Disease In Lebanon Research Articles

Association of CYP3A4/5 genotypes and expression with the survival of patients with neuroblastoma.

Neuroblastoma (NB) is a rare pediatric disease in Lebanon for which poor prognosis remains a major challenge. Genetic polymorphism of genes coding for drug‑metabolizing enzymes may influence the response of a patient to chemotherapy. This study investigates a possible association between CYP3A4/5 polymorphism and expression levels and survival in NB patients. All patients with stageIII andIV NB diagnosed between 1993 and 2012 in three major hospitals in Beirut were included(n=27). Demographic information and survival time were obtained from medical records. CYP3A4 and CYP3A5 genotypes and expression levels were determined in archival tumors by polymerase chain reaction (PCR) and restriction fragment length polymorphism and quantitative PCR, respectively. Additionally, MYCN amplification was assessed. A Cox proportional hazards model was used to evaluate potential associations, adjusting for MYCN amplification. A statistically significant increase in the risk of mortality was observed in patients with MYCN amplification [hazard ratio(HR) 4.11, 95% confidence interval(CI)1.14‑14.80]. Patients with CYP3A5 expression levels above the median had a lower risk of mortality (HR 0.61, 95%CI0.21‑1.74) and patients with CYP3A4 expression levels above the median had a higher risk of mortality (HR2.00, 95%CI0.67‑5.90). CYP3A5*3/*3 homozygote mutants had a 4.3‑fold increase in the risk of mortality compared with that of homozygote wild‑type or heterozygote mutants (HR 4.30, 95%CI0.56‑33.30). Carriers of the CYP3A4*1B mutant allele had a 52% lower risk of mortality compared with that of non‑carriers (HR0.48, 95%CI0.06‑3.76). Although the results of the present study did not achieve statistical significance, associations were observed, which indicates that CYP3A4 and CYP3A5 may modulate the clinical outcome of NB. Further studies with larger sample sizes are required to characterize the effects of the polymorphism and expression levels of CYP3A4/5 on the survival of patients with NB.

Heart health in Lebanon and considerations for addressing the burden of cardiovascular disease

Lebanon is a small country located at the western boundary of the Middle East. Approximately 40% of health care in Lebanon is financed by the public sector. Cardiovascular diseases in Lebanon are scarcely addressed in the literature raising the need for baseline data on these health condition to be better treated. To (1) aggregate and define the burden of cardiovascular disease in Lebanon and (2) describe implications for policy, practice and research to improve health outcomes in Lebanon. An integrative review was conducted of both peer-reviewed papers and unpublished reports. CINAHL, Medline, Google Scholar and Academic Search Complete were searched along with the websites of The World Health Organization, Ministry of Public Health Lebanon and Central Intelligence Agency of Lebanon. No year limit was applied to our search. The search yielded 28 peer-reviewed articles and 15 reports. Cardiovascular diseases are the leading cause of morbidity and mortality in Lebanon and is also the primary cause of hospital admission. A range of social, political, economic and cultural factors explain the burden of cardiovascular diseases, some of these risks are culture specific such as the arghile smoking and the high rates of familial hypercholesterolemia. Workforce shortage produced by high rates of migrating nurses also has an implication on the patients' outcomes. Conclusion: Much of the presented data are sourced from the gray literature; more research, using systematic and prospective data collection methods, are needed to inform health services planning, delivery and evaluation. Primary care needs to be enhanced to produce better outcomes for a population with high profile of cardiovascular risk factors.

Urinary Bladder Cancer Risk Factors: A Lebanese Case-Control Study

Bladder cancer is the second most incident malignancy among Lebanese men. The purpose of this study was to investigate potential risk factors associated with this observed high incidence. A case-control study (54 cases and 105 hospital-based controls) was conducted in two major hospitals in Beirut. Cases were randomly selected from patients diagnosed in the period of 2002-2008. Controls were conveniently selected from the same settings. Data were collected using interview questionnaire and blood analysis. Exposure data were collected using a structured face-to-face interview questionnaire. Blood samples were collected to determine N-acetyltransferase1 (NAT1) genotype by PCR-RFLP. Analyses revolved around univariate, bivariate and multivariate logistic regression, along with checks for effect modification. The odds of having bladder cancer among smokers was 1.02 times significantly higher in cases vs. controls. The odds of exposure to occupational diesel or fuel combustion fumes were 4.1 times significantly higher in cases vs controls. The odds of prostate-related morbidity were 5.6 times significantly higher in cases vs controls. Cases and controls showed different clustering patterns of NAT1 alleles. No significant differences between cases and controls were found for consumption of alcohol, coffee, tea, or artificial sweeteners. This is the first case-control study investigating bladder cancer risk factors in the Lebanese context. Results confirmed established risk factors in the literature, particularly smoking and occupational exposure to diesel. The herein observed associations should be used to develop appropriate prevention policies and intervention strategies, in order to control this alarming disease in Lebanon.

