You are on page 1of 71

RESEARCH AT HADASSAH

Department of
ANESTHESIOLOGY AND
CRITIC AL C ARE MEDICINE
STAFF
Professors Emeritus: Aronson, H.B., MB, ChB, DA, FFARCS
Cotev, S., MD
Magora, F., MD
Professors: Weissman, C., MD
(Head of Department)
Sprung, C., MD
(Head of Intensive Care Unit)
Associate Professor: Drenger, B., MD
(Head of Anesthesiology Unit, Mt. Scopus)
Shir, Y., MD
(Head of Pain Services)
Clinical Associate Professor: Donchin, Y., MD
(Head of Critical Care Transport Unit)
Senior Lecturers: Gozal, Y., MD

Department of Anesthesiology and Critical Care Medicine


(Head of Recovery Room/Operating Room Services)
Landesberg, G., MD, DSc
Weiss, Y., MD
Clinical Senior Lecturer: Kadari, A., MD
(Head of Pediatric Anesthesiology Services)
Lecturers: Davidson, E., MD
Ginosar, Y., MD
Matot, I., MD
Instructors: Avidan, A., MD Levine, P., MD
Einav, S., MD Raphael, J., MD
Goodman, S., MD, PhD Weineger, C., MD
Physicians Participating Eimerl, D., MD
in Teaching: (Head of Neuroanesthesiology Unit)
Gozal, D., MD
Shamir, M., MD

Medical Research and Development 175


RESEARCH AT HADASSAH

INTRODUCTION
The Department of Anesthesiology and Critical Care Medicine is active in both
clinical and basic research. This research revolves around the care of patients
during the perioperative period, the care of the critically ill patient and the
management of acute and chronic pain. Basic research is performed in various
laboratories of the medical center, including the Laboratory for Experimental
Surgery and the Institute for Gene Therapy, while clinical research is conducted
in the operating rooms, intensive care units and pain clinic of the Hadassah-
University Hospital.There are many active and productive collaborations
between departmental researchers and other Hadassah and Hebrew University
investigators.

Basic Research:
The basic research endeavors of the department involve investigating: (a)
Ischemia - reperfusion injury to the lung. (b) Gene therapy for the acute
respiratory distress syndrome. (c) The effects of nutrients on the development of
neuropathic pain. (d) Attenuation of ischemic myocardial damage during
Department of Anesthesiology and Critical Care Medicine

coronary artery occlusion and (e) Spinal cord protection during vascular surgery.

Clinical Research:
The care of the patient during the perioperative period: Departmental research
activities include studies examining various aspects of the anesthetic care of
patients during the perioperative period. These studies focus on a number of key
topics: (a) The incidence and mechanisms of myocardial ischemia and infarction
in high risk patients during the intraoperative and postoperative periods. (b)
Methods of managing the intraoperative care of patients undergoing major
abdominal surgery, specifically hepatic resections. (c) Protecting the myocardium
from ischemic damage during coronary artery surgery without cardiopulmonary
bypass. (d) Epidural analgesia during labor.

The care of the critically ill patient: Improving the care of the critically ill patient
is an active area of departmental investigation. Studies in this area include (a) The

176 Medical Research and Development


RESEARCH AT HADASSAH

adrenal axis during critical illness. (b) Ethical aspects of caring for the critically
ill. (c) Metabolic-ventilation interactions during critical illness. (d) Triage of ICU
admissions. (e) Respiratory failure.

Pain Management: Various issues related to acute and chronic pain management
are being studied: (a) The effects of nutrient intake on the development of chronic
pain. (b) Novel local anesthetic agents. (c) Genetic aspects of post-mastectomy
pain.

RESEARCH AREAS
Novel Local Anesthetics Pulmonary Pharmacology
(Davidson) (Matot)

Errors in Medical Practice Management during Hepatectomy


(Donchin) (Matot)

Inter-Institutional Transport Nutrition and Pain


(Donchin, Einav, Shamir) (Shir)

Spinal Cord Protection Post-Mastectomy Pain Genetics


(Drenger, Gozal) (Shir)

Department of Anesthesiology and Critical Care Medicine


Cardiopulmonary Resuscitation Ethics in Critical Care
(Einav) (Sprung)

Obstetrical Anesthesia Triage of ICU Admissions


(Ginosar, Weineger) (Sprung, Levine, Einav)

Adrenocortical Responses Sepsis


(Goodman, Sprung) (Sprung, Goodman)

Attenuating Myocardial Damage Gene Therapy and ARDS


(Gozal, Drenger, Raphael) (Weiss)

Sedating Pediatric Patients Enhanced Postoperative Care


(Gozal, Kadari, Gozal) (Weissman)

Perioperative Myocardial Ischemia Analyzing Perioperative Activities


(Landesberg, Gozal, Drenger) (Weissman)

Medical Research and Development 177


RESEARCH AT HADASSAH

RECENT PUBLICATIONS
Analyzing Intensive Care Unit and Operating Room Activities
Weissman C. (2000) Factors influencing changes in surgical ICU utilization
Critical Care Medicine 28:1766-1771.
Weissman C. (2000) Analyzing the impact of long-term patients on ICU bed
utilization. Intensive Care Medicine 26:1319-1325.
Klein N., Weissman C. (2002) Evaluating intraoperative therapeutic and
diagnostic interventions. Anesthesia & Analgesia 95:1373-1380.
Myocardial Ischemia/Infarction in the Perioperative Period
Landesberg G. (2000) Pro: Preoperative thallium testing should be routinely
performed before vascular surgery. Journal of Cardiothoracic & Vascular
Anesthesia. 14:217-220.
Glantz, L., Drenger, B., Gozal Y. (2000) Perioperative myocardial ischemia in
cataract surgery patients: general versus local anesthesia. Anesthesia & Analgesia
91:1415-1419.
Wolf Y.G., Landesberg G., Mosseri M., Schechter D., Anner H., Weissman C.,
Department of Anesthesiology and Critical Care Medicine

Berlatsky Y. (2001) Preoperative dipyridamol-thallium scanning, selective


coronary revascularization and long-term survivial in patients with critical lower
limb ischemia. Journal of Cardiovascular Surgery (Torino) 42:89-95.
Landesberg G., Mosseri M., Zahger D., Wolf Y., Perouansky M., Anner H.,
Drenger B., Hasin Y., Berlatsky Y., Weissman C. (2001) Myocardial infarction
after vascular surgery: the role of prolonged, stress induced, ST-depression-type
ischemia. Journal of the American College of Cardiology 37:1839-1845.
Landesberg G., Mosseri M., Wolf Y., Vesselov Y., Weissman C. (2002)
Perioperative myocardial ischemia and infarction: identification by continuous
12-lead electrocardiogram with online ST-segment monitoring. Anesthesiology
96:264-70.
Pulmonary Pharmacology
Matot I., Jurim O. (2001) The protective effect of acadesine on lung ischemia-
reperfusion injury. Anesthesia & Analgesia 92:590-595.

178 Medical Research and Development


RESEARCH AT HADASSAH

Matot I., Pizov, R. (2000) Pulmonary extraction and accumulation of lipid


formulations of amphotericin B. Critical Care Medicine 28:2528-2532.
Intraoperative Management during Hepatectomy
Lyass S, Zamir G, Matot I, Goitein D, Eid A, Jurim O. (2001) Combined colon
and hepatic resection for synchronous colorectal liver metastases. Journal of
Surgical Oncology 78:17-21.
Nutritional Intake and Neuropathic Pain
Shir, Y., Sheth, R., Campbell, J.N., Raja, S.N., Seltzer, Z. (2001) Soy-containing
diet suppresses chronic neuropathic sensory disorders in rats. Anesthesia &
Analgesia 92:1029-1034.
Shir, Y., Raja, S.N., Weissman, C., Campbell, J.N., Seltzer, Z. (2001)
Consumption of soy diet before nerve injury preempts the development of
neuropathic pain in rats. Anesthesiology 95:1238-1244.
Shir, Y., Campbell, J.N., Raja, S.N., Seltzer Z. (2002) The correlation between
dietary soy phytoestrogens and neuropathic pain behavior in rats after partial
denervation. Anesthesia & Analgesia. 2002 94:421-426.
Neuropathic Pain

Department of Anesthesiology and Critical Care Medicine


Shir, Y., Zeltser, R., Vatine, J.J., Carmi, G., Belfer, I., Zangen, A., Overstreet, D.,
Raber, P., Seltzer, Z. (2001) Correlation of intact sensibility and neuropathic pain-
related behaviors in eight inbred and outbred rat strains and selection lines. Pain
90:75-82.
Shir, Y., Seltzer, Z. (2001) Heat hyperalgesia following partial sciatic ligation in
rats: interacting nature and nurture. Neuroreport 12:809-813.
Pain
Carlton, S.M., Du, J., Davidson, E., Zhou, S., Coggeshall, R.E. (2001)
Somatostatin receptors on peripheral primary afferent terminals: inhibition of
sensitized nociceptors. Pain. 90:233-244.
Davidson, E.M., Doursout, M.F., Szmuk, P., Chelly, J.E. (2001) Antinociceptive
and cardiovascular properties of esmolol following formalin injection in rats.
Canadian Journal of Anaesthesia 48:59-64.

Medical Research and Development 179


RESEARCH AT HADASSAH

Shir, Y., Rosen, G., Zeldin, A, Davidson, E.M. (2001) Methadone is safe for
treating hospitalized patients with severe pain. Canadian Journal of Anaesthesia
48:1109-1113.
Babchenko, A., Davidson, E., Adler, D., Ginosar, Y., Kurz, V., Nitzan, M. (2000)
Increase in pulse transit time to the foot after epidural anaesthesia treatment.
Medical Biological Engineering & Computing. 38:674-679.
Babchenko, A., Davidson, E., Ginosar, Y., Kurz, V., Faib, I., Adler, D., Nitzan, M.
(2001) Photoplethysmographic measurement of changes in total and pulsatile
tissue blood volume, following sympathetic blockade. Physiological
Measurements 22:389-396.
Ethical Issues in Critical Care
Nyman, D.J., Sprung, C. (2000) End-of-life decision making in the intensive care
unit. Intensive Care Medicine. 26:1414-1420.
Levin, P.D., Sprung, C.L. (2000) Are ethics consultations worthwhile? Critical
Care Medicine 28:3942-3944.
Truog, R.D., Cist, A.F., Brackett, S.E., Burns, J.P., Curley, M.A., Danis, M.,
DeVita, M.A., Rosenbaum, S.H., Rothenberg, D.M., Sprung C.L., Webb, S.A.,
Department of Anesthesiology and Critical Care Medicine

Wlody, G.S., Hurford, W.E. (2001) Recommendations for end-of-life care in the
intensive care unit: The Ethics Committee of the Society of Critical Care
Medicine. Critical Care Medicine. 29:2332-2348.
Triage of Intensive Care Unit Admission
Levin, P.D., Sprung, C.L. (2001) The process of intensive care triage. Intensive
Care Medicine 27:1441-1445.
Sepsis
de Mendonca, A., Vincent, J.L., Suter, P.M., Moreno, R., Dearden, N.M.,
Antonelli, M., Takala, J., Sprung, C., Cantraine, F. (2000) Acute renal failure in
the ICU: risk factors and outcome evaluated by the SOFA score. Intensive Care
Medicine 26:915-921.
Matot, I., Sprung, C.L. (2001) Definition of sepsis. Intensive Care Medicine 27:
Suppl 1:S3-9.

180 Medical Research and Development


RESEARCH AT HADASSAH

Bernard, G., Artigas, A,. Dellinger, P., Esmon, C., Faist, E., Faust, S.N., Fischer,
C.J., Fumagalli, R., Grinnell, B.W., Sprung, C. (2001) Clinical expert round table
discussion at the Margaux Conference on Critical Illness: the role of activated
protein C in severe sepsis. Critical Care Medicine 29(7 Suppl):S75-7
Vincent, J.L., Akca, S., De Mendonca, A., Haji-Michael, P., Sprung, C., Moreno,
R., Antonelli. M., Suter, P.M. (2002) The epidemiology of acute respiratory
failure in critically ill patients. Chest. 121:1602-1609.
Alberti, C., Brun-Buisson, C., Burchardi, H., Martin, C., Goodman, S., Artigas,
A., Sicignano, A., Palazzo, M., Moreno, R., Boulme, R., Lepage, E,. Le Gall, R.
(2002) Epidemiology of sepsis and infection in ICU patients from an
international multicentre cohort study. Intensive Care Medicine 28:525-526.
Sedating Pediatric Patients for Invasive and Noninvasive Procedures
Gozal, D., Gozal, Y. (2000) Nonpharmacologic sedation in a deaf child.
Anesthesia & Analgesia 90:1007
Gozal, D., Gozal, Y. (2000) An unusual cause of failed sedation. Anesthesia &
Analgesia 91:1043.

Gozal, D., Rein, A.J., (2001) Propofol does not modify the hemodynamic status

Department of Anesthesiology and Critical Care Medicine


of children with intracardiac shunts undergoing cardiac catheterization. Pediatric
Cardiology 22:488-490.
Gene Therapy and the Acute Respiratory Distress Syndrome (ARDS)

Weiss, Y.G., Bouwman, A., Gehan, B., Schears, G., Raj, N., Deutschman, C.S.
(2000) Cecal ligation and double puncture impairs heat shock protein 70 (HSP-
70) expression in the lungs of rats. Shock 13:19-23.
Weiss, Y.G., Deutschman, C.S. (2000) Modulation of gene expression in critical
illness: a new millennium or a brave new world? Critical Care Medicine.
28:3078-3079.
Weiss, Y.G., Tazelaar, J., Gehan, B.A., Bouwman, A., Christofidou-Solomidou,
M., Yu, Q.C., Raj, N., Deutschman, C.S. (2001) Adenoviral vector transfection
into the pulmonary epithelium after cecal ligation and puncture in rats.
Anesthesiology 95:974-982.

Medical Research and Development 181


RESEARCH AT HADASSAH
Department of
BLOOD B ANK

STAFF
Associate Clinical Professor: Manny, N., MD
(Head of Department)

Teaching Fellow: Zelig, O., MD

Participating in Teaching: Dakosta, Y. PhD

INTRODUCTION
The department of transfusion medicine and blood bank is comprised of 3
interconnected subunits : Donor-room, Infectious diseases detection laboratory
and the patients’ service laboratory.

The donor unit acts as an independent blood collecting and blood processing
facility. Some of the functions performed include :
Whole blood collection, processing into blood components, further treatment of
blood products (filtration, washing and freezing of rare blood units etc.) and
collection of Single-donor platelets units by apheresis.
All donated blood units are tested for the presence of blood borne pathogens like
HIV, HTLV, HBV, HCV and RPR by ELISA methods.
The patients’ service laboratory conducts the immunohematology work-up
needed for providing safe blood products to hospitalized patients as well as
Department of Blood Bank

diagnosis and follow-up of out-patients.


In addition screening tests for Heparin-Induced-Thrombocytopenia and PNH are
performed. The Hadassah blood bank is the only laboratory in the country that
carries out the MMA test to establish the clinical significance of RBC antibodies.

182 Medical Research and Development


RESEARCH AT HADASSAH

RESEARCH AREAS
Acceptance/deferal criteria Rheology of stored blood
for blood donors (Yedgar, Manny)
(Manny, Dakosta, Zelig)
Function of stored platelets
Auto-immune Hemolytic Anemia (Zelig, Manny, Varon)
(Zelig, Dakosta, Manny)
Bacterial contamination
Alloantibodies in Thalassemia of blood components
(Dakosta, Manny, Zelig) (Zelig, Block, Shinar, Manny)

RECENT PUBLICATIONS
Maayan S., Zhang L., Shinar E., Ho T., Manny N, Neuman A.U. (2000) Evidence
for recent selection on the CCR - ( 32 deletion from differences in its frequency
between Ashkenazi and Sepharadi jews. Genes and Immunity 1:358-361.
Safadi R., Ergunay K., Ilan A., Shouval D., Manny N., Harush N., Galun E.
(2000) TT virus infection in Israeli patients with fulminant hepatic failure. Vox
Sang. 79:242-245.
Manny N., Zelig O. (2000) Laboratory diagnostic of autoimmune cytopenias.
Curr. Opin. Hematol 7:414-419.
Cohen Y., Polliack A., Zelig O., Goldfarb A. (2001) Monotherapy with rituximab
induces rapid remission of recurrent cold-agglutinin-mediated hemolytic anemia
in a patient with indolent lympho-plasmacytic lymphoma. Leuk. Lymph.
42:1405-1408.
Department of Blood Bank

Yahalom V., Ellis M.H., Pole J., Rahimi-levene N., Shinar E., DaCosta Y., Manny
N, Levene C. (2002) The rare Lu:-6 phenotype in Israel and the clinical
significance of anti-Lu6. Transfusion 42:247-250.
Donchin Y., Levi A., Kalif E., Stern Z., Manny N. (2002) The impact of adding
a graphic check list to blood units on the medical team compliance to blood
administration protocol. Brit. Med. J ( In press).

Medical Research and Development 183


RESEARCH AT HADASSAH
Department of
BONE MARROW TRANSPLANTATION
STAFF
Professor: Slavin S., MD
(Head of the Department)

Associate Professor: Or R., MD

Lecturer: Shapira M., MD

Staff members: Resnick I., MD


Zilberman I., MD
Miron S., MD
Bitan M., MD

Researchers: Weiss L., PhD Panigrahi S.,MD


Morecki S., PhD Ackerstein A.
Gurevich O., PhD Kassir Y., PhD
Zeira M., PhD Dagan A., PhD
Elkin G.,PhD Gazit A., PhD
Preghozina T., PhD Zilberstein T., PhD
Abdel-Hai A.,PhD Kurkalli BG., PhD student
Department of Bone Marrow Transplatation

INTRODUCTION
The Department of Bone Marrow Transplantation (BMT) at Hadassah University
Hospital serves as Israel’s national BMT center. Presently, approximately 150
BMT procedures are carried out yearly, including autologous and allogeneic bone
marrow, blood stem cells and cord blood transplantation procedures for patients
with a variety of non-malignant disorders, hematological malignancies and
metastatic solid tumors. Likewise, the department is involved in cell therapy for
a large variety of marrow deficiency diseases (e.g. aplastic anemia); immune
deficiencies (e.g. severe combined immunodeficiency); genetic diseases (e.g.
thalassemia major, Gaucher’s disease, etc) autoimmune disorders and gene

184 Medical Research and Development


RESEARCH AT HADASSAH

therapy (e.g. adenosine deaminase deficiency). The BMT Department operates


in conjunction with the Cell Therapy and Cancer Immunobiology Research
Center, and the Danny Cunniff Leukemia Research Center, which are all involved
in basic and clinically oriented research.

