Cell free fetal DNA in the plasma of pregnant women with preeclampsia.

OBJECTIVE: Insufficient cytotrophoblast invasion to the myometrium is associated with preeclampsia, especially with the early-onset preeclampsia (before 34 gestational weeks). Several investigations have marked changes in the concentration of cell free fetal DNA in the maternal circulation of women with preeclampsia. However, these studies were not performed for early or late preeclampsia subgroups individually. The present authors planned to determine the levels of the cell free both fetal and maternal DNA in the maternal circulation in early preeclampsia subgroup and compare it with normotensive control cohort. MATERIALS AND METHODS: A total of 16 women; eight of these with preeclampsia and eight normotensive control cohorts with singleton male pregnancy between 28 and 32 gestational weeks were included in the study. Real-time PCR analysis was performed for determining the circulating cell free DNA levels. RESULTS: Cell free fetal DNA concentrations were higher in early preeclamptic women than control subjects. The authors found no statistically significant difference in each levels of maternal and total DNA between hypertensive and normotensive groups. CONCLUSIONS: The present findings suggest that the levels of cell free fetal DNA in maternal circulation were higher in pregnancies which are complicated with early preeclampsia than normotensive controls.

Association of methylenetetrahydrofolate reductase C677T-A1298C polymorphisms with risk for esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis.

Incidence of the esophagus adenocarcinoma has been dramatically increasing in Western countries since the last decade. Gastroesophageal reflux disease and Barrett's esophagus are risk factors for adenocarcinoma. Methylenetetrahydrofolate reductase (MTHFR) genes play a key role not only in folate metabolism but also in esophagus, stomach, pancreatic carcinoma, and acute leukemias. Studies have suggested that genetic polymorphisms of MTHFR (C677T) may clarify the causes and events involved in esophageal carcinogenesis. In this study, we evaluated MTHFR C677T and A1298C polymorphisms, and vitamin B12, folate, and plasma homocystein levels in patients with esophageal adenocarcinoma (EAC), Barrett's esophagus (BE), chronic esophagitis, and healthy controls (n = 26, n = 14, n = 30, and n = 30, respectively). The mean age of patients in the EAC and BE groups was significantly higher compared with the control group (P < 0.001, P = 0.003, respectively). In all patient groups, serum folate levels were significantly lower than that of the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). There was no statistically significant association between folate levels and MTHFR gene polymorphisms. No differences were found in terms of MTHFR gene polymorphisms, homocystein, and B12 levels among the groups. MTHFR gene polymorphisms and folate deficiency are not predictors of early esophageal carcinoma. However, further studies using larger series of patients are needed to evaluate the effect of genetic polymorphisms in the folate metabolic pathway and to clarify the role of folate deficiency and folate metabolism in the development of esophagus adenocarcinoma.

New treatment strategy and assessment questionnaire for external auditory canal pruritus: topical pimecrolimus therapy and Modified Itch Severity Scale.

OBJECTIVE: We aimed to compare the efficacy of topical pimecrolimus versus hydrocortisone in treating external auditory canal pruritus, using the Modified Itch Severity Scale as an assessment tool. METHODS: We included in the study 40 patients with isolated itching of the external auditory canal who had not received any benefit from previous topical and systemic treatments. Topical 1 per cent pimecrolimus or topical hydrocortisone was applied to each patient's external auditory canal for three months. A Modified Itch Severity Scale was developed and used to assess treatment response. RESULTS: Compared with itching scores on initial assessment, the scores of patients receiving topical pimecrolimus had decreased by 52.3 per cent by the third week of treatment and by 77.6 per cent by the third month, whereas the scores of patients receiving topical hydrocortisone had decreased by 34.4 per cent by the third week and by 64.2 per cent by the third month. CONCLUSIONS: Topical pimecrolimus appears to be as effective as topical hydrocortisone in relieving external auditory canal pruritus. We used a novel scoring system, the Modified Itch Severity Scale, to evaluate external auditory canal pruritus; this is the first self-reporting questionnaire for the quantification of external auditory canal pruritus severity. Further studies are needed to validate this scoring system.

Results for audiology and distortion product and transient evoked otoacoustic emissions in patients with systemic lupus erythematosus.

