Genetics analysis with down syndrome and histopathological examination of buccal epithelial cells / Análisis genético y examen histopatológico de las células epiteliales bucales en pacientes con síndrome de down

Down syndrome is primarily caused by trisomy of chromosome 21. We reviewed cytogenetic studies performed on 1048 patients who were referred to the Cytogenetics Unit at Dicle University Hospital, Diyarbakir, Southeast Turkey, between 2000 and 2009. The cases were grouped according to the reason of referral for cytogenetic analysis. The highest frequencies of abnormal karyotypes were found among cases that were referred due to suspicion of Down syndrome (84.8 percent). For histologic examination to persons with Down syndrome and normal, buccal mucosa smear was prepared by rubbing. Down syndrome are disabled and control groups were compared statistically buccal epithelial cells and nuclei (p<0.05). Periphery of the nucleus in some patients with Down's syndrome, while the bud structures in the form of micronuclei was observed in the karyolytic cells.

El síndrome de Down es causado principalmente por la trisomía del cromosoma 21. Se revisaron los estudios citogenéticos realizados en 1.048 pacientes que fueron remitidos a la Unidad de Citogenética del Dicle University Hospital, Diyarbakir, sudeste de Turquía, entre los años 2000 y 2009. Los casos se agruparon de acuerdo a la razón de referencia para el análisis citogenético. Las frecuencias más altas de cariotipos anormales se encontraron ent los casos que fueron remitidos por sospecha de síndrome de Down (84,8 por ciento). Para el estudio histológico de las personas con y sin síndrome de Down, se realizó el frotis de mucosa oral por hisopado. Los grupos con síndrome de Down y de control (sin síndrome) se compararon estadísticamente en relación a las células epiteliales orales y los núcleos (p <0,05). Se observaron núcleos periféricos en algunos pacientes con síndrome de Down, mientras que estructuras de tipo brotes en la forma de micronúcleos se observaron en las células cariolíticas.

The insertion/deletion polymorphism in the ACE gene and chronic obstructive pulmonary disease.

An insertion/deletion (I/D) polymorphism was identified in intron 16 of the gene encoding the human angiotensin I-converting enzyme (ACE), a candidate gene for chronic obstructive pulmonary disease (COPD). We investigated the relationship between this polymorphism in the ACE gene and the risk of developing COPD. Sixty-six COPD in-patients and 40 non-smoking control individuals were recruited for this study. The distribution of ACE genotypes in these individuals was studied. The frequencies of ACE genotypes were found to be 47.0% for DD, 30.3% for ID, and 22.7% for II in the COPD group and 32.5% for DD, 47.5% for ID, and 20.0% for II in the control group. The allele frequencies were found to be 0.62% for the D allele and 0.38% for the I allele in the COPD group and 0.56% for the D allele and 0.44% for the I allele in the control group. A significant difference was found between I and D allele frequencies (P < 0.05) of the study and control groups. Our results suggest that this ACE polymorphism may be associated with the development of COPD.

Effect of losartan on circulating TNFalpha levels and left ventricular systolic performance in patients with heart failure.

BACKGROUND: Tumor necrosis factor alpha (TNFalpha) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFalpha levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFalpha levels and ejection fraction (EF) in patients with congestive heart failure. METHODS: Forty patients with heart failure and EF < or = 40% were enrolled into the study. All of the patients have been given diuretic and digitalis therapy. Twenty patients were given losartan (50 mg/d) (Group I, 10 women, 10 men, 12 dilated cardiomyopathy, 8 ischemic heart disease, mean age 64.9 + 8.9), and another 20 patients were not given losartan because of hypotension or renal dysfunction (Group II, 13 men, 7 women, 10 dilated cardiomyopathy, 10 ischemic heart disease, mean age 61.2 +/- 10.5). EF was measured at the initial evaluation and on the fifteenth day of the therapy by echocardiographic examination using an acoustic quantification method. Circulating TNFalpha levels were also measured at the initial evaluation and on the fifteenth day of therapy by the ELISA method. RESULTS: Losartan significantly increased EF and decreased TNFalpha (EF increased from 29.4 +/- 7.3% to 36.0 +/- 8.5%, P < 0.001, and TNFalpha decreased from 39.2 +/- 37.4 pg/ml to 27.0 +/- 30.0 pg/ml, P < 0.05). Changes in TNFalpha levels and EF were not found to be correlated (r=-0.28, P=0.24). However, in the control group, EF and TNFalpha levels were similar at baseline and at the fifteenth day (EF 31.4 + 8.1% vs 31.7 +/- 7.8%, P=0.1, and TNFalpha 91.5 + 86.0 pg/ml vs 110.0 +/- 80.7 pg/ml, P=0.1, respectively). CONCLUSIONS: Losartan improves left ventricular systolic function and decreases TNFalpha level. The decreased TNFalpha level seems to be independent of EF.

Association between the severity of heart failure and the susceptibility of myocytes to apoptosis in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Bcl-2 proto-oncogene, an inhibitor of apoptosis and Bax proto-oncogene, an inducer of apoptosis play critical roles in the molecular circuit controlling apoptosis in cardiac muscle. The ratio of Bax to Bcl-2 proto-oncogene determines survival or death after an apoptotic stimulus. We speculated that susceptibility of myocytes to apoptosis determined as the Bax/Bcl-2 ratio might vary with the severity of heart failure. METHODS AND RESULTS: We studied immunohistochemically 108 endomyocardial biopsy specimens from 30 patients with idiopathic dilated cardiomyopathy (mild heart failure, n=14; moderate or severe heart failure, n=16) with the use of Bcl-2 and Bax monoclonal antibodies. The expression of each protein was determined semiquantitatively as the fraction of myocytes labeled with specific monoclonal antibodies using a digital morphometric analysis system. Patients with mild heart failure showed significantly increased Bax/Bcl-2 ratio than the patients with advanced heart failure (1.59+/-1.26 vs. 0.34+/-0.43, P=0.002). The expression of Bcl-2 was found to be independent of the severity of heart failure whereas the expression of Bax was significantly higher in patients with mild heart failure compared to the patients with moderate or severe heart failure (52.1+/-29.3 vs. 21.6+/-22.4%, P=0.005). Additionally, Bax/Bac-2 ratio was inversely correlated with the mitral E-interventricular septum distance, left ventricular end-systolic and end-diastolic diameter. CONCLUSION: The susceptibility of myocytes to apoptosis is significantly increased in the early phase of heart failure but it decreases with worsening of the disease due to depressed expression of Bax onco-protein. Increased myocyte susceptibility to apoptosis may have a role in the transition from mild heart failure to severe in patients with idiopathic dilated cardiomyopathy.

Predictive value of mitral annular calcification for the diagnosis of coronary artery disease in patients with dilated cardiomyopathy.

Mitral annulus calcification (MAC) is an independent predictor of coronary artery disease (CAD). The present study was designed to determine whether an association exists between MAC and CAD in patients with dilated cardiomyopathy. Among the 286 patients with MAC on echocardiographic examination who underwent coronary angiography, 55 patients with echocardiographic findings of dilated cardiomyopathy (group I) were compared to 60 age-matched controls without MAC and an echocardiographic diagnosis of dilated cardiomyopathy (group II) who underwent coronary angiography during the same time. There were no differences in echocardiographic findings between two groups. The prevalence of CAD was higher in group I when compared to group II (74% vs 28%, p<0.001). With regard to severity of CAD, two-vessel, three-vessel, and left main coronary artery disease were found to be significantly frequent in group I (p<0.001). Multivariate analysis revealed that MAC (p=0.001), diabetes mellitus (p=0.048), and history of anginal chest pain (p=0.009) are the independent predictors for the presence of CAD in patients with dilated cardiomyopathy. In conclusion, MAC may be a marker for the presence of coronary artery disease in patients with dilated cardiomyopathy.

Methylenetetrahydrofolate reductase gene polymorphism and risk of premature myocardial infarction.

BACKGROUND: Elevated plasma homocysteine level is an independent risk factor for cardiovascular disease. A common mutation (nucleotid 677C-T) in the gene coding for methylenetetrahydrofolate reductase (MTHFR) has been reported to reduce the enzymatic activity of MTHFR and is associated with elevated plasma levels of homocysteine, especially in subjects with low folate intake. HYPOTHESIS: Methylenetetrahydrofolate reductase T/T genotype may be a risk factor for premature MI in Turkish population who are known to have low folate levels. METHODS: The study group was comprised of 96 men (aged <45 years) with premature myocardial infarction (MI) and 100 age- and gender-matched controls who had no history or clinical evidence of coronary artery disease (CAD) and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with HinfI, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. RESULTS: Allele and genotype frequencies among cases and control subjects were compatible with Hardy-Weinberg equilibrium. The frequencies of T/T, C/T, and C/C genotypes among patients with MI and control subjects were 15.6, 40.6, and 43.8%, and 5, 35, and 60%, respectively. Multivariate analyses identified smoking, MTHFR C/T polymorphism, diabetes mellitus, family history of CAD, and hypertension as the independent predictors of premature MI. Defining patients with non-T/T genotype (C/C and C/T combined) as reference, the relative risk of MI for subjects with T/T genotype was 5.94 (95% confidence interval: 1.96-18.02, p = 0.0016). CONCLUSIONS: Our findings suggest that C677T transition in the MTHFR gene may be a risk factor for premature MI in Turkish men.

