Post Syrian war impact on susceptibility rates and trends in molecular characterization of Enterobacteriaceae.

OBJECTIVE: Describe susceptibility and molecular profiles among Enterobacteriaceae pathogens and to explore if war, among other factors, can affect antimicrobial resistance. METHODS: Clinical isolates from the Study for Monitoring Antimicrobial Resistance Trends associated with urinary tract and intra-abdominal infections between 2011 and 2015 were identified in Lebanon and Jordan. Susceptibility testing and molecular characterization were performed as per standard methods. RESULTS: A total of 1486 Enterobacteriaceae pathogens (including unusual pathogens) were identified. Incidence rates of  extended spectrum ß-lactamases were high with an overall higher prevalence of resistance in Jordan compared with Lebanon. CTX-M-15 was the most prevalent extended spectrum ß-lactamases produced and OXA-48 the most reported carbapenemases subtype. CONCLUSION: Changes in healthcare system due to war could impact regional resistance patterns and which requires a continuous surveillance program and containment plan.

Assessment of Molecular Markers in AML Patients: A Hospital-Based Study in Lebanon.

BACKGROUND: In the past, research has been focused on elucidating the molecular genetics and epigenetic basis of acute myelogenous leukemia (AML). This has led to the change in the classification and management of AML patients. Because no molecular studies regarding AML characterization in Lebanese patients had yet been reported, we decided to determine in our institution the prevalence of the recurrent genetic rearrangements t(8;21), inv(16), t(15;17) and Fms-like (Suzanne McDonough feline sarcoma) tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) mutations. MATERIALS AND METHODS: Fusion gene transcripts from chromosome aberrations were analyzed according to standardized reverse transcription polymerase chain reactions after the report of BIOMED-1 concerted action: investigation of minimal residual disease in acute leukemia. FLT3 and NPM1 mutations were screened using home-brew methodologies. RESULTS: We reviewed 144 bone marrow samples from AML patients referred to Saint George Hospital for molecular and cytogenetic studies from September 2006 to July 2014. The male to female patient ratio was 1.34 to 1. We detected the inv(16) in 6 patients [4.2%] (type A, 5 [83%]; type D, 1 [17%]), t(8;21) in 7 patients [4.9%] (e5e2), and t(15;17) in 36 patients [25.0%] (24 [67%] breakpoint cluster region 1 (bcr1), 12 [33%] bcr3). Other chromosomal abnormalities (trisomy 8, complex karyotype, t(6;9),…) were found in 44 patients [31.4%] and 51 [35.5%] cases showed normal karyotype. Among the normal karyotypes, 6 patients [11.8%] were FLT3-positive (4 [67%] internal tandem duplication [ITD], 2 [33%] D835V), 8 [15.7%] had type A NPM1 mutation and 8 [15.7%] type A NPM1 and FLT3/ITD concomitantly. CONCLUSION: Our results, except for the prevalence of acute promyelocytic leukemia, are concordant with those reported in the literature with approximately 35% of the patients cytogenetically normal. Testing patients with normal karyotype for other molecular markers such as CCAAT/enhancer-binding protein alpha mutations, isocitrate dehydrogenase 1/2 mutations, and mixed lineage leukemia rearrangements could therefore provide additional prognostic, predictive, and therapeutic values for AML patients.

A nationwide non-interventional epidemiological data registry on myelodysplastic syndromes in Lebanon.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders characterized by peripheral blood cytopenias, blood cells dysplasia, and increased risk for progression to acute leukemia.Physicians should be vigilant in diagnosing MDS and should be aware of the contemporary therapies that are always in progress. Most of the data on MDS epidemiology and management comes from developed countries. The incidence and features of MDS in the Arab countries, among them Lebanon, are not known. We undertook a nationwide epidemiological registry study of all newly diagnosed MDS cases through 2010-2011. Patients were referred by 21 hematologists/oncologists practicing in 17 hospitals and medical centers distributed across the entire country. 58 patients (29 males and 29 females) with confirmed MDS were included. The calculated incidence rate of MDS was 0.71 per 100,000 people. The median age at diagnosis was 73 years (range 16-86). The most common complaints on presentation were fatigue (70.7%), weakness (60.3%) and pallor (43.1%). Most patients were diagnosed as refractory anemia with excess blasts (RAEB; 36.2%) and refractory cytopenia with multilineage dysplasia (RCMD; 32.8%). This paper constitutes the first epidemiological report on the incidence and specific subtypes of MDS in Lebanon.

Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Lebanese subjects.

We tested the association of TCF7L2 variants with type 2 diabetes (T2DM) in 691 Lebanese people and 919 controls. rs7901695, rs4506565, rs7903146, rs12243326, rs7895340, and rs12255372 minor allele frequencies were higher in T2DM. Haplotype analysis (rs7901695-rs4506565-rs7903146-rs12243326-rs7895340-rs11196205-rs12255372) identified positively- (2122112, 2222222) and negatively- (1111111) T2DM-associated haplotypes. TCF7L2 is a common T2DM candidate gene in Lebanese people.

Influenza A (H1N1) 2009 pandemia. The experience of a tertiary care center in Beirut.

INTRODUCTION: In March 2009, a new influenza virus strain emerged, currently known as the 2009 pandemic H1N1 virus. The virus first appeared in Mexico and rapidly spread globally to reach a pandemic level in June of the same year. We describe here the experience of one major referral center in Beirut, Lebanon. MATERIALS AND METHODS: The laboratory department at St. George Hospital University Medical Center received respiratory specimens from hospital wards, the emergency department, in addition to a considerable proportion collected directly from "outpatients" in the lab. We used the real time RT-PCR as our main diagnostic test. We collected data about the patients from the laboratory information system and from the hospital medical records department. RESULTS: From mid-August 2009 till the end of January 2010, a total of 1771 specimens were analyzed, with 948 (53.5%) returning positive for influenza A (H1N1) by RT-PCR. Only 79 patients with H1N1 infection required hospitalization. Most of H1N1 confirmed patients were children and adolescents aged 5 to 17 years and young adults between 25 and 44 years. The most common symptoms at presentation were: fever, cough, shortness of breath, chills, rhinorrhea or nasal congestion, as well as gastrointestinal symptoms. Twenty-three patients required ICU care and eight patients died. The vast majority had an uncomplicated course of illness and was managed in an outpatient setting. CONCLUSION: The percentage of positive tests during the pandemia was significantly elevated, although few patients experienced drastic clinical outcomes.

Acquired and genetic risk factors for deep vein thrombosis of lower extremities among Lebanese patients.

AIM: Venous thrombosis results from the interaction of environmental and genetic risk factors. These factors vary according to the ethnic and geographic distribution of the populations. The aim of this study is to define the role of acquired and genetic risk factors for venous thrombosis of lower extremities among Lebanese patients assessed in a university hospital and to discuss them according to the international literature. MATERIAL AND METHODS: From January 2005 to January 2010, 166 patients (72 males and 94 females) were diagnosed with lower extremity deep vein thrombosis. Mean age was 67 years (range: 25 to 96 years). RESULTS: The most frequently reported acquired risk factors for venous thrombosis in this study were advanced age, obesity, history of venous thromboembolism, immobilization, surgery, varicose veins and malignancy. Screening for prothrombotic genetic abnormalities was requested in patients with conditions highly suggestive of hypercoagulation state such as young patients, patients with spontaneous, recurrent or extensive venous thrombosis, patients with family history, oral contraceptives, air travel and pregnancy. All the 45 patients (27.1%) tested for thrombophilia were positive and were carriers for factors V-Leiden (17.4%), MTHFR C 677 T (16.8%), MTHFR A 1298 C (4.8%), II G 20210 A (1.8%) and V H 1299 R (1.2%) mutation. Twelve patients (7.2%) had increased homocysteine level. CONCLUSION: Advanced age is the most common risk factor for venous thrombosis in these series. Thrombophilia is the second most frequently observed risk factor and is related to the high prevalence of factor V-Leiden and MTHFR C 677 T mutation among the Lebanese population.

Strong association of common variants in the IGF2BP2 gene with type 2 diabetes in Lebanese Arabs.

OBJECTIVE: Several genome-wide association studies and replication analyses have identified common variation at the insulin-like binding protein 2 (IGF2BP2) gene to be associated with type 2 diabetes (T2DM). The aim of this study was to replicate in a Lebanese Arab population identified associations of IGF2BP2 variants rs4402960 and rs1470579 with T2DM. METHODS: This case-control study involved 544 T2DM patients and 606 control subjects. Genotyping was done by the allelic exclusion method. RESULTS: T allele of rs440960 (P=6.5 × 10(-6)) and C allele of rs1470579 (P=5.3 × 10(-4)) were significantly associated with T2DM; both SNPs were in strong LD (D'=0.83, r(2)=0.58). While both IGF2BP2 SNPs were significantly associated with T2DM under additive and recessive models, only rs4402960 remained significantly associated with T2DM under the dominant model. Taking the common rs4402960/rs1470579 GA haplotype as reference, multivariate analysis confirmed the positive association of TC (P=0.009; OR, 1.43; 95%CI, 1.09-1.87), and TA (P<0.001; OR=5.49; 95%CI=2.09-14.39) haplotypes with increased T2DM risk. These differences remained significant after applying the Bonferroni correction for multiple testing. CONCLUSION: We validate that IGF2BP2 susceptibility variants rs4402960 and rs1470579 associate with T2DM in Lebanese Arabs.

Pharmacogenetics of coumarin dosing: prevalence of CYP2C9 and VKORC1 polymorphisms in the Lebanese population.

BACKGROUND: Polymorphisms in the genes encoding the cytochrome P450 2C9 enzyme (CYP2C9) and the vitamin K epoxide reductase (VKORC1) are known to contribute to variability in sensitivity to coumarins. Patients with certain common genetic variants of CYP2C9 (*2 & *3) or a VKORC1 polymorphism (-1639A Allele) require a lower dose of coumarin and are also at higher risk for over-anticoagulation and serious bleeding. In August 2007, the FDA label for warfarin was updated to highlight the benefit of genetic testing to predict warfarin response. AIM: Since the prevalence of these variants in the Lebanese population has not yet been reported, our aim was to determine the genotypes of CYP2C9 and VKORC1 in our population and to compare allele frequencies with previous findings from other ethnic groups. MATERIALS AND METHODS: CYP2C9 (*1/*2/*3) and VKORC1 (*A/*G) allelic variants were assessed by polymerase chain reaction-restriction fragment length polymorphism assays in a diversified sample of 161 unrelated healthy Lebanese volunteers. RESULTS: The allele frequencies of CYP2C9 *2 and *3 were 0.112 and 0.096 respectively, whereas VKORC1-1639A was 0.528. Carriers of the CYP2C9 *2 or *3 represented 34.2% of the subjects, whereas those of the VKORC1-1639A represented 73.9%. CONCLUSION: Our data show no significant difference in the frequency of CYP2C9 allelic variants when compared to the Caucasian population, whereas the allelic frequency of VKORC1-1639A was very high. Over 50% of the Lebanese population seem to be carrying more than two independent risk alleles, and is therefore potentially at high risk of over-anticoagulation.

Prevalence of CYP2C19 polymorphisms in the Lebanese population.

Clopidogrel is one of the most commonly prescribed drugs, as its combination with low-dose aspirin is the recommended oral anti-platelet therapy, to prevent ischaemic events following coronary syndromes or stent placement. Numerous recent studies have shown that polymorphisms in the gene encoding the cytochrome P450 (CYP450) 2C19 enzyme (CYP2C19) contribute to variability in response to clopidogrel; patients with certain common genetic variants of CYP2C19 (2, 3) have a reduced metabolism of clopidogrel and have a higher rate of cardiovascular events or stent thrombosis compared to patients with the CYP2C19 (1) allele. CYP2C19 2 is most common in Caucasians, Africans and Asians while CYP2C19 3 has been found mostly in Asians. Since the prevalence of these variants in the Lebanese population has not yet been reported, our aim was to determine the genotypes of CYP2C19 in our population. CYP2C19 (1/2/3) variants were assessed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) assays in a representative sample of 161 unrelated healthy Lebanese volunteers. The allele frequencies of CYP2C19 2 and 3 were 0.13 and 0.03. Carriers of the CYP2C19 2 or 3 represented 24.2% of the subjects. Our data show no significant difference in the frequency of CYP2C19 allelic variants when compared to Caucasian populations and demonstrate that the application of the recent FDA recommendations would also be beneficial in Lebanon, allowing physicians to identify patients at high risk for atherothrombotic events, and eventually advising them to consider other antiplatelet medications or alternative dosing strategies in poor metabolizers.