The Department of Bone Marrow Transplantation has pioneered clinical


applications of BMT in Israel. Research activities include adoptive cellular
immunotherapy of cancer and tumor cell vaccination, new approaches for
autologous and allogeneic BMT, focusing on induction transplantation tolerance
to bone marrow and organ allografts, using reduced intensity conditioning and
understanding the mechanisms of unresponsiveness, induction of self-tolerance
in autoimmune diseases, as well as developing new approaches for enhancing
hematopoietic and immunological reconstitution following BMT.

Topics currently under investigation at the Immunobiology Research Laboratory


include: (1) Induction and mechanisms of transplantation tolerance; (2)
Development of new approaches in cancer immunotherapy by amplification of
host’s adaptive and natural anti-tumor effector mechanisms; utilizing cell-
mediated adoptive immunotherapy and development of tumor cell vaccines; (3)
Development of new approaches for allogeneic stem cell transplantation focusing
on non-myeloablative conditioning; (4) Enhancement of immunohematopoietic
reconstitution following BMT using biological response modifiers and
recombinant cytokines; and (5)development of new therapeutic strategies for
autoimmune disorders using new therapeutic approaches for reinduction of

Department of Bone Marrow Transplatation


unresponsiveness towards self; (6) Gene therapy; (7) Stem cell plasticity.

The BMT Department has a positively pressurized GMP-like Cell Therapy


Center; a large cryopreservation unit; a leukopheresis and lymphopheresis unit,
for cellular adoptive immunotherapy; cord blood bank; and cryopreservation
Center. Prof. Slavin is in charge of the research animal facility at the Ulman
building. Services include outpatient clinics for BMT, candidates and recipients
of cancer immunotherapy focusing on Cell therapy, monoclonal antibody therapy
and recombinant cytokines for induction of anti-tumor responses in patients with
cancer at the stage of minimal residual disease.

Medical Research and Development 185


RESEARCH AT HADASSAH

RESEARCH AREAS
Bone marrow transplantation Cell therapy
(Or, Shapira, Resnick, Zielberman, (Slavin, Or, Shapira, Resnick, Aker,
Miron, Bitan, Samuel, Slavin) Morecki)

Stem cell (transplantation, plasticity) Tumor cell vaccines


(Or, Shapira, Resnick, Zielberman, (Morecki, Ackerstein, Slavin)
Miron, Bitan, Samuel, Slavin)
Graft-vs-host disease (GVHD)
Immunotherapy (Preghozina, Slavin)
(Or, Morecki, Weiss, Shapira,
Resnick, Samuel, Slavin) Transplantation tolerance
(Preghozina, Slavin)
Gene therapy
(Morecki, Aker, Slavin) Graft-vs-malignancy (GVM)
(Preghozina, Slavin, Morecki)
Genetic diseases
(Morecki, Or, Shapira, Slavin) Heparanase
(Bitan, Vlodavski)
Immune deficiency
(Resnick, Aker, Slavin) Targeted chemotherapy of cancer
(Slavin, Levitzki, Dagan, Gazit)
Cord blood transplantation
(Or, Samuel, Slavin)
Department of Bone Marrow Transplatation

Bone and cartilage disorders


(Gurevich, Kurkalli, Slavin)
Molecular biology
(Kassir, Morecki, Slavin) AIDS
(Zeira, Slavin)
Cytokines
(Ackerstein, Or, Shapira, Slavin)

Autoimmune diseases
(Slavin, Shapira, Resnick, Or)

186 Medical Research and Development


RESEARCH AT HADASSAH

LIST OF PUBLICATIONS
Immunotherapy of cancer
Slavin S., Or R., Prighozina T., Gurevitch O., Aker M., Panighari S., Shapira M.,
Nagler A. (2000) Immunotherapy of hematologic malignancies and metastatic
solid tumors in experimental animals and man. Bone Marrow Transplantation.
25(2):S54-S57.
Morecki S., Yacovlev E., Gelfand Y., Trembovler V., Shoshami E., Slavin S.
(2000) Induction of anti-tumor immunity by indomethacin. Cancer Immunol
Immunother. 48:613-620.
Morecki S., Slavin S. (2000) Toward amplification of a graft vs leukemia (GVL)
effect while minimizing graft vs host disease (GVHD). Journal of
Hematotherapy. 9:355-366.
Nagler A., Ackerstein A., Or R., Naparstek E., Slavin S. (2000) Adoptive
immunotherapy with haploidentical allogeneic peripheral blood lymphocytes
(PBL) following autologous bone marrow transplantation (ABMT). Exp
Hematol. 28(11);1225-1231.
Slavin S. (2000) Cancer immunotherapy with alloreactive lymphocytes. The New
England Journal of Medicine. 343(11);802-803.

Leshem B., Vourka Karussis U., Slavin S. (2000) Correlation between


enhancement of graft vs leukemia effects following allogeneic bone marrow

Department of Bone Marrow Transplatation


transplantation by rIL-2 and increased frequency of cytotoxic t-lymphocyte
precursors in murine myeloid leukemia. Cytokines, Cellular & Molecular
therapy. 6;141-147.
Morecki S., Yacovlev E., Gelfand Y., Uzi I., Slavin S. (2001) Cell therapy with
pre-immunized effector cells mismatched for minor histocompatible antigens, in
the treatment of a murine mammary carcinoma. Journal of Immunotherapy.
24(2):114-121.
Slavin S. (2001) Immunotherapy of cancer with alloreactive lymphocytes. Lancet
Oncology. 2:491-498.
Slavin S., Ackerstein A., Morecki S., Gelfand Y., Cividalli G. (2001)
Immunotherapy of relapsed resistant chronic myelogenous leukemia post

Medical Research and Development 187


RESEARCH AT HADASSAH

allogeneic bone marrow transplantation with alloantigens pulsed donor


lymphocytes. Bone Marrow Transplant.28:795-798.
Slavin S., Nagler A., Shapira MY., Aker M., Cividalli G., Or R. (2002) Treatment
of leukemia by alloreactive lymphocytes and non-myeloablative stem cell
transplantation. Clinical Immunology. 22(2):64-69.
Slavin S., Morecki S., Weiss L., Or R. (2002) Donor lymphocyte infusion (DLI):
the use of alloreactive and tumor reactive lymphocytes for immunotherapy of
malignant and non-malignant diseases in conjunction with allogeneic stem cell
transplantation. Journal of Hematotherapy & Stem Cell Research. 1:265-276.
Prigozhina T., Gurevitch O., Morecki S., Yakovlev E., Elkin G., Slavin S.
(2002) Non-myeloablative allogeneic bone marrow transplantation as
immunotherapy for hematologic malignancies and metastatic solid tumors in pre-
clinical models. Exp Hematol.30:89-96.
Slavin S., Morecki S., Weiss L., Shapira MY., Or R. Immunotherapy of
hematologic malignancies and metastatic solid tumors in experimental animals
and man. Critical Reviews in Hematology/Oncology. (in press).

Autoimmune diseases

Weiss L., Slavin S., Reich S., Cohen P., Shuster S., Stern R., Kaganovsky E.,
Okon E., Rubinstein AM., Naor D. (2000) Induction of resistance to diabetes in
non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody.
Proc. Natl. Acad. Sci. (PNAS). (4);97:285-90.
Department of Bone Marrow Transplatation

Slavin S., Nagler A., Varadi G., Or R. (2000) Graft vs autoimmune lymphocytes
(GVA) following allogeneic bone marrow transplantation in a patient with
chronic myelogenous leukemia and severe systemic psoriasis and psoriatic
polyarthritis. Exp Hematol. 28(7);853-7.

Gross DJ., Weiss L., Reibstein I., Hedlund G., Dalen E., Rapoport M., Slavin S.
(2001) The immunomodulator Linomide: Role in treatment and prevention of
autoimmune diabetes mellitus. International Immunopharmacology:1131-1139.
Richard K. Burt, Walter Barr, Yu Oyama, Ann Traynor, Shimon Slavin. (2001)
Future strategies in hematopoietic stem cell transplantation for rheumatoid
arthritis. J of Rheumatology.;28(64);42-48.

188 Medical Research and Development


RESEARCH AT HADASSAH

Burt R.K., Slavin S., Burns W.H., Marmont A.M. (2001) Induction of tolerance
in autoimmune diseases by hematopoietic stem cell transplantation:Getting closer
to a cure? Blood.99(3)768-784.
Weiss L., Abdul-Hai A., Shufaro Y., Reich S., Slavin S. Linomide administration
following bone marrow transplantation in mice. Cancer Immunol Immunother.
(in press).
Bone marrow transplantation
Carella AM., Champlin R., Slavin S., McSweeney P., Strob R. (2000) “Mini-
allografts”: ongoing trials in humans. Bone Marrow Transplant. 25(4):345-350.
Carella AM., Giralt S., Slavin S. (2000) Low intensity regimens with allogeneic
hematopoietic stem cell transplantation as treatment of hematologic neoplasia.
Haematologica. 85(3):304-313.
Nagler A., Slavin S., Varadi G., Naparstek E., Samuel S., Or R. (2000)
Allogeneic peripheral blood stem cell transplantation using a fludarabine-based
low intensity conditioning regimen for a malignant lymphoma. Bone Marrow
Transplant.25(10):1021-1028.
Nagler A., Or R., Naparstek E., Varadi G., Slavin S. (2000) Second allogeneic
stem cell transplantation using non-myeloablative conditioning for patients who
relapsed or developed secondary malignancies following autologous
transplantation. Experimental Hematol. 28:1096-1104.
Slavin S., Or R., Aker M., Shapira MY., Panigrahi S., Symeonidis A., Cividalli

Department of Bone Marrow Transplatation


G., Nagler A. (2001) Nonmyeloablative stem cell transplantation for the
treatment of cancer and life-threatening nonmalignant disorders: past
accomplishments and future goals. Cancer Chemotherapy & Pharmacology.
489(1)S79-S84.
Slavin S., Nagler A. Shapira M., Panigrahi S., Samuel S., Or R. (2001) Non-
myeloablative allogeneic stem cell transplantation focusing on immunotherapy of
life-threatening malignant and non-malignant diseases. Critical Reviews in
Hematology/Oncology. 9:25-29.
Nagler A., Aker M., Or R., Naparstek E., Varadi G., Brautbar C., Slavin S. (2001)
Low intensity conditioning is sufficient to ensure engraftment in matched
unrelated bone marrow transplantation. Experimental Hematol. 29:362-370.

Medical Research and Development 189


RESEARCH AT HADASSAH

Slavin S., Nagler A., Aker M., Shapira MY., Cividalli G., Or R. (2001) Non-
myeloablative stem cell transplantation and donor lymphocyte infusion for the
treatment of cancer and life-threatening non-malignant disorders. Reviews in
Clinical and Experimental Hematology. 135-146.
Slavin S. (2002) Non-myeloablative stem cell transplantation for immunotherapy
of cancer and non-malignant diseases with allogeneic lymphocytes. Israel Journal
Med Assoc (IMAJ). 4(4);284-287.
Slavin S. Non myeloablative stem cell transplantation. Biomedical progress. (In
press).
Slavin S., Aker M., Shapira MY., Panigrahi S., Cividalli G., Or R. (2002) Non-
myeloablative stem cell transplantation for the treatment of cancer and life-
threatening non-malignant disorders: Past accomplishments and future goals.
Transf Apher Sci. 27(2):159-166.
Or R, Shapira MY, Amar A, Ackerstein A, Samuel S, Aker M, Naparstek E,
Nagler A, Slavin S. Non-myeloablative allogeneic stem cell transplantation for
the treatment of chronic myeloid leukemia in first chronic phase. Blood. (In
press).
Slavin S. Non-myeloablative stem cell transplantation (NST) for induction of
host vs graft tolerance for adoptive immunotherapy of malignant and non
malignant diseases and towards transplantation of organ allografts.
Transplantation Proceedings.(In press).
Department of Bone Marrow Transplatation

Gene therapy and genetic engineering


Hiller C., Wittmann S., Slavin S., Fickenscher H. (2000) Functional long-term
thymidine kinase suicide gene expression in T cells using a herpesvirus saimiri
vector. Gene Therapy.7(8):664-674.
Hiller C., Tamguney G., Stolte N., Matz-Resing K., Lorenzen D., Hor S., Thurau
M., Wittmann S., Slavin S., Fickenscher H. (2000) Herpesvirus siamiri
pathogenicity enhanced by thymidine kinase of herpes simplex virus.
Virology.278:445-455.
Aiuti A., Slavin S., Aker M., Ficara F., Deola S., Mortellaro A., Morecki S.,
Andolfi G, Tabucchi A., Carlucci F., Murinello E., Cattaneo F., Vai S., Servida P.,

190 Medical Research and Development


RESEARCH AT HADASSAH

Miniero R., Grazia Roncarolo M., Bordignon C. (2002) Correction of ADA-


SCID by stem cell gene therapy combined with non-myeloablative conditioning.
Science 296;2410-2413.

Immune regulation

Nagler RM., Reznick AZ., Slavin S., Nagler A. (2000) Partial protection of rat
parotid glands from irradiation-induced hyposalivation by manganese superoxide
dismutase. Archives of Oral Biology.45(9).

Ilan Y., Nagler A., Zeira E., Adler R., Slavin S., Shouval D. (2000) Maintenance
of immune memory to the hepatitis B envelope protein following adoptive
transfer of immunity in bone marrow transplant recipients. Bone Marrow
Transplant. 26(6):633-8.

Panigrahi S., Nagler A., Or R., Wolf DG., Slavin S., Shapira MY. (2001) Idolent
aspergillus arthritis complicating Fludarabine-based non-myeloablative stem cell
transplantation. Bone Marrow Transplantation. 27(6):659-61.

Weiss L., Barak V., Zeira M., Abdul-Hai A., Raibstein I., Reich S, Hirschfeld E.,
Gross D., Slavin S. Cytokine production in Linomide treated NOD mice and the
potential role of Th1/Th2 shift on the autoimmune and the anti-inflammatory
process. Cytokine. (In press).

Immune reconstitution

Levy J., Amar A., Brautbar C., Slavin S., Kapelushnik J. (2000) Transient

Department of Bone Marrow Transplatation


recovery of endogenous immune function following haploidentical peripheral
stem cell transplantation in a patient with severe combined immunodeficiency
without evidence of engraftment. Acta Paediatr. 89(2):248-50.

Morecki S., Gelfand Y., Nagler A., Or R., Naparstek E., Varadi G., Engelhard D.,
Ackerstein A., Slavin S. (2001) Immune reconstitution following allogeneic
stem cell transplantation in recipients conditioned by low intensity vs
myeloablative regimen. Bone Marrow Transplant. 28:243-249.

Medical Research and Development 191


RESEARCH AT HADASSAH
Department of
C ARDIOTHORACIC SURGERY
STAFF
Professor Emeritus: Borman, J.B. FRCS (Eng.), FACS
Head, Cardiac Surgery
(Research Center)

Professor: Merin, G., MD


(Head of Department)

Senior Lecturers: Elami, A., MD


(Head, Heart Transplant Unit)
Milgalter, E., MD
(Head, Pediatric Cardiac Surgery Unit)

Lecturers: Rudis, E., MD


Izhar, U., MD

Research Associates: Schwalb, H., PhD


Olivson, A., PhD

Physicians Participating in Ad, N., MD


Research and Teaching: Korach, A., MD
Viola, N., MD

INTRODUCTION
Department of Cardiothoracic Surger y

The Department of Cardiothoracic Surgery has a research laboratory, The Joseph


Lunenfeld Cardiac Surgery Research Center, involved in pure research and in the
development and testing of innovative devices.
Current research in the laboratory focuses on methods to improve the ability of
the myocardium to withstand induced ischemia. Preconditioning and
pharmacological alternatives are investigated in the isolated rat heart model and
in cardiomyocyte preparations. In collaboration with the Department of
Anesthesia, these approaches are also investigated in the canine model of
regional ischemia, and in a prospective randomized study in patients undergoing
off-pump myocardial revascularization.

192 Medical Research and Development


RESEARCH AT HADASSAH

Postoperative atrial fibrillation is recognized as a morbid complication of open-


heart surgery, with an incidence of 30% or higher. Different aspects of this
intriguing problem are now studied. Mitochondrial function, adrenoreceptor
function, and endogenous cardiac glycosides are investigated as possible
contributing factors in the development of this phenomenon. A prospective
randomized study in patients examines the optimal duration of medical treatment
after the occurrence of this complication.
The surgical treatment of chronic or paroxysmal atrial fibrillation is investigated
in patients undergoing valve surgery.
The response of the smooth muscle in blood vessels and airways to adrenergic
stimuli may be genetically determined. The organ-bath model in the laboratory is
used for ex-vivo experiments to study the influence of the polymorphism of the
α and β2-adrenergic receptors on the reactivity of the human internal thoracic
artery and bronchial segments from resected lungs. This project is performed in
collaboration with the Division of Clinical Pharmacology.
A novel bioprosthetic aortic valve, to be implanted in the future by
catheterization, is presently developed by a US company (PVT). A series of
experiments in which prototypes of this valve are implanted surgically in large
animals using open-heart techniques, is conducted in the laboratory.