Hospital based surveillance of rotavirus gastroenteritis in children

Background: Rotavirus (RV) is the single most common cause of severe gastroenteritis (GE) in children aged <5 years worldwide. Data on the burden and epidemiology of RV disease in Lebanon is limited. Therefore, this study aimed to determine the attributable fraction (AF) of RV as the etiologic agent of GE, RV strain distribution and seasonality of RVGE in children aged <5 years in Lebanon. Methods: This multicenter, hospital-based surveillance conducted between May 2007 and May 2008, enrolled children <5 years hospitalized with GE episodes. Stool samples were tested for the presence of RV by enzyme immuno assay (EIA). RV positive samples were genotyped by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Seasonality of RVGE cases was recorded during the study period. Severity of the RVGE episodes was measured using the Vesikari scale, where a score of ≥11 was considered severe. Results: Of the 534 children enrolled in this study, 491 (91.9%) were included in the final analysis in the according-to-protocol cohort; 27.7% (136/491) of subjects were RV positive, 71.5% (351/491) were RV negative and 0.8% (4/491) had unknown RV status. Of the RV positive subjects, 75% (102/136) of cases were seen in children <2 years of age. Although RVGE cases occurred throughout the year, the peak season was observed between December 2007 and March 2008 (65.4%; 89/136). Severe GE cases observed before hospitalization was 79.4% (108/136) in RV positive and 76.1% (267/351) in RV negative subjects (p = 0.44). G4 (36.9%) and P[8]WT (77.7%) were the most common RV types detected among RV positive samples that were genotyped (N = 130). Conclusion: The data generated from this first burden of disease study in Lebanon showed that the AF of Rotavirus in children <5 years of age corresponded to 27.7% of hospitalized GE. Most of the RV cases (75%) were in children aged <2 years. These baseline epidemiology data might guide policy makers in initiating nationwide public health strategies, including vaccination to reduce the RV disease burden in Lebanese children <5 years of age.

OP35.08: How good are we in prenatal diagnosis of congenital heart disease in Lebanon?

OP35.08: How good are we in prenatal diagnosis of congenital heart disease in Lebanon?

Response to a cardiac event in relation to cardiac knowledge and risk perception in a Lebanese sample: A cross sectional survey

Background Heart disease is the leading cause of morbidity and mortality in many countries, including Lebanon. The continuing advances in the treatment of heart disease have improved patient outcomes significantly over the years. Nevertheless, prompt treatment remains essential to treatment success, which depends on the person's early recognition of cardiac symptoms and quick seeking of care. Objective The purpose of the study was to examine the relationship between knowledge of symptoms of heart disease, perceived cardiac risk and the potential response to a heart attack in a sample of Lebanese adults. Design A cross sectional descriptive survey design was used. A convenience sample of 399 adult hospital visitors who did not have heart disease were interviewed in two major referral hospitals in Beirut. Measures The Illness Perception Questionnaire and the Behavioral Risk Factor Surveillance System were used; in addition an open-ended question was asked to elicit what the visitor would do in case he/she experienced cardiac symptoms. Results While most participants (94%) correctly recognized major symptoms of heart disease (like chest pain and dyspnea), they also reported irrelevant symptoms to be associated with heart disease (like irritability by 68% and muscle cramps by 52%). Only 21% of participants reported that they would seek emergency care as their first response if they were experiencing a heart attack. Knowledge of symptoms and perceived cardiac risk were not associated with the response to a heart attack. Being single was the only significant predictor of choosing the appropriate response when experiencing a cardiac event. Conclusion The findings suggest lack of adequate knowledge of cardiac symptoms and a high potential for inappropriate responses when symptoms occur. Public health heart health campaigns are needed to raise awareness about heart disease in Lebanon.

Chronic Urticaria and Autoimmune Thyroid Disease in Lebanon

RATIONALE: Autoimmune thyroid disease with elevated anti-thyroid antibodies has been implicated as a cause of chronic urticaria (CU). We examined the incidence of thyroid autoimmunity in patients with CU in the Lebanese population.