Livedoid vasculopathy associated with combined prothrombin G20210A and factor V (Leiden) heterozygosity and MTHFR C677T homozygosity.

Livedoid vasculopathy (LV) is an occlusive thrombotic disease of lower extremities. A 34-year-old woman presented with 4-year history of recurrent necrotic and painful lesions with violaceous and purpuric border on both legs. Initial treatment with hydroxychloroquine, dapsone and prednisone were unsuccessful. Skin biopsy showed inflammatory infiltrate with epidermal necrosis. Prothrombin G20210A and factor V-Leiden heterozygosity, and MTHFR C677T homozygosity with hyperhomocysteinemia were confirmed. LV diagnosis was made; acetylsalicylic acid, folic acid, vitamin B12, and prednisone treatement resulted in complete healing. This is the first report on coexistence of prothrombin G20210A, factor V-Leiden, and homozygous MTHFR C677T with hyperhomocysteinemia in LV.

Association of selective HLA class II susceptibility-conferring and protective haplotypes with type 2 diabetes in patients from Bahrain and Lebanon.

The association of HLA class II with type 2 diabetes (T2DM) was investigated in Bahraini and Lebanese subjects. DRB1*070101 (Lebanese and Bahraini) and DQB1*0201 (Lebanese) were susceptibility-conferring alleles, and unique susceptibility-conferring/protective haplotypes were found in both patient groups. Regression analysis confirmed that DRB1*070101-DQB1*0201 (Bahraini) and DRB1*110101-DQB1*0201 (Lebanese) were susceptibility-conferring haplotypes.

Extended spectrum beta-lactamase producing Enterobacteriaceae in Lebanese ICU patients: epidemiology and patterns of resistance.

Our study aims to investigate and describe the epidemiology of the intestinal carriage of ESBL-PS in intensive care units of five Lebanese hospitals and to analyze the potential risk factors for the acquisition of these strains. At the same time, we intend to determine the patterns of susceptibility of these strains, exploring therefore the availability of alternative treatment. One thousand, four hundred forty-two fecal samples were collected between January 1, 2003 and March 31, 2003 from 378 patients admitted to the ICUs of five Lebanese tertiary care general hospitals located in different areas of Lebanon. ESBL production was detected by the double disk synergy test and antibiotic susceptibility of ESBL-producing strains as well as minimum inhibitory concentrations were determined. A paired case-control study was undertaken to identify risk factors for carriage of ESBL-PS. One hundred eighteen strains isolated from 72 subjects were identified as ESBL producers, including 95 (80.5%) E. coli, 16 (13.6%) Klebsiella pneumoniae, and 7 (5.6%) Enterobacter cloacae. A higher rate of multiple ESBL-PS carriage was described among these acquisition cases (21 double carriages and 3 triple carriages of ESBL-PS compared to only 1 double carriage of ESBL-PS at admission). In general, similar trends of susceptibility were observed in the different hospitals. As expected, the lowest MIC was observed with imipenem for all E. coli, Klebsiella, and Enterobacter isolates. Ciprofloxacin, followed by trimethoprim-sulfamethoxazole seem to be associated with the lowest susceptibility. In vitro susceptibility to cefoxitin for all isolates was 74.6%; more resistance was associated to ceftazidime (90.7%) than to cefotaxime (69.7%). Our data agree with other national and international reports showing the increase in ESBL-PS carriage in ICU patients. They demonstrate the endemic character of this carriage in Lebanese hospitals and the important risk factors including immunosuppression and evidence of ESBL infection. The highly resistant profile of ESBL-PS to antimicrobial agents available for treatment reflects the severity of this issue. The significance of this study resides in the direct correlation between our results and the nationwide increase in multi-drug resistant bacteria and the continuous change in bacterial resistance epidemiology. Our data may have an important impact on infection control policies in hospitals and on treatment of infectious diseases.