RESEARCH AREAS
Coronary artery disease Organ cryopreservation
(Elami, Merin, Ad, Rudis, Izhar) (Elami)

Smooth muscle reactivity Future Aortic Value Prostesis Department of Cardiothoracic Surger y

(Elami) (Ad, Elami)

Vasoplegia after bypass


(Elami)

Myocardial ischemia, Cardioprotection, Preconditioning


(Ad, Schwalb, Borman, Merin, Elami)

Atrial fibrillation
(Ad, Elami, Izhar, Merin, Korach)

Medical Research and Development 193


RESEARCH AT HADASSAH

RECENT PUBLICATIONS
Minners J., van den Bos EJ., Yellon DM., Schwalb H., Opie LH., Sack MN.,
(2000) Dinitrophenol, cyclosporin A, and trimetazidine modulate
preconditioning in the isolated rat heart: support for a mitochondrial role in
cardioprotection.Cardiovasc Res. 47(1):68-73.
Korach A., Izhar U., Rudis E., Elami A., (2000) Concomitant coronary artery
bypass surgery and pulmonary lobectomy. Harefuah 138:825-828.
Elami A., (2000) More about obstructive lesions of the right aortic arch. (letter)
Ann Thorac Surg 69:1295-1296.
Weiss YG., Merin G., Koganov E., Ribo A., Oppenheim-Eden A., Medalion B.,
Peruanski M., Reider E., Bar-Ziv J., Hanson WC., Pizov R., (2000)
Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk
factors, and clinical significance. J Cardiothorac Vasc Anesth. 14(5):506-513.
Elami A., Korach A., Rudis E., (2001) Lung cancer resection or aortic graft
replacement with simultaneous myocardial revascularization without
cardiopulmonary bypass. Chest 119:1941-1943.
Izhar U., Schwalb H., Borman JB., Hellener GR., Hotoveli-Salomon A., Marom
G., Stern T., Cohn D., (2001) Novel synthetic selectively degradable vascular
prostheses: a preliminary implantation study. J Surg Res. 95(2):152-160.
Gerrah R., Abramovits Y., Elami A., (2001) Traumatic memory - a cause for
postoperative delirium. A diagnostic dilemma. IMAJ 3:858-859.
Mosseri M., Haviv B., Weshler Z., Schwalb H., (2001) The effect of ionizing
Department of Cardiothoracic Surger y

irradiation on vasomotor reactivity in the rat thoracic aorta in vitro. Cardiovasc


Radiat Med. 2(3):151-156.
Schwalb H., Olivson A., Li J, Houminer E., Wahezi SE., Opie LH., Maulik D.,
Borman JB., Powell SR., (2001) Nicorandil decreases postischemic actin
oxidation. Free Radic Biol Med 31(5):607-614.
Deeb ME., Shargal Y., Merin G., Milgalter E., (2002) Incidental finding of
myeloproliferative disorders during sternotomy. Ann Thorac Surg 73: 1951-
1952.

194 Medical Research and Development


RESEARCH AT HADASSAH

Ekstein S., Elami A., Merin G., Gotsman MS., Lotan C., (2002) Balloon
angioplasty versus bypass grafting in the era of coronary stenting. IMAJ 4:583-
589.
Elami A., Merin G., (2002) Stented Angioplasty of CABG for multivessel
disease? (letter). J Am Coll Cardiol 40:2063-4.
Elami A., (2003) Cerebral protection using retrograde cerebral perfusion (letter).
J Thorac Cardiovasc Surg 125:441.
Ad N., Cox JL., (2002) Combined mitral valve surgery and the Maze III
procedure. Semin Thorac Cardiovasc Surg 14 (3): 206-9.
Viola N., Williams MR., Oz MC., Ad N., (2002 The technology in use for the
surgical abalation of atrial fibrillation. Semin Thorac Cardiovasc Surg 14 (3):
198-205.
Ad N., Cox JL., (2002) The significance of atrial fibrillation in patients
undergoing mitral valve surgery. Semin Thorac Cardiovasc Surg 14 (3): 193-7.
Ad N., (2002) Intraoperative alternatives for treating atrial fibrillation associated
with mitral valve disease: Introduction. Semin Thorac Cardiovasc Surg 14 (3):
192.
Bar I., Friedman T., Shargal Y., Rudis E., Friedman M., Elami A., (2003) Isolated
sternal fracture - a benign condition? IMAJ (in press).
Elami A., Ad N. Merin G., (2003) The Significance of subclavian artery injection
prior to surgical myocardial revascularization. Internet J Cardiovasc Interv 125:
441.
Gotsman I., Gilon D., Elami A., (2003) Images in cardiology: Transesophageal Department of Cardiothoracic Surger y
echocardiography of a large tricuspid valve vegetation : A perfect image of
reality. Heart (in press).
Gerrah R., Shargal Y., Bdolah-Abram T., Elami A., (2003) Impaired oxygenation
and increased hemolysis after cardiopulmonary bypass in patients with Glucose-
6-Phosphate dehydrogenase deficiency. Ann Thorac Surg (in press).

Medical Research and Development 195


RESEARCH AT HADASSAH
Department of
CLINIC AL BIOCHEMISTRY
STAFF
Professors Emeritus: Shafrir, E., Ph.D.
Gutman, A., M.D.

Professor: Mayer, M., D.Sc.


(Head of Department)

Senior Lecturers: Korman, S., M.D.


Higazi, A-R., M.D.

Research Staff Barash, V., Ph.D.


Finci-Yeheskel, D., M.Sc.

INTRODUCTION
The department of Clinical Biochemistry provides extensive laboratory services
in the two Hadassah hospitals, and is active in research and teaching. The major
areas of research in the department are related to metabolic diseases and the to
the fibrinolytic system. The academic personnel teach in the courses of
Metabolism and Human Nutrition, Physiological Biochemistry, Pediatrics, and in
several Post Graduate Courses. In addition, individual guidance is provided for
M.Sc. and Ph.D. students.

RESEARCH AREAS
Metabolism Ovarian biochemistry
(Korman, Gutman, Barash) (Mayer)
Department of Clinical Biochemistr y

Fatty acid oxidation Clinical Biochemistry


(Korman, Gutman) (Mayer)
Amino acid metabolism Plasminogen activation
(Korman) (Higazi)
Peroxisomal metabolism Urokinase receptor
(Korman, Gutman) (Higazi)
Mitochondrial metabolism Laboratory management
(Barash) (Mayer)

196 Medical Research and Development


RESEARCH AT HADASSAH

RECENT PUBLICATIONS
Metabolism
Levy-Khademi F., Korman SH., and Amitai Y. (2000) Henoch-Schˆnlein purpura:
simulataneous occurrence in two siblings. Pediatr. Dermatol. 17:139-140.
Korman SH., Mandel H., and Gutman A. (2000) Characteristic urine organic acid
profile in peroxisomal biogenesis disorders. J. Inherit. Metab. Dis. 23:425-428.
Fattal-Valevski A., Bassan H., Korman SH., Gutman A., Sagie T., and Harel S.
(2000) Methylenetetrahydrofolate reductase deficiency: the importance of early
diagnosis. J. Child Neurol. 15: 539-543.
Straussberg R., Saiag E., Harel L., Korman SH., and Amir J. (2000) Reversible
deafness due to biotinidase deficiency. Pediatr. Neurol. 23:269-270.
Elpeleg O., and Korman SH. (2001) Sustained oral lysine treatment in ornithine-
aminotransferase deficiency. J. Inherit. Metab. Dis. 24: 423-424.
Korman SH., Cohen E., and Preminger A. (2001) “Pseudo-maple syrup urine
disease” due to maternal prenatal ingestion of fenugreek. J. Paediatr. Child Health
37:403-404.
Nissenkorn A., Korman SH., Vardi O., Levin A., Katzir Z., Ballin A., and
Lerman-Sagie T. (2001) Carnitine-deficient myopathy as a presentation of
tyrosinemia type I. J. Child Neurol. 16(9):642-644.
Wang Y., Korman SH., Ye J., Gargus JJ., Gutman A., Taroni F., Garavaglia B.,
and Longo N. (2001) Phenotype and genotype variation in primary carnitine Department of Clinical Biochemistr y
deficiency. Genet. Med. 3(6):387-392.
Raas-Rothschild A., Wanders RJA., Mooijer PAW., Gootjes J., Waterham HR.,
Gutman A., Suzuki Y., Shimozawa N., Kondo N., Eshel G., Roels F., Espeel M.,
and Korman SH. (2002) A PEX6-defective peroxisomal biogenesis disorder with
severe phenotype in an infant, versus mild phenotype resembling Usher
syndrome in the affected parents. Am. J. Hum. Genet. 70(4):1062-1068.
Korman SH., Raas-Rothschild A., Elpeleg O., and Gutman A. (2002)
Hypocarnitinemia in lysinuric protein intolerance: potential mechanisms. Molec.
Genet. Metab. 76(1):81-83

Medical Research and Development 197


RESEARCH AT HADASSAH

Metzger S., Hassin T., Barash V., Pappo O., and Chajek-Shaul T. (2001) Reduced
body fat and increased hepatic lipid synthesis in mice bearing interleukin 6
secreting tumor. Am. J. Physiol. Endocrinol. Metab. 281(5): E957-65.
Haftel LT., Lev D., Barash V.,.Gutman A., Bujanover Y., and Lerman-Sagie T.
(2000) Familial mitochondrial intestinal pseudo-obstraction and neurogenic
bladder. J. Child Neurol. 15(6): 386-9.
Korman SH., and Gutman A. (2002) Pitfalls in the diagnosis of glycine
encephalopathy (nonketotic hyperglycinemia) Dev. Med. Child Neurol. 44: (in
press)
Gynecological Biochemistry
Dresner-Pollak R., Mayer, M., and Hochner-Celnikier D. (2000) The decrease in
serum bone-specific alkaline phosphatase predicts bone mineral density response
to hormone replacement therapy in early postmenopausal women. Calcif. Tissue
Int. 66: 104-107.
Hurwitz A., Finci-Yeheskel., Z, Milwidsky A., and Mayer M. (2002) Regulation
of cyclooxygenase activity and progesterone production in the rat corpus luteum
by inducible nitric oxide synthase. Reproduction 123: (In press)
Plasminogen Activation
Guo Y., Higazi AR., Anakelian A., Sachais BS., Cines DB., Goldfarb RH., Jones
TR., Kwaan H., Mazar AP., and Rabbani SA. (2000) A peptide derived from non-
receptor binding region of urokinase plasminogen activator (uPA) inhibits tumor
progression and angiogenesis and induces tumor cell death in vivo. FASEB J. 14:
1400-1410.
Department of Clinical Biochemistr y

Haj-Yejia A., Nassar T., Sachais BS., Kuo A., Bdeir KH., Al-Medhi AB., Mazar
A., Cines DB., and Higazi AR. (2000) Urokinase-derived peptides regulate
vascular smooth muscle cell contraction in vitro and in vivo. FASEB J. 14: 1411-
1422.
Higazi AR., Nassar T., Ganz T., Rader D., Udassin R., Bdeir K., Hiss E., Sachais
BS., Williams KJ., Leitersdorf E., and Cines DB. (2000) (-Defensin stimulates
proteoglycan-dependent catabolism of low density lipoprotein by vascular cells:
A new class of inflammatory apolipoprotein and a possible contributor to
atherogenesis. Blood 96: 1393-1398.

198 Medical Research and Development


RESEARCH AT HADASSAH

Shloim O., Huang M., Sachais BS., Kuo A., Weisel JW., Nagaswami C., Nassar
T., Bdeir K., Hiss E., Gawlak S., Harris S., Mazar A., and Higazi AR. (2000)
Novel Interactions Between Urokinase and its Receptor. J Biol. Chem. 275:
24304-12.
Bdeir K., Muciano JC., Tomaszewski J., Koniares L., Martinez J., Muzykantov
V., and Higazi AR. (2000) Urokinase contributes to fibrinolysis in the pulmonary
microcirculation. Blood 96: 1820-6.
Sachais BS., Kuo A., Nassar T., Morgan J., Kariko K., Williams KJ., Feldman M.,
Aviram M., Neelima Shah N., Jarett L., Poncz M., Cines DB., and Higazi, AR.
(2002) Platelet factor 4 binds to low-density lipoprotein receptors and disrupts
the endocytic itinerary, resulting in retention of low-density lipoprotein on the
cell surface. Blood 99: 3613-3622.
Nassar T., Akkawi S., Bar-Shavit R., Haj-Yehia A., Bdeir K., Al-Mehdi A.,
Tarshis M., and Higazi AR. (2002) Human (-Defensin Regulates Smooth Muscle
Cell Contraction. A role for low-density lipoprotein receptor-related protein/(2-
macroglobulin receptor. Blood (In press)
Nassar T., Haj-Yehia A., Akkawi S., Kuo A., Bdeir K., Mazar A., Cines DB., and
Higazi AR. (2002) Binding of urokinase to low density lipoprotein-related
receptor (LRP) regulates vascular smooth muscle cell contraction. J. Biol. Chem.
(In press).
Laboratory Management
Mayer M., Chou D., and Eytan T. (2001) Unit-independent reporting of
laboratory test results. Clin. Chem. Lab. Med. 39: 50-52. Department of Clinical Biochemistr y
Clinical Biochemistry
Mayer M. (2000) Association of serum bilirubin concentration with risk of
coronary artery disease.
Clin. Chem. 46: 1723-1727.
Rajs G., Finzi-Yeheskel Z., Rajs A., and Mayer M. (2002) C-Reactive protein
concentrations in cerebral spinal fluid in gram-positive and gram-negative
bacterial meningitis. Clin. Chem. 48: 591-592.

Medical Research and Development 199


RESEARCH AT HADASSAH
Department of
CLINIC AL MICROBIOLOGY &
INFECTIOUS DISEASES
STAFF
Professor Emeritus: Sacks, T., M.B.Ch.B., M.Med (Path), F.R. C. Path

Professor: Brautbar, C., Ph.D.

Associate Professors: Shapiro, M., M.B.Ch.B


(Head of Department)
Polacheck, I., Ph.D.

Clinical Associate Professor: Maayan, S., MD.

Senior Lecturers: Block, C., M.B.B.Ch. Ph.D.


Moses, A., M.D.
Rahav, G., M.D.
Wolf, D., M.D.
Department of Clinical Microbiology & Infectious Diseases

Instructors: Nir-Paz, R., M.D.


Cohen, R., M.D.

Physicians Participating Averbukh, D., M.D.


in Teaching: Guslitser, T., M.D.
Temper V., M.D.

INTRODUCTION
The Department of Clinical Microbiology and Infectious Diseases incorporates
units of Clinical Microbiology, Clinical Infectious Diseases, Clinical Virology,
and Tissue Typing. The Units of Clinical Microbiology and Clinical Virology are
responsible for the routine microbiological diagnostic services for the wards and
outpatient clinics of the Hadassah University Hospitals at Ein Kerem and Mount

200 Medical Research and Development


RESEARCH AT HADASSAH

Scopus, and conducts laboratory tests and environmental surveillance. The


department is responsible for the control of hospital-acquired infections, and
provides a consultation service in clinical infectious diseases, including control
of antibiotic use. Out-patient clinics for infectious diseases and for AIDS control
and treatment are run weekly. The Clinical Virology unit is a WHO center for
influenza.

Prof. Mervyn Shapiro studies the emergence of resistant bacteria, antibiotic use,
and molecular epidemiology of infections caused by nosocomial pathogens.

Dr.Colin Block’s specific interest focuses on meningococcal disease in Israel, and


on antimicrobial susceptibility to biocides or disinfectants. He is intimately
involved in studying the emergence of resistant organisms and nosocomial
infections.

Prof. Itzhack Polacheck studies the pathogenic mechanisms of the fungus


Cryptococcus neoformans; development of new antifungals and novel drug
delivery systems, and resistance mechanism of non-albicans yeasts.

Prof. Shlomo Ma’ayan studies genetic variations in the AIDS virus, and AIDS
vaccines.

Department of Clinical Microbiology & Infectious Diseases


Dr. Allon E. Moses studies the molecular pathogenesis, virulence factors and
epidemiology of group A streptococcal infections and other streptococci.

Dr. Dana G. Wolf focuses on the pathogenesis and molecular detection of human
cytomegalovirus infection and disease; emergence of antiviral drug resistance in
transplant recipients using direct genotypic analysis and studying the process of
viral maturation as a target for novel antiviral drugs. Recent studies include the
mechanism of transmission and disease in congenital cytomegalovirus infection.

Dr. Galya Rahav has particular interests in the molecular epidemiology of


Mycobacterium tuberculosis , the molecular pathogenesis of tuberculosis, and the
pathogenesis of urinary tract infections.

Medical Research and Development 201


RESEARCH AT HADASSAH

RESEARCH AREAS
Pathogenesis streptococci epidemiology Community pneumonia mycoplasma
(Moses) (Nir-Paz, Shapiro)

Neisseria meningitidis epidemiology Urinary infection pathogenesis


(Block) (Rahav)

Nosocomial infection antiseptics Tuberculosis pathogenesis epidemiology


(Shapiro, Block) (Rahav)

AIDS viral genetics Antibiotic resistance


(Ma’ayan) (Cohen, Shapiro)

CMV pathogenesis resistance Fungal pathogenesis


(Wolf) (Polacheck)

Human metapneumovirus (hMPV) Fungal resistance epidemiology


(Wolf) (Polacheck, Shapiro)
Department of Clinical Microbiology & Infectious Diseases

RECENT PUBLICATIONS
Nosocomial Infection

Schwaber M.J., Simhon A., Block C., Roval V., Ferderber N., Shapiro M., (2000)
Factors Associated with Nosocomial Diarrhea and Clostridium difficile-
Associated Disease in an Urban Teaching Hospital. Eur. J. Clin. Microbiol. Infect
Dis.19:9-15.