UNLABELLED: The aim of the current study was to investigate hearing loss and cochlear function in patients with systemic lupus erythematosus, using audiology, distortion product otoacoustic emissions and transient evoked otoacoustic emissions. STUDY DESIGN: Prospective, case-control study. METHODS: The study included 26 randomised patients with systemic lupus erythematosus (52 ears) and 30 healthy control subjects (60 ears). Pure tone audiometry was performed at 250 and 500 Hz and at 1, 2, 4, 6, 8, 10, 12, 14 and 16 kHz. Distortion product otoacoustic emissions and transient evoked otoacoustic emissions were measured using Biologic System equipment with Scout Acoustic Emissions System software. RESULTS: The distortion product otoacoustic emission signal responses were significantly different only at 750 Hz, while the distortion product otoacoustic emission signal-noise ratios were significantly different at 750 Hz and 6 kHz (p < 0.05), comparing patients and controls. The transient evoked otoacoustic emission signal-noise ratios were significantly different at 2 and 3 kHz, comparing patients and controls (p < 0.05). The transient evoked otoacoustic emission total signal-noise ratios were significantly different, comparing patients and controls (p < 0.05). In addition, the pure tone audiometry thresholds were significantly different at 250 and 500 Hz and at 1, 2, 10 and 12 kHz, comparing patients and controls (p < 0.05). CONCLUSION: Our findings do not completely agree with those of previous temporal bone histopathological studies. However, our results do support a general picture of low frequency hearing loss in systemic lupus erythematosus patients. We consider these results to be related to endolymphatic and cochlear hydrops, and we suggest that electrocochleography could be performed in further studies for clarification of this subject.

An unusual cause of dysphonia: laryngeal verruca vulgaris.

PROBLEMS/OBJECTIVES: Verruca vulgaris of the larynx (VVL) is an uncommon lesion with clinical and histopathological features that are easily misdiagnosed as verrucous carcinoma, and thus may lead to unnecessary surgery. This case study investigated clinical and pathological features that might distinguish VVL from other keratotic laryngeal lesions. METHODOLOGY: A 35-year-old man presented with a 3-month history of progressive hoarseness and superficial, keratotic, vocal cord lesions. The verrucoid configuration of the surface and lack of nuclear atypia enabled treatment by local excision. The biopsied lesion was sectioned and examined by immunohistochemistry, and in situ hybridization. RESULTS: The patient was disease-free up to 1 year and 6 months after surgery. The exophytic, keratotic lesions of the larynx had features of cutaneous verruca vulgaris. No human papilloma virus was detected. CONCLUSIONS: We described histopathological features of VVL that will facilitate its distinction from laryngeal keratosis, squamous papillomas, verrucous hyperplasia, and verrucous carcinoma.

Peak expiratory flow monitoring to screen for asthma in patients with allergic rhinitis.

AIM: To investigate the benefit of using peak expiratory flow (PEF) monitoring to screen for asthma in allergic rhinitis patients. METHODS: Eighty-nine consecutive patients with allergic rhinitis but never assessed for asthma were included in this prospective study. Their allergic status was determined by skin prick tests. All of the subjects filled in a questionnaire on asthma-like symptoms. If they reported such symptoms, pulmonary function tests were carried out. Then, PEF was checked twice daily for 3 weeks. RESULTS: Thirty-six percent of our study group were male and 64% were female patients with a mean (SD) age of 36.3 (14.0) years. Skin prick tests were positive to grass mixture in 71 (79.8%) patients, to tree mixture in 51 (57.3%), to mite in 46 (51.7%), and to epidermal mix in 26 (29.2%) patients. Thirty-six patients (41%) reported 3 or more asthma symptoms. Lung function test results for these 36 patients showed obstruction for 11.1% (4 patients); the remaining patients (88.9%) had normal function parameters. The subjects who reported 3 or more asthma symptoms but had normal lung function monitored their PEF for 3 weeks. Sixteen (50%) patients from this group and the 4 patients with demonstrated airway obstruction had more than 20% diurnal variation in PEF. These 20 patients' asthma symptoms disappeared after they received 3 months of low-dose inhaled corticosteroid therapy. CONCLUSION: It is necessary to look for asthma in patients suffering from allergic rhinitis. PEF monitoring is a low-cost, objective approach to asthma diagnosis that can be performed by a patient with allergic rhinitis even if spirometry is normal. Knowledge of this technique is of utmost importance because delay in diagnosis will result in the unsatisfactory treatment of the disease.

Endovascular stent-graft treatment of type A dissection: case report and review of literature.

We report a successful endovascular stent-graft treatment of a patient with type A dissection with primary entry tear at the ascending aorta. Simultaneous coronary stenting was performed. A literature review was performed and the possible use of endovascular treatment for ascending aortic dissections is discussed.

Hybrid treatment of ascending aortic pseudoaneurysm: endovascular stent-graft placement and extraanatomic reconstruction without sternotomy.

