Molecular Spectrum of β-Thalassemia Mutations in Northwestern Iran

β-Thalassemia (β-thal) is a hereditary autosomal disorder with decreased or absent β-globin chain synthesis. This study was designed to identify the common and rare β-thal mutations in the Azerbaijan provinces, Northwestern Iran, and to set up a prenatal diagnostic laboratory. One hundred unrelated patients with known β-thal major and intermedia, registered with the thalassemia clinics in the provincial capitals of Tabriz and Ardebil, were included. Mutations were studied in 200 chromosomes, by polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) and direct sequencing methods. We found 17 β-thal mutations in this region of Iran. The results showed that IVS-II-1 (G→A) was the most frequent mutation, comprising 21% of all mutations. Other common mutations were IVS-I-110 (G→A) 18%, frameshift codons (FSC) 8/9 (+G) 14.5%, FSC 8 (?AA) 8% and IVS-I-1 (G→A) 7.5%. This is the first comprehensive study in this region and could be useful for developing a β-thal molecular screening in Azerbaijan-Iran     

Coincidence of coronary artery disease and Tako-Tsubo cardiomyopathy

Tako-Tsubo cardiomyopathy (TTC) predominantly affects elderly people with a high prevalence of cardiovascular risk factors. Therefore, one would expect to encounter incidental coronary artery disease in a significant number of cases. In fact, the prevalence of mild coronary artery disease (CAD), by angiography, has been reported to be in the range of 30%-60%. Similarly, more severe stenotic lesions in at least one coronary vessel were incidentally found in 10%-35% of patients with the disease. Using intravascular ultrasound in a series of 10 patients with TTC, coronary atherosclerosis was demonstrable in all patients, although five patients had normal coronary angiograms. Therefore, TTC and CAD are not mutually exclusive disease entities. The incidental finding of coronary lesions, even if significant, should not automatically lead to a dismissal of the diagnosis of TTC. Rather, a case-by-case approach using additional imaging modalities should be endorsed.     

Study on JV Virus in Patients with Colon Cancer Type Adenocarcinoma

Colorectal cancer is the most repetitious malignancies with high mortality worldwide. JC virus (JCV) is ubiquitousPolyomavirus, with seroprevalence rates ranging from 70% to 90% in adult population. Recently the role of JCV havebeen reported in many malignant tumors worldwide. The association of JCV was reported in patients with colon andrectum cancers. Thus this study was conducted to evaluate the association of JCV DNA in patients with colon cancertype Adenocarcinoma. Material and Methods: A total of 120 formalin-fixed paraffin-embedded tissue blocks sampleswere collected including 20/40(50%) males, 20/40(50%) females patients with Colorectal Cancer(CRC), and 80 (50%males, 50% females) patients with benign tumor as a control. DNA was extracted for all the samples. Nested PCR wascarried out for detection of Vp1/T-Ag junction genome in JCV genome by Nested-PCR assay. Randomly, PCR productsof 6 samples were sequenced to analysis the partial JCV DNA. The phylogeny tree was constructed to determinehomology identity with other JCV. Results: 4/40(10%) samples of test group and 10/80 (12.5%) of control sampleswere positive for JCV DNA (P= 0.69). Out of 4 samples positive for JC DNA, 3(7.5%) were males and 1(2.4%) female(P=0.29). The frequency of JCV DNA in age group> 50 years was 4/32(10%), while in age group (0%) (p= 0.29). Conclusion: prevalence of JCV DNA was among 10% patients with CRC and 12.5% benign tumors(p=0.69). The distribution of JCV DNA was among 7.5% male and 2.5% female (p= 0.29). The frequency of JCVDNA was among 10% cases of age group >50 years and 0% of age group protein expression might explain the increased risk of colorectal cancer and requires further investigation.     

Two year follow-up after treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter

Background  We are presenting an extension of a previously published trial on the efficacy and safety of a paclitaxel-coated balloon in coronary ISR in a larger patient population and after a complete follow-up of 2 years. Methods  Hundred eight patients were enrolled in two separately randomized, double-blind multicenter trials on efficacy and safety using an identical protocol. Patients were treated by the paclitaxel-coated (3 μg/mm² balloon surface; Paccocath) or an uncoated balloon. The main inclusion criteria were a diameter stenosis of ≥70% and <30 mm length with a vessel diameter of 2.5–3.5 mm. The primary endpoint was angiographic late lumen loss in-segment. Secondary endpoints included binary restenosis rate and major adverse cardiovascular events (MACE). Results  Quantitative coronary angiography revealed no differences in baseline parameters. After six months in-segment late lumen loss was 0.81 ± 0.79 mm in the uncoated balloon group vs. 0.11 ± 0.45 mm (P < 0.001) in the drug-coated balloon group resulting in a binary restenosis rate of 25/49 vs. 3/47 (P < 0.001). Until 12 months post procedure 20 patients in the uncoated balloon group compared to two patients in the coated balloon group required target lesion revascularization (P = 0.001). Between 12 and 24 only two MACE were recorded, a stroke in the uncoated and a target lesion revascularization in the coated balloon group. Conclusion  Treatment of coronary ISR with paclitaxel-coated balloon catheters persistently reduces repeat restenosis up to 2 years. (ClinicalTrials.gov Identifier: NCT00106587, NCT00409981).     

Systemic and local levels of fetuin-A in calcific aortic valve stenosis

Calcific aortic valve stenosis, the most frequent heart valve disorder in developed countries, is an actively regulated process with similarities to bone formation. Fetuin-A has recently been identified as a potent circulating inhibitor of calcification. While several studies involving patients with end-stage renal disease have shown an association between low serum fetuin-A and cardiovascular calcification, nothing is known about fetuin-A serum levels in non-renal patients with calcific aortic valve stenosis. Furthermore, while fetuin-A has been localized in calcified areas of atherosclerotic arteries, data about fetuin-A deposition in stenotic aortic valves are unavailable at present. Serum fetuin-A levels were determined in patients with (n=31) and without (n=28) calcified aortic valve stenosis by ELISA. Creatinine and CRP levels were determined and glomerular filtration rate (GFR) was calculated by the MDRD formula. Immunohistochemistry for fetuin-A was performed on human calcified stenotic (n=14) and control (n=8) aortic valves using a monoclonal antibody. Serum fetuin-A levels were lower in patients with calcific aortic stenosis as compared to the control group (1.41+/-0.33 versus 1.57+/-0,27 mg/dl; p=0.046). This difference was particularly evident in individuals with a normal GFR >or=60 ml/min (1.36+/-0.24 versus 1.63+/-0.27 mg/dl; p=0.007). Furthermore, specific staining of fetuin-A was found in stenotic valves but not in healthy control valves. The data suggest a role of fetuin-A in the pathogenesis calcific aortic valve stenosis independently of the renal function and support the concept that mechanisms of calcium homeostasis are involved in the development of calcific aortic stenosis.     

Extent of myocardial hyperenhancement on late gadolinium-enhanced cardiovascular magnetic resonance correlates with q waves in hypertrophic cardiomyopathy.

PURPOSE: Despite several electrocardiographic, echocardiographic, electrophysiologic and pathologic studies, the cause of abnormal Q waves in patients with HCM remains unclear. Cardiovascular magnetic resonance (CMR) is a powerful in vivo diagnostic tool for evaluating cardiac morphology and function. We hypothesized that estimation of segmental and transmural extent of myocardial enhancement by late gadolinium enhancement (LGE) CMR could clarify the basis of Q waves. The purpose of this prospective study was to evaluate the morphological basis of abnormal Q waves in hypertrophic cardiomyopathy (HCM) as assessed by CMR. METHODS: Thirty-eight patients with HCM underwent gadolinium-enhanced CMR and 12 lead electrocardiography (ECG). Left ventricular function, volumes, segmental and transmural extent of myocardial LGE were assessed and analysed in relation to the presence of abnormal Q waves. RESULTS: Twelve (31%) of the 38 patients had abnormal Q waves on the ECG. Patients with Q waves exhibited significantly more myocardial LGE segmentally as well as transmurally than patients without Q waves. As the segmental and the transmural extent of LGE increased, the probability of Q wave increased (anterior: segmental extent chi2 = 10, p = 0.0013, transmural extent chi2 = 10, p = 0.0013; inferior: segmental extent chi2 = 13, p = 0.0003, transmural extent chi2 = 15, P < 0.0001: lateral: segmental extent chi2 = 10, p = 0.0016, transmural extent chi2 = 10, p = 0.0012). Additionally, the ratio of septal to posterior wall thickness was significantly higher in patients with Q waves than in patients without Q waves (2.3 vs. 1.6, p = 0.012). CONCLUSIONS: It seems that segmental and transmural extent rather than the mere presence of myocardial LGE is the underlying mechanism of abnormal Q waves in HCM. Additionally, distribution of hypertrophy as indicated by differences in the ratio of septal to posterior wall thickness seems to play an important role.     

