Enhanced sensitivity to oxidant-induced micronucleus frequency in elderly individuals is not associated with glutathione S-transferase M1 (GSTM1) null genotype in lymphocytes

BACKGROUND: A large number of studies have demonstrated that various kinds of DNA damage accumulate during aging and that oxidative stress possibly contributes to this process. Glutathione S-transferase M1 (GSTM1) can prevent their possible effects on DNA via detoxification of reactive substances that induced oxidative stress. OBJECTIVE: To investigate the relationship between GSTM1 polymorphism and DNA sensitivity to oxidative stress with age, we used micronucleus (MN) frequency as a marker of DNA damage in lymphocytes from young and elderly subjects. Methods: This study was performed in 30 young (age range 20-36 years) and 30 elderly (age range 66-87 years) healthy individuals who were chosen on the basis of their GSTM1 genotype (15 GSTM1 null and 15 GSTM1 positive for each group). Lymphocytes were cultured after Ficoll isolation and treated for 48 h with a 30-muM dose of cumene hydroperoxide (CumOOH), a dose that does not decrease cell viability. RESULTS: There was no significant difference in the MN frequency observed in control cultures from young and elderly individuals. However, the MN frequency in CumOOH-treated cultures was significantly higher in the elderly group than the young group (p < 0.001). No association was found between the GSTM1 phenotype and CumOOH-induced MN frequency. CONCLUSIONS: The results suggest that lymphocytes of elderly individuals are more susceptible to in vitro MN induction by CumOOH. However, this difference in susceptibility is not explained by the lack of GSTM1.     

Increased immunoglobulin E response in acute coronary syndromes

The role of inflammation and mast cell activation has been implicated in atherosclerotic plaque destabilization and rupture. To investigate the role of immunoglobulin E (IgE) in acute coronary syndrome, a prospective clinical study was conducted in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP), stable angina pectoris (SAP), and healthy controls. IgE levels were serially measured and compared in consecutive patients with AMI (n = 16) and UAP (n = 14) on days 1, 3, 7, 21 after admission and 3 months later and only once in stable angina pectoris (n = 15) and healthy controls (n = 14). In addition, blood eosinophil and basophil levels on admission were measured in all groups and compared. Initial IgE levels determined at admission in patients with AMI, UAP, and SAP were significantly higher than levels in the control group (p = 0.002). Initial high IgE level in AMI on day 1 increased to a peak by day 7 (p = 0.024), then gradually decreased by day 21 and at 3 months (p = 0.052). High IgE level in UAP persisted by day 7 and gradually decreased by day 21 and 3 months (p = 0.037 and p = 0.018, respectively). Blood eosinophil count on admission was significantly higher in UAP than in the control group (p = 0.005). Basophil levels of both AMI and UAP groups on admission were found to be elevated as opposed to control group (p = 0.02 and p = 0.012, respectively). This study demonstrates that the level of IgE significantly increased during the acute phase of acute coronary syndromes and gradually decreased, supporting the role of acute inflammatory response and mast cell involvement in plaque rupture.     

Application of the vena contracta method for the calculation of the mitral valve area in mitral stenosis

OBJECTIVES: The vena contracta is the narrowest region of the regurgitant or stenotic jet just downstream the orifice and reflects the size of that orifice. This study was performed to assess the accuracy of the vena contracta width (VCW) in evaluating the severity of mitral stenosis (MS) and to compare the mitral valve area (MVA) determined by VCW with MVAs obtained by other more traditional echocardiographic methods. METHODS: We studied 59 patients (43 females, 42 +/- 14 years) with MS. VCW was measured in the apical four chamber view by Doppler color flow mapping. The largest diameter of the VCW during diastole was measured for at least three cardiac cycles and averaged. MVA was calculated from the following equation: pir(2), where r = VCW/2. MVA was also determined by planimetry, the pressure half-time method, and by the Gorlin formula. RESULTS: In this study, the width of the vena contracta ranged from 0.89 to 1.73 cm (mean 1.30 +/- 0.21). MVA, calculated based on the VCW, ranged from 0.63 to 2.35 cm(2) (mean 1.36 +/- 0.41). MVA by VCW (1.36 +/- 0.41 cm(2)) showed good correlations with three comparative techniques: (1) the cross-sectional area by planimetry (1.35 +/- 0.36 cm(2), mean difference = 0.21 +/- 0.16 cm(2), y = 0.91x + 0.14, r = 0.79, SEE = 0.26 cm(2), p < 0.001); (2) the area derived from the Doppler pressure half-time (1.27 +/- 0.32 cm(2), mean difference = 0.22 +/- 0.19 cm(2), y = 0.97x + 0.13, r = 0.76, SEE = 0.27 cm(2), p < 0.001), and (3) the area derived from the Gorlin equation in the 18 patients who underwent catheterization (1.27 +/- 0.35 cm(2), mean difference = 0.19 +/- 0.16, y = 0.98x + 0.05, r = 0.81, SEE = 0.26 cm(2), p < 0.001). CONCLUSIONS: These findings suggest that Doppler color flow imaging of the MS jet in the vena contracta can provide an accurate estimation of MVA and appears to be potentially applicable in the assessment of the severity of MS.     

