Research Projects
Association of altered T cell proliferative responses with insulin-dependent diabetes mellitus (IDDM) Patients
with IDDM are recruited from the Chronic Care Center and blood is drawn
and T cell proliferation responses are assessed in chronic IDDM and acute
IDDM patients. W. Almawi, H. N. Beyhum and S. T. Azar.
Twenty-four hour blood pressure monitoring of insulin-dependent diabetes mellitus (IDDM) patients on conventional insulin regimen versus multiple insulin injection regimen Two groups of IDDM patients were compared: the standard treatment group and the intensive insulin treated group. By determining the amount of blood pressure dipping at night, the tightly controlled patients revealed less dipping compared to the other group. This may suggest that tight control may have a deleterious effect on blood pressure control in IDDM. S.
T. Azar and A. Birbari.
Alendronate treatment of adult thalassemic patients with osteoporosis A
group of adult patients with thalassemia are evaluated by bone densitometry
to assess the extent of their osteoporosis. Preliminary data reveals significant
osteoporosis in all patients. Urinary pyridoline cross-links are measured
to correlate the extent of osteopenia to the biochemical alterations. Patients
will ultimately be put on a bone anti-resorptive agent, alendronate, and
will be followed by BMD and biochemically. S. T. Azar and A.
Taher.
Osteoporosis in Lebanese children with thalassemia This
is an ongoing study at the Chronic Care Center and AUH evaluating the extent
of osteoporosis in children with thalassemia. S. T. Azar, A.
Taher, C. Saab and S. Kussa.
Growth pattern of children with short stature secondary to thalassemia This
is an ongoing study at the Chronic Care Center evaluating the rate of growth
of Lebanese children with thalassemia. Various hormonal profiles are done
in order to understand the causes of short stature in these children. S.
T. Azar, A. Taher, C. Saab and S. Kussa.
A multicenter, open-label expanded use study to evaluate the tolerability of Simvastatin 80 mg in patients with heterozygous familial hypercholesterolemia This
is a multi-center study supported by Merk and Co. assessing the efficacy
of high dose Simvastatin in the treatment of familial hypercholesterolemia.
Patients who fail to respond to the 40 mg Simvastatin regimen are switched
to the 80 mg regimen and the medicine is offered on a compassionate basis
for free. Occasional blood tests are also offered. This study is awaiting
the institutional research committee approval. S. T. Azar and I.
Salti. (Supported by Merk & Co., MEDPED/985-0A.)
An open label crossover study to compare the efficacy, safety and tolerability of Simvastatin versus atorvastatin in patients with combined hyperlipidemia This
is a multi-center study supported by Merk and Co. It compares the efficacy,
safety and tolerability of simvastatin versus atorvastatin in patients
with combined hyperlipidemia: LDL cholesterol > 130 and triglycerides >
200. S. T. Azar and I. Salti. (Supported by Merk & Co,
Simvastatin CDSP 984-0A-multi-center.)
Metabolic alterations in patients with HDL deficiency Prevalence
of insulin resistance in patients with isolated low HDL cholesterol is
not known. Evidence suggests that this low HDL syndrome may be another
facet of insulin resistance or it may be the result of unidentified postprandial
hypertriglyceridemia. This study assesses the extent of metabolic alterations
in these patients and measures the extent of postprandial hypertriglyceridemia
in such patients. S. T. Azar and I. Salti. (Supported by
LNCSR.)
Multiple sclerosis is associated with alteration in prolactin secretion Evidence
supports a role of prolactin in the immune alterations existing in patients
with multiple sclerosis. Work is completed on this study, evaluating patients
with multiple sclerosis for the presence of basal and post TRH hyperprolactinemia.
S. T. Azar and B. Yamout. (Supported by AUB Medical Practice
Plan; URB.)
The mechanism of action of zidovudine and alpha interferon (IFN-A) in treating HTLV-I associated adult t-cell leukemia/lymphoma (ATL) ATL
is an agressive lympho-proliferative disorder associated with the HTLV-I
virus with drug resistance and median survival of patients less than 6
months. Recently, the combination of AZT and IFN-a, was reported by us
and others to be potent treatment of ATL. However, the exact mechanism
of action of this combination remains to be established. The specific aims
of the current project is to investigate the scope and dose-dependency
of AZT and IFN-a effects (cytotoxicity, proliferation, growth factor dependency).