Extent of late gadolinium enhancement detected by cardiovascular magnetic resonance correlates with the inducibility of ventricular tachyarrhythmia in hypertrophic cardiomyopathy

Background

Myocardial fibrosis is frequently identified in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to investigate the role of myocardial fibrosis detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR) as a potential arrhythmogenic substrate in HCM. We hypothesized that the extent of LGE might be associated with the inducibility of ventricular tachyarrhythmias (VT) during programmed ventricular stimulation (PVS).

Methods

We evaluated retrospectively LGE CMR of 76 consecutive HCM patients, of which 43 presented with one or more risk factors for sudden cardiac death (SCD) and were therefore clinically classified as high-risk patients. Of these 43 patients, 38 additionally underwent an electrophysiological testing (EP). CMR indices and the extent of LGE, given as the % of LV mass with LGE were correlated with the presence of risk factors for SCD and the results of EP.

Results

High-risk patients had a significant higher prevalence of LGE than low-risk patients (29/43 [67%] versus 14/33 [47%]; p = 0.03). Also the % of LV mass with LGE was significantly higher in high-risk patients than in low-risk patients (14% versus 3%, p = 0.001, respectively). Of the 38 high- risk patients, 12 had inducible VT during EP. LV function, volumes and mass were comparable in patients with and without inducible VT. However, the % of LV mass with LGE was significantly higher in patients with inducible VT compared to those without (22% versus 10%, p = 0.03). The prevalence of LGE was, however, comparable between HCM patients with and those without inducible VT (10/12 [83%] versus 15/26 [58%]; p = 0.12). In the univariate analysis the % of LV mass with LGE and the septal wall thickness were significantly associated with the high-risk group (p = 0.001 and 0.004, respectively). Multivariate analysis demonstrated that the extent of LGE was the only independent predictor of the risk group (p = 0.03).

Conclusions

The extent of LGE in HCM patients correlated with risk factors of SCD and the likelihood of inducible VT. Furthermore, LGE extent was the only independent predictor of the risk group. This supports the hypothesis that the extent of fibrosis may serve as potential arrhythmogenic substrate for the occurrence of VT, especially in patients with clinical risk factors for SCD.     

Assessment of the anterior chamber parameters after laser iridotomy in primary angle close suspect using Pentacam and gonioscopy

AIM:To investigate the role of fundus autofluorescence (FAF) both in the diagnosis and the preoperative and postoperative evaluation of patients with idiopathic macular hole (MH).METHODS: Forty eyes of 40 patients diagnosed as idiopathic MH between May 2010 and May 2011 were included in this retrospective study. All patients underwent full ophthalmologic examinations and imagings including fluorescein angiography, fundus autofluorescence (FAF) and optical coherence tomography. Thirty of these patients underwent MH surgery. FAF findings were associated with duration of symptoms, visual acuity at presentation, stage of MH, and postoperative anatomical correction.RESULTS:The mean duration of patients’ symptoms was 3.8±2.0 (1-9) months. The MH was stage 2 in 4 (10%), stage 3 in 24 (60%) and stage 4 in 12 (30%) eyes. The median preoperative best corrected visual acuity was 20/200 (between 20/800 and 20/100). Twenty-eight of cases (70%) showed a stellate appearance with dark radiating striae. Having a visual acuity ≥20/200 was significantly more common in eyes with stellate appearance (P<0.001). The mean duration of symptoms was significantly shorter in eyes with stellate appearance (2.75±0.8 vs 6.33±1.61 months) (P<0.001). The frequency of stage 4 MH was significantly higher in eyes with non-stellate appearance (P<0.001). Anatomical correction of MH was achieved in 91.3% (21/23) of eyes with stellate appearance and 71.4% (5/7) of eyes without this appearance (P=0.225).CONCLUSION: Stellate appearance in FAF is associated with earlier stages of macular hole, better visual acuity at presentation, shorter duration of symptoms, thus more favorable prognosis.