Hyperhomocysteinemia and restenosis.

OBJECTIVE: This study was undertaken to assess the effect of plasma homocysteine level on angiographic restenosis 6 months after coronary angioplasty. METHODS: The plasma homocysteine level was measured in 100 consecutive patients at the time of coronary angioplasty, 56 patients who attended a 6-month follow-up angiogram being enrolled to the study; the 44 patients without a control coronary angiogram were not enrolled. Patients with and without angiographic restenosis were designated as groups A (n = 34) and B (n = 22) respectively. RESULTS: The baseline demographic (groups A and B), angiographic (groups A and B) and procedural characteristics were similar in both groups. The mean plasma homocysteine level (SD) was 15.2 (7.7) and 11.1 (2.5) mumol/l in groups A and B respectively (P = 0.007; 95% CI -6.9 to -1.1). With respect to the plasma homocysteine level, the upper and the lower thirds were compared by binary logistic regression (the lower third homocysteine level being < 10.6 mumol/l and the upper third homocysteine level > 14.1 mumol/l). The angiographic restenosis rate for the lower and upper tertiles was 47.4% and 89.5% respectively (P = 0.01; OR = 9.4; 95% CI 1.6-52.7). After adjustment for age and sex, the statistical significance did not change (P = 0.013; OR = 9.43; 95% CI 1.6-54.9). Even after adjustment for age, sex, smoking, hypertension, hypercholesterolemia, and diabetes mellitus, there was a statistically significant difference between the upper and lower tertiles (P = 0.008; OR = 41.3; 95% CI 2.6-635). CONCLUSION: Increased plasma homocysteine level and diabetes mellitus were independent risk factors for angiographic restenosis after percutaneous transluminal coronary angioplasty and coronary stenting.

A recurrent right heart thrombus in a patient with Behçet's disease.

We report the case of a patient who was admitted to the immunology unit of our medical facility. The patient had a history of recurrent oral ulcers, low-grade fever, weight loss, and fatigue. Echocardiographic examination revealed a right ventricular mass that was initially thought to be a myxoma in an unusual location, and the patient was sent to surgery. Surgery revealed the mass to be a thrombus. After 5 months of anticoagulation therapy, the patient was readmitted to our institution with the same complaints, and a right atrial thrombus was found on echocardiographic examination. After a careful reevaluation of the patient's history and episodes of recurrent oral and genital ulcers, as well as the papulopustular lesions found on his first admission to hospital, Behçet's disease was diagnosed. The patient received thrombolytic therapy with a regression of thrombus, and continued with immunosuppressive and anticoagulation therapy. Five months later, echocardiographic examination showed complete disappearance of thrombus.

How previous angina influences early prognosis of patients with acute myocardial infarction.

BACKGROUND: There is little information about how previous angina influences the complications of myocardial infarction and also contradictory results have been reported. OBJECTIVE: To compare the risk factors for myocardial infarction, complications, performance of left ventricle, and coronary angiography findings of patients who had suffered acute myocardial infarction with those for patients who had not. METHODS: We studied 600 patients diagnosed to have suffered acute myocardial infarction. Patients are grouped into those having previously had angina for at least 1 month preceding acute myocardial infarction (group I, n = 308 patients; 223 men and 85 women, mean age 60.4 +/- 10.6 years) and those who had not had angina (group II, n = 292 patients; 221 men and 71 women, mean age 58 +/- 9 years). The risk factors, complications (cardiogenic shock, heart failure, disturbances of rhythm and conduction, cardiac rupture and death), left-ventricle ejection fraction, and echocardiography and coronary angiographic findings during hospitalization are compared. RESULTS: There was no difference with respect to localization of myocardial infarction (anterior, inferior, and non-Q) between groups I and II (P> 0.05). Hypertension in members of group I was higher (P < 0.05). There was no statistically significant difference with respect to diabetes mellitus, hypercholesterolemia and cigarette smoking (P > 0.05). Heart failure (P< 0.05), cardiogenic shock (P< 0.01), incidence of ventricular premature systole > 3/min (P< 0.001) and atrial fibrillation (P< 0.05) were seen more prevalently in group II than they were in group I. There was no difference between the two groups with respect to bundle-branch blockage and third-degree atrioventricular blockage. Incidences of ventricular fibrillation, rupture of interventricular septum (IVS) and death in hospital were higher in group II (6.2 versus 3.6%, 6.2 versus 3.2%, 2.1 versus 0.6%) but were not statistically significant. Coronary angiography detected no statistically significant difference with respect to disease in left main coronary artery, and one-vessel and two-vessel disease; but three-vessel disease was significantly more prevalent in group II (P < 0.01). CONCLUSION: Heart failure, cardiogenic shock, arrhythmia (more than three VPS within 1 min and atrial fibrillation), and three-vessel disease detected by coronary angiography were found more often in the myocardial infarct patients without previous angina and these differences were statistically significant. In-hospital mortality and cardiac rupture were also found more commonly in this group and ejection fractions measured by echocardiography were found to be less, but these differences were statistically insignificant.