Prevalence of antibodies against hepatitis B virus and hepatitis C virus among blood donors in Lebanon, 1997-2003.

The prevalence of hepatitis B virus (HBV) antigens (HBsAg) and antibody to hepatitis C virus (anti-HCV) was determined among 16,084 blood donors (14,993 males; mean age, 31.7 +/- 8.2 years and 1084 females; mean age, 31.4 +/- 8.2 years) in the period 1997-2003. Of the donors screened, 149 were HBsAg positive (0.926%), and 65 were anti-HCV positive (0.404%). There was a steady decline in HBsAg prevalence from 1.56% (1997) to 0.33% (2003) and in anti-HCV from 1.22% (1997) to 0.16% (2003). Females had a higher prevalence of anti-HCV (P = .031) and HBsAg (P = .047). Results obtained are of value in light of the occurrence of HBV and HCV transmission by nonparenteral routes.

Factor V G1691A (Leiden) and prothrombin G20210A single-nucleotide polymorphisms in type 2 diabetes mellitus.

The association of the single nucleotide polymorphisms (SNPs) G1691A in coagulation factor V (FV)-Leiden and G20210A in prothrombin (PRT) genes with type 2 diabetes mellitus (T2DM) were analyzed in 112 T2DM patients (58 males, 54 females; mean age 55.24 +/- 13.5 years) and 249 healthy control subjects (118 males, 131 females; mean age 53.03 +/- 13.8 years). No association was found for FV-Leiden with T2DM, as the frequency of the G/G (82.1% vs. 85.5%), G/A (17.0% vs. 14.1%), and A/A (0.9% vs. 0.4%) genotypes was not different between patients and controls, respectively (P = 0.644). Similarly, lack of association of PRT G20210A with T2DM was seen among the population studied, and the frequency of the G/G (92.9% vs. 97.2%), G/A (6.3% vs. 2.8%), and A/A (0.9% vs. 0.0%) genotypes was similar among patients and controls, respectively (P = 0.094). Neither FV-Leiden nor PRT G20210A was associated with, and no evidence for interactions between these mutations was seen in, T2DM.

A case control study on the contribution of factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations to the genetic susceptibility of deep venous thrombosis.

BACKGROUND: Insofar as the inherited prothrombotic single nucleotide polymorphisms (SNPs) factor V G1691A (FV-Leiden), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR), C677T are inherited risk factors of venous thromboembolism (VTE), the aim of this study was to determine the prevalence of single and combined SNPs in 198 patients with documented deep venous thrombosis (DVT), and 697 control subjects, and to estimate the associated risks. METHODS: Factor V-Leiden, PRT G20210A, and MTHFR C677T were analyzed by PCR and restriction fragment length polymorphism (RFLP). RESULTS: The prevalence of the heterozygote and homozygous variants for FV-Leiden (52.02 vs. 14.78%, RR 6.28), PRT G20210A (19.2 vs. 3.6%; RR 6.38), and to a lesser extent the T/T genotype of MTHFR C677T (20.71 vs. 11.0%; RR 1.49) were higher among DVT patients vs. controls, respectively. Two or more SNPs were detected in 90 of 198 patients (45.5%) and in 60 of 697 controls (8.6%), with odds ratios of 16.754 for joint occurrence of FV-Leiden and PRT G20210A, 10.471 for FV-Leiden and MTHFR C677T, and 6.283 for PRT G20210A SNPs and MTHFR 677T/T. Logistic regression analysis showed a further increased odds for FV-Leiden in combination with PRT G20210A (85.198) or homozygous MTHFR C677T (81.133), and to a lesser extent for PRT G20210A in combination with homozygous MTHFR C677T (20.812). CONCLUSIONS: This indicates that FV-Leiden and PRT G20210A, more than MTHFR C677T, are important risk factors for DVT, and that the presence of more than one prothrombotic SNPs was associated with a significant risk of DVT.

