RESEARCH PROJECTS
 

ENTEROCOCCI: speciation and prevalence of vancomycin and aminoglycoside resistance in clinical isolates at AUBMC

Enterococci can cause several serious human infections and recently, they have also been recognized as an important cause of nosocomial infections, worldwide. Development of antibiotic resistance in gram positive bacteria such as the emerging resistance to vancomycin and high level aminoglycosides in Enterococci has become a crucial problem in many countries around the world. These pose a number of clinical, diagnostic and infection control challenges. To counter their threats, surveillance programs were initiated to monitor these resistant Enterococci, using special non routine laboratory techniques. In Lebanon, there are no studies on these multidrug-resistant Enterococci; thus, the purpose of this project. G. F. Araj and M. G. Zouain
 
 

Detection of antibodies to Brucella cytoplasmic protein antigens in the cerebrospinal fluid of patients with neurobrucellosis

Neurobrucellosis is a serious complication of Brucella infection and its diagnosis necessitates using specific tests. The most commonly relied upon tests are the agglutination and ELISA to detect anti-Brucella lipopolysaccharide (LPS) antibodies in the CSF but this antigen may detect cross reacting antibodies. Alternatively, Brucella cytoplasmic protein (CP) antigen proved its superiority in the diagnosis of patients with systemic brucellosis but was not tested in the diagnosis of neurobrucellosis. We aim at using ELISA to detect IgG to CP antigen of Brucella in the CSF of patients with neurobrucellosis and controls in order to assess its reliability in the diagnosis of this morbid CNS infection. An immunoblot technique will be used, to confirm and possibly to reveal predictor and differentiating reactive bands. P. C. Baldi* and G. F. Araj.
 
 

Variation in prostate specific antigen (PSA) free-to-total ratio (F/T) with changes in alpha2-macroglobulin (A2M) and c-reactive protein (CRP) concentrations

Prostate specific antigen (PSA) exists in serum in the free form or complexed to different protease inhibitors like alpha1-antichymotrypsin (ACT) and alpha2-macroglobulin (A2M). Current assays for PSA measure the free PSA and PSA linked to ACT complex. PSA complexed to A2M is occult and cannot be determined. Conditions that lead to a change in A2M, will affect the amount of total PSA determined. In a study by Honda et al., a significant negative correlation was determined between A2M levels and total PSA concentrations in acutely ill individuals. None of the other acute phase proteins was found to have an effect on the total PSA. However, the effect on free-to-total ratio, which is currently being used to differentiate between cancer and benign conditions of the prostate, has not been investigated. The purpose of this study is to determine the effect of changes in A2M and CRP concentrations on the F/T, which might in turn affect its proper interpretation. R. Daher, R. Mahfouz, M. Beaini, N. Cortas. (Supported by Department Chairman’s fund.)
 
 

The effect of hormone replacement therapy on lipoprotein(a) and coagulation indices: long term follow-up

Cardiovascular disease is the leading cause of mortality and morbidity in women after menopause. A protective role of estrogen is suggested by the low risk of cardiovascular disease in premenopausal women. Therefore hormone replacement therapy (HRT) was shown to have protective effects against that state through lipid and non-lipid mechanisms. This project will evaluate the effect of different HRT (duration, type, route of administration) on lipid parameters including Lp(a) and several coagulation parameters. The effect of age and weight on these parameters will also be evaluated. Established methodologies for the different chemistry (total cholesterol, triglycerides, HDL-C, LDL-C, Lp(a)) and coagulation (fibrinogen, protein C, protein S, antithrombin III, plasminogen activator inhibitor, plasminogen activator, and antiphospholipid antibody) parameters will be utilized for the analysis of patients and controls samples. This study might show the interplay of previously mentioned factors on Lp(a) levels and thus its consequences on the health of the patients. R. Daher, I. Usta, Z. Habbal, M. Beaini. (Supported by Massabki Fund.)
 