Bronchial hyperreactivity in patients with mitral stenosis before and after successful percutaneous mitral balloon valvulotomy.

OBJECTIVES: We aimed to identify the bronchial response to inhaled methacholine in patients with mitral stenosis (MS) and to clarify whether or not the bronchial hyperreactivity (BHR) is reversible after percutaneous mitral balloon valvulotomy (PBMV). PATIENTS AND SETTING: Thirty patients with MS and 28 age-matched healthy control subjects were prospectively evaluated with pulmonary function tests and methacholine challenge. The productive concentration of methacholine causing 20% decrease in FEV(1) (PC(20)) was calculated and used as a parameter of bronchial responsiveness. BHR was defined as a PC(20) < 8 mg/mL. Mean pulmonary artery pressure (PAP) and mean pulmonary capillary wedge pressure (PCWP) were recorded in all patients through a Swan-Ganz balloon-tipped catheter. Sixteen patients underwent PMBV, and a methacholine test was repeated after each procedure. RESULTS: Bronchial response to methacholine was significantly increased in patients with MS, so that 53% of them had BHR, whereas all control subjects were nonresponders. The PC(20) was closely correlated with the PAP (r = - 0.777; p < 0.001), PCWP (r = - 0.723; p < 0.001), and mitral valve area (MVA; r = 0.676; p < 0. 001). Balloon valvulotomy was successfully performed in all of the 16 patients, and the cardiac parameters (MVA, PAP, and PCWP) significantly improved after the procedure. In contrast, no significant changes were shown in pulmonary function test variables (total lung capacity, vital capacity [VC], FEV(1), and FEV(1)/VC). Although significant improvement was observed in the mean PC(20) values (from 4.97 +/- 5.24 to 7.47 +/- 6.96 mg/mL; p = 0.0006), BHR was completely eliminated in only one patient. CONCLUSIONS: Our data shows that BHR is fairly common among patients with MS, and severity of bronchial responsiveness is significantly correlated with the severity of MS. Moreover, PMBV leads to significant reduction in pulmonary congestion and a consequent improvement in BHR.

Restenosis after transluminal coronary angioplasty: a risk factor analysis.

BACKGROUND: Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a major problem limiting the long-term efficacy of the procedure. The purpose of this study was to determine whether risk factors such as cigarette smoking, diabetes mellitus, hypertension or hypercholesterolaemia correlate with restenosis after PTCA. We also studied the relationship between a history of previous myocardial infarction and the extent of coronary artery disease (single-, two- or three-vessel) with restenosis after coronary angioplasty. METHODS: A total of 360 patients underwent successful PTCA. Follow-up coronary angiograms were performed in 181 patients after a mean +/- SD period of 6 +/- 4 months. RESULTS: The restenosis rate was 49%. We divided the patients into two groups: 89 patients with restenosis (8 women and 81 men) and 92 patients with no restenosis (14 women and 78 men). Age, sex, a history of cigarette smoking, diabetes mellitus and a history of previous myocardial infarction were not associated with restenosis. Serum levels of triglyceride were also unrelated to the restenosis rate. Restenosis was associated with hypertension, low levels of high-density-lipoprotein cholesterol, high levels of low-density-lipoprotein cholesterol and high total cholesterol levels (P < 0.001). Patients with two-vessel or multivessel disease had significantly higher restenosis rates than patients with single-vessel disease (P < 0.001). CONCLUSION: Patients with hyperlipidaemia, hypertension and multi-vessel disease appear to be higher risk of recurrent restenosis.