Countrywide spread of community- and hospital-acquired extended-spectrum beta-lactamase (CTX-M-15)-producing Enterobacteriaceae in Lebanon.

A prospective study was carried out to assess the extent of carriage of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae at both hospital and community levels in Lebanon. A total of 1,442 fecal samples were collected from hospital-based patients and 58 from health care workers of six Lebanese tertiary care general hospitals located in different areas of Lebanon between January and March 2003. A total of 382 fecal samples were also collected from healthy subjects between April and June 2003. The samples analysis led to the identification of 118 strains as ESBL producers based on the synergistic effects between clavulanate and selected beta-lactams (ceftazidime and cefotaxime). These strains were isolated from 72 subjects: 61 patients, 2 health care workers, and 9 healthy subjects. One representative strain per subject was selected, and a total of 72 nonduplicate ESBL producers, including a high majority of Escherichia coli (n = 56), Klebsiella pneumoniae (n = 9), Enterobacter cloacae (n = 6), and Citrobacter freundii (n = 1), were characterized. The molecular analysis revealed that the majority of the strains (83%) express CTX-M-15 ESBL (pI 8.6). SHV-5a ESBL (pI 8.2) was produced by 18% of the strains. DNA macrorestriction analysis of ESBL-producing E. coli presented 38 different genotypes, revealing the absence of clonal link among these strains. In addition to the fact that the present study highlights the emergence and the countrywide dissemination of CTX-M-15-producing E. coli in Lebanon, it represents the first report of an SHV-5a-producing C. freundii.

Contribution of selective HLA-DRB1/DQB1 alleles and haplotypes to the genetic susceptibility of type 1 diabetes among Lebanese and Bahraini Arabs.

CONTEXT: Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility of type 1 diabetes (T1D), and both susceptible and protective alleles were implicated with its pathogenesis, which varies among various ethnic/racial groups. OBJECTIVE: This study investigated the heterogeneity in HLA class II haplotypes distribution among Bahraini and Lebanese T1D patients. DESIGN: This was a cross-sectional retrospective study. SETTING: The study was conducted at primary care private and public health centers. PATIENTS AND OTHER PARTICIPANTS: Subjects comprised 126 T1D patients and 126 healthy controls from Bahrain and 78 Lebanese T1D patients and 111 control subjects. INTERVENTION(S): There were no interventions. RESULTS: Although Lebanese and Bahraini patients share DRB1*030101, DQB1*0201 as susceptible and DRB1*100101 and DQB1*030101 as protective alleles, DRB1*040101 was an additional susceptible allele in Bahraini patients, and DRB1*130701 and DQB1*050101 were additional susceptible and protective alleles in Lebanese, respectively. DRB1*030101-DQB1*0201 was susceptible, whereas DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 were protective haplotypes in Bahraini and Lebanese. DRB1*040101-DQB1*0302 and DRB1*040101-DQB1*050101 displayed different associations: they were protective in Lebanese but susceptible or neutral among Bahrainis. Whereas the frequency of homozygous DRB1*03011-DQB1*0201 was higher in Bahraini and to a lesser extent Lebanese patients, homozygous DRB1*110101-DQB1*030101 was significantly more frequent in Lebanese but not Bahraini controls, whereas DRB1*030101-DQB1*0201/DRB1*040101-DQB1*0201 was the major genotype among Bahraini patients but not Lebanese subjects in whom it was present at very low frequencies. CONCLUSION: In view of these differences between Bahraini and Lebanese, this demonstrates that the contribution of HLA class II to the genetic susceptibility to T1D must be evaluated with regard to specific HLA haplotypes and also ethnic origin and racial background.

Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T gene polymorphism in angiographically documented coronary artery disease.