In addition, we shall assess the anti-viral effect of AZT and IFN-a on
HTLV-I messenger RNA and protein expression, and on the production of viral
particles. The ATL-derived T cell lines will be utilized as prototype of
HTLV-1 infected ATL cells. A careful assessment of the mechanism of action
of this drug combination will be instrumental in the design of effective
therapy aimed at abrogating this and other related disorders. A. Bazarbachi.
(AUB Medical Practice Plan; URB.)
Treatment by a combination of zidovudine (AZT) and alpha interferon (IFN) in naive and pretreated adult t-cell leukemia/lymphoma (ATL) patients ATL
is an aggressive malignancy of mature activated T cells, associated with
HTLV-I infection. ATL has a poor prognosis, mainly due to its resistance
to conventional chemotherapy. Recent important advances in the treatment
of ATL were obtained by us and others using a combination of AZT and IFN.
In our phase II clinical study, nine ATL patients received this combination.
Eight responses were obtained, with two complete remissions, four very
good partial remissions (PR) with 95% reduction of the tumor burden and
two 50% PR. Seven patients are still alive with a median follow-up of 15
months. Toxicity was mild in all patients. In conclusion, we showed that
the combination of AZT and IFN exhibits a high response rate in ATL patients
and seems to prolong survival. The success of this potentially antiretroviral
approach in the treatment of ATL, suggests the existence of a possible
late effect of HTLV-I replication in vivo. A. Bazarbachi and O.
Hermine*. (Supported by French National Prize for Cancer Research,
1996.)
Mycosis fungoides (MF) and sezary syndrome (SS) are not associated with HTLV-I infection: an international study Association
between MF and HTLV-I has been controversial, with the incidence varying
between 0% and 100%. We studied 127 patients originating from Europe (France,
Spain, UK, Portugal) or from USA for HTLV-I infection markers. HTLV-I and
-II serology were performed on 78 patients using standard methods. Reverse
transcriptase (RT) assay was performed in 26 cases using an RT-PCR-based
method of high sensitivity. Molecular analysis was performed on 215 DNA
samples (121 from fresh PBMCs, 26 from PBMCs after short term culture and
68 from skin lesions) by PCR amplification using HTLV-I and -II specific
primers. Immunological tests were negative. PCR with all HTLV-I and -II
primer pairs showed negative results in all 215 samples investigated. No
RT activity was detected in short term PBMC cultures. The results of this
large study from five different countries, clearly indicate that MF and
SS are not associated with HTLV-I infection. A. Bazarbachi, V. Soriano*,
R. Pawson*, A. Vallejo*, T. Moudgil*, E. Matutes*,
J. Peries*, A. Molina*, H. de The*, T.F. Schulz*,
D. Catovsky* and P.S Gill*. (Supported by the Leukaemia Research
Fund, UK.)
Epidemiology of non-insulin-dependent diabetes mellitus and impaired glucose tolerance in relation to other cardiovascular risk factors in Lebanon A
study of 2518 Lebanese subjects (1138 males, 1380 females), aged 30 years
and above revealed an over-all prevalence of non-insulin dependent diabetes
mellitus (NIDDM) and impaired glucose tolerance (IGT) of 13.1% and 6.0%
respectively. The results are comparable to those reported recently from
some Middle Eastern and other countries. The prevalence was very low (1%)
below the age of 40 but increased steadily with age. The main risk factor
was obesity (55% in males, 67% in females) which probably accounts, at
least in part, to the observed higher prevalence with age and amongst lower
socio-economic groups. A positive family history (40%) but not consanguinity
was another risk factor. Subjects with diabetes and IGT were more likely
to have heart diseases, had a slightly higher mean systolic and diastolic
blood pressure and serum triglycerides. An increase in serum total cholesterol
and LDL-cholesterol and a decrease in serum HDL-cholesterol were also observed
but they were more obvious in female subjects than in male subjects with
NIDDM and Igt. I. S. Salti, M. Khogali, S. Alam, N. Abu-Haidar*
and A. Masri. (Supported by LNCSR; WHO-EMRO; Lebanese Ministry of
Health.)