Wolf D.G., Polacheck I., Block C., Sprung C.L., Muggia -Sullam M., Wolf Y.G.,
Oppenheim-Eden A., Rivkind A., Shapiro M. (2000) High rate of candidemia in
patients sustaining blast injury in a marketplace: a possible environmental source.
Clinical Infectious diseases. 31:712-716.

202 Medical Research and Development


RESEARCH AT HADASSAH

Bar-Oz B., Preminger A., Peleg O., Block C., Arad I. (2001) Enterobacter
sakazakii infection in the newborn. Acta Paediatr, 90:356-358.

Simhon A., Rahav G., Shapiro M., Block C. (2001) Skin disease presenting as
an outbreak of pseudobacteremia in a laboratory worker. J Clin Microbiol, 39:
392-393.

Simhon A., Rahav G., Shazberg G., Block C., Bercovier H., Shapiro M. (2001)
Acinetobacter baumannii at a tertiary-care teaching hospital in Jerusalem, Israel.
J Clin Microbiol, 39: 389-391.

Block C., Furman N. (2002) Association between intensity of chlorhexidine use


and micro-organisms of reduced susceptibility in a hospital environment. J Hosp
Infect, 51: 201-206.

Stalnikowicz R., Block C. (2001) The yield of blood cultures in a department of


emergency medicine. Eur J Emerg Med, 8:93-97.

Block C., Peleg O., Minster N., Bar-Oz B., Simhon A., Arad I., Shapiro M. (2002)
Cluster of neonatal infections in Jerusalem due to unusual biochemical variant of
Enterobacter sakazakii. Eur J Clin Microbiol Infect Dis, 21: 613-616.

Department of Clinical Microbiology & Infectious Diseases


AIDS

Maayan S., Zhang L., Shinar E., Ho J., Manni N., Kostrikis L.G., Neumann A.V.
(2000) Evidence for recent selection of the CCR5 - Delta 32 deletion from
differences in it’s frequency between askenazi & sepharadi Jews. Genes and
Immunity 1:358-361.

Loemba H., Brenner B., Parniak M.A., Ma’ayan S., Spira B., Moisi D., Oliveira
M., Detorio M., Wainberg M.A. (2002) Genetic Divergence of Human
Immunodeficiency Virus Type 1 Ethiopian Clade C Reverse Transcriptase (RT)
and Rapid Development of Resistance against Nonnucleoside Inhibitors of RT.
Antimicrob Agents Chemother, 46:2087-2094.

Medical Research and Development 203


RESEARCH AT HADASSAH

Antiseptics

Block C., Robenshtok E., Simhon A., Shapiro M. (2000) Evaluation of


chlorhexidine and povidone iodine activity against methicillin-resistant
Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis using a
surface test. J Hosp Infect, 46:147-152.

Block C., Furman N. (2002) Association between intensity of chlorhexidine use


and micro-organisms of reduced susceptibility in a hospital environment. J Hosp
Infect., 51:201-206.

Fungal disease

Panigrahi S., Nagler A., Or R., Wolf D.G., Slavin S., Shapira M.Y. (2001)
Indolent aspergillus arthritis complicating fludarabine-based non-myeloablative
stem cell transplantation. Bone Marrow Transplant., 27:659-661.

Polacheck, I., Strahilevitz J., Donnelly S., Sullivan D., Salkin I.F., Coleman D.C.
(2000) Recovery of Candida dubliniensis from non-Human Immunodeficiency
Virus-Infected Patients in Israel, J. Clin. Microbiol. 38: 170-174.
Department of Clinical Microbiology & Infectious Diseases

Wolf, G.D., Falk R., Hacham M., Theelen B., Boekhout T., Scorzetti G., Shapiro
M., Block1 C., Salkin I.F. and Polacheck Itzhack (2001) Multidrug-Resistant
Trichosporon asahii Infection of Nongranulocytopenic Patients in Three
Intensive Care Units. J. Clin. Microbiol. 39: 4420-4425.

Ehrenfreund-Kleinman, T., Azzam T. , Falk R., Polacheck I., Golenser J. and


Domb A.J. (2002) Synthesis and characterization of novel water soluble
amphotericin Barabinogalactan conjugates. Biomaterials 23: 1327-1333.

Averbuch D., Boekhout T., Falk R., Engelhard D., Shapiro M., Block C. and
Polacheck I. (2002) Fungemia in a cancer patient caused by fluconazole resistant
Cryptococcus laurentii. Medical Mycology, 40: 479-484.

Gee, S.F., Joly S., Soll D.R., Meis J.F., Verweij P.E., Polacheck I., Sullivan D.J.
and Coleman D.C. (2002) Identification of four distinct genotypes of Candida
dubliniensis and detection of microevolution in vitro and in vivo. J. Clin.
Microbiol. 40: 556-574.

204 Medical Research and Development


RESEARCH AT HADASSAH

Neisseria epidemiology

Shapira-Nahor O., Grotto I., Adler A., Mandel Y., Ashkenazi I., Block C. (2002)
Anticapsular polysaccharide meningococcal antibodies in Israeli military
recruits: immune status and the effect of simultaneous administration of immune
globulin on the response to polysaccharide vaccine. Vaccine, 20:2851-2856.

Viral disease

Sarid R., Pizov G., Rubinger D., Bekenroth R., Friedlander M.M., Schwarz F.,
Wolf D.G. (2001) Detection of human herpes virus-8 DNA in kidney allografts
prior to the development of kaposi’s sarcoma. Clin Infect Dis; 32:1502-1505.

Wolf D.G., Tan Courcelle C., Prichard M.N., Mocarski E.S. (2001) Distinct and
separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA
synthesis and encapsidation. Proc Natl Acad Sci; 98:1895-1900.

Wolf D.G., Yaniv I., Ashkenazi S., Honigman A. (2001) Emergence of multiple
human cytomegalovirus ganciclovir-resistant mutants with deletions and
substitutions within the UL97 gene in a patient with severe combined
immunodeficiency. Antimicrob Agents Chemother. 45:593-595.

Department of Clinical Microbiology & Infectious Diseases


Levy I., Verstandig A., Sasson T., Wolf D., Krichon I., Libson E., Levensart P.,
Papo O., Yurim O., Id A., Shouval D. (2000) [Transarterial oil
chemoembolization for hepatocellular carcinoma, in 100 cases] Harefuah.
138:89-93, 174. Hebrew.

Markel G., Wolf D., Hanna J., Gazit R., Goldman-Wohl D., Lavy Y., Yagel S.,
Mandelboim O. (2002) Pivotal role of CEACAM1 protein in the inhibition of
activated decidual lymphocyte functions. J Clin Invest; 110:943-953.

Shibolet O., Kalish Y., Wolf D., Pappo O., Laxer U., Berkman N., Shaham D.,
Ashur Y., Ilan Y. (2002) Exacerbation of pulmonary sarcoidosis after liver
transplantation. J Clin Gastroenterol; 35:356-358.

Medical Research and Development 205


RESEARCH AT HADASSAH

Wolf D.G., Lurain N.S., Zuckerman T., Hoffman R., Satinger J., Honigman A.,
Saleh N., Robert E.S., Rowe J.M., Kra-Oz Z. Emergence of late cytomegalovirus
central nervous system disease in hematopoietic stem cell transplant recipients.
Blood. (In Press).

Moses A., Cohen -Poradosu R., (2002) Eczema Vaccinatum - a timely reminder.
New England J Med, 346:1287.

Streptococcal disease

Ravins M., Jaffe J., Hanski E., Shetzigovski I., Natanson-Yaron S., Moses A.E.
(2000) Characterization of a mouse-passaged, highly encapsulated variant of
group A streptococcus in vitro and in vivo studies. J Infect Dis.;182:1702-1711.

Moses A.E., Goldberg S., Korenman Z., Ravins M., Hanski E., Shapiro M. (2002)
Invasive group a streptococcal infections, Israel. Emerg Infect Dis.; 8:421-426.

Hidalgo-Grass C., Ravins M., Dan-Goor M., Jaffe J., Moses A.E., Hanski E.
(2002) A locus of group A streptococcus involved in invasive disease and DNA
transfer. Mol Microbiol., 46: 87-99.
Department of Clinical Microbiology & Infectious Diseases

Tuberculosis

Ravins M., Bercovier H., Chemtob D., Fishman Y., Rahav G. (2001) Molecular
epidemiology of Mycobacterium tuberculosis infection in Israel. J Clin
Microbiol.; 39:1175-1177.

206 Medical Research and Development


RESEARCH AT HADASSAH
Department of
COMMUNITY DENTISTRY
STAFF
Professor: Mann, J., DMD, MSc
(Head of Department and Dean of the Faculty)

Associate Professor: Sgan-Cohen H.D., DMD, MPH


(Acting Head of the Department)

Instructor: Vered Y., DMD, MPH

Physicians Participing Adut R., DMD, MPH


in Teaching: Horev T., DMD, MPH
Livny A., DMD
Shevah, A., RDH
Zilkah, E., RDH, MPH
Zioni E., RDH

INTRODUCTION
The Department of Community Dentistry is concerned with examining levels of
dental health and disease within the Israeli community, analyzing the variables
associated with these distributions and planning programs aimed at promoting
oral health of Israeli communities.
The Department is affiliated with the Jerusalem Municipality Public Health
Division and is responsible for outreach oral health promotion programs among
infants in Mother and Child Health centers and among school children in primary Department of Community Dentistr y

schools. The Department is also affiliated with Yad Sarah, where it is involved in
the planning, monitoring and implementation of the geriatric dental clinic.
Department staff are responsible for conducting on-going dental health surveys
in the Israel Defense Forces Medical Corps.
Research in the Department of Community Dentistry focuses on the
epidemiology of oral disease in Israel; the relationship between oral diseases and
environmental, microbiological, behavioral and other factors; the changing
prevalence of oral health within the Israeli population; the effect of dental health
education on oral health; preventive dentistry methodologies and fluoridation of
water.

Medical Research and Development 207


RESEARCH AT HADASSAH

RESEARCH AREAS
Dental epidemiology Dental needs, demands
(Mann, Sgan-Cohen, Vered, Adut) (Mann, Vered)

Immigrants’ oral health Dental human resources


(Mann, Sgan-Cohen, Vered) (Mann, Vered)

Oral health promotion Gerodontology


(Sgan-Cohen, Vered, Livny) (Mann, Vered, Adut, Livny)

Preventive dentistry
(Mann, Sgan-Cohen, Vered)

RECENT PUBLICATIONS
Epidemiology of caries and periodontal disease

Katz J., Peretz B., Sgan-Cohen H.D., Eldad A. (2000) Periodontal status by
CPITN and associated variables in an Israeli military population. J Clin
Periodontol: 27: 319-324.

Sgan-Cohen H.D., Katz J., Horev T., Dinte A., Eldad A. (2000) Trends in caries
and associated variables among young Israeli adults over five decades.
Community Dent Oral Epidemiol 28: 234-240.
Department of Community Dentistr y

Katz J., Chaushu G., Sgan-Cohen H.D. (2000) Relationship of blood glucose
level to CPITN and BMI in an Israeli permanent military population. J
Periodontol: 71: 1521-1527.

Oral health promotion community programs

Vered Y., Sgan-Cohen H.D.( 2002) The fight over water fluoridation in Israel. J
Israel Dent Assoc: 19: 19-23.

208 Medical Research and Development


RESEARCH AT HADASSAH

Vered Y., Sgan-Cohen H.D. (2002) The fight over water fluoridation in Israel -
Potential modes of action in light of the “American experience”. J Public Health
Dent: 62: 67-69.

New methodologies in Preventive Dentistry

Mann J., Vered Y., Babayof I., Sintes J., Petrone M., Volpe A., Stewart B.,
DeVizio W., McCool J. (2001) The comparative anticaries efficacy of a dentifrice
containing 0.3% triclosan and 2.0% copolymer in a 0.243% sodium
fluoride/silica base and a dentifrice containing 0.243% sodium fluoride/silica
base: a two-year coronal caries clinical trial on adults in Israel. J Clin Dent:
12(3):71-76.

Department of Community Dentistr y

Medical Research and Development 209


RESEARCH AT HADASSAH
Department of
DERMATOLOGY
STAFF
Clinical Associate Professor: Ingber, A. M.D,
(Head of Department)

Senior Lecturer: Enk, C.D. M.D, Ph.D

Clinical Senior Lecturer: Zlotogorski, A. M.D

Lecturer: Lotem, M, M.D

Instructors: Horev, L, M.D


Hershko, K, M.D
Merimes, S, M.D

Research Associates: Hochberg, M, Ph.D


Frankenburg, S. Ph.D

Laboratory Technicians: Jonas, F.


Westerman, M. M.sc

Physicians Participating in Gilead. L. M.D, Ph.D


Teaching: Lebovici, V. M.D
Sagi, E. M.D
Shamroth, J. M.D
Klapholz, L. M.D

INTRODUCTION
Department of Dermatology

The Department of Dermatology has a number of specific clinics and


laboratories, some involved in pure research, others combining research with
clinical services.
Contact Dermatitis Clinic: Provides patch tests services for patients with contact
dermatitis and occupational dermatoses, and conducts research on metal

210 Medical Research and Development


RESEARCH AT HADASSAH

sensitivity, cosmetic allergy and diagnostic methods of occupational skin


diseases.
Hair Clinic: Provides diagnostic and treatment services for different hair diseases.
Conducts basic genetic researches on hair disorders.
Phototherapy Clinic: Is involved in phototherapy of different skin diseases by
UVB, PUVA and Photodynamic (PDT) radiations. Conducts studies on the
ultraviolet radiation influence on the skin, at the molecular level.
Ulcers Clinic: Provides treatment services for various ulcer types, among them
unique treatments like: Maggot Biotherapy and Vacuum therapy. Is involved in
studies on new wound healing modalities.
Pediatric Dermatology Clinic: Provides diagnostic and treatment services for
children with skin diseases. In the clinic surgical of pediatric dermatology,
services for skin lesion like: moles, hemangiomas and warts.
Mohs Micrographic Surgery : Provides Mohs Surgery services for complicated
basal cell carcinoma, sqamous cell carcinoma and bowen’s disease.
Dermato-Oncology Clinic: Provides diagnostic and treatments services for skin
tumors: melanoma, cutaneous T-cell lymphoma and other skin malignancies. Is
involved in studies on new melanoma treatment modalities like: melanoma
vaccination.
Pigmented moles Clinic: Provides unique computerized follow-up of atypical
moles in patients with dysplastic moles, or personal or familial history of
melanoma.
Fungus Laboratory: Provides diagnostic services for fungal diseases by advanced
methods (PCR). Is involved in studies on epidemiology of fungal diseases.
Immuno-Histopathology Laboratory: Provides diagnostic services for bullous
diseases. Is involved in studies on bullous diseases.
Leishmaniasis Laboratory (National): Provides advanced diagnostic services for
Department of Dermatology

leishmaniasis. Is involved in clinical and basic studies on leishmaniasis


treatment.
Investigative Dermatology Laboratory: Is involved in various basic
dermatological studies and their practical application.
Molecular Dermatology laboratory: Provides diagnostic services for various
inherited skin diseases. Is involved in basic studies on dermatological genetics.

Medical Research and Development 211


RESEARCH AT HADASSAH

RESEARCH AREAS
Contact dermatitis Pediatric dermatology
(Ingber) (Sagi)
Hair diseases Dermato-oncology
(Zlotogorski) (Lotem, Merims)
Photodermatology Molecular dermatology
(Enk) (Zlotogorski, Horev)
Skin ulcers
(Gilead)

RECENT PUBLICATIONS
Zlotogorski A., Martinez-Mir A., Green J. et al: (2002) Evidence for Pseudo-
dominant Inheritance of Atrichia with papular Lesions. Journal of Investigative
Dermatology 118:881-886.
Martinez-Mir A., Gordon D., Horev L. et al: (2002) Multiple Cutaneous and and
Uterine Leiomyomas: Refinement of the genetic locus for multiple cutaneous
and uterine leimyomas on chromosome 1q42 .3-43. Journal of Investigative
Dermatology 118:876-880.
Hochberg M., Lotem M., Gimon Z.. et al: (2002) Expression of tyrosinase, MiA
and MART-1 in sentinel lymphnodes of patients with Malignant Melanoma.
British Journal of Dermatology 146:244-249.
Enk C.D., Fritsh C., Jonas F. et al: Treatment of Cutaneous Leishmaniasis with
Photodynamic Therapy (PDT). Archives of Dermatology (in press).
Department of Dermatology

Ingber A.: (2002) Intermittent low dose Itraconazole treatment for toenail
onychomycosis. Long term follow-up. Medical Mycology 39:471-473.
Basketter D., Horev L., Slodovnik D. et al: (2001) Investigation of the treshhold
for allergic reactivity to chromium. Contact Dermatitis 44:70-74.
Sagiv A.E., Dikstein S., Ingber A.: (2001) The efficiency of humectants as skin
moisturizers in presence of oil. Skin Research and Technology 7:32-35.

212 Medical Research and Development


RESEARCH AT HADASSAH
Department of
EMERGENCY MEDICINE
Mount Scopus
STAFF
Clinical Senior Lecturer: Stalnikowicz, R, MD
(Head of Department)

Physicians: Mintzen, S, MD
Levy, F, MD

INTRODUCTION
Research in the Department of Emergency Medicine focuses on clinical studies
which try to evaluate the best strategy in the management of common medical
problems seen in the department of emergency medicine, with particular
emphasis on diagnosis and treatment. We have been also involved in quality
projects such as pain management in the emergency department and
interpretation of chest X-rays by emergency physicians.

RECENT PUBLICATIONS
Stalnikowicz R., Block C. (2001) The yield of blood cultures in the Emergency Department of Emergency Medicine
Department. Eur J Emergency Med 8:93-97.

Stalnikowicz R. (2002) Hemorrhagic corpus luteum mimicking acute


gastroenteritis. Am J Emerg Med 20:133.