 

Membrane bound Flt3 ligand synthesis is inhibited when anchored to its receptor on stem cells

Serum FLT3 Ligand (FL) is a secreted and membrane bound cytokine capable of stimulating stem cell proliferation rather than differentiation. FL is produced by bone marrow stromal cells and fibroblasts. FL can also augment the action of other stimulatory cytokines. In a previous study we were able to proof that FL is a marker that assess Bone Marrow (BM) capacity in severe aplasia, and that a FL level of less than 250 ng/l can be used to segregate patients undergoing Autologous Peripheral Stem Cell Transplantation (APSCT) for ambulatory mobilization phase. We were able to reconfirm the reciprocal relation between BM cellularity and serum FL level. At this we predict that membrane bound FL has a feed back inhibitory mechanism that regulate its production, which is also in tight relation to BM cellularity. To proof this hypothesis we need to assemble in-vitro a cellular model of BM stromal cells and fibroblasts confluent in a plate with and without Stem Cell, then measure FL in the media and its mRNA in stromal cells and fibroblasts. A feed back inhibitory process, located to the cytoplasmic membrane of stromal cells and fibroblasts, is a logical mechanism to explain the steady state low levels of FL and its marked increase in severe BM aplasia. J.H. Haidar, A. Bazarbachi, R. Daher.
 
 

Serum Flt3 Ligand an indicator of bone marrow capacity during autologous peripheral stem cell transplantation

FLT-3 ligand is a good indicator of bone marrow cellularity in severe aplastic anemia and post chemotherapy induced myelosuppression. The relationship between bone marrow cellularity and FLT-3 ligand level is reciprocal. We measure serum FLT-3 ligand level of patients undergoing autologous peripheral stem cell transplantation (APSCT). All patients received ablative chemotherapy followed by transfusion of more than 2x10⁶/kg CD34 positive cells. FLT-3 ligand level was measured by ELISA technique using selected sera, around 12 levels from each patient (premobilization, peaks and nadirs of WBC during the mobilization and the post-transplant period). Patients with serum FLT-3 ligand level below 250 ng/l did not develop severe neutropenia during mobilization, while 2 patients with a premobilization level more than 250 ng/l went through severe neutropenia for a period of 2 days during mobilization. In conclusion, an initial low level of FLT-3 ligand may predict absence of neutropenia post-cyclophosphamide suggesting the possibility of a full ambulatory mobilization procedure, and may be used as a discriminatory marker in a selective group of patients. J.H. Haidar, R. Daher, R. Mahfouz, and A. Bazarbachi. (Supported by URB & LNCSR.)
 
 

RBCs Creatine level may discriminate between mechanical and immune types Hemolytic anemia

Senescent RBCs contain less creatine than early released RBCs and reticulocytes. Mechanical hemolytic anemia caused by valve disease probably doesn’t discriminate between young and senescent RBCs or effect preferentially older ones. While an immune induced hemolytic anemia most probably effect younger more than older RBCs. We will collect fresh samples from patients with hemolytic anemia proven by clinical presentation, elevated LDH, CBC, and peripheral smear. Sample will be prepared and stored frozen to be run at a later time. Normal controls, positive control (acute external blood lose), and possible negative control (refractory anemia). We will try to show significant difference to utilize this test to discriminate between mechanical and immune induced hemolytic anemia, and part of transfusion related hemolytic reaction work-up. J.H. Haidar, M. Shuaib, M. Shehab. (Supported by DeChairman Fund.)
 
 

Thalassaemia intermedia in Lebanon

We have analyzed three factors in a panel of 73 patients with thalassaemia intermedia in our population: mild b-globin gene mutations, deletions in the a- globin gene and the presence of a polymorphism for the enzyme XmnI in the ^gg-promoter region. The results show that the most important contributing factor is the b-genotype: 68% of patients have a mild b+ mutation, while 26% of patients are positive for the XmnI polymorphism associated with increased production of HbF, which showed strong linkage to particular mutations. M. Qatanani, A. Taher, S. Koussa*, C. Fisher*, M. Rugless*, J. Old* and L. Zahed. (Supported partly by LNCSR.)
 
 

Analysis of telomeric chromosome rearrangements using fluorescence in situ hybridization

We have collected a number of samples with chromosome rearrangements involving the telomeres. These include ring chromosomes, terminal deletions or terminal translocations. Using DNA probes for the common telomeric sequences, as well as chromosome-specific subtelomeric sequences, we are currently investigating the breakpoints involved in these rearrangements. L. Zahed, G. Al-Oreibi and N. Darwiche. (Supported by URB.)
 
 

Acceptance of prenatal diagnosis for genetic disorders in Lebanon

We have interviewed 90 couples at risk for a variety of genetic disorders in Lebanon, in order to assess their acceptance of prenatal diagnosis and the variables that might influence their choice. Overall, 54% of couples said they would request prenatal diagnosis in their next pregnancy, while 26% were opposed to such a procedure. In 87.5% of cases, the reason for refusal was because of religious conviction against termination of pregnancy. Refusal of prenatal diagnosis was also related to lower socio-economic background and poorer education. L. Zahed, M. Nabulsi, M. Bou-Ghanim and I. Usta. (Supported by URB.)
 