Childhood Anemias - A Success Story of Basic Science and Clinical Care

&lt;P&gt;Anemia is the most common hematologic problem encountered in pediatric practice and constitutes the most common reason for referral to pediatric hematologists. It is estimated that 30% of children suffer from anemia. The evaluation of the child with anemia presents a challenging task for pediatric healthcare providers and poses difficult questions. In addition to providing appropriate screening, surveillance, and diagnosis, offering optimal state-of-the art treatment and prevention are priorities in any pediatric primary care facility. Although the role of pediatric hematologists is pivotal, the pediatric healthcare provider is on the frontline of patient care and faces the many challenges involved in diagnosing the various types of anemia. Facing these challenges is possible only through knowledge of both basic science and clinical care and can be very rewarding.&lt;/P&gt;&lt;h4&gt;ABOUT THE GUEST EDITOR&lt;/h4&gt;&lt;P&gt;Adlette Inati, MD, is the Head of the Division of Pediatric Hematology-Oncology and the Medical Director of the Children’s Center for Cancer and Blood Diseases at Rafik Hariri University Hospital, Beirut, Lebanon. She is a Consultant Hematologist at the Chronic Care Center (a comprehensive hemoglobinopathy center) and a Research Associate at Balamand University, Lebanon. In addition, she is the Clinical Scientific Director of the Italian-Lebanese International Cooperation in the Fields of Health and Medical Sciences.&lt;/P&gt;&lt;P&gt;Dr. Inati received her bachelor and medical degrees from the American University of Beirut and had her first-year residency in pediatrics at Johns Hopkins University. She completed her pediatric residency and her fellowship in pediatric hematology-oncology at Boston Children’s Hospital Medical Center and Sidney Farber Cancer Institute, Harvard Medical School. She is American-Board certified and is a member of the Alpha Omega Alpha Honor Medical Society.&lt;/P&gt;&lt;P&gt;Dr. Inati has contributed significantly to clinical scientific research and patient care delivery in her field. Her major fields of interest are sickle cell disease, thalassemia, and bleeding disorders. She has published extensively in international journals and has been an invited speaker in national and international scientific meetings. Dr. Inati has been involved in multiple global and national trials on sickle cell disease and thalassemia. She is on the steering committees of several hemoglobin and bleeding disorders international studies. She runs the largest sickle cell disease clinic in Lebanon and has published the first two large-scale national reports about sickle cell disease in Lebanon. She has shown leadership in initiating the first Middle East Thought Leaders and Investigators Sickle Cell Disease Scientific Meeting, which promoted partnership in science and dissemination of knowledge both to physicians and the community. Currently, she directs the Pediatric Hematology Oncology teaching and training program for medical students and residents from various disciplines at Rafik Hariri University Hospital.&lt;/P&gt;&lt;P&gt;Dr. Inati is a member of several international scientific and medical societies. She is also a member of the Lebanese National Cancer Control Program, of the Institutional Review Board, and the Board of Trustees of the Chronic Care Center. She has been active in health policy and in addressing important child healthcare issues particularly related to blood disorders, cancer, life quality issues, and violence against children.&lt;/P&gt;&lt;P&gt;She has been recognized for the promotion of medical growth in her country and officially represented Lebanon at several global scientific meetings. She received two silver medals from the First Lady of Lebanon in recognition of her commitment to the control of inherited hemoglobin disorders in Lebanon.&lt;/P&gt;

Clinical characteristics of multiple sclerosis in Lebanon

The epidemiologic, clinical, radiological and laboratory characterization of multiple sclerosis (MS) is very well documented in Caucasian and Japanese populations, but very little is known about MS in the Arab world. Such knowledge is becoming of paramount importance, with the recent advances in therapies, MRI techniques and other diagnostic procedures. We report a cohort of Lebanese MS patients, including details of their clinical and laboratory characteristics. The medical records of 202 patients fulfilling the Mc Donald's diagnostic criteria, and followed in our tertiary care center were reviewed. This cohort is highly representative of the disease in Lebanon where the number of MS patients is estimated to be between 1200 and 1700. The peak age of onset of MS in our cohort was in the third decade with 62.4% of patients developing their first symptoms between 20 and 39 years. The female/male ratio was 1.8/1.0. A positive family history for MS was present in 5% of patients. The most frequent presenting symptoms were brainstem-cerebellar (46.2%) followed by sensory (42.5%), motor (33.9%) and visual (29.6%). Of the total number of patients, 85.1% had relapsing remitting MS at onset, and 7.9% primary progressive MS. Benign MS defined as EDSS<=2.0 after 10 years from onset was present in 20% of patients. The mean time from onset to secondary progressive MS was around 9 years. Visual, brainstem, and somatosensory evoked potentials were abnormal in 65.6%, 27.8%, and 50.7% of patients tested respectively. Cerebrospinal fluid showed pleocytosis in 32.6%, increased IgG synthesis in 45.2%, positive oligoclonal bands in 40%, and elevated protein in 34% of patients tested. Although some of the clinical characteristics of our MS population were different compared to western series, the natural history of the disease was similar.