Conventional surgical repair of ascending aortic pseudoaneurysms following prior cardiac operations is performed with a high operative mortality. We report a 67 year old female patient with an ascending aortic pseudoaneurysm detected 3 years after coronary bypass surgery. The patient was treated with ascending aortic endovascular stent graft placement and extraanatomic reconstruction of supraaortic branches without using sternotomy.

Evaluation of hearing loss in patients with ankylosing spondylitis.

AIMS: The aim of this study was to investigate hearing loss in patients with ankylosing spondylitis. STUDY DESIGN: Prospective, case-control study. METHODS: Fifty-nine ankylosing spondylitis patients (118 ears) and 52 healthy control subjects (104 ears) were included. Pure tone audiometry at 250, 500, 1000, 2000, 4000 and 6000 Hz and immittance measures, including tympanometry and acoustic reflex tests, were performed in the patients and controls. RESULTS: Sensorineural hearing loss was found in 21 patients (35.5 per cent), bilateral in 15 patients and unilateral in six. Pure tone thresholds significantly differed between patients and controls at all frequencies (p<0.05). There was no statistically significant difference between the right and the left ears' thresholds at all frequencies, except at 4000 Hz in ankylosing spondylitis patients. The right ears' thresholds were higher than those of the left ears. Patients' pure tone average (PTA) thresholds were significantly different from those of controls in all three PTA groups (i.e. 250 Hz; 500, 1000 and 2000 Hz; and 4000 and 6000 Hz) (p<0.05). The differences were most prominent in the higher frequencies. CONCLUSION: Our findings suggest a decreased hearing level in ankylosing spondylitis patients, mostly at high frequencies, although the pure tone thresholds of patients and controls significantly differed at all frequencies.

EuroSCORE overestimates the cardiac operative risk.

INTRODUCTION: It was the purpose of our study to assess the validity of EuroSCORE (European system for cardiac operative risk evaluation) in our patient population. MATERIALS AND METHODS: Between March 1999 and August 2001, information on risk factors and mortality was collected for 1123 consecutive adult patients undergoing heart surgery with cardiopulmonary bypass. EuroSCORE was used for risk stratification. Mean age +/- standard deviation was 58.6 +/- 10.9 and 29.1% of the patients were female. The area under the receiver operating characteristic (ROC) curve was calculated as an index for the predictive value of the scoring system. RESULTS: The area under the ROC curve was 0.824 for all patients and 0.828 for the isolated CABG subgroup which shows an excellent predictive ability. When the scoring system was applied in low, medium, and high risk groups, there was no overlap between 95% confidence intervals of observed and expected mortality in all three groups both for the isolated CABG cases and for all patients. Decreased left ventricular ejection fraction, emergent operation, and preoperative unstable angina requiring i.v. nitrate treatment were significant predictive variables for early mortality. CONCLUSION: EuroSCORE is a simple and objective system for predicting the risk of heart surgery. The predictive power of the EuroSCORE is excellent, however it seems that mortality is considerably overestimated by this score.

The effect of lipoprotein-a on thrombolytic therapy and spontaneous reperfusion in acute myocardial infarction. A comparative study.

BACKGROUND: To evaluate the role of serum lipoprotein-a (Lp-a) levels on the success of thrombolytic therapy (TT) in patients with acute myocardial infarction (MI). PATIENTS: 56 patients randomly allocated into 2 groups (A and B) with an approximately 1 to 2 ratio. Group A consisted of 18 patients who received 1,5 million IU streptokinase. Group B: 38 patients receiving 100 mg t-PA totally and Group C: 22 patients who did not received any TT as controls. All patients had undergone coronary angiography in the first 7 days and the degree of TIMI flow was determined in the infarct related artery with TIMI-0 and I being considered as unsuccessful perfusion, whereas TIMI-II and III as successful. Lp-a level gs;30 mg/dl was considered as high Lp-a level. RESULTS: Patency rates were similar in Group A and B, in cases with high or low Lp-a levels (p>0.05 for both). In Group C patency rate was found significantly higher in patients with high Lp-a level compared to patients with low Lp-a (p<0.01). Lp-a level in Group C was similar with Group A and B (p>0.05). The time interval for coronary angiography was similar in all groups (p>0.05 for all). CONCLUSIONS: Lp-a level does not effect the reperfusion outcome of TT in patients with MI. However in those patients who not received TT, spontaneous reperfusion rate was found significantly higher in patients with low Lp-a level compared to those with high Lp-a level.

Estimation of left ventricular end-diastolic pressure by color M-mode Doppler echocardiography and tissue Doppler imaging.