Stalnikowicz R., Zafrir A. (2002) Acute psychosocial stress and cardiovascular


events Am J Emerg Med 20:488-491.

Stalnikowicz R. The significance of routine serum magnesium determination in


the emergency department. Am J Emerg Med 2003 (in press).

Medical Research and Development 213


RESEARCH AT HADASSAH
Department of
ENDODONTICS
STAFF
Professor: Stabholz, A., DMD
(Head of Department)

Associate Professor (Emeritus): Heling, B., MD,DMD

Clinical Associate Professor: Heling, I., DMD

Clinical Senior Lecturer: Moshonov, J., DMD

Clinical Lecturer: Cohenca, N., DO

Instructor: Mor, C., DMD

INTRODUCTION
Research in the Department of Endodontics focuses on the factors influencing the
success and failure of root canal therapy. Specific topics under study include the
effects of lasers on the tooth hard tissues and the root canal system, morphology
and anatomy of endodontically prepared teeth; the use of intra-canal medications,
bleaching of discolored teeth.

RESEARCH AREAS
Lasers in Dentistry Traumatic injuries
(Stabholz, Moshonov) (Cohenca)

Intra-canal medication Bleaching of teeth


(Heling) (Mor)
Department of Endodontics

RECENT PUBLICATIONS
Stabholz A., Stabholz A., Leopold Y., Rosenberg YY., Moshonov J. (2001) Lasers
in dentistry. Part A-Development, characteristics, structure, principles of
operation and types of lasers. Refuat Hapeh Vehashinayim, 18(2):11-23, 61.

214 Medical Research and Development


RESEARCH AT HADASSAH

Moshonov J., Stabholz A., Leopold Y., Rosenberg I., Stabholz A. (2001) Lasers
in dentistry. Part B-Interaction with biological tissues and the effect of the soft
tissues of the oral cavity, the hard tissues of the tooth and the dental pulp. Refuat
Hapeh Vehashinayim, 18(3-4):21-8, 107-8.

Goodis EH., Pashley D., Stabholz A. (2000) Pulpal effect of thermal and
mechanical irritants. The Dental Pulp. Quintessence publishing co, INC.

Moshonov J., Peretz B., Ben-Zvi K., Cohenca N., Rotstein I. (2000) Effect of
gutta-percha solvents on surface microhardness of IRM fillings. J Endod,
26(3):142-3.

Heling I., Gorfil C., Slutzky H., Kopolovic K., Zalkind M., Slutzky-Goldberg I.
(2002) Endodontic failurecaused by inadequate restorative procedures: Review
and treatment recommendations. J Prosthet Dent, 87(6):674-8.

Slutzky-Goldberg I., Liberman R., Heling I. (2002) The effect of instrumentation


with two different file types, each with 2.5% NaOCl irrigation on the
microhardness of root dentin. J Endod, 28(4):311-2.

Heling I., Rotstein I., Dinur T., Szwec-Levine Y., Steinberg D. (2001)
Bactericidal and cytotoxic effects of sodium hypochlorite and sodium
dichloroisocyanurate solutions in vitro. J Endod, 27(4):278-80.

Heling I., Bialla-Shenkman S., Turetzky A., Horwitz J., Sela J. (2001) The
outcome of teeth with periapical periodontitis treated with nonsurgical
endodontic treatment: a computerized morphometric study. Quintessence Int,
32(5):397-400

Heling I., Morag-Hezroni M., Marva E., Hochman N., Zakay-Rones Z., Morag
A., (2001) Is herpes simplex virus associated with pulp/periapical inflammation
? Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 91(3):359-61

Heling I., Slutzky-Goldberg I., Lustmann J., Ehrlich Y., Becker A. (2000) Bone-
Department of Endodontics

like tissue growth in the root canal of immature permanent teeth after traumatic
injuries. Endod Dent Traumatol, 16(6):298-303.

Brin I., Ben-Bassat Y., Heling I., Brezniak N. (2000) Profile of an orthodontic
patient at risk of dental trauma. Endod Dent Traumatol, 16(3):111-5.

Zalkind M., Shkury S., Stern N., Heling I. (2000) Effect of prefabricated metal
post-head design on the retention of various core materials. J Oral Rehabil,
27(6):483-7.

Medical Research and Development 215


RESEARCH AT HADASSAH
Department of
HEALTH CARE ADMINISTRATION
STAFF
Professor: Penchas, S., M.D., M.Sc., D.I.C. ,

Associate Professors: Israeli, A., M.D., M.B.A., M.P.H. ,


Mor-Yosef, S., M.D., M.P.A. (Director General)
Shapira, S.C., M.D., M.P.H.
Stern, Z., M.D.

Instructor: Levtzion-Korach, O.

Other Staff: Birnbaum, Y. M.D., M.P.A.


Rotem, O., R.N., M.A.
Weis, Y. M.D.

INTRODUCTION
The Department of Health Care Administration is responsible for the
organization and administration of Hadassah’s medical services at the Hadassah-
Hebrew University Medical Center at Ein Kerem and at the Hadassah University
Hospital on Mount Scopus. It is also responsible for the administration of health
care services at Modi’in and Community and Family Health Center at Kiryat-
Hayovel. The department coordinates clinical studies at the Hebrew University-
Hadassah Schools of Medicine and Dental Medicine, Nursing, Public Health and
Community Medicine, and Occupational Therapy. It supervises the training of
residents in the various fields of medicine as well as the postgraduate training of
Department of Health Care Administration

physicians, dentists, nurses and students working towards degrees in Public


Health. The staff of the department represents Hadassah in all governing bodies
of the Hebrew University-Hadassah Schools and thus participates in managing
their academic activities. The department provides full specialization training and
Board Certification in Health Care Administration. In addition, it supervises
students at various stages in the field of medical administration and public health.
Research in the department deals with problems relating to the regionalization of
health care services; the organization of primary health care; the integration of
health care within a university hospital; specialization in hospital management;
the organization, management and manpower requirements of a general hospital;
cost effectiveness of medical care, methods of reimbursement for services
rendered, quality assessment and risk management, technology assessment.

216 Medical Research and Development


RESEARCH AT HADASSAH

RESEARCH AREAS
Health Policy, Quality and Safety in Medicine,
(Israeli, Mor-Yosef, Penchas, Stern) (Israeli, Mor-Yosef, Penchas, Stern, Shapira)
Cost Benefit and Cost Effectiveness, Trauma,Terror and Medicine,
(Isreali, Mor-Yosef, Penchas, Stern) (Shapira)
Risk Management,
(Israeli, Mor-Yosef, Shapira, Stern)

RECENT PUBLICATIONS
Health Policy

Mor-Yosef, S. (2000): The future Ministry of Health, The annual Conference of


Health Policy, The Israel National Institute for health Policy and Health Services
Research 2000.

Zelinger, J., Mor-Yosef, S., Reuveni, H. (2000): The impact of physicians strike in
the Year 2000 on health parameters in hospitals and community in the Negev area.
The Annual Conference of Health Policy, The Israel National Institute for Health
Policy and Health Services Research.

Chinitz, D., and Israeli, A. (2001): The uninsured and the rationing of health care.
Diagnosis and cure in international perspective. In: Changing Health Care Systems
from Ethical, Economic and Cross Cultural Perspectives. Eds. Loewy EH and
Department of Health Care Administration
Loewy RS. Kluwer Academic/Plenum Publishers, N.Y.

Chinitz, D., Shalev, C., Lev, B., Galay, N., and Israeli, A.(2000): Israel’s basic
basket of health services: the importance of being exp licitly implicit.I: The Global
Challenge of Health Care Rationing. Eds: Coulter A. Ham C. Open University
Press, U.K.

Shmueli, A., and Israeli, A.(2002): The effect of introducing prospective payment
to general hospitals in Israel. In: The changing face of health systems. Editor:
Chinitz DP. Gefen Pub. NY Jerusalem.

Penchas, S.(2000): On the Failure of Health Reforms. Recent Advances in Tissue


and organ transplantation. Baskent University, Ankara, Turkey, Transplantation
Proceedings. 32(3):638-641.

Medical Research and Development 217


RESEARCH AT HADASSAH

Penchas, S.(2002): Impossibility theorems and health care systems. 25 years in


Renal Transplantation Baskent University, Ankara, Turkey Transplantation
Proceedings. 34:2014-2016.

Shmueli, O., Intrator, and Israeli, A. (2002): The effects of introducing


prospective payments to general hospitals on length of stay, quality of care, and
hospitals’ income: the early experience of Israel Soc. Sci. Med. 55:981-989.

Stern, Z. (2002): Opening Pandora’s Box - Residents’ work hours. Int J. Qual
Health Care.

Quality and Safety in Medicine

Rotem, R., Mor-Yosef, S., Meydan, N. (2000): The impact of clinical


pharmacists on quality of treatment and cost in Soroka University Medical center,
The Annual Conference of Health Policy, The National Institute for health Policy
and Health Services Research.

Stern, Z. (2001):Hospital campaign anti-bug 2000 as leverage for promoting


continuous Quality improvement. IMAJ. 3/1:3-4.

Stern, Z. (2002): The future of Quality leadership. Int J. Qual Health Care.
14:2:85-86. (Editorial).

Israeli, A., and Peterburg, I. (2002):The Application of Clinical Guideline


Harefuah. 141: 362-363. ( in Hebrew)

Schreiber S., Shmueli D., Grunhaus L., Dolberg O.T., Feldinger E., Magora F.
and Shapira S.C. The influence of electroconvulsive therapy (ECT) on pain
threshold and pain tolerance in major depression patients before, during and after
treatment. European Journal of Pain. (In press).
Department of Health Care Administration

Mintz, Y., Shapira, SC., Pikarsky, AJ., Goitein, IE., Mor-Yosef, S., Rivkind, A.,
Shapira S.C. and Shemer J.(2000): Learning life saving skills on newly deceased.
Harefuah. 138:658-660.

Manor, O., Eisenbacha, Z., Israeli, A., and Friedlander,Y.(2000):


Mortality differentials among women: the Israel longitudinal mortality study.
Social Science & Medicine. 51:1175-1188.

Paltiel, O., Salakhov, E., Ronen, I., Berg, D., and. Israeli, A. (2001):
Management of severe hypokalemia in hospitalized patients: a study of quality
of care based on computerized databases. Arch Intern Med. 161:1089-1095.

Paltiel, O., Gordon, E.L., Berg, D., and Israeli, A. (2002): Impact of a
computerized alert in the Management in hypokalemia in hospitalized patients.
Arch Intern Medicine.

218 Medical Research and Development


RESEARCH AT HADASSAH

Penchas, S. (2002): Health care quality. Harefuah 141:988. Cost benefit and cost
effectiveness.

Sikuler, E., Shapira, A., Mor-Yosef, S., Shlaeffer, P., Slovik, D., Brutin, M.,
Gurman, G.,: Rational use of albumin. Harefuah (in Hebrew), 139-190-193,

Richter, DE,. Barach, P., Ben - Michael, E., Krikler, S., and Israeli, A. (2002)
Raised speed limits, speed spillover, case fatality and road death in Israel: a five
- year follow up. Amer. J. Pub. Health. ( In press).

Gofrit, O.N., Shemer, J., Leibovici, D., Modan, B. and Shapira, S.C.(2000)
Quaternary prevention: A new look at an old challenge. Isreal Medical
Association Journal. 2:498-500.

Sikron, F., Wilf- Miron, R., and Israeli, A.(2002),:Adolescent pregnancy in


Israel: a methodology for rate estimation and analysis of characteristics and
trends. Harefuah (in press) ( In Hebrew).

Trauma, Terror and medicine

Shapira, S.C.(2001) Trauma registry and injury. Harefuah 140:938-939.

Shemer,J., and Shapira, S.C.,(2001) Terror and medicine - the challenge. Isreal
Medical Association Journal. 3:799-802.

Shapira, S.C.,(2001): Beware of comparing international health systems,


including trauma units. Isreal Medical Association Journal. 4:117-118.

Shapira, S.C., and Shemer, J.,(2002): Medical management of terrorist attacks.


Israel Medical Association Journal. 4:489-492.

Department of Health Care Administration


Shapira, S.C., Shemer, J., and Oren, M.(2002): Hospital management of a
bioterror event. Israel Medical Association Journal. 4:493-494.

Mintz, Y., Shapira, S.C., Pikarsky, A.J., Goitein, D., Gertcenchtein, I., Mor-Yosef,
S. and Rivkind, A. (2002): The experience of one institution dealing with terror:
The El Aqsa Intifada riots. Isreal Medical Association Journal. 4:554-556.

Peleg, K., Aharonson-Daniel, L., Stein, M. and Shapira, S.C. Terror - Severe
form of external injury: Pattern of injury during 15 months of terror
hospitalizations. American Journal of Emergency Medicine. (in press).

Penchas, S., and Faigenblat, P.(2002): Professor Nathan Saltz and surgery in
Israel. Korot. (in press).

Medical Research and Development 219


RESEARCH AT HADASSAH
Department of
HEART INSTITUTE
STAFF
Professor Emeritus: Gotsman, M.S., MD, FRCP, FACC

Associate Professors: Lotan, C.S., MD, FACC


(Head of Department)
Weiss, A.T., MD, FACC
Mosseri, M., MD, FACC
Gilon, D., MD, FACC
Rein, A.J.J.T., MD
Senior Lecturers: Rosenheck, S., MD
Nir, A., MD

Lecturers: Pollak, A., MD


Danenberg, H. MD

Research Associate: Pugatsch, T., PhD

Physicians Participating Admon, D., MD Varshitski, B., MD


in Teaching: Nassar, H., MD Jabara, R., MD
Beeri, R., MD

INTRODUCTION
The study of the pathophysiology of cardiac dysfunction and the search for
improved treatments are at the forefront of the research carried out at the Heart
Institute.
Within the Molecular Cardiac Research Facility, we focus on the genetics of
Department of Heart Institute

cardiovascular disease, molecular pharmacology and ischemic injury. In the


Physiology-Cardiac Research Facility, we concentrate on the study of
physiological changes in response to cardiac insults, vascular injury and micro-
environmental effects. Discovering innovative ways for preventing vascular
injury and restenosis post-percutaneous coronary intervention is the focus in the
Interventional Cardiology Research Facility. Major emphasis is placed in the
Echocardiography Research Facility on expanding the application of
echocardiography for patients with genetic diseases and for pediatric patients.

220 Medical Research and Development


RESEARCH AT HADASSAH

Last but not least, foremost importance is given in the Clinical Cardiac Research
Facility on establishing new methods for the prevention, prognosis and treatment
of patients.

RESEARCH AREAS
Molecular Cardiac Research
(Pugatsch, Perles, Alcalai, Danenberg, Beeri, Durst)
Physiology-Cardiac Research Echocardiography Research
(Nir, Beeri) (Gilon, Pollak, Rein, Nir, Beeri)
Interventional Cardiology Research Clinical Cardiac Research Facility
(Lotan, Mosseri, Danenberg, Meerkin) (Lotan, Mosseri, Weiss, Pollak, Nassar)

RECENT PUBLICATIONS
Molecular Cardiac Research
Grauer E., Ben-Nathan D., Lustig S., Kobiler D., Kapon J., Danenberg H.D.
(2001) Viral neuroinvasion as a marker for BBB integrity following exposure to
cholinesterase inhibitors. Life Sci 68:986-990.
Raas-Rothschild A., Shteyer E., Lerer I., Nir A., Granot E., Rein A.J.J.T. (2002)
Jagged 1 gene mutation for abdominal coarctation of the Aorta in Alagille
syndrome. Am J Med Gen 112:75-78
Beeri R, Guerrero JL, Supple G, Sullivan S, Levine RA, Hajjar RJ. (2002) A New
Efficient Catheter-Based System for Myocardial Gene Delivery. Circulation 106:
1756-1759.
Department of Heart Institute

Physiology-Cardiac Research
Lev I., Rian (Rein) A.J.J.T. (2001) Iron supplementation in ACE inhibition as a
treatment for cough: is it really inoffensive (letter). Hypertension,38:E38-8.
Fixler R., Hasin Y., Eilam Y., Zhang D.F., Nir A. (2001) Opposing effects of
endothelin-1 on C-type natriuretic peptide actions in rat cardiomyocytes. Eu J
Pharmacol 423:95-98.

Medical Research and Development 221


RESEARCH AT HADASSAH

Mosseri M. , Haviv B., Weshler Z., Schwalb H. (2001) The Effect of Ionizing
Irradiation on Vasomotor Reactivity in the Rat Thoracic Aorta in-vitro.
Cardiovascular Radiation Medicine 2(3):151-156.
Nir A., Zhang D.F., Fixler R., Eilam Y., Burnett, J.C. Jr., Hasin Y. (2001) C-Type
natriuretic peptide has a negative inotropic effect on cardiac myocytes. Eu J
Pharmacol 412:195-201.
Danenberg H.D., Welt F.G.P., Walker M., Seifert P., Toegel G.S., Edelman E.R.
(2002) Systemic Inflammation Induced by Lipopolysaccharide Increases
Neointimal Formation Following Balloon and Stent Injury in Rabbits.
Circulation 105:2917-2922.
Danenberg H.D., Fishbein I., Gao J., Mônkkônen J., Reich R., Gati I., Moerman
E., Golomb G. (2002) Macrophage depletion by clodronate-containing
liposomes reduce neointimal formation following balloon injury in rats and
rabbits. Circulation 106:1007-1013.
Bendayan D., Fink G., Aravot D., Ygla M., Bendov I., Bliden L., Nir A., Kramer
M.R. (2002) Continuous intravenous epoprosterenol in pulmonary hypertension:
the Israel experience. IMAJ 4:255-258.
Gilon D., Cape E.G., Handschumacher M.D., Song J.K., Solheim J., VanAuker
M., King M.E., Levine R.A. (2002) Effect of three-dimensional valve shape on
the hemodynamics of Aortic stenosis: three-dimensional echocardiographic
stereolithography and patient studies. J Am Coll Cardiol 40:1479-1486.
Leibowitz D., Pollak A., Gilon D. (2002) Left atrial appendage emptying
velocity does not predict postoperative atrial fibrillation in patients undergoing
cardiopulmonary bypass, European Journal of Echocardiography 3:283-286.
Strehblow C., Gyôngyôsi M., Sperker W., Shirazi M., Windberger U., Pugatsch
T., Ben-Sasson S., Lotan C. and Glogar D. (2002) Usefulness of intravascular
Department of Heart Institute

ultrasound-guided histological measurements after stenting in porcine coronary


artery. Coronary Artery Disease 13:291-294.