The genetics of Pendred syndrome Patients
with Pendred syndrome suffer from hypothyroidism accompanied with goiters
and deafness. In this study we were able to achieve refinement of the Pendred
syndrome locus by homozygosity analysis to 0.8-cM interval flanked by D7S496
and D7S2456. R. Slim and S. T. Azar.
Bazarbachi, A. and Gessain, A.*, Human T-cell leukemia virus type I (HTLV-I) and transplantation. In Cancer in Transplantation: Prevention and Treatment, J.L. Touraine et al. (eds), 81-87. Kluwer Academic Publishers, 1996. Bazarbachi, A., Huang, M.*, Gessain, A.*, Saal, F.*, Saib, A.*, Peries, J.*, de The, H.*, Galibert, F.*, HTLV-I complete proviral sequence from uncultured peripheral blood mononuclear cells derived from a subacute post-transfusional spastic paraparesis. International Journal of Cancer, 63, 1-6, 1995. Deeb, L., Yamout, B., Shamseddine, A., Shabb, N. and Uthman, S., Meningeal carcinomatisis as the presenting manifestation of gastric adenocarcinoma. American Journal of Gastroenterology, 92, 329-331,1997. Francis, G.S., Bonni, A., Shen Hechtman, P., Yamout, B., Carpenter, S., Karpati, G. and Chang, P.L., Metachromatic leukodystrophy: multiple nonfunctional and pseudodeficiency alleles in a pedigree: problem with diagnosis and counseling. Annals of Neurolology, 34, 212-218, 1993. Khalil, A., Yamout, B., Tabbal, S., Salem, Z. and Mroueh, A., Case report and review of literature: leptomeningeal relapse in epithelial ovarian cancer. Gynecologic Oncology, 54, 227-231, 1994. Melby, J. C. and Azar, S.T., Hypoaldosteronism and mineralocorticoid resistance. In De Groot Textbook of Endocrinology, 3rd Ed, 1804-1812. W. B. Saunders, 1995. Salti, I.S., Continuing medical education. Medical Education, 29 (Supplement 1), 97-99, 1995. Yamout, B., Farhat, W., Nuweihed, I. and Hushaymi, I., Changes in migraines symptoms from childhood to adolescence. European Neurology, 36, 174-176, 1996. Yamout, B., Kyriakides, T.*, Tamim, W. and Drousiotov, A.*, Myaglia, neuromyopathy and internalized capillaries. An ateroid-responsive syndrome. Acta Neurologica Scandinavica, 91, 294-296, 1995. Yamout, B., Nassar, N., Ghayyad, E. and Habbal, A., Neurobrucellosis: Clinical presentation, treatment and outcome in seven cases. Mediterranean Journal of Infectious and Parasitic Diseases, 11, 111-115, 1996. Yamout,
B., Tayyim, A. and Farhat, W., Meralgia paresthetica as a complication
of laparoscopic cholecystectomy. Clinical neurology and neurosurgery, 96,
143-144, 1994.
Abstracts, Presentations, Communications and Proceedings Almawi, W.Y., Beyhum, H.N., Kaidbey, H., Nuwayri-Salti, N. and Azar, S., Dysregulation of cytokine expression in diabetes. FASEB Journal, 10, 1376 (2169), 1996. , Dysregulation of cytokine expression in diabetes (poster). Proceedings of the American Society for Biochemistry and Molecular Biology/American Society for Ivestigative Pathology/American Association of Immunologists, Joint Meeting, Seattle, USA, June 1996. Azar, S.T., Secondary hypertension: Apparent mineralocorticoid excess. Pan Arab Hypertension Society Meeting, Broumana, Lebanon, April 1996. , Insulin resistance and hypertension. Post Graduate Course of the Lebanese Hypertension League on Update in Hypertension, Ain Wa Zein, Lebanon, May, 1996. , Pathophysiology of diabetic foot ulceration. The Lebanese Society of Reconstructive Microsurgery Conference on Management and Rehabilitation of Diabetic Foot Ulcers, Beirut, Lebanon, December 7, 1996. , Nutrition and osteoporosis. Nutrition 97 Conference of the Lebanese Association for Food Sciences and Nutrition, Beirut, Lebanon, May 2-4, 1997. , Nutritional aspects of osteoporosis. Thirty-Second Middle East Medical Assembly, Beirut, Lebanon, May 8-11, 1997. , Metabolic alterations in patients with hypertension. Post Graduate Course of the Lebanese Hypertension League on Update in Hypertension, Beirut, Lebanon, May 24, 1997 Bachmeyer, C.