OBJECTIVES: The aim of this study was to estimate left ventricular end-diastolic pressure (LVEDP) noninvasively by tissue Doppler imaging and color M-mode echocardiography. MATERIAL AND METHODS: We studied 3 groups of patients who were proven by angiography to be free of significant coronary artery lesions (<40% stenosis) with an LVEDP < 10 mm Hg (group A: n = 24; 16 men, 18 women; mean age +/- SD = 55 +/- 13 years), an LVEDP of 10 to 15 mm Hg (group B: n = 21; 17 men, 4 women; mean age 56 +/- 11 years), or an LVEDP > 15 mm Hg (group C: n = 35; 20 men, 15 women; mean age 58 +/- 9 years). Tissue Doppler imaging of the lateral mitral annulus and color M-mode imaging of the mitral valve in the apical 4-chamber view were obtained with an echocardiographic system. Early and late diastolic velocities (Em and Am, respectively), Em deceleration time (EmDT), Am time (Am-t), and mitral propagation velocity time delay (VpDT) were measured in each patient. RESULTS: In group A, sensitivity and specificity for EmDT < or = 100 ms, Am-t < or = 90 ms, Em/Am > or = 1, and VpDT < or = 45 ms were found to be 0.57 and 0.89, 0.66 and 0.88, 0.86 and 0.92, and 0.73 and 0.89, respectively. In group B, sensitivity and specificity for EmDT 100 to 120 ms, Am-t 90 to 110 ms, Em/Am 1 to 0.5, and VpDT 45 to 60 ms were found to be 0.57 and 0.84, 0.69 and 0.82, 0.66 and 0.75, and 0.55 and 0.83, respectively. In group C, sensitivity and specificity for EmDT > 120 ms, Am-t > 110 ms, Em/Am < 0.5, and VpDT > 60 ms were found to be 0.88 and 0.81, 0.71 and 0.80, 0.86 and 0.72, and 0.78 and 0.86, respectively. CONCLUSION: The EmDT, Am-t, Em/Am, and VpDT measurements obtained noninvasively by left ventricular tissue Doppler imaging and mitral flow propagation velocity were found to be useful in the estimation of LVEDP.

Coronary artery stabilization causes endothelial damage: an electron microscopic study on dogs.

In recent years, to protect patients from adverse effects of cardiopulmonary bypass, off-pump coronary artery bypass operations are performed. In these operations, effective coronary artery immobilization is the standard for a fine anastomosis. This is usually maintained with the help of prolene immobilization sutures, bulldog occluders or mechanical epicardial devices. The aim of this study is to show whether these stabilization devices cause any damage to the coronary artery endothelium. Sixteen dogs are included in this study and are divided into four groups. The control group consisted of one dog (Group I) and different immobilization techniques are applied to the other groups, which were five dogs each (Groups II, III, and IV). Coronary artery biopsies are obtained, then the samples are studied under scanning electron microscope (SEM) for endothelial injury and all samples are scored. Among the techniques used, bulldog occluders caused less injury on the coronary endothelium than the prolene sutures.

Relation between the insertion/deletion polymorphism of the angiotensin I converting enzyme gene and restenosis after coronary stenting.

BACKGROUND: Observations with intravascular ultrasound demonstrated that neointimal hyperplasia is the predominant factor responsible for in-stent restenosis. Experimental data suggest that angiotensin I converting enzyme (ACE) plays a role in the thickening of neointima after balloon denudation. Insertion/deletion (I/D) polymorphism of the ACE gene is significantly associated with plasma level of ACE and subjects with D/D genotype have significantly higher plasma levels of ACE than normal. OBJECTIVE: To investigate whether this polymorphism influences the risk of restenosis after coronary stenting. METHODS: We genotyped 158 patients who had undergone single-vessel coronary stenting for the ACE I/D polymorphism. RESULTS: Of the 158 patients, 56 (35%) had the D/D genotype, 71 (45%) had the I/D genotype and 31 (20%) had the I/I genotype. Prevalences of genotypes were compatible with Hardy-Weinberg equilibrium and distributions of ACE genotype among patients and 132 healthy controls from the same geographic area did not differ. At follow-up (after a median duration of 5.4 months), overall rates of angiographic restenosis and of revascularization of target lesion (RTL) were 32.3 and 22.8%, respectively. Of 51 patients with angiographic restenosis, 31 (60.8%) had focal and 20 (39.2%) had diffuse patterns of restenosis. Diffuse in-stent restenosis was significantly more prevalent among patients with D/D genotype (P = 0.016). Multiple stepwise logistic regression analysis identified ACE I/D polymorphism as the independent predictor of angiographic restenosis and RTL. Relative risk of angiographic restenosis was 6.29 [95% confidence interval (CI), 1.80-22.05, P = 0.0004] for D/D genotype and 3.88 (95% CI 1.11-13.12, P = 0.029) for I/D genotype, whereas relative risk of RTL was 7.44 (95% CI 1.60-34.58, P = 0.01) for D/D genotype and 3.88 (95% CI 0.083-18.15, P = 0.085) for I/D genotype. CONCLUSIONS: The ACE I/D polymorphism is significantly associated with risk of angiographic and clinical restenosis after coronary stenting. Angiographic pattern of restenosis is also significantly associated with I/D polymorphism, diffuse type being more prevalent among subjects with D/D genotype.