Interventional Cardiology
Haj-Yehia A., Nassar T., Lotan C., Munzel T., Benet L., Anggard E.A. (2000)
Development of 3-Nitratomethyl-PROXYL (NMP): A Novel, Bifunctional
Superoxide Dismutase-Mimic-Nitric Oxide-Donor. Drug Development Research
50:528-536.

222 Medical Research and Development


RESEARCH AT HADASSAH

Mosseri M., Ershov T., Gilon D., Pollak A., Admon D., Gotsman M.S. (2000)
Total occlusion of the right coronary artery: Localization and significance. J Isr
Heart Soc 10(1): 12-19.
Gozal D., Rein A.J.J.T., Nir A., Gozal J. (2001) Propofol does not modify the
hemodynamic status of children with intracardiac shunts undergoing cardiac
catheterization. Pediatr Cardiol 22:488-490.
Fishbein I., Chorny M., Banai S., Levitzki A., Danenberg H.D., Gao J., Chen X.,
Moerman E., Gati I., Goldwasser V., Golomb G. (2001) Formulation and delivery
mode affect disposition and activity of tyrphostin-loaded nanoparticles in the rat
carotid model. Art. Thr. & Vasc. Biol 21:1434-1439.
Ziv G., Specter-Himber G., Gomori M.J., Matot I., Rein A.J.J.T., Nir A.,
Constantini S. (2001) Association between increased central venous pressure and
hydrocephalus in children undergoing cardiac catheterization: a prospective
study. Childs Nerv Sys, 17:478-482.
Nassar T., Kadery B., Lotan C., Daas N., Kleinman Y., Haj-Yehia A. (2002)
Effects of the superoxide dismutase-mimetic compund tempol on endothelial
dysfunction in streptozotocin-induced diabetic rats. Eur J of Pharm 436(1-2):111-
118.

Echocardiography Research
Leibowitz D., Rozenheck S., Pollak A., Geist M., Gilon D. (2000) Tricuspid
regurgitation in patients with pacemaker leads. Cardiology 93(1-2):74-77(0.784,
29/62)
Gilon D. (2000) Infected thrombi in the right atrium related to central venous
catheter: an ongoing challenge. European J. of Echocardiography 1:151
(Editorial).
Department of Heart Institute

Rein A.J.J.T., Nir A., Nadjary M. (2000) The coronary sinus in the fetus.
Ultrasound in Obstet Gynecol 15:1-6.
Rein A.J.J.T., Omokhodion S.I., Nir A. (2000) The significance of a cardiac
murmur as a sole clinical sign in the newborn. Clin Pediatr 39:511-520.
Rein A.J.J.T., Levine J.C., Nir A. (2001) Use of high frame rate imaging and
tissue Doppler-echocardiography in the diagnosis of fetal ventricular tachycardia.
J Am Soc Echocardiogr.14:149-151.

Medical Research and Development 223


RESEARCH AT HADASSAH

Rein A.J.J.T. (2001) Tissue Doppler imaging in fetal cardiac arrhythmias: the
fetal kinetocardiogram. Frontiers in Fetal health, 3:175-176.
Moore A.G., Eagle K.A., Bruckman D., Moon B.S., Malouf J.F., Fattori R.,
Evangelista A., Isselbacher E.M., Suzuki T., Nienaber C.A., Gilon D., Oh J.K.
(2002) Choice of computed tomography, transesophageal echocardiography,
magnetic resonance imaging, and aortography in acute aortic dissection:
International Registry of Acute Aortic Dissection (IRAD). American J of
Cardiology 89(10):1235-1238.

Clinical Cardiac Research


Hagan P., Nienaber C.A., Das S., Evangelista A., Fattori R., Suzuki T., Oh J.,
Sechtem U., Robles J.M.Y., Deutsch H.J., Gilon D., Bhakta D., Karavite D.,
Russman P., Armstrong W.F., Deeb G.M., Isselbacher E., Eagle K. (2000) Aortic
dissection. The International Registry of Aortic Dissection: New insights into an
old disease. J Am Med Assoc 16: 283(7): 897-903.(9.522, 4/107;15;15)
Gilon D., Leitersdorf I., Sapoznikov D., Zahger D., Gotsman M.S., Weiss A.T.
(2000) Reduction of congestive heart failure symptoms by very early fibrinolytic
therapy in acute myocardial infarction: A long-term follow-up. Am Heart J.
136:(June ).(1.850, 16/62:0)
Mosseri M., Beyar R., Guetta V., Meerkin D., Miller H. (2000) Radiation
Brachytherapy for the Prevention of Restenosis - statement of the Israel Invasive
Cardiology Working Group, The Israel Heart Society. Harefua 140: 361-364.
Lotan C., Hendler A., Turgeman O., Ayzenberg T., Beyar R., Disegni E., Almagor
Y., Tamari I., Ben-Horin Y., Bakst A., Peled B. (The Israeli Working Group for
Interventional Cardiology). (2000) The STOP study - a randomized multicenter
Israeli study for stents in total occlusion and restenosis prevention. Eur Heart J
21(23):1960-1966.
Department of Heart Institute

Raas-Rothschild A.R., Nir A., Gillis R., Rein A.J.J.T. (2000) Giant congenital
aortic aneurysm with cleft sternum, supraumbilical raphe, and hemangiomatosis:
report and review, Am J Med Genetics 90:243-245.
Perles Z., Nir A., Cohen E., Bashary A., Engelhard D. (2000) Atrio-ventricular block
in a toxic child. Do not forget the diphtheria. Pediatric Cardiology 21:282-283.
Cohen E., Rein A.J.J.T. (2000) Antenatal diagnosis of cardiac malformations: a
structural study. Fetal Diag Ther, 15:54-60.

224 Medical Research and Development


RESEARCH AT HADASSAH

Danenberg H.D., Lotan C., Hasin Y., Gotsman M.S., Rozenman Y. (2000) Acute
myocardial infarction - a late complication of intracoronary stenting. Clin Cardiol
23:376-378.
Danenberg H.D., Hasin Y. (2000) Polymorphic Ventricular Tachycardia
Following Intracerebral Hemmorhage. Circulation 101:81.
Beeri M., Haramati Z., Rein A.J.J.T., Nir A. (2001) Parental knowledge and
understanding of congenital heart disease. Israel Med Assoc J 3:194-197.
Nir A., Ekstein S., Nadjari M., Raas-Rothschild A., Rein A.J.J.T. (2001)
Rhabdomyoma in the fetus: illustration of tumor growth during the second half
of gestation. Pediatr Cardiol, 22:515-518.
Wolf Y.G., Landsberg G., Mosseri M., Schechter D., Anner H., Weisman C.,
Berlatzky Y. (2001) Preoperative dipyridamole-thallium scanning, selective
coronary revascularization and long-term survival in patients with critical lower
limb ischemia. J Cardiovasc Surg 42:89-95.
Landesberg G., Mosseri M., Zahger D., Wolf Y., Perouansky M., Anner H.,
Drenger B., Hasin Y., Berlatzky Y., Weissman C. (2001) Myocardial infarction
following vascular surgery: The role of prolonged, stress-induced, ST-
depression-type ischemia. J Am Coll Cardiol 1;37(7):1839-1845.
Januzzi J.L., Sabatine M.S., Eagle K.A., Evangelista A., Bruckman D., Fattori R.,
Oh J.K., Moore A.G., Sechtem U., Llovet A., Gilon D., Pape L., O’Gara P.T.,
Mehta R., Cooper J.V., Hagan P.G., Armstrong W.F., Deeb M., Suzuki T.,
Nienaber C.A., Isselbacher E.M. (2002) Iatrogenic Aortic Dissection. American
J of Cardiology 89:623-626.
Hochner-Celnikier D., Manor O., Gotzman O., Lotan C., Chajec-Shaul T. (2002)
Gender Gap in Coronary Artery Disease: Comparison of the Extent, Severity and
Risk Factors in Men and Women Aged 45-65 Year. Cardiology 97:18-23.
Department of Heart Institute

Raas-Rothschild A., Ergaz-Schaltiel Z., Bar-Ziv J., Rein A.J.J.T. (2002)


Cardiovascular abnormalities associated with the Stuve-Wiedeman syndrome.
Am J Med Gen (in press).
Landesberg G., Mosseri M., Wolf Y., Vesselov Y., Weissman C. (2002)
Perioperative myocardial ischemia and infarction identification by continuous
12-lead electrocardiogram with online ST-segment monitoring. Anesthesiology
96:264 -270.

Medical Research and Development 225


RESEARCH AT HADASSAH
Department of
HEMATOLOGY
STAFF
Professors: Fibach, E. Ph.D.
Oppenheim, A. Ph.D.
Polliack, A. M.D.
Rachmilewitz, E.A. M.D.

Associate Professors: Ben-Yehuda, D. M.D.


(Head of Department)
Rund, D. M.D.
(Head, Hemapheresis Unit)
Varon, D. M.D.
(Head, Coagulation Unit)

Clinical Senior Lecturer: Goldfarb, A. M.D.

Instructors: Goldschmidt, N. M.D.


Gural, A. M.D.
Spectre, G. M.D.
Kalish, J. M.D.

Mount Scopus: Levin, M. M.D.


(Head of Service)
Libster, D. M.D.

Research Associates: D. Filon, Ph.D.


A. Brill, Ph.D.
E. Prus, Ph.D.
S. Cohen, Ph.D.
Y. Ashhab, Ph.D.
Department of Hematology

S. Shuval, Ph.D.

INTRODUCTION
The clinical research activities comprise a large range of novel therapeutic
studies. Some of these are observational and some are therapeutic, based on
cross-fertilization that occurs between the clinicians and these scientists (MD’s
and Ph.D’s).

226 Medical Research and Development


RESEARCH AT HADASSAH

The Laboratory for Molecular Diagnosis and Research of Hematological


Malignancies: molecular development and implementation of diagnostic tests
detecting specific gene changes associated with a wide range of leukemias and
lymphomas. Focus on the genes of the DNA repair system and the studies on a
new found gene which encodes to an inhibition of apoptosis protein (IAP).
Hereditary anemias (thalassemia and hemoglobinopathies) Laboratory:
Molecular diagnosis of alpha and beta thalassemia and accurate assessment of the
carrier status. Biology of globin gene regulation. Genetic analysis of Ashkenazim
for alpha thalassemia. Search for genetic modifiers of globin gene expression.
Multidrug Resistance and Genetic Predisposition to Leukemia: Research and
a functional test of drug resistance based on the activity MDR1 gene.
Investigating the genetic basis for development of hematological malignancies,
(studying mutations in: CYP3A, NQ01 and FLT3). Studies on the use of SV40-
based pseudoviral vectors for transfer of the MDR1 gene.
Coagulation Laboratory: Studies on platelet interaction with vessel wall under
physiological flow conditions. Development of a novel method and a device
which allows to study the following interactions: The effect of thrombogenic
modulators including homocystein and oxidized LDL on platelet adhesion to
endothelial cells, under defined flow conditions. Studies of the role of platelets
in the complex interaction of tumor cells with vessel wall under flow conditions.
The potential role of platelets, their receptors and granular content, in
angiogenesis.
The laboratory for immunophenotyping of leukemias/lymphomas and other
hematological diseases: Detection of surface and intracellular antigens on
normal and malignant cells for quantification of sub-population diagnosis of
hematological malignancies. Developing techniques for measuring the
production of free radicals in cell populations, granulocytes and in RBC.
Department of Hematology

Laboratory for hematopoiesis: Developing unique techniques for ex-vivo


culturing of hematopoietic stem and progenitor cells and culturing of myeloid
cells (for diagnoses of polycythemia, red cell aplasia, Fanconi’s anemia etc.) and
to determine the therapeutic effect of various drugs. Developmental method
based on inhibition of differentiation, for ex-vivo expansion of hematopoietic
stem cells and various sub-populations of progenitor cells.

Medical Research and Development 227


RESEARCH AT HADASSAH

Clinical research in Thalassemia:


Study on Hypercoagulable state in thalassemia, iron overload - chelation therapy,
induction of fetal Hb synthesis for the treatment of thalassemia, oxidation and
macrophage activation, measurements of cytokines levels, free radical
scavengers in the plasma, skin and saliva. Bone disease in thalassemia.
The Gene Therapy Laboratory: Development of somatic gene therapy-an
innovative SV40 pseudo viral vector, followed by improvement of the basic
vector, and the development of specific vectors for various target diseases.

RESEARCH AREAS
Leukemia/Lymphoma DNA repair system
(Ben-Yehuda, Ashhab, Fibach, Prus, (Ben-Yehuda, Ashhab)
Polliack, Rachmilewitiz, Rund, Gural,
Goldschmidt) Globin
(Rund, Oppenheim, Goldfarb, Filon
Hereditary Anemias
Thalassemia Multidrug Resistance
(Rund, Oppenheim, Goldfarb, (Rund, Cohen, Filon)
Rachmilewitz, Filon)
Somatic Gene Therapy
Coagulation disorders Genetic diversity in Israel
(Varon) (Oppenheim, Rund, Filon)

Hemapheresis Immunophenotyping
(Rund) Cell Culturing
Flow cytometry analysis
Molecular Diagnosis (Fibach, Prus)
(Ben-Yehuda, Ashhab, Rund,
Department of Hematology

Oppenheim, Goldfarb, Filon)

228 Medical Research and Development


RESEARCH AT HADASSAH

RECENT PUBLICATIONS
Leukemia/Lymphoma - Molecular Diagnosis

Peylan-Ramu N., Diment J., Krichevsky S., Ben-Yehuda D., Bhatia K. and
Magrath IT. (2001) Expression of EBV encoded nuclear small non-
polyadenylated RNA (EBER) molecules in 32 cases of childhood Burkitt’s
lymphoma from Israel. Leuk. & Lymph. 40(3-4): 405-411.

Shteper P.J., Siegfried Z., Asimakopoulos F.A., Palumbo G.A., Rachmilewitz


E.A., Ben-Neriah Y. and Ben-Yehuda D. (2001) ABL1 methylation in Ph-positive
ALL is exclusively associated with the P210 form of BCR-ABL. Leukemia
15(4):575-582.

Shteper P.J. and Ben-Yehuda D. (2001) Molecular evolution of chronic myeloid


leukemia. Seminars in Cancer Biology, 11:313-322.

DNA repair system

Ben Yehuda A., Globerson A., Krichevsky S., Bar On H., Kidron M., Friedlander
Y., Friedman G. and Ben Yehuda D. (2000) Aging and the mismatch repair
system. Mech. Ageing Dev. 20;121(1-3):173-179.

Ashhab Y., Alian A., Polliack A., Panet A. and Ben-Yehuda D. (2001) Two
splicing variants of a new inhibitor of apoptosis gene with different biological
properties and tissue distribution pattern. FEBS Letters 495: 56-60.

Coagulation Disorders

Brill A.G., Shenkman B, Brill G.E., Tamarin I., Dardik R., Kirichuk V.F., Savion
N. and Varon D. (2000) Blood irradiation by He-Ne laser induces a decrease in
platelet responses to physiological agonists and an increase in platelet cyclic
Department of Hematology

GMP. Platelets 11:87-93.

Shenkman B., Rubinstein E., Tamarin I., Dardik R., Savion N. and Varon D.
(2000) Staphylococcus aureus adherence to thrombin treated endothelial cells is
mediated by fibrinogen but not by platelets. J Lab Clin Med 135:43-51.

Dardik R., Varon D., Eskaraev R., Tamarin I. and Inbal A. (2000) Recombinant
fragment of von Willebrand factor AR545C inhibits platelets binding to thrombin

Medical Research and Development 229


RESEARCH AT HADASSAH

and platelet adhesion of thrombin- treated endothelial cells. British J. of


Haematol 109:512-518.

Kenet G., Lubetsky A., Gitel S., Luboshitz J., Varon D. and Martinowitz U.
(2000) Treatment of bleeding episodes in patients with hemophilia and an
inhibitor: comparison of two treatment protocols with recombinant activated
factor VII. Blood Coag and Fib 11:35-38.

Schneiderman J., Benyamina M., Gerniak A., Rimon U., Varon D., Seligshon U.,
Shotan A. and Adar R. (2000) Abciximab in carotid stenting for postsurgical
carotid restenosis: intermediate results. J. Endovasc. Ther. 7: 263-272.

Dardik R., Varon D., Tamarin I., Zivelin A., Salomon O., Shenkman B. and
Savion N. (2000) Homocysteine and oxidized low density lipoprotein enhance
platelet adhesion to endothelial cells under flow conditions: distinct mechanisms
of thrombogenic modulation. Thromb. Haemost. 83: 338-344.

Ariel A., Lider O., Brill A., Cahalon L., Savion N., Varon D. and Hershkoviz R.
(2000) Induction of interactions between CD44 and hyaluronic acid by a short
exposure of human T cells to diverse pro-inflammatory mediators. Immunology
100:345-351.

Shenkman B., Savion N., Dardik R., Tamarin I. and Varon D. (2000) Testing of
platelet deposition on polystyrene surface under flow conditions by the cone and
plate(let) analyzer: role of platelet activation, fibrinogen and von Willebrand
factor. Thromb. Res. 99: 353-361.