A multicenter retrospective study defining the clinical and hematological manifestations of brucellosis and pancytopenia in a large series: Hematological malignancies, the unusual cause of pancytopenia in patients with brucellosis

The aim of the study is to review the clinical manifestations and the hematological findings of brucellosis and pancytopenia, with or without hematological malignancies. The records of 202 patients with brucellosis were evaluated retrospectively. Among these cases of brucellosis seen in a 6 year period between April 1999 and June 2005, 30 patients with pancytopenia were identified. The most common manifestation was fever, followed by weight loss, anorexia, malaise, arthralgia, and hepatosplenomegaly. Bone marrow biopsies revealed hypercellularity or normocellularity. The most common findings in the bone marrow evaluation were histiocytic hemophagocytosis and granulomas. Among all cases, we diagnosed 5 hematological malignancies (1 acute myelogenous leukemia, 2 acute lymphoblastic leukemia, and 2 multiple myeloma) concurrently with brucellosis. The clinical symptoms and findings were similar in patients with and without malignancies. In cases with malignancies, the bone marrow biopsy revealed predominant primary disease involvement. Significant increases in ESR and CRP, severe anemia and thrombocytopenia were observed in patients with malignancies. Peripheral blood counts in patients without malignancies returned to normal after antibiotic treatment for brucellosis. However, pancytopenia in two patients with malignancies did not recover because of primary resistant disease. We conclude that while histiocytic hemophagocytosis may be considered as a major cause of pancytopenia, leukemic infiltration can also be an extreme and unusual cause of pancytopenia in patients in whom brucellosis was concurrently diagnosed with hematological malignancies.     

Sildenafil Citrate Does Not Alter Ventricular Repolarization Properties: Novel Evidence from Dynamic QT Analysis

Background: Sildenafil citrate may have direct cardiac electrophysiological effects, and is possibly responsible for some cardiac events. The aim of our study was to investigate the effects of sildenafil citrate on QT dynamicity properties with a new QT analysis program showing even small changes in ventricular repolarization. Methods: Twenty‐four‐hour Holter electrocardiographic recordings were used to obtain the data in the predrug phase (1‐hour rest position before drug administration), and in the postdrug phase (1‐hour rest position, which began 60 minutes after 50 mg oral sildenafil citrate administration). With the special QT analysis program (Verda, Reynolds Medical Ltd., UK); mean values of RR, QT, QT_o (corrected QT), J (the exponent of correction formula) and S (QT/RR plots slope) parameters together with QT variability indexes (QTVI) were calculated for study phases. Results: Mean ± SEM values for RR and QT were higher in postdrug phase than in predrug phase (RR: 845 ± 42 ms vs 816 ± 46 ms, P < 0.05; QT: 371 ± 8 ms vs 361 ± 9 ms, P < 0.05). However, sildenafil did not induce any significant change in mean ± SEM values for QT_o, J, and S in postdrug phase compared with predrug phase (408 ± 10 ms vs 406 ± 8 ms, 0.474 ± 0.030 vs 0.433 ± 0.025, 0221 ± 0.020 vs 0.198 ± 0.017, respectively; P > 0.05). QTVIs were also not different in each phase (predrug: ?0.874 ± 0.071 vs postdrug: ?0.997 ± 0.067, P = 0.109). Conclusions: Fifty milligrams sildenafil does not affect QT dynamicity properties. The cardiac events associated with sildenafil could not be explained with ventricular arrhythmias.     

Arch-first technique via clamshell incision: successful surgical reoperation for aortic arch dissection

We report a case of successful reoperation for aortic arch dissection with use of the "arch-first" technique in a patient who had Marfan syndrome. Extracorporeal circulation was initiated via right subclavian artery cannulation, and the chest was entered through a clamshell incision for the best exposure. When the patient was cooled to 18 degrees C, the perfusion was stopped. After the 1st aortic arch anastomosis to a 30-mm Dacron graft, cerebral perfusion was reestablished via the right subclavian artery. The aortic repair was then completed. The cerebral ischemic time was 18 minutes, the aortic cross-clamp time was 69 minutes, and the total extracorporeal circulation time was 334 minutes. The patient was discharged from the hospital on postoperative day 10 with no neurologic impairment. The arch-first technique shortens the duration of brain ischemia. When combined with a clamshell incision, the technique is particularly helpful for reoperation of the aortic arch and thoracic aorta.     

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment.We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1­75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.     

Effects of primary selective laser trabeculoplasty on anterior segment parameters

AIM:To investigate the effects of selective laser trabeculoplasty (SLT) on the main numerical parameters of anterior segment with Pentacam rotating Scheimpflug camera in patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG).METHODