Search PubMed⌕ Search

Biomedical subjects

A Hendler

Publications and source records attributed to A Hendler.

15 recordsLinked to original sources
PubMed2002

A phase I study of 99mTc-hR3 (DiaCIM), a humanized immunoconjugate directed towards the epidermal growth factor receptor.

A phase I trial was conducted to evaluate the safety, tumour and normal tissue localization, pharmacokinetics and radiation dosimetry of Tc-hR3, a humanized monoclonal antibody directed towards the epidermal growth factor receptor, in 12 patients with recurrent or metastatic epithelial malignancies. Patients were injected intravenously with 3.0 mg or 6.0 mg (1010 MBq) of Tc-hR3. Blood and plasma concentrations of radioactivity were measured and a complete 24 h urine collection was obtained. Whole-body images were acquired up to 24 h post-injection and normal organ uptake quantified. Radiation dosimetry was estimated using MIRDose. Safety was evaluated by clinical observation, biochemical/haematological testing and by measuring immune response to Tc-hR3. There were no adverse effects, no changes in biochemical/haematological indices and no immune response to Tc-hR3. Tc-hR3 was rapidly cleared from the blood with a distribution half-life of 10.8+/-3.8 min. The volume of distribution, and clearance, were 180+/-37 ml.kg and 14+/-3 ml.kg.min, respectively. The elimination phase could not be discerned due to increasing blood radioactivity at later times. About 19-24% was excreted in the urine. Normal tissue uptake was mainly in the liver (44-50%), spleen (3-4%) and kidneys (3%). Imaging was positive in one patient with squamous cell carcinoma of the mouth and an involved cervical lymph node. The whole-body radiation dose from Tc-hR3 was 1.34+/-0.02x10 mSv.Bq. We conclude that Tc-hR3 exhibited an excellent safety profile. Future studies to determine the sensitivity and specificity of imaging with Tc-hR3 in a larger group of patients with pre-selection for epidermal growth factor receptor positivity are planned.

Adolescent↗
PubMed2001

Appropriate procedures for the safe handling and pathologic examination of technetium-99m-labelled specimens.

Technetium 99m may now be used to identify sentinel nodes for surgical excision in a growing number of cancer sites. The pathology specimens of these sentinel nodes and of any injected tumoural sites are radioactive. Consequently, specific clinical and laboratory procedures must be developed to handle these specimens safely. It is recommended that specimens containing the injection site should be quarantined for a period to permit decay of radioactivity. This quarantine does delay the reporting of pathology results to surgeons, oncologists and other clinicians, but it does not adversely affect final patient management.

Canada↗
PubMed2001

Amplified delivery of indium-111 to EGFR-positive human breast cancer cells.

A method is described to amplify the delivery of 111In to human breast cancer cells utilizing a novel human serum albumin-human EGF (HSA-hEGF) bioconjugate substituted preferentially in the HSA domain with multiple DTPA metal chelators for 111In. 111In-DTPA-HSA-hEGF exhibited a lower receptor-binding affinity than 111In-DTPA-hEGF but was rapidly and specifically bound, internalized and translocated to the nucleus in EGFR-positive MDA-MB-468 breast cancer cells. 111In-DTPA-HSA-hEGF was cytotoxic in vitro mainly through the emission of short-range Auger electrons and partially through the effects of the hEGF moiety to MDA-MB-468 cells overexpressing EGFR (1-2 x 10(6) receptors/cell) but not towards MCF-7 breast cancer cells with a 100-fold lower level of EGFR on their surface. The cytotoxicity in vitro against MDA-MB-468 cells of 111In-DTPA-HSA-hEGF substituted with nine DTPA chelators was enhanced 4-fold compared to 111In-DTPA-hEGF monosubstituted with DTPA. Studies are planned to further evaluate 111In-DTPA-HSA-hEGF in vivo as a new imaging and targeted radiotherapeutic agent for breast cancer.

Breast Neoplasms↗
PubMed2000

Minimal heparinization in coronary angioplasty--how much heparin is really warranted?

The purpose of the study was to assess the results of percutaneous transluminal coronary angioplasty (PTCA), performed with a single intravenous bolus of 2,500 U of heparin, in a nonemergency PTCA cohort. Three hundred of 341 consecutive patients (87.9%) undergoing PTCA were prospectively enrolled in the study. They received heparin, 2,500-U intravenous bolus, before PTCA, with intention of no additional heparin administration. Patient and lesion characteristics as well as PTCA results were evaluated independently by 2 physicians. Patients were followed up by structured telephone questionnaires at 1 and 6 months after PTCA. Mean activated clotting time obtained 5 minutes after heparin administration was 185+/-19 seconds (range 157 to 238). There were 3 (1%) in-hospital major adverse cardiovascular events: 2 deaths (0.66%), 1 (0.33%) Q-wave myocardial infarction. Emergency coronary surgery and stroke were not reported. Six patients (2%) experienced abrupt coronary occlusion within 14 days after PTCA, warranting repeat target vessel revascularization. Angiographic and clinical success were achieved in 96% and 93.3%, respectively. No bleeding or vascular complications were recorded. Six-month follow-up (184 patients) revealed 3 cardiac deaths (1 arrhythmic, 2 after cardiac surgery), 1 Q-wave myocardial infarction, and 9.7% repeat target vessel revascularization. This study suggests that very low doses of heparin and reduced activated clotting time target values are safe in non-emergency PTCA, and can reduce bleeding complications, hospital stay, and costs. Larger, randomized, double-blind heparin dose optimization studies need to confirm this notion.

Angioplasty, Balloon, Coronary↗
PubMed2000

Stents in total occlusion for restenosis prevention. The multicentre randomized STOP study. The Israeli Working Group for Interventional Cardiology.

AIMS: This multicentre randomized study set out to evaluate whether coronary stenting improves the results of successful balloon angioplasty for chronic total occlusion. Balloon angioplasty for chronic total occlusion has a high restenosis rate. Several reports have suggested that coronary stenting may decrease the likelihood of restenosis and reocclusion. METHODS AND RESULTS: Patients with total coronary artery occlusions who had an optimal PTCA result were randomized either to no further treatment or additional stent implantation. The AVE microstent was used and all patients were scheduled for a 1-, 3-, and 6-month clinical follow-up. Repeat coronary angiography to assess the rate and pattern of restenosis was performed at 6 months or earlier if clinically indicated. Ninety-six patients were enrolled in this study. The mean age was 59. 3+/-10.3 years and 15 were females. Forty-eight patients were randomized to the stent arm, receiving 52 stents (lengths 18-39 mm). Stent implantation was successful in all and there were no major procedure-related complications. Sixty-nine patients (72%) were restudied after 6 months. The binary restenosis rates (50%), in the PTCA arm were 70.9% with a minimal lumen diameter of 1.01+/-0.79 mm compared to 42.1% in the stent arm with a minimal lumen diameter of 1.63+/-1.02 mm (P=0.034). Reocclusion occurred in 7.9% in the stent group compared to 16.1% in the PTCA group. Restenosis in the PTCA group was focal in 88% of patients and occurred at the point of total obstruction (within 5 mm), compared to diffuse instent restenosis, which occurred in 54% of the patients in the stent group. CONCLUSION: Coronary stenting can significantly decrease the rate of restenosis and reocclusion of total occlusions. As restenosis in the stent group was more diffuse, care should be taken to implant short stents at the site of occlusion.

Angioplasty, Balloon, Coronary↗
PubMed2000

111In-labeled EGF is selectively radiotoxic to human breast cancer cells overexpressing EGFR.

UNLABELLED: Our objective was to determine whether the internalization and nuclear translocation of human epidermal growth factor (hEGF) after binding to its cell surface receptor (EGFR) could be exploited to deliver the Auger electron emitter 111In into EGFR-positive breast cancer cells for targeted radiotherapy. METHODS: hEGF was derivatized with diethylenetriamine pentaacetic acid (DTPA) and radiolabeled with 111In-acetate. The internalization of 111In-DTPA-hEGF by MDA-MB-468 breast cancer cells (1.3x10(6) EGFRs/cell) was determined by displacement of surface-bound radioactivity by an acid wash. The radioactivity in the cell nucleus and chromatin, isolated by differential centrifugation, was measured. The effect on the growth rate of MDA-MB-468 or MCF-7 (1.5x10(4) EGFRs/cell) cells was determined after treatment in vitro with 111In-DTPA-hEGF, unlabeled DTPA-hEGF, or 111In-DTPA. The surviving fraction of MDA-MB-468 or MCF-7 cells treated in vitro with 111In-DTPA-hEGF was determined in a clonogenic assay. The radiotoxicity in vivo against normal hepatocytes or renal tubular cells was evaluated by measuring alanine aminotransferase (ALT) or creatinine levels in mice administered high amounts of 111In-DTPA-hEGF (equivalent to human doses up to 14,208 MBq) and by light and electron microscopy of the tissues. RESULTS: Approximately 70% of 111In-DTPA-hEGF was internalized by MDA-MB-468 cells within 15 min at 37 degrees C and up to 15% was translocated to the nucleus within 24 h. Chromatin contained 10% of internalized radioactivity. The growth rate of MDA-MB-468 cells was decreased 3-fold by treatment with 111In-DTPA-hEGF (45-60 mBq/cell). Treatment with unlabeled DTPA-hEGF caused a 1.5-fold decrease in growth rate, whereas treatment with 111In-DTPA had no effect. Targeting of MDA-MB-468 cells with up to 130 mBq/cell of 111In-DTPA-hEGF resulted in a 2-logarithm decrease in their surviving fraction. No decrease in the growth rate or surviving fraction of MCF-7 cells was evident. There was no evidence of hepatotoxicity or renal toxicity in mice administered high amounts of 111In-DTPA-hEGF. Radiation dosimetry estimates suggest that the radiation dose to an MDA-MB-468 cell targeted with 111In-DTPA-hEGF could be as high as 25 Gy with up to 19 Gy delivered to the cell nucleus. CONCLUSION: 111In-DTPA-hEGF is a promising novel radiopharmaceutical for targeted Auger electron radiotherapy of advanced, hormone-resistant breast cancer.

Animals↗
PubMed2000

A comparison of EGF and MAb 528 labeled with 111In for imaging human breast cancer.

UNLABELLED: Our objective was to compare 111In-labeled human epidermal growth factor (hEGF), a 53-amino acid peptide with anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb) 528 (IgG2a) for imaging EGFR-positive breast cancer. METHODS: hEGF and MAb 528 were derivatized with diethylenetriamine pentaacetic acid (DTPA) and labeled with 111In acetate. Receptor binding assays were conducted in vitro against MDA-MB-468 human breast cancer cells. Biodistribution and tumor imaging studies were conducted after intravenous injection of the radiopharmaceuticals in athymic mice bearing subcutaneous MCF-7, MDA-MB-231, or MDA-MB-468 human breast cancer xenografts or in severe combined immunodeficiency mice implanted with a breast cancer metastasis (JW-97 cells). MCF-7, MDA-MB-231, JW-97, and MDA-MB-468 cells expressed 1.5 x 10(4), 1.3 x 10(5), 2.7 x 10(5), and 1.3 x 106 EGFR/cell, respectively in vitro. RESULTS: 111In-DTPA-hEGF and 111In-DTPA-MAb 528 bound with high affinity to MDA-MB-468 cells (Ka of 7.5 x 10(8) and 1.2 x 10(8) L/mol, respectively). 111In-DTPA-hEGF was eliminated rapidly from the blood with < 0.2% injected dose/g (%ID/g) circulating at 72 h after injection, whereas 111In-DTPA-MAb 528 was cleared more slowly (3%ID/g in the blood at 72 h). Maximum localization of 111In-DTPA-hEGF in MDA-MB-468 tumors (2.2 %ID/g) was 10-fold lower than with 111In-DTPA-MAb 528 (21.6 %ID/g). There was high uptake in the liver and kidneys for both radiopharmaceuticals. Tumor-to-blood ratios were greater for 111In-labeled hEGF than for MAb 528 (12:1 versus 6:1), but all other tumor-to-normal tissue ratios were higher for MAb 528. MDA-MB-468 and JW-97 tumors were imaged successfully with both radiopharmaceuticals, but tumors were more easily visualized using 111In-labeled MAb 528. There was no direct quantitative relationship between EGFR expression on breast cancer cell lines in vitro, and tumor uptake of the radiopharmaceuticals in vivo, but control studies showed that tumor uptake was receptor mediated. CONCLUSION: Our results suggest that the tumor uptake in vivo of receptor-binding radiopharmaceuticals is controlled to a greater extent by their elimination rate from the blood than by the level of receptor expression on the cancer cells. Radiolabeled anti-EGFR MAbs would be more effective for tumor imaging in cancer patients than peptide-based radiopharmaceuticals such as hEGF, because they exhibit higher tumor uptake at only moderately lower tumor-to-blood ratios.

Animals↗
PubMed1999

Initial and long-term results with the CrossFlex stent--data from a national registry.

The Cordis CrossFlex trade mark stent is a balloon expandable helical coil made of stainless steel. OBJECTIVE: To assess the short- and long-term safety and efficacy of this stent by conducting a multi-center national registry. METHODS: One hundred and sixteen stents were implanted in 109 patients (mean age 59 3 10 years, 95 males). The lesions were classified as type B2 or C in 56 patients (51%). Successful deployment was achieved in 103 patients (94.5%). Failure was due to damage to the stent (two patients) or inability to reach the lesion (four patients). High-pressure deployment (>14 atm) was used in 68% of cases. RESULTS: Edge dissections occurred in nine patients after high-pressure deployment and necessitated implantation of a second stent. One patient with a large acute myocardial infarction died during hospitalization. Side branch occlusion occurred in five patients (4.6%). Subacute thrombosis occurred in two patients (1.8%) during the first four weeks. During a six-month follow-up period, 18 patients (16.5%) were rehospitalized with recurrent angina. Fifteen patients had coronary angiography and 13 (12.1%) needed additional target lesion revascularization (TLR). Twelve patients required a second PTCA for in-stent restenosis, and one needed a coronary artery bypass graft operation. CONCLUSIONS: The CrossFlex coronary stent can successfully be used in complex coronary lesions, with few short-term complications and a low TLR rate. Operators should be aware of the possibility of edge dissection during high-pressure implantation.