 

The study of haplotypes linked to b-thalassaemia mutations in Lebanon

The molecular basis of b-thalassaemia in Lebanon has revealed the presence of at least 18 different mutations. Analysis of the chromosomal background of these mutations, through the study of haplotypes in the b-globin gene cluster, will allow the study of the origin of these mutations and will constitute an additional confirmatory approach for prenatal diagnosis. L. Zahed, M. Qatanani and M. Nabulsi. (Supported by Diana Tamari Sabbagh fund.)
 
 
 
 

ARTICLES, BOOKS AND REPORTS
 
 

———, Antibiotics: a need for a regional surveillance and control program (Letter). Annals of Saudi Medicine 17 (4): 488, 1997.

———, The changes and current status of antimicrobial resistance in Lebanon. Alliance for the Prudent use of Antibiotics Newsletter, 17 (1), 1-44, 1999.

Araj, G.F., Daher, N.M. and El- Zaatari, M.M., CANDIFAST identifies some clinical yeast isolates, needs to improve in antifungal susceptibility. Laboratory Medicine 30 (3): 199- 202, 1999.

Araj, G.F., Daher, N.K. and Tabbarah, Z.A., Antifungal susceptibility of Candida isolates at the American University of Beirut Medical Center. International Journal of Antimicrobial Agents, 10, 291-296, 1998.

Araj, G.F., Talhouk, R.S., Simaan, C.J. and Massad, M.J., Discrepancies between mecA PCR and conventional tests used for detection of methicillin resistant Staphylococcus aureus. International Journal of Antimicrobial Agents 11: 47-52, 1999.

Baba, N., Antoniades, K. and Habbal, Z.M., Effects of canola, olive, and linolenic acid enriched olive oils on plasma lipids, lipid peroxidation and lipoprotein lipase activity in rats. Nutrition Research 19 (4), 601-612-1999.

Baba N., and Habbal Z.M., Glycemic and insulinemic responses of normal subjects to selected meals commonly consumed in the Middle East. Journal of Nutritional and Environmental Medicine, 7, 275-286, 1997.

Bitar, F., El-Zein, C., Tawil, A., Gharzuddine, W. and Obeid, M., Intrapericardial teratoma in an adult -a rare presentation. Medicine and Pediatric Oncology, 30, 249-251, 1998.

Bulbul, M., Farhat, W., Shabb, N. and Salem, Z., Late recurrence with malignant degeneration of testicular teratoma, case report. The Lebanese MedicalJournal, 46 (2), 1998.

Daher, R. and Beaini, M., Prostate-specific antigen and new related markers for prostate cancer. Clinical Chemistry and Laboratory Medicine, 36 (9), 671-681, 1998.

Deeb, L., Yamout, B., Shamseddine, A., Shabb, N. and Uthman, S., Meningeal Carcinomatosis as the Presenting Manifestation of Gastric Adenocarcinoma. The American Journal of Gastrentorolog, 92 (2), 329-331, 1997.

El Saghir, N.S.*, Adib, S., Mufarrij, A.A., Kahwaji, S., Taher, A., Issa, P. and Shamseddine, A.I., Cancer in Lebanon: analysis of 10220 cases from the American University of Beirut Medical Center. Lebanese Medical Journal, 46, 4-11, 1998.

El Saghir, N.S*, Bizri, A.R., Shabb, N., Husami, T., Salem, Z. and Shamseddine, A., Pressure Ulcer Accelerated Healing with Local Injections of Granulocyte Macrophage-Colon Stimulating Factor. Journal of infection, 35, 179-182, 1997.

Habbal, Z.M. and Muwakkit, S., Apparent positive interference from an eptoposide metabolite, but not etoposide, in measurement of urinary VMA. Clinical Chemistry, 42 (2), 415-416, 1997.

Habbal, Z.M. and Sakr, A., Rapid, specific HPLC method from the determination of argininosuccinic acid following pre-column derivatization vith 0- Phthalaldehyde. Clinical Chimica Acta, 264 (2), 239-243, 1997.

Haddad, F.S., Haddad, G.F. and Zaatari, G., Cranial osteomas: their classification and management. Report on a giant osteoma and review of the literature. Surgical Neurology, 48, 143-7, 1997.