Hirshberg, B., Gural, A. and Caraco, Y. (2000) Zuclopenthixol-associated


neutropenia and thrombocytopenia. Annals of Pharmacotherapy June (34): 740-
742.

Savion N., Shenkman B., Tamarin I., Dardik R., Frojmovic M. and Varon D.
(2001) Transient adhesion refractoriness of circulating platelets under shear
Department of Hematology

stress: the role of partial activation and microaggregate formation by suboptimal


ADP concentration. Brit. J. Hematol 112, 1055-1061.

Osende J.I., Fuster V., Lev E., Shimbo D., Rauch U., Marmur J., Richard M.,
Varon D. and Badimon J.J. (2001) Testing platelet activation with a shear-
dependent platelet function test versus aggregation - based tests. Relevance for
monitoring long term Glycoprotein IIb/IIIa inhibition. Circulation 807:29-35.

230 Medical Research and Development


RESEARCH AT HADASSAH

Shenkman B., Schneiderman J., Tamarin I., Kotev-Emeth S., Savion N. and
Varon D. (2001) Testing the effect of GPIIb-IIIa antagonist in patients undergoing
carotid stenting: correlation between standard aggregometry, flow cytometry and
the cone and plate (let) analyzer (CPA) methods. Thromb. Res. 102:311-317.

Shenkman B., Rubinstein E., Cheung AL., Brill G.E., Dardik R., Tamarin I.,
Savion N. and Varon D. (2001) Adherence properties of Staphylococcus Aureus
under static flow conditions: the role of agr and sar loci as well as of platelets and
plasma ligands. Infections and Immunity. 69: 4473-4478.

Merli G., Spiro T.E., et al. for the Enoxaparin clinical trial Group: (2001)
Subcutaneous enoxaparin once or twice daily compared with intravenous
unfractionated heparin for treatment of venous thromboembolic disease. Ann.
Intern. Med. 134:191-202.

Cohen, Y. and Polliack, A. (2002) Sustained complete remission of chronic ITP


of ten years duration after only two infusions of rituximab. The Hematology
Journal 3 : 61-62.

Dardik, R., Shenkman, B,., Tamarin, I., Eskaraev, R., Harsfalvi, J., Varon, D. and
Inbal. Factor XIII mediates adhesion of platelets to endothelial cells through
αvβ3 and glycoprotein IIb/IIIa integrins. In Press.

Fallgren, C., Ljungh, A., Shenkman, B., Varon, D. and Savion, N. Venous shear
stress enhances platelet mediated staphylococcal adhesion to artificial and
damaged biological surfaces. Biomaterials. In Press.

Linder, N., Shenkman, B., Levin, E., Sirota, L., Vishne, T.H., Tamarin, I., Dardik,
R., Lubin, D., Savion, N. and Varon, D. Whole blood platelets deposition on
extracellular matrix under flow conditions in perinatal infants. Arch. Dis. Child.
In Press.

Dardik, R., Savion, N., Gal, N. and Varon, D. Flow conditions modulate
Department of Hematology

homocysteine induced changes in the expression of endothelial cell genes


associated with cell-cell interaction and cytoskeletal rearrangement. Thromb. &
Haemost. In Press.

Flow cytometry analysis

Tsafrir, A., Y Abramov, Y., Preminger, A., Ezra, Y. and Fibach, E. (2002) Severe
fetomaternal hemorrhage confirmed and quantified by flow cytometry using anti
HbF antibodies. Acta Obstet Gynecol Scand. 81(4):364-5.

Medical Research and Development 231


RESEARCH AT HADASSAH

Progenitor cells culturing

Pope, S.H., Fibach, E. & Rodgers, G.P. (2000) Two-phase liquid culture system
models normal human adult erythropoiesis at the molecular level. Europ. J.
Haematology, 62:292-303.

Vaisman, B., Fibach, E. & Konijn, A.M. (2000) Ferritin expression in maturing
normal human erythroid precursors. Brit. J. Haematol. 110(2):394-401.

Nudelman, A., Gnizi, E., Katz, Y., Azulai, R., Cohen-Ohana, M., Zhuk, R.,
Sampson, S.R., Langzam, L., Fibach, E., Prus, E., Pugach, V. & Rephali, A.
(2001) Prodruds of butyric acid (III). 1. Novel derivatives possessing increased
aqueous solubility and potential for treating cancer and blood diseases. Eur. J.
Med. Chem., 1;36(1):63-74.

Bianchi, N., Chiarabelli, C., Borgatti, M., Mischiati, C., Fibach, E. & Roberto G.
(2001) Accumulation of γ-globin mRNA and induction of erythroid
differentiation after treatment of human leukemic K562 cells with tallimustine.
Brit. J. Haematol. 113(4): 951-61.

Peled, T., Landau, E., Prus, E., Treves, AJ. and Fibach, E. (2002) Cellular copper
content modulates differentiation and self-renewal in cultures of cord-blood
derived CD34+ cells. Brit. J. Haematol. 116(3): 655-61.

Wang, M., Tang, D.C., Liu, W., Chin, K., Zhu, J., Fibach, E. and Rodgers, G. P.
Hydroxyurea exerts bi-modal dose-dependent effects on erythropoiesis in human
cultured erythroid cells. In Press.

Thalassemia

Rund, D. and Rachmilewitz, E.A. (2000) New trends in the treatment of β-


thalassemia. Crit. Rev. Hematol. Oncol. 33:105-118.
Department of Hematology

Dresner-Pollak, R., Rachmilewitz, E.A. and Goldfarb, A. (2000) Bone Mineral


Metabolism in Adult Homozygous β-thalassemia major and intermedia. Br. J.
Haematol., 111(3):902-907.

Filon, D., Oppenheim, A., Rachmilewitz, E.A., Kot, R. and Ba Truc, D. (2000)
Molecular analysis of β-thalassemia in Vietnam. Hemoglobin, 24(2): 99-104.

Dresner-Pollak, R., Rachmilewitz, E.A. and Goldfarb, A. (2000) Bone Mineral

232 Medical Research and Development


RESEARCH AT HADASSAH

Metabolism in Adults β-thalassemia major and intermedia. Br. J. Haematol.


111:902-907.

Rund, D. and Rachmilewitz, E.A. (2001) Pathophysiology of α and β-


thalassesmia; treatment implications. Sem. Hematol., 38:343-349.

Fibach, E. (2001) Cell culture and animal model to screen for promising fetal
hemoglobin-stimulating compounds. Seminars in Hematology, 38(4):374-381.

Simon I., Tenzen T., Mostoslavsky R., Fibach E., Lande L., Milot E., Grosveld F.,
Fraser P. & Ceder H. (2001) Developmental regulation of DNA replication timing
at the human b globin locus. Embo Journal. 20(21):6150-6157.

Eldor A. and Rachmilewitz, E.A. (2002) Review: Hypercoagulable state in


Thalassemia . Blood, 1 Vol. 99,. 36-43.

Altarescu, G., Rodanski, D., Goldfarb, A., Abramov, A., Rund, D., Elstein, D.,
Zimran, A. (2002) Plasma Chitotriosidase Activity in Patients with β-thalassemia.
American Journal of Hematology. In Press.

Nitzan, D.W., Goldfarb, A., Gati, I. and Kohen, R. (2002) Changes in the
reducing power of the synovialfluid from Temporomandibular joint presenting
“Anchored Disc Phenomenon”. J. Oral Maxillofacial Surg. In Press.

Somatic Gene Therapy

Dalyot-Hermann N., Rund D. and Oppenheim, A. (2000) Expression of b-globin


in primary erythroid progenitors of β-thalassemia patients using an SV40-based
gene delivery system. J. Hematotherapy, 8: 593-599.

Wrobel Borys, Yael Yosef, Amos B. Oppenheim and Ariella Oppenheim. (2001)
Production and purification of SV40 major capsid protein (VP1) in Eschericia
coli strains deficient for the GroELS chaperone machine. Biotechnology 84, 285-
Department of Hematology

289.

Chava Kimchi-Sarfaty, Orly Ben-Nun-Shaul, Deborah Rund, Ariella Oppenheim


and Michael M. Gottesman. (2002) In Vitro-Packaged SV40 Pseudovirions as
Highly Efficient Vectors for Gene Transfer. Human Gene Therapy 13:299-310.

Leonard C, Howard A. Norkin, Scott A. Anderson and Ariella Oppenheim. (2002)


Caveolae-mediated simian virus 40 entry is followed by brefeldin A-sensitive

Medical Research and Development 233


RESEARCH AT HADASSAH

transport to the endoplasmic reticulum where the virus disassembles. J. Virol.


76:5156-5166.

Ariela Gordon-Shaag, Orly Ben-Nun-Shaul, Vered Roitman, Yael Yosef and


Ariella Oppenheim. (2002) Cellular Transcription Factor Sp1 Recruits the SV40
Capsid Proteins to the Viral Packaging Signal ses. J. Virol. 76:5915-5924.

Globin - Novel mutations

Oron-Karni, V., Filon, D., Shifrin, Y., Fried, E., Pogrebijsky, G., Oppenhiem, A.
and Rund, D. (2000) Diversity of a-globin mutations and clinical presentation of
a-thalassemia in Israel. Am J. Hematol. 65: 196-203.

Genetic diversity in Israel

Hammer M.F., Redd A.J., Wood E.T., Bonner M.R., Jarjanazi H., Karafet T.,
Santachiara-Benerecetti S., Oppenheim A., Jobling MA., Jenkins T., Ostrer H.,
Bonne-Tamir B. (2000) Jewish and Middle Eastern non-Jewish populations
share a common pool of Y-chromosome biallelic haplotypes. Proc Natl Acad Sci
U. S. A., 97:6769-6774.

Varda Oron-Karni., Dvora Filon., Yulia Shifrin., Elchanan Fried., Galina


Pogrebijsky., Ariella Oppenheim and Deborah Rund. (2000) Diversity of a-
globin mutations and clinical presentation of a-thalassemia.in Israel. Amer. J.
Hematol. 65:196-203.

Almut Nebel., Dvora Filon., Carsten Hohoff., Marina Faerman., Bernd


Brinkmann and Ariella Oppenheim. (2001) Haplogroup-specific deviation from
the stepwise mutation model at the microsatellite loci DYS388 and DYS392. Eur.
J. Hum. Genet. 9:22-26.

Mahmoud Abd El-latif, M., Filon, D., Rund, D., Oppenheim, A. and Kanaan, M.
(2002) The beta-globin mutation IVS1-6 accounts for half of the thalassemia
Department of Hematology

chromosomes in the Palestinian population of the mountain region. Hemoglobin,


26: 33-40.

Past populations genetics

Faerman, Marina., Almut Nebel., Dvora Filon., Mark G. Thomas., Neil


Bradman., Bruce D. Ragsdale., Michael Schultz and Ariella Oppenheim (2000).

234 Medical Research and Development


RESEARCH AT HADASSAH

From a dry bone to a genetic portrait: A case study of sickle cell anemia. Am J
Phys. Anthropol. 111:153-163.

Richards M., Macaulay V., Hickey E., Vega E., Sykes B., Guida V., Rengo C.,
Sellitto D., Cruciani F., et al. (2000) Tracing European Founder Lineages in the
Near Eastern mtDNA Pool. Amer. J. Hum. Genet. 67:1251-1276.

Almut Nebel., Dvora Filon., Deborah A. Weiss., Michael Weale., Marina


Faerman., Ariella Oppenheim., Mark G. Thomas. (2000) High-resolution Y
chromosome haplotypes of Israeli and Palestinian Arabs reveal geographic
substructure and substantial overlap with haplotypes of Jews. Human Genetics
107: 630-641.

Almut Nebel, Dvora Filon, Bernd Brinkmann, Partha P, Majumder, Marina


Faerman, Ariella Oppenheim. (2001) The Y chromosome pool of Jews as part of
the genetic landscape of the Middle East. Amer. J. Hum. Genet. Am. J. Hum.
Genet. 69:1095-1112.

Namita Mukherjee, Almut Nebel, Ariella Oppenhein and Partha P. Majumder.


(2001) High resolution mapping of Y-chromosomal polymorphisms reveals
signatures of population movements from central and west Asia into India. J.
Genet., 80:125-135.

Almut Nebel, Ella Landau-Tasseron, Dvora Filon, Ariella Oppenheim, and


Marina Faerman. (2002) Genetic evidence for the expansion of Arabian tribes
into the Southern Levant and North Africa Am. J. Hum. Genet. 70:1594-1596.

Leukemia/Lymphoma

Hirshberg, B., Shouval, D., Fibach, E., Friedman, G. & Ben-Yehuda, D. (2000)
The role of flow cytometric analysis of autonomous growth of erythroid
precursors in liquid culture in the detection of occult polycythemia vera in the
Budd-Chiari syndrome. J. Hepatol. 32:574-578.
Department of Hematology

Paltiel O., Schmit T., Adler B., Rachmilewitz E.A., Polliack A., Cohen A., Haim
N., Ben-Shachar M., Epelbaum R., Barchana M., Cohen R. and Ben-Yehuda D.
(2000) The incidence of lymphoma in first degree relatives of patients with
Hodgkin’s disease and non-Hodgkin’s lymphoma-a registry linked study. Cancer
88(10):2357-2366.

Sklair-Levy M., Polliack A., Shaham D., Applbaum YH., Gillis S., Ben-Yehuda

Medical Research and Development 235


RESEARCH AT HADASSAH

D., Sherman Y. and Libson E. (2000) CT-guided core-needle biopsy in the


diagnosis of mediastinal lymphoma. Eur. Radiol. 10(5):714-718.

Or, R., Weiss, L., Teijman, S. and Polliack, A. (2000) The prophylactic potential
of fludarabine monophosphate in GVHD after bone marrow transplantation in
murine models. Bone Marrow Transplantation, 25:263-266.

Gillis, S., Amir, G., Bennett, M. and Polliack, A. (2000) Unexpectedly high
incidence of focal bone marrow hypoplasia in patients after long term follow up
of hairy cell leukemia after therapy with 2-CdA. Europ. J. Haematology 65:1-4.

Yu, Y., Rabinowitz, R., Polliack, A., Ben-Bassat, H. and Schlesinger, M. (2000)
B-lymphocytes in CLL and NHL differ in the M-RNA splicing pattern of the
CD45 molecule. Europ. J. Haematology 64:376-384.

Matutes, E. and Polliack, A. (2000) Biology of Chronic Lymphocytic Leukemia:


Morphological and Immunophenotypic features of CLL. Reviews in Clinical &
Experim. Hematology Vol 4(1):22-47.

Paltiel O., Zelenetz A., Sverdlin I., Gordon L. and Ben-Yehuda D. (2000)
Translocation t(14;18) in healthy individuals: Preliminary study of its association
with family history and agricultural exposure. Annals of Oncology 11 (1):75-80.

Daas, N., Polliack, A., Amir, G., Darman, D., Kleinman, Y., Goldfarb, A.W. and
Ben-Yehuda, D. (2001) Kidney involvement and renal manifestations in non-
Hodgkin’s lymphoma and lymphocytic leukemia: A retrospective study in 700
patients. Europ. Journal of Haematology 67: 158-164.

Cohen, Y., Polliack, A., Daas, N., Zelig, O. and Goldfarb, A. (2001)
Monotherapy with Rituximab induces rapid remission of recurrent cold
agglutinin-mediated hemolytic anemia in indolent lympho-plasmacytic
lymphoma. Leukemia & Lymphoma 42(6):1405-1408.
Department of Hematology

Daas, N., Kleinman, Y., Polliack, A., Amir, G., Nee’man, Bits, H. and Darmon,
D. (2001) Immunotactoid glomerulopathy in a patient with Monoclonal
Gammopathy and Hypocomplentemia. American J. Kidney Diseases 38(2):395-
399.
Bitan, M., Polliack, A., Nagler, A., Friedman, Y., Nadav, L., Deutsch, V., Pecker,
I., Eldor, A., Vlodavsky, I. and Katz, B-Z. (2002) Heparanase Expression in
Human Leukemias is Restricted to AML. Exp. Hematology 30:34-41.

236 Medical Research and Development


RESEARCH AT HADASSAH

Cohen, Y., Amir, G., Rachmilewitz, E.A. and Polliack, A. (2002) Rituximab
combined with vincristine and low dose oral etoposide induces sustained
remission in an elderly patient with Burkitt’s lymphoma. Hematologica
87(01)EL.TO4.

Cohen, Y., Lossos, A. and Polliack, A. (2002) Neurotoxicity with


leukoencephalopathy after a single IV - High dose of methotrexate in lymphoma.
Acta Haematologica 107(3) :185-186.

Cohen, Y., Daas, N., Libster, D., Amir, G., Berrebi, A. and Polliack, A. (2002)
Large cell transformation of CLL and follicular lymphoma during or soon after
treatment with fludarabine - rituximab containing regimens: Therapy related
complication? European Journal of Haematology 68(2): 80-83.

Cohen, Y., Amir, G. and Polliack, A. (2002) Development and rapid


dissemination of Merkel-cell carcinomatosis following therapy with fludarabine
and rituximab for relapsing follicular lymphoma. European Journal of
Haematology 68:1-8.

Cohen, Y., Daas, N., Libster, D., Gillon, D. and Polliack, A. (2002) Large B-cell
lymphoma manifesting as an invasive large cardiac tumor: Sustained remission
following combination of methotrexate and rituximab. Leukemia & Lymphoma
43(7):1485-1488.

Yu, Y., Rabinowitz, R., Polliack, A., Ben Bassat, H., Schlesinger, M. (2002)
Hyposialated 185 Kda CD45RA+ molecules attain a high concentration in B
lymphoma cells and activated lymphocytes. European J Haematology 68(1):22-30.

Cohen, Y., Rund, D., Amir, G., Moualem, E. and Polliack, A. (2002)
Carbamazepine induced generalised lymphadenopathy, leukopenia and
thrombocytopenia - a pseudolymphoma - leukemia-like syndrome. Israel Medical
Association. In Press.