Human leukocyte antigen (HLA) associations, antibody titers and circulating immune complexes in patients with cystic echinococcosis

AbstractCystic echinococcosis (CE), caused by the parasite Echinococcus granulosus, is a prominent disease in Lebanon. The objectives of this study were to determine HLA allele-CE association in patients, and relate its presence to high anti-Echinococcus antibody titers and the presence of circulating immune complexes (CIC). Thirty patients and 20 controls were included. HLA profiles were determined by DNA-SSP typing. Relative risk and P-values were determined for each allele using Statcalc (EpiInfo, Version 6). Linkage disequilibrium was determined for associated alleles using SPSS 12.0 for Windows. Antibody titers were determined by indirect hemagglutination (IHA) and CIC by polyethylene glycol (PEG) precipitation. HLA-B*14 and HLA-DRB1*01 appeared to associate with protection against CE (P1 = P2 = 0.007 and P1 = P2 = 0.0007, respectively). However, it appeared that linkage disequilibrium did not exist between these 2 alleles (P = 0.250). HLA-B*35 was found to associate with susceptibility to disease (RR = 1.70, P = 0.02). Twenty five patients had anti-Echinococcus antibodies and 9 patients had CICs. However, there did not appear to be a correlation between the presence of HLA-B*35 and high antibody titers, or the presence of CICs. In conclusion, 2 HLA alleles that associate with resistance and 1 that associates with susceptibility to E. granulosus infection have been identified. The joint pain reported by some of the patients might be attributed to CIC deposits.

Behçet's disease in Lebanon: clinical profile, severity and two-decade comparison

The aim of this study is to describe the clinical features of Lebanese patients with Behçet's disease (BD) followed up at a tertiary care center in Lebanon. A retrospective review of medical records of 90 patients who fulfilled the International Study Group (ISG) criteria for diagnosis was performed. The clinical characteristics and severity score were compared with those reported from other populations of Arab and of Turkish origin using the same diagnostic criteria, and a comparison over two decades for the Lebanese population was made. The male-to-female ratio was 2.9:1, the mean age at onset, 25.4 years, and mean age at diagnosis, 29.2 years. One hundred percent of the patients had mouth ulceration; 72.2%, genital ulceration; 59.1%, arthritis; 55.7%, papulopustular skin lesion; 53.9%, ocular disease; 36.8%, vascular disease; 29.5%, erythema nodosum; and 23.0%, neurologic disease. The characteristics of our patient population are similar to that reported from other countries in the region. However, we found a higher prevalence of vascular and neurologic disease.

β‐Globin gene cluster haplotypes and HbF levels are not the only modulators of sickle cell disease in Lebanon

Sickle cell disease (SCD) is an inherited autosomal recessive disorder of the beta-globin chain. Despite the fact that all subjects with SCD have the same single base pair mutation, the severity of the clinical and hematological manifestations is extremely variable. This study examined for the first time in Lebanon the correlation between the clinical manifestation of SCD and the beta-globin gene haplotypes. The haplotypes of 50 patients diagnosed with SCD were determined using polymerase chain reaction amplification of fragments containing nine polymorphic restriction sites around and within the epsilon-Ggamma-Agamma-psibeta-delta-beta-globin gene complex. Most reported haplotypes were found in our population with the Benin haplotype as the most prevalent one. When the patients were divided according to their HbF levels into three groups (Group A: HbF < 5%, Group B: HbF between 5 and 15%, and Group C: HbF > 15%), surprisingly, the highest levels of HbF were associated with the most severe clinical cases. Our findings suggest that fetal hemoglobin levels are important but not the only parameters that affect the severity of the disease. In addition, the high levels of HbF in patients with CAR haplotypes did not seem to ameliorate the severity of symptoms, suggesting that genetic factors other than haplotypes are the major determinants of increased HbF levels in Lebanon.

First Report of Grapevine "Bois Noir" Disease and a New Phytoplasma Infecting Solanaceous Plants in Lebanon.