Haddad, G.F., Haddad, F.S. and Zaatari, G., Dural osteochondroma: case report, review of the literature and proposal of a new classification. British Journal of Neurosurgery, 12, 380-4, 1998.

Haddad, G.F., Hanbali, F., Mufarrij, A. A., Nassar, A. and Haddad, F.S., Concomitant fibrous dyplasia and aneurymal bone cyst of the skull base. Case report and review of the literature. Pediatric Neurosurgery, 28, 147-153, 1998.

Nabulsi, M.M., Araj, G.F., Farah, A.E. and Khalil, A.M., Hepatitis C virus antibodies in pregnant Lebanese women. Journal of Obstetrics and Gynecology, l7 (6), 548, 1997.

Nabulsi, M.M., Khalil, A.M., Farah, A.E. and Araj, G.F., Prevalence of Hepatitis B surface antigen in pregnant Lebanese women. International Journal of Gynecology & Obstetrics, 58, 243-244, 1997.

Shabb, N., Phyllodes tumor, fine needle aspiration cytology of eight cases. Acta Cytologica, 41, 321-326, 1997.

Shabb, N., Fahl, M., Haswani, P., Zaatari, G. and Shabb, B., Fine Needle Aspiration of Mediastinal Tumors. A clinical radiologic, cytologic and pathologic study of 42 cases. Diagnostic Cytopathology, 119, 428-436, 1998.

Shabb, N., Tawil, A., Gergeos, F., Saleh, M. and Azar, S., Multinucleated Giant cells in fine needle aspiration of the thyroid: their diagnostic significance. Diagnostic Cytopathology, March, 1999.

Shabb, N., Tawil, A., Mufarrij, A., Obeid, S. and Halabi, J., Mammary Carcinoma with Osteoclast-like Giant Cells: Cytology mimicking benign breast disease. Acta Cytologica, 41, 1284-1288, 1997.

Shamseddine, A., Medawar, W., Habbal, Z.M. and Khalil, A., The relatiobetween serum levels of Erythropoietin (EPO) and insulin like growth gactor-1 (ILGF-1) and Hematocrit (HCT) in Breast Cancer Patients Receiving Non-nephrotoxic chemotherapy. European Journal of Gynecological Oncology, 19 (6), 591-593. 1998.

Talhouk, R.S., El Dana, R.A., Araj, G.F.*, Barbour, E. and Hashwa, F., Prevalence, antimicrobial susceptibility and molecular characterization of campylobacter strains recovered from humans and poultry in Lebanon. Lebanese Medical Journal 46 (6), 310- 316 , 1998.

Tawil, A., Cox, J.N, Arnaud D.R., Briner, J., Droz, J.P. and Remadi, S., Wilms’ tumor in the adult -report of a case and review of the literature. Pathology Research and Practice, 195, 105-111, 1999.

Uthman, I., Bizri, A.R., Shabb,N., Khury, M. and Khalifeh, M., Peritoneal Sarcoidosis: Case report and review of the literature. Seminars in Arthritis Rheumatism, 28, 351-354, 1999.

Uwaydah, M., Khalil, A., Shamseddine, N., Matar, F. and Araj, G.F., Brucella-infected ovarian dermoid cyst causing initial treatment failure in a patient with acute brucellosis. Infection, 26 (2), 131-132, 1998.

Zafatayeff, S*., Zahed, L., Souraty, N*. and Megarbane, A* ., Retrospective study of 9 Lebanese families affected with the fragile-X syndrome and review. Lebanese Medical Journal, 46, 317-320, 1998.

Zahed, L, Der Kaloustian*, V. and Batanian, J*., A familial complex chromosome rearrangement with balanced and unbalanced recombination products. American Journal of Medical Genetics, 79, 30-34, 1998.

Zahed, L. and Megarbane, A*., A cytogenetic register of Down syndrome in Lebanon. Community Genetics, 1, 84-89, 1998.
 
 
 

ABSTRACTS, PRESENTATIONS AND PROCEEDINGS
 

Araj, G.F., Pneumococcal drug-resistance at the American University of Beirut Medical Center (AUBMC) in Lebanon. 99^th Annual Meeting of the American Society for Microbiology, Abstract C- 279, Chicago, Ill, USA, May 30- June 3, 1999.

Araj, G.F., Talhouk, R.S., Itani, L.Y., Jaber, W. and Hashwa, F., The Performance of Two PCRs for the Detection of Mycobacteria spp. in Clinical Respiratory Specimens in a Country. 99^th Annual Meeting of the American Society for Microbiology, Abstract U- 17, Chicago, Ill., USA, May 30- June 3, 1999.