Cohen, Y., Amir, G., Gillis, S., Rund, D. and Polliack, A. (2002) Acute
Department of Hematology

myeloblastic leukemia with extreme hyperleukocytosis presenting with acute


myocardial infarction due to leukostasis. American Journal of Hematology. In
Press.

Cohen, Y., Paltiel, O., Amir, G., Gillis, S., Daas, N., Engelhard, D. and Polliack,
A. (2002) Lifethreatening GIT hemorrhage due to CMV after autologous stem
cell transplantation for diffuse large B-cell lymphoma. Bone Marrow
Transplantation. In Press.

Medical Research and Development 237


RESEARCH AT HADASSAH
Department of
HUMAN GENETICS
STAFF
Professor Emeritus: Cohen, T., MD

Professor: Bach, G., PhD


(Head of Department)

Associate Professor: Abeliovich, D., PhD

Senior Lecturer: Meiner, V., MD

Lecturers: Sagi, M., PhD


Raas-Rothschild, A., MD

Physician Participating in Teaching: Ben-Neriah, Z., MD

Teaching Fellow: Frumkin, A., PhD

Research Associate: Zeigler, M., PhD

INTRODUCTION
The Department of Human Genetics integrates clinical and laboratory work with
research. We have genetic counseling clinic and laboratories specialized in
various areas; cytogenetic and molecular cytogenetic, tissue culture, biochemical
genetic and molecular genetic. Each of these units perform clinical services as
Department of Human Genetics

well as research, in an attempt to better understand genetic disorders and develop


accurate means for their diagnosis. Special emphasis is given to inherited
diseases that are common in the Israeli population, Jewish and Arabic alike.
The genetic counseling clinics serve a wide range of patients, the main chalenges
are to reach an accurate diagnosis, thus allowing a better counseling as to future
pregnancies and risk assesment to all family members; this is done in close
collaboration with the various laboratories.
In the frame of the Genetic Counseling Clinics, specialized clinics operate in
collaboration with other disciplines, such as the onco-genetic clinics,

238 Medical Research and Development


RESEARCH AT HADASSAH

ophthalmology genetics, craniofacial genetics, birth defects and prenatal


diagnoses clinic.
In the laboratories’ section in addition to the clinical diagnosis, the two main
activities are prenatal diagnosis; amniocentesis, chorionic villi sampling and
preimplantation genetic diagnosis (PGD). The cytogenetic laboratory performs
about 2000 tests per year of prenatal diagnoses, hundreds of cytogenetic
diagnoses of patients that are referred from the genetic counseling clinic, fertility
clinic and external physicians. Fluorescence in-situ hybridization is an integral
part of the cytogenetic work-up of patients. In collaboration with hematology,
bone marrow transplantation and oncopediatric departments, we perform
cytogenetic analysis in bone marrow cells of cancer patients mainly leukemia and
lymphoma. As part of the prenatal diagnosis, we also perform population
screening for the common genetic diseases in the various ethnic groups in Israel
and first and second trimester tests (triple test).
The biochemical laboratory is specialized in lysosomal storage diseases and is a
national referral lab. Research in this laboratory focuses on the lysosomal storage
disorders. Recently, the gene for mucolipidosis type IV was identified in our
laboratory.
The molecular genetic laboratory Involves in the molecular diagnosis of wide
range of diseases, including cystic fibrosis, myotonic dystrophy,
neurofibromatosis 1, fragile X syndrome, X-linked mental retardation, deafness,
spinocerebellar atexia, Huntington dis., breast & ovarian cancer predispong
genes (BRCA1 & BRCA2), Retinoblastoma, Charcot-Marie-Tooth disease,
Prader-Willi and Angelman syndromes. Beckwith-Wiedemann synd., uniparental
disomy, familial dysautonomia, canavan disease, glycogen storage I diseases and
others.

RESEARCH AREAS
Department of Human Genetics

Lysosomal storage diseases Genetic counseling


(Bach, Zeigler, Frumkin, Raas-Rothschild) (Sagi)

Mutations in metabolic disorders Preimplantation genetic diagnosis


(Bach, Zeigler) (Abeliovich)

Function of the MLIV gene product Inherited diseases; analysis


(Bach, Frumkin) (Abeliovich)

Medical Research and Development 239


RESEARCH AT HADASSAH

Enzyme-therapy Cancer genetics


(Bach, Raas-Rothschild) (Abeliovich, Sagi)

Genetic of cardio-vascular diseases Genomic imprinting


(Meiner) (Abeliovich)

RECENT PUBLICATIONS
Molecular genetics

Woodward K., Kirtland K., Dlouhy S., Raskind W., Bird T., malcolm S.,
Abeliovich D. (2000): X inactivation phenotype in carriers of Pelzaeous-
Merzbacher disease: skewed in carriers of duplication and random in carriers of
point mutations. Eur J Hum Genet 8:8:449-454.

Abeliovich D. (2000) Prader-Willi and Angelman syndromes: Diagnostic


Approach (review). J Endocrine Genetics 1115-1124.

Silverstein S., Lerer I., Buiting K., Abeliovich D. (2001) The 28 kb deletion
spanning D15S63 is a polymorphic variant in the Jewish Ashkenazi population.
Am J Hum Genet 68:261-263.

Reish O., Lerer I., Amiel A., Heyman E., Dolfin T., Abeliovich D. (2002)
Beckwith Wiedemann: Further Prenatal Characterization of the syndrome. Am J
Med Genet 107:209-213.

Silverstein S., lerer I., Sagi M., Frumkin A., Ben-Neriah Z., Abeliovich D. (2002)
Uniparental disomy diagnosed with balanced Robertsonian translocations: Risk
estimate. Prenatal Diagnosis 22:649-651.
Department of Human Genetics

Lerer I., Sagi M., Malamud E., Levi H., Raas-Rothschild A., Abeliovich D.
(2000) The contribution of connexin 26 Mutations to non syndromic deafness In
Ashkenazi patients and the variable phenotypic effect of the mutation 167delT.
Am J Med Genet 95:53-56.

Lerer I., Sagi M., Ben-Neriah Z., Wang T., Levi H., Abeliovich D. (2001) A
deletion mutation in GJB6 cooperating with a GJB2 mutation in trans in non-
syndromic deafness: A novel founder mutation in Ashkenazi Jews. Human
Mutation 18:460 (MIB ( 458).

240 Medical Research and Development


RESEARCH AT HADASSAH

Falik-Zaccai T., Shochak E., Abeliovich D., Lerer I., Shefer R., Carmi R., Reis
L., Frydman M., Shoat M., Borochwitz Z. (2000) Achondroplasia in diverse
Jewish and Arab populations in Israel. Clinical and molecular characterization.
IMAJ ( The Israel Med Association Journal) 2:601-604.

Reeval S., Silverstein S., Lerer I., Kahana E., Meir R., Sagi M., Zilber N.,
Korczyn AD., Shapira Y., Argov Z., Abeliovich D. (2002) The prevalence of
myotonic dystrophy in Israeli Jewish communities: Inter-community variation
and founder permutations. Am J Med Genet (accepted for publication June 2002).

Ben-Chetrit E., Lerer I., Malamud E., Domingo C., Abeliovich D. (2000) The
E148Q mutation in the MEFV gene: is it a disease-causing mutation or a
sequence variant? Hum Mutation 15:385-386 (MIB #313).

Ben-Chetrit E., Sagi M. (2001) Genetic counselling in familial Mediterranean


fever: has the time come? Rheumatology 40:606-609.

Raas-Rothschild A., Wanders RJ., Mooijer PA., Gootjes J., Waterham HR.,
Gutman A., Suzuki Y., Shimozawa N., Kondo N., Eshel G., Espeel M., Roels F.,
Korman SH. (2002) A PEX6-defective peroxisomal biogenesis disorder with
severe phenotype in an infant, versus mild phenotype resembling Usher
syndrome in the affected parents. Am J Hum Genet 70:1062-1068.

Frishberg Y., Rinat C., Megged O., Shapira E., Feinstein S., Raas-Rothschild A.
(2002) Mutations in NPHS2 encoding podocin are a prevalent cause of steroid-
resistant nephrotic syndrome among Israeli-Arab children.J Am Soc Nephrol.
13:400-405.

Cancer Genetic and cytogenetics Department of Human Genetics

Wang T., Lerer I., Gueta Z., Sagi M., Kadouri L., Peretz T., Abeliovich D. (2001)
A deletion/Insertion mutation in the BRCA2 gene in a breast cancer family: A
possible role of the Alu -polyA tail in the evolution of the deletion. Gene,
chromosome & Cancer 31:91-95.

Kadouri L., Easton DF., Edwards S., Hubert A., Kote-Jarai Z., Glaser B.,
Durocher F., Abeliovich D., Peretz T., Eeles RA. (2001) CAG and GGC repeat
polymorphisms in the androgen receptor gene and breast cancer susceptibility in
BRCA1/2carriers and non-carriers. Brit J Canc 85:36-40.

Medical Research and Development 241


RESEARCH AT HADASSAH

Manning AP., Abelovich D., Ghadirian P., Lambert JA., Frappier D., Provencher
D., Robidoux A., Peretz T., Narod SA., Mes-Masson AM., Foulkes WD., Wang
T., Morgan KT., Fujiwara M., Tonin PN. (2001) Haplotype Analysis of BRCA2
8765delAG Mutation Carriers in French Canadian and Yemenite Jewish
Hereditary Breast Cancer Families. Human Heredity 52:116-120.

Yehuda-Gafni O., Cividalli G., Abrahmov A., Weintrob M., Ben Neriah S.,
Cohen R., Dvorah Abeliovich D. (2002) FISH analysis of the cryptic
t(12;21)(p13;q22) in childhood B-lineage acute lymphoblastic leukemia and
normal karyotype. Cancer Genet. And Cytogenet 132:61-64.

Lysosomal storage diseases

Bach G. (2001) Mucolipidosis type IV. Mol Genet Metab 73:197-203.

Bargal R,, Avidan N,, Olender T,, Ben Asher E,, Zeigler M,, Raas-Rothschild A,,
Frumkin A., Ben-Yoseph O., Friedlender Y., Lancet D., Bach G. (2001)
Mucolipidosis type IV: novel MCOLN1 mutations in Jewish and non-Jewish
patients and the frequency of the disease in the Ashkenazi Jewish population.
Hum Mutat 17:397-402.

Bach G., Tomczak J., Risch N., Ekstein J. (2001) Tay-Sachs screening in the
Jewish Ashkenazi population: DNA testing is the preferred procedure. Am J Med
Genet 99:70-75.

Bargal R., Avidan N., Ben-Asher E., Olender Z., Zeigler M., Frumkin A., Raas-
Rothschild A., Glusman G., Lancet D., Bach G. (2000) Identification of the gene
causing mucolipidosis type IV. Nat Genet 26:118-123.

Zlotogora J., Bach G., Munnich A. (2000) Molecular basis of mendelian


disorders among Jews. Mol Genet Metab 69:169-180.
Department of Human Genetics

Raas-Rothschild A., Cormier-Daire V., Bao M., Genin E., Salomon R., Brewer
K., Zeigler M., Mandel H., Toth S., Roe B., Munnich A., Canfield WM. (2000)
Molecular basis of variant pseudo-hurler polydystrophy (mucolipidosis IIIC). J
Clin Invest 105:673-681.

Zschenker O., Jung N., Rethmeier J., Trautwein S., Hertel S., Zeigler M., Ameis
D. (2001) Characterization of lysosomal acid lipase mutations in the signal
peptide and mature polypeptide region causing Wolman disease. J Lipid Res
42:1033-1040.

242 Medical Research and Development


RESEARCH AT HADASSAH

Raas-Rothschild A., Cormier-Daire V., Bao M., Genin E., Salomon R., Brewer
K., Zeigler M., Mandel H., Toth S., Roe B., Munnich A., Canfield WM,. (2000)
Molecular basis of variant pseudo-hurler polydystrophy. J Clin Invest 105:673-
681.

Clinical genetics

Mykytyn K., Braun T., Carmi R., Haider NB., Searby CC., Shastri M., Beck G.,
Wright AF., Iannaccone A., Elbedour K., Riise R., Baldi A., Raas-Rothschild A.,
Gorman SW., Duhl DM., Jacobson SG., Casavant T., Stone EM., Sheffield VC.
(2001) Identification of the gene that, when mutated, causes the human obesity
syndrome BBS4. Nat Genet 28:188-191.

Morle L., Bozon M., Zech JC., Alloisio N., Raas-Rothschild A., Philippe C.,
Lambert JC., Godet J., Plauchu H., Edery P. (2000) A locus for autosomal
dominant colobomatous microphthalmia maps to chromosome 15q12-q15. Am J
Hum Genet 67:1592-1597.

Nadjari M., Fasouliotis SJ., Ariel I., Raas-Rothschild A., Bar-Ziv J., Elchalal U.
(2000) Ultrasonographic prenatal diagnosis of microcephalic osteodysplastic
primordial dwarfism types I/III. Prenat Diagn 20:666-669.

Nir A., Ekstein S., Nadjari M., Raas-Rothschild A., Rein AJ. (2001)
Rhabdomyoma in the fetus: illustration of tumor growth during the second half
of gestation. Pediatr Cardiol 22:515-518.

Raas-Rothschild A., Nir A., Gillis R., Rein AJ. (2000) Giant congenital aortic
aneurysm with cleft sternum, supraumbilical raphe, and hemangiomatosis: report
and review. Am J Med Genet 90:243-245.

Sagi M., Meiner V., Reshef N., Dagan J., Zlotogora J. (2001) Prenatal diagnosis
of sex chromosome aneuploidy: possible reasons for high rates of pregnancy
Department of Human Genetics

termination.
Prenat Diagn 21:461-465.

Ben-Neriah Z., Ackerman Z. (2001) WAGR syndrome in a baby-the result of 6-


MP treatment in a father affected by Crohn’s disease. Am J Gastroenterol 96:251.

Hadj-Rabia S., Salomon R., Pelet A., Penet C., Rotschild A (Raas-Rothschild A),
de Laet MH., Chaouachi B., Hannachi R., Bakiri F., Brauner R., Chaussain JL.,
Munnich A., Lyonnet S. (2000) Linkage disequilibrium in inbred North African

Medical Research and Development 243


RESEARCH AT HADASSAH

families allows fine genetic and physical mapping of triple A syndrome. Eur J
Hum Genet 8:613-620.

Van Brokhoven H., Hamel BC., Bamshad M., Sangiorgi E., Gurrieri F., Duijf
PH., Vanmolkot KR., van Beusekom E., van Beersum SE., Celli J., Merkx GF.,
Tenconi R., Fryns JP., Verloes A., Newbury-Ecob RA., Raas-Rotschild A.,
Majewski F., Beemer FA., Janecke A., Chitayat D., Crisponi G., Kayserili H.,
Yates JR., Neri G., Brunner HG. (2001) p63 Gene Mutations in EEC Syndrome,
Limb-Mammary Syndrome, and Isolated Split Hand-Split Foot Malformation
Suggest a Genotype-Phenotype Correlation. Am J Hum Genet 69:481-492.

Schenk B., Imbach T., Frank CG., Grubenmann CE., Raymond GV., Hurvitz H.,
Raas-Rotschild A., Luder AS., Jaeken J., Berger EG., Matthijs G., Hennet T.,
Aebi M. (2001) MPDU1 mutations underlie a novel human congenital disorder
of glycosylation, designated type If. J Clin Invest 108:1687-1695.

Raas-Rothschild A., Shteyer E., Lerer I., Nir A., Granot E., Rein A. (2002) Jagged
1 gene mutation for abdominal coarctation of the Aorta in Alagille syndrome. Am
J Med Genet (Accepted).

Korman SH., Raas-Rothschild A., Elpeleg O., Gutman A. (2002)


Hypocarnitinemia in lysinuric protein intolerance. Mol Genet and Metab 76:81-
83.

Cardio-vascular diseases

Meir K., Kitsberg D., Alkalay I., Szafer F., Rosen H., Shpitzen S., Ben Avi L.,
Staels B., Fievet C., Meiner V., Bjorkhem I., Leitersdorf E.,. (2002) Human sterol
27-hydroxylase (Cyp27) overexpressor transgenic mouse model. Evidence
against 27-hydroxycholesterol as a critical regulator of cholesterol homeostasis.
Department of Human Genetics

J Biol Chem (Accepted).

Ben-Dov IZ., Meiner V., Eid A. (2001) Kidney transplantation unraveling


Wolfram syndrome: a case report. Transplantation 72:958-960.

Meiner V., Shpitzen S., Mandel H., Klar A., Ben-Neriah Z., Zlotogora J., Sagi M.,
Lossos A., Bargal R., Sury V., Carmi R., Leitersdorf E., Zeigler M. (2001)
Clinical-biochemical correlation in molecularly characterized patients with
Niemann-Pick type C. Genet Med 3:343-348.

244 Medical Research and Development


RESEARCH AT HADASSAH

Durst R., Colombo R., Shpitzen S., Avi LB., Friedlander Y., Wexler R., Raal FJ.,
Marais DA., Defesche JC., Mandelshtam MY., Kotze MJ., Leitersdorf E., Meiner
V. (2001) Recent origin and spread of a common Lithuanian mutation, G197del
LDLR, causing familial hypercholesterolemia: positive selection is not always
necessary to account for disease incidence among Ashkenazi Jews. Am J Hum
Genet 68:1172-1188.

Genetic counseling

Shiloh S., Eini Jaffe N., Ben-Neria Z., Sagi M (2002) Framing of prenatal
screening test results and women’s health-illness orientations as determinants of
perceptions of fetal health and approval of amniocentesis. Phychology and
Health (in press).

Dagan O., Hochner H., Raas-Rothschild A., Levi I., Sagi M. Genetic testing for
hearing impairmentdifferent motivations for the same outcome. Am J Med Genet
(in press).

Department of Human Genetics

Medical Research and Development 245

You might also like