous thrombosis. Two patients (2.6%) had complications related with femoral cannulation, with one having trauma to an atherosclerotic femoral artery requiring repair with vein interposition, and the other a tear of iliac vein requiring laparotomy. Groin wound infection occurred in five patients (6.6%), and groin hematoma in four patients (5.3%). All complications were treated successfully with no permanent damage. Operative mortality was 9% (seven patients). Causes of death included myocardial infarction (2), infection (3), respiratory (1), and cirrhosis (1). We conclude that femoro-femoral bypass prior to sternotomy is a safe and easy method to reduce the risk of sternal re-entry by allowing early decompression of the heart, and in unstable patients it offers better myocardial protection by earlier connection to CPB. Proper selection of patients is important in order to minimize related comorbidity. We recommend this method in redo patients in whom femoral cannulation is feasible.

Adult↗
PubMed1998

The Sorin Bicarbon valve: clinical evaluation in Israel.

BACKGROUND: Four collaborating centers pooled their results with the Sorin Bicarbon Bileaflet valve. MATERIAL AND METHODS: Between 6/91 and 11/95, 431 patients, 235 males and 196 females, underwent valve replacement using the new Sorin prosthesis; age range: 16-88, mean 61.4 yrs. OPERATIONS: AVR - 206, MVR - 177, TVR - 1, DVR - 47. Additional procedures - 139: CAB -117, valve repair - 22. AV sizes: 19-27, MV sizes: 21-33. RESULTS: Thirty day mortality was 4.3%. Early complications included: CVA - 1.4%, +ve blood culture - 2%, reop for bleeding - 5%. Late complications: infective endocarditis - 2.3%, valve thrombosis - 0.2%, thromboemboli - 2.5%, major bleeding - 1.6%, reoperation - 3%, late deaths (all causes) - 4.3%. No structural deterioration has been reported with this valve and acceptable gradients have been observed. Hemolysis is negligible. CONCLUSIONS: Based on this intermediate experience the Sorin Bicarbon prosthesis is well-designed with good hemodynamic properties, and an acceptably low incidence of complications.

Aortic Valve↗
PubMed1997

Characterization of downstream Ras signals that induce alternative protease-dependent invasive phenotypes.

Invasive and metastatic cells require protease expression for migration through the extracellular matrix. Metastatic NIH 3T3 fibroblasts transformed by different activated ras genes showed two different protease phenotypes, rasuPA+/CL- and rasCL+/uPA- (Zhang, J-Y., and Schultz, R. M. (1992) Cancer Research 52, 6682-6689). Phenotype rasuPA+/CL- is dependent on expression of the serine-type protease urokinase plasminogen activator (uPA) and the phenotype rasCL+/uPA- on the cystine-type protease cathepsin L (CL) for lung colonization in experimental metastasis. The existence of multiple invasive phenotypes on ras-isoform transformation implied the activation of alternative pathways downstream from Ras. We now show that c-Raf-1, extracellular signal-regulated protein kinase (ERK)-1, and ERK-2 are hyperphosphorylated, and the ERK activity is high in both the uPA- and CL-dependent ras-transformed invasive phenotypes. Levels of c-Jun and c-Jun NH2-terminal kinase (JNK) activity are also high in the uPA-dependent phenotype, but they are almost undetectable in the CL-dependent phenotype. The uPA Ras-response element is a PEA3/URTF element, and mobility shift assays show a strong PEA3/URTF protein band in the uPA-dependent phenotype. This band is competed by a consensus AP-1 DNA sequence and by antibodies to PEA3 and c-Jun. Thus, the uPA-invasive phenotype appears to require the activation of Ets/PEA3 and c-Jun transcription factors activated by the ERK and JNK pathways, while the CL-invasive phenotype appears to require ERK activity with suppression of JNK and c-Jun activities. These postulates are supported by the introduction of a dominant negative c-Jun, TAM67, into cells of phenotype rasuPA+/CL-, which down-regulated the high uPA mRNA levels characteristic of this phenotype to basal levels and up-regulated basal levels of CL mRNA to levels similar to those observed in cells of phenotype rasCL+/uPA-. We conclude that the JNK pathway acts as a switch between two distinct protease phenotypes that are redundant in their abilities to grow tumors and metastasize.

3T3 Cells↗