*, Bazarbachi A., Hunault, H.*, Aractingi, S.*, Grateau, G.*, Le Tourneau, A.*, Diebold, J.*, Zittoun, R.*, Specific cutaneous involvement indicating Burkitts lymphoma relapse. Thirteenth Congress of the European Association of Internal Medicine, Athens, Greece, 1995. European Journal of Internal Medicine, 6, 14, 1995. Bachmeyer, C.*, Bazarbachi, A., Rio, B.*, Delmer, A.*, Hunault, M.*, Zittoun, R.*, Le Tourneau, A.* and Aractingi, S.*, Specific cutaneous involvement indicating relapse of Burkitts lymphoma. American Journal of Hematology, 54, 176, 1997. Bachmeyer, C.*, Hunault, H.*, Bazarbachi A., Hamant, N.*, Aractingi, S.*, Grateau, G.*, Le Tourneau, A.*, Marie, J.P.*, Diebold, J.*, Zittoun, R.*, Unusual cutaneous involvement indicating B prolymphocytic leukemia. Thirteenth Congress of the European Association of Internal Medicine, Athens, Greece, 1995. European Journal of Internal Medicine, 6, 15, 1995. Bachmeyer, C.*, Hunault, M.*, Bazarbachi A., Hamant, N.*, Aractingi, S., Le Tourneau, N.*, Marie, J.P.*, Diebold, J.* and Zittoun, R.*, Specific cutaneous involvement in B-cell prolymphocytic leukaemia. British Journal of Dermatology, 4, 979-980, 1996. Bazarbachi, A., Bachelez, H.*, Dehen, L.*, Delmer, A.*, Zittoun, R.*, and Dubertret, L.*, Lethal paraneoplastic pemphigus after Fludarabine treatment for chronic lymphocytic leukaemia. Annals of Oncology, 7, 731-732, 1995. Bazarbachi, A., Bouscary, D.*, Gessain, A.*, Turlure, P.*, Leblond, V.*, Franck, N.*, Buzyn-Veil, A.*, Rio, B.*, Macintyre, E.*, Soussain, C.*, Gardin, C.*, Bachelez, H.*, Vernant, J.P.*, Dreyfus, F.* and Hermine, O.*, Treatment of HTLV-I associated adult T-cell leukemia-lymphoma with a combination of zidovudine and interferon alpha. Thirty-Seventh Annual Meeting of the American Society of Hematology, Seattle, USA, 1995. Blood, 86, 931a, 1995. , Treatment of HTLV-I associated adult T-cell leukemia-lymphoma with a combination of zidovudine and interferon alpha. Eighth International Conference on Human Retrovirology: HTLV, Paris, France, 1995. Journal of AIDS and Human Retrovirology, 2, 284, 1995. Bazarbachi, A. and Hermine, O.*, Treatment by A combination of zidovudine and alpha interferon in naive and pretreated Adult T-cell leukemia/ lymphoma patients. Journal of AIDS and Human Retrovirology, 13, s186-190, 1996. Bazarbachi, A., Huang, M.*, Gessain, A.*, Saal, F.*, Saib, A.*, Peries, J.*, de The, H.* and Galibert, F.*, Human T-cell leukemia virus type I in post-transfusional spastic paraparesis: complete proviral sequence from uncultured blood cells. Thirty-Seventh Annual meeting of the American Society of Hematology, Seattle, USA, 1995. Blood, 86, 928a, 1995. , Human T-cell leukemia vitype I in post-transfusional spastic paraparesis: complete proviral sequence from uncultured blood cells. Eighth International Conference on Human Retrovirology: HTLV, Paris, France, 1995. Journal of AIDS and Human Retrovirology, 2, 283, 1995 Bazarbachi, A., Soriano, V.*, Vallejo, A.*, Moudgil, T.*, .Peries, J.*, de The, H,.* and Gill, P.S.*, Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection: an international study. Thirty-Seventh Annual meeting of the American Society of Hematology, Seattle, USA, 1995. Blood, 86, 928a, 1995. , Mycosis Fungoides and Sezary syndrome are not associated with HTLV-I infection: an international study. Eighth International Conference on Human Retrovirology: HTLV. Paris, France, 1995. Journal of AIDS and Human Retrovirology, 2, 237, 1995. Beyhum, H. N., Azar, S., Nuwayri-Salti, N. and Almawi, W.Y., Association of altered T cell immunity with the onset and progression of type I diabetes (poster). Annual Conference on Clinical Immunology, New Orleans, USA, May 31-June 3, 1996. Hermine, O.