Molecular alterations in the TP53 gene of peripheral blood cells of patients with chronic myeloid leukemia.

The TP53 gene has been extensively studied in patients with chronic myeloid leukemia (CML), both in chronic phase and in blast crisis. Mutations in the gene were found in up to 30% of the patients, especially among those in blast crisis. We report the results of an analysis of 29 blood samples from CML patients: 8 samples from chronic phase patients, 8 from patients in the accelerated phase, and 13 from patients in blast crisis. By using genomic DNA, we sequenced PCR products of the coding exons and most introns of the TP53 gene, finding genetic changes in 30% of the blast crisis samples and 12% in chronic phase. All mutations were found in introns and were previously unreported. Immunocytochemical studies revealed accumulation of TP53 in blood cells of samples both from chronic phase and blast crisis patients. Since these samples had no TP53 mutations, we believe that wild type TP53 accumulates in blood cells of CML patients. Our results, therefore, indicate that molecular changes in coding regions of the TP53 gene are rare. The significance of the abundance of intronic changes should be investigated further. Accumulation of wild type TP53 in CML cells may indicate an additional mechanism involving this gene in the pathogenesis of this disease.

Effects of hypothermia on blood endogenous endotoxin levels during cardiopulmonary bypass.

Endotoxin activates white blood cells and complement and produces a spectrum of clinical syndromes ranging from fever to septic shock. Although production of endogenous endotoxemia during cardiopulmonary bypass (CPB) has recently been reported, the role of hypothermia on endotoxemia is not clear. In this study, we evaluated the effects of moderate (24-28 degrees C) and mild (32-34 degrees C) hypothermia on blood endotoxin levels. The study population consisted of 20 patients who underwent coronary artery bypass grafting (CABG) with CPB. Moderate systemic hypothermia was applied during aortic cross-clamping in ten patients (group 1) and mild hypothermia in the remaining ten patients (group 2). The mean rectal temperatures were 26.8 +/- 1.2 degrees C in group 1 and 33.8 +/- 0.8 degrees C in group 2. The blood samples for endotoxin level measurements were obtained before CPB, during aortic cross-clamping, immediately after the release of the cross-clamp, 20 minutes after the release of the cross-clamp, after CPB, and 2 hours postoperatively. There were no endotoxins in any of the samples before CPB, but it was detected after CPB in both groups. The endotoxin levels were significantly higher in group 1 than in group 2. The present study suggests that when hypothermia is the technique of choice, the deleterious effects of endotoxemia on patients with comorbidity must be considered.

Intermittent aortic cross-clamping and cold crystalloid cardioplegia for low-risk coronary patients.

BACKGROUND: Blood cardioplegic strategies have been shown to increase myocardial oxygen uptake, replenish depleted energy stores, and improve myocardial function and survival in the high-risk subset of patients. However, the superiority of these techniques over intermittent aortic cross-clamping and crystalloid cardioplegia in low-risk patients is still controversial. METHODS: This study consisted of two parts. In the first part, we assessed the results of a recent cohort of 399 consecutive low-risk patients undergoing their first coronary artery bypass grafting between 1993 and 1995 using cold crystalloid cardioplegia (n = 128) and intermittent aortic cross-clamping (n = 271). In the second part of the study, 40 consecutive low-risk patients undergoing elective first time coronary artery bypass grafting were randomly divided into two equal groups. One group received cold crystalloid cardioplegia and the other group had myocardial management with intermittent aortic cross-clamping. The two groups were compared with respect to hemodynamic, biochemical and ultrastructural changes. RESULTS: The overall mortality rate, the perioperative myocardial in the need for intraaortic balloon pumps, and the need for inotropic agents were 0.25%, 1.5%, 1%, and 5.8%, respectively. No significant differences were observed between the groups with respect to these clinically defined end points. CONCLUSIONS: Both intermittent aortic cross-clamping and cold crystalloid cardioplegia techniques may be used safely in low-risk patients undergoing first-time coronary artery bypass grafting.