Journal Article↗
PubMed1998

[Emergency stenting for acute left main coronary artery closure during cardiac catheterization].

We report a case of acute closure of the left main coronary artery, a rare complication of diagnostic cardiac catheterization, treated by emergency stenting prior to aorto-coronary bypass surgery. We suggest encroachment of the Judkins catheter into a calcified left main ostium; with dissection and acute thrombosis of this segment, as the possible mechanism. Clinically, the patient's condition deteriorated to cardiogenic shock and loss of consciousness. Remarkably, there was no angiographic evidence of significant left main coronary artery disease, besides the presence of calcification in the proximal part of the left coronary system and ventricularization of coronary pressure at the time of engagement. We chose to slide quickly the angioplasty guidewire through the left main coronary artery, which allowed prompt mechanical recanalization and rapid restoration of coronary flow, with dramatic clinical and hemodynamic improvement. This relatively simple procedure allowed stenting the left main artery after brief predilation, and the patient came to by-pass surgery in excellent condition. The rationale for surgery in this case was the need for complete coronary revascularization because of significant 3-vessel coronary artery disease.

Angioplasty, Balloon, Coronary↗
PubMed1998

When to use bone scintigraphy. It can reveal things other studies cannot.

Despite advances in nuclear medicine, bone scintigraphy remains an important imaging technique. It is sensitive in detecting stress fractures and bone metastases and can assess suspected injury that is difficult to see on plain films (e.g., rib fracture). Scintigraphy is useful in evaluating new symptoms, response to therapy, and prognosis in patients with known malignant tumor. In patients with low back pain, the technique can determine the age of fractures to help identify osteoporosis and can uncover other causes of the pain (e.g., spondylolysis, arthritis). When Paget's disease is suggested by unexplained bone pain or an elevated serum alkaline phosphatase level, bone scintigraphy is a useful screening test. Combined with other appropriate nuclear medicine studies, it helps in early identification and localization of osteomyelitis. Scintigraphic scans can provide a general indicator of malignant versus benign disease (according to the amount of lesion activity seen) and may produce characteristic findings in certain primary tumors (e.g., osteoid osteoma) that are difficult to evaluate with other methods.

Bone Diseases↗
PubMed1991

A right atrial mass in the presence of a permanent pacemaker electrode in a patient with polycythemia vera.

A case of a huge right atrial mass that developed 2 years after a permanent pacemaker implantation is described. The patient had a history of polycythemia vera, which is known to present a high tendency towards the development of thrombosis. In light of this fact, we suggest that in similar cases a full echocardiography follow-up should be performed, and long-term anticoagulant therapy should be considered in selected cases.

Aged↗
PubMed1990

Preoperative magnetic resonance imaging in Marfan syndrome.

We report one of the first cases in Israel of composite-graft repair of an aortic aneurysm in Marfan syndrome, in which preoperative evaluation was done noninvasively using magnetic resonance imaging (MRI). Because of the relatively favorable outcome of surgical compared with medical treatment of aortic aneurysm in patients with Marfan syndrome, surgery is now more frequently considered, even in asymptomatic patients. MRI is an excellent diagnostic tool for evaluating the thoracic aorta and has been suggested as a replacement for preoperative cardiac catheterization. In the case presented here, MRI preoperative confirmation of a 6.0-cm aortic aneurysm in an asymptomatic 38-year-old man with Marfan syndrome, was followed by composite ascending aorta and aortic valve replacement. The postoperative course was good. This case supports the view that aortic aneurysm replacement can be performed based on a noninvasive preoperative evaluation using MRI.

Adult↗
PubMed1988

Myocardial rupture in acute myocardial infarction: urgent management.

Myocardial rupture complicated acute myocardial infarction in a 50 year old man. Resuscitation was started immediately and he was treated with pericardiocentesis and a massive intravascular infusion of fluid. The torn area was plicated with Teflon felt and reinforced with an uninterrupted suture. The postoperative course was uncomplicated. This report points out the crucial importance of prompt clinical recognition and management of the acute stage of cardiac rupture in acute myocardial infarction.

Acute Disease↗