*, Bouscary, D.*, Gessain, A.*, Turlure, P.*, Leblond, V.*, Franck, N.*, Buzyn-Veil, A.*, Rio, B.*, Macintyre, E.*, Dreyfus, F.* and Bazarbachi, A., Treatment of HTLV-I associated adult T-cell leukemia-lymphoma with a combination of Zidovudine and Alpha-Interferon. New England Journal of Medicine, 332, 1749-1751, 1995. Levy, V.*, Azoulay, D.*, Rio, B.*, Vincent, F.*, Rabbat, A.*, Hunault, M.*, Bazarbachi, A., Delmer, A.* and Zittoun, R.*, Successful treatment of severe hepatic veno-occlusive disease after allogenic bone marrow transplantation by transjugular intrahepatic portosystemic stent shunt (TIPS). Bone Marrow Transplantation, 18, 443-445, 1996. Levy, V.*, Rio, B.*, Azoulay, D.*, Hunault, M.*, Bazarbachi, A., Delmer, A.* and Zittoun, R.*, Successfull treatment of severe venoocclusive disease of the liver after allogenic BMT by transjugular intrahepatic portosystemic shunt (TIPS). Annual Meeting of the European Bone Marrow Transplantation Group, Vienna, Austria, 1996. Levy, V.*, Rio, B.*, Bazarbachi, A., Hunault, M.*, Delmer, A.*, Zittoun, R.*, Blanc, V.* and Wolff, M.*, Two cases of epidemic mucomycosis infection in patients with acute lymphoblastic leukemia. American Journal of Hematology, 52, 64-65, 1996. Nuwayri-Salti, N., Shoucair, M., Azar, S., Jaber, R., Salti, I. and Halabi, G., Class I immunogenetic markers in Lebanese patients with Graves disease (poster). Twelfth International Histocompatibility Conference, Paris, June 1996. Rio, B.*, Marjanovic, Z.*, Levy, V.*, Hunault, M.*, Bazarbachi, A. and Zittoun, R.*, Vaccination for yellow fever after bone marrow transplantation. Annual Meeting of the European Bone Marrow Transplantation Group, Vienna, Austria, 1996. Salti, I.S., The genetic aspects of auto-immune thyroid diseases. Proceedings of the Annual Scientific Conference: Current concepts in Thyroid Diseases, Hamad Medical Corporation, Doha, Qatar, April 6-8, 1996. , Diabetic nephropathy. Fifth Syrian Diabetes Conference, Latakia, Syria, June 26-28, 1996. , Oral and dental problems in some metabolic and endocrine disorders. Sixth International Conference of the Lebanese Order of Dentists, Beirut, September 5-7, 1996. , Unusual pituitary tumors. Second Annual Meeting of the Syrian Endocrine Society, Homs, Syria, November 21-22, 1996. , Autoimmune hypophysitis. Second Annual Meeting of the Syrian Endocrine Society, Homs, Syria, November 21-22, 1996. , The problem of osteoporosis in Lebanon : Suggested ideas for a consensus in a developing country. International Meeting on Osteoporosis, Beit Miri, Lebanon, April 16-18, 1997. , Recent advances in insulin therapy. Symposium sponsored by E. Lilly. Damascus, May 1 and Aleppo, May 4, 1997. , Is there a consensus for the management of osteoporosis in Lebanon? Symposium at the Thirty-Second Middle East Medical Assembly, Beirut, May 9-11, 1997. , Medullary carcinoma of the thyroid. Third Symposium of the Syrian Endocrine Society, Busra, Syria, May 22-23, 1997. Salti, I.S., Khogali, M. and Alam, S., The epidemiology of diabetes and other cardiovascular risk factors in the adult Lebanese population. Third International Congress of Cardiology, Beit Miri, Lebanon, October 24-27,1996. , Diabetes and other cardiovascular risk factors in the adult Lebanese. Thirty-First Middle East Medical Assembly, Beirut, May 10-12, 1996.
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