BACKGROUND: Single point mutations in the genes coding for factor V [G1691A; Leiden], prothrombin [PRT; G20210A], and methylenetetrahydrofolate reductase [MTHFR, C677T] were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of coronary artery disease [CAD] remains controversial. The aim of the study was to examine the association of these mutations in CAD. METHODS: A total of 96 patients with angiographically-demonstrated CAD [mean age 55.3 +/- 11.3], and 404 healthy subjects [mean age 50.7 +/- 8.9] were recruited into the study. Fasting plasma homocysteine was determined by HPLC, and genotype analysis was assessed by PCR-RFLP. RESULTS: The carrier frequency of factor V-Leiden (14.6% vs. 15.1%, p = 0.617) and PRT G20210A (3.1% vs. 3.0%; p = 0.936) were similar between patients and controls, respectively. In contrast, the frequency of the MTHFR variant C677T was 71.9% among patients compared with 45.5% in controls (p < 0.001), of which the T/T genotype was significantly higher among patients (31.3%) than controls (4.5%; p < 0.001). Significantly higher homocysteine levels were seen among T/T genotype in both groups compared to non-T/T carriers (p < 0.05), and among patients compared with controls (18.47 +/- 3.73 micromol/L vs. 16.28 +/- 4.16 micromol/L). In addition, the coexistence of MTHFR C677T with FV-Leiden was seen in 10.4% of CAD patients compared 6.9% of controls (p = 0.001). CONCLUSION: While results from this study clearly demonstrate a strong association of hyperhomocysteinemia and homozygosity of the MTHFR C677T, but not FV-Leiden or PRT G20210A, mutations with confirmed CAD, they also suggest a potential role for factor V-Leiden in MTHFR C677T carriers.

Differences in the frequency of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene among the Lebanese population.

In view of its role in precipitating mild hyperhomocysteinemia as well as being a risk factor for vascular thrombosis, we investigated the frequency of the C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene among 589 healthy Lebanese subjects by PCR-RFLP analysis (HinfI digestion) and compared them with those of other countries of Caucasian and non-Caucasian origin. The prevalence of the mutated homozygous (T/T) and heterozygous (C/T) C677T MTHFR genotype was 11.04% and 39.73%, respectively, giving an allele frequency of 0.309. While the prevalence of the T/T genotype was similar with respect to gender, higher prevalence was noted among Christian (13.08%) compared to Moslem (7.66%) subjects (P < 0.001), and heterogeneity in its distribution was seen in the different Lebanese provinces, and was directly related to the Christian/Moslem composition of each province. The distribution of the MTHFR C677T in Lebanon is unique with regard to its higher occurrence among Christians compared to Moslems, adding to the existing body of literature on the heterogeneity of its prevalence and distribution.

Outbreak of Burkholderia cepacia bacteremia traced to contaminated hospital water used for dilution of an alcohol skin antiseptic.

OBJECTIVE: To identify the source of an epidemic of Burkholderia cepacia bloodstream infections during 7 years (411 episodes in 361 patients). DESIGN: Outbreak investigation. SETTING: A 250-bed university hospital in Beirut, Lebanon. METHODS: Matched case-control and retrospective cohort studies, and microbiological surveillance and polymerase chain reaction-restriction fragment length ascertainment were employed. Special media and filtration techniques were used to isolate organisms from water and diluted alcohol solutions. RESULTS: In a group of 50 randomly selected case-matched patients from 1999, the positive blood cultures were concomitant with fever in 98%, intravenous phlebitis in 44%, and recurrent bacteremia in 20%. Fever disappeared approximately 6 hours after intravenous catheter removal. Polymerase chain reaction-restriction fragment length polymorphism revealed strain homogeneity in patient, water, and alcohol isolates. Contaminated tap water had been used to dilute alcohol for skin antisepsis and for decontamination of the caps of heparin vials. Only sporadic cases directly attributable to breach of protocol were reported after single-use alcohol swabs were substituted. CONCLUSION: This is potentially the largest single-source nosocomial bloodstream infection outbreak ever reported, and the first report of an alcohol skin antiseptic contaminated by tap water as a source for nosocomial bacteremia.