Awaraji, C., Cortas, N. and Daher, R., Adaptation of the assay for dibucaine and fluoride inhibition of acetylchloine esterase to a dry chemistry analyzer. The 9^th Scientific Meeting of the International Academy of Pathology - Arab Division, Beirut, Lebanon, 4-7 September 1997.

Daher, R., Cortas, N., Baba, N., Bu Khuzam, G. and Habbal, Z., Serum concentrations of lipoprotein (a) in a selected Lebanese sample population: comparison of distribution with other populations. The 49^th Annual American Association for Clinical Chemistry meeting, Atlanta Georgia, 20-24 July 1997. Clinical Chemistry, 43 (S6), S263, 1997.

———, Serum concentrations of lipoprotein (a) in a selected Lebanese sample population: Comparison of distribution with other populations. Clinical Chemistry, 45. Abstract no. 730, 1997.

Daher, R., Kanj, N. and Cortas, N., Evaluation of a homogeneous assay for direct determination of high-density lipoprotein cholesterol (HDL-C). The 49^th Annual American Association for Clinical Chemistry meeting, Atlanta Georgia, 20-24 July 1997. Clinical Chemistry, 43 (S6), S259, 1997.

Daher, R., Mahfouz, R., Beaini, M. and Cortas, N., Variation in prostate specific antigen (PSA) free-to-total ratio (F/T) with changes in alpha2-macroglobulin (A2M) and c-reactive protein (CRP) concentrations. IFCC-WorldLab, Firenze, Italy, 6-11 June 1999.

Daher, R., Mahfouz, M. and Cortas N., Monitoring of ionized calcium and magnesium for citrate-anticoagulated apheresis. Pre-analytical phase workshop during ARAB-LAB’99, Dubai, UAE, 17 February 1999.

EL Saghir, N., Shamseddine, A., Tawil, A., Taher, A., Salem, A., Khalil, A. and Seoud, M., Breast Cancer at the American University of Beirut Medical Center: Update 1998. Egyptian National Cancer Society and Pan Arab Oncology Meeting, April 14, 1999.

Haidar, J.H., Daher, R., Mahfouz, R. and Bazarbachi, A., Serum FLT-3 Ligand: A predictive marker for neutropenia during the course of stem cell mobilization for autologous peripheral stem cell transplantation. Blood, 92(10) suppl 1:122a. (Abstract#495), 1998.

Hatoum, C. and Tawil, A., Breast Ductal Carcinoma in Situ and Infiltrating Carcinoma at a tertiary care center in Lebanon: a review of 243 breast malignancies. Middle East Medical Oncology Congress (COMO), May 1999.

Kanj, N., Cortas, N. and Daher, R., PSA free/total ratio: analytical evaluation and correlation with pathological diagnosis. The 9^th Scientific Meeting of the International Academy of Pathology-Arab Division, Beirut, Lebanon, 4-7 September 1997.

Shabb, N., Khoury, N., Birjawi, G., Fakhreddine, N. and El-Zein, Y., Mammographically detected breast lesions with wire localization excisional biopsy: The American University of Beirut Experience. Second AUB Jordanian Alumni meeting, Amman Jordan, April 1999.

Shabb, N., Tawil, A., Gergeos, F., Saleh, M., and Azar, S., Multinucleated giant cells in fine needle aspiration of thyroid nodules: Their diagnostic significance. International Academy of Pathology, International congress, Nice, France, October,1998.

Yunis, K., Mroueh, S., Rashid, R., Ghaziri, G., Cortas, N., and Habbal, Z.M. et. al., Early C-Reactive protein (CRP) as predictor of neonatal morbidity. Pediatric Research vol. 41 (1118), 1997

Zaatari, G., Tumor markers–an update. The Second AUB Medical Conference, Amman, Jordan, April 8-10, 1999.

Zahed, L., Der Kaloustian, V.* and Batanian, J.R.,* A familial complex chromosome rearrangement giving rise to balanced and unbalanced recombination products. Annual meeting of the American Society of Human Genetics. The American Journal of Human Genetics, 61, 4, A145,1997.

Zahed, L., Qatanani, M., Taher, A., Koussa, S.*, Dana, R. and Old, J*., The molecular basis of b-thalassaemia intermedia in Lebanon. Annual meeting of the American Society of Human Genetics. The American Journal of Human Genetics, 63, 4, A225, 1998.
 
 
 

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