During a 2001 survey to evaluate the incidence of phytoplasma diseases in Lebanon, samples were collected from plants showing symptoms suggestive of phytoplasmal infections. Samples were also collected from symptomless plants. Sampled hosts from the Bekaa Valley included: 3 samples of tomato (Lycopersicum esculentum), 4 samples of pepper (Capsicum annuum), 10 samples of grapevine (Vitis vinifera) cvs. Chardonnay and Alicante Bouschet; 7 samples of ornamental periwinkle (Catharantus roseus) from the Tyr area; and 4 samples of weeds (Lactucca serratia). DNA was extracted from leaf midveins of diseased and symptomless plants, and from healthy periwinkle, grapevine, tomato, and pepper plants grown in a greenhouse in France. Polymerase chain reaction (PCR) with universal primers for the amplification of phytoplasma ribosomal RNA genes (3) only produced a 1.8-kbp rDNA fragment from symptomatic samples. The amplified DNAs were analyzed by restriction fragment length polymorphism (RFLP) with several restriction enzymes and sequenced. The analysis showed extracts of diseased grapevines, and two periwinkle plants had identical rDNA sequences and restriction profiles of the stolbur cluster (4). The sequences had 98% identity with two European stolbur isolates from grapevine and periwinkle (GenBank Accession Nos. X76428 and AF248959, respectively). In grapevine, the disease induced by the stolbur phytoplasma is "bois noir." Bois noir is present in Europe where its incidence is predominant in northern vineyards and has been reported in Israel (2). To our knowledge, this is the first report of the stolbur/bois noir disease in Lebanon. In tomato and pepper, the restriction profiles and sequences of the phytoplasma rDNAs were identical. Sequencing and phylogenetic analysis indicated that the phytoplasma belonged to the clover proliferation (CP) cluster, as does the eggplant little leaf phytoplasma of solanaceous plants in Asia. They differed from the stolbur phytoplasma, known to infect solanaceaous plants in Europe. Lastly, a phytoplasma belonging to the pigeon pea witches' broom (PPWB) cluster was found in L. serratia and in some periwinkle plants. A phytoplasma of the PPWB cluster was recently shown to be responsible for an emerging lethal disease of almond trees in Lebanon (1).

The mutation mechanism causing juvenile‐onset Tay‐Sachs disease among Lebanese

Expression of the hexosaminidase isozymes was evaluated in fibroblast cell lines obtained from two sibs of Lebanese-Christian origin who presented with juvenile-onset Tay-Sachs disease. In the normal control fibroblasts the alpha subunit of hexosaminidase A (hex A) is synthesized as a 67 KD precursor which is cleaved in lysosomes to a mature 54 KD peptide. The patients' fibroblasts were capable of synthesizing the 67 KD precursor but failed to convert it to the mature subunit. The alpha subunit precursor synthesized by patients' cells could not be phosphorylated, nor was the patients' alpha subunit precursor secreted into the medium in response to NH4Cl, which caused accumulation of both alpha and beta subunit precursor in the medium of the normal control fibroblasts. The measurement of residual enzyme activity in the fibroblasts of patients which best correlated with the onset of the illness was the ion exchange chromatographic separation of Hex A-associated hydrolysis of the synthetic substrate 4-methylumbelliferyl N-acetyl-beta-D-glucosamine-6-sulfate (4MUGS). The patients had 0.32% and 0.36% of Hex A-associated 4MUGS cleaving activity compared to normal control fibroblasts as compared to less than 0.016% for infantile Tay-Sachs disease fibroblasts. The residual Hex A activity in patients' cells had a pH optimum identical with normal enzyme (pH 3.9-4.0), a reduced specific activity for 4MUGS (relative to hydrolysis of unsulfated synthetic substrate), and a greatly enhanced thermal stability. The occurrence of this form of Tay-Sachs disease in Lebanon, the fact that the condition has been described in three unrelated Lebanese immigrant families in Canada, together with the fact that the grandparents of the unrelated probands come from villages in both the northern and southern regions of Lebanon, leads us to speculate that a gene causing juvenile-onset Tay-Sachs disease may not be infrequent in Lebanon.

Psychosocial and economic profile of a sample of families with thalassaemic children in Lebanon.

Thalassaemia major is a relatively common disease in Lebanon. This study of 41 families with 54 patients attending the American University of Beirut Medical Center was conducted to define some aspects of the disease in Lebanon and to assess the attitudes of affected families on relevant psychosocial and economic issues. We conclude that because of the high frequency of consanguineous marriage, thalassaemia major is more common in Lebanon than might be expected on the basis of the incidence of the trait. Most patients are diagnosed early in life, but their treatment is generally far from adequate; securing desferrioxamine and paying for follow up visits to the doctor seem to be the most important financial burdens. The general population of the country is not properly informed yet and about 70% of the families had not heard about the disease before having an affected child. The inherited nature of the disease is not clear in the minds of a high percentage of the families, and in about 30% of cases the family had not been told about the advisability of screening to detect heterozygotes. The great majority of families favour a preventive approach to thalassaemia, based on heterozygote screening and the possibility of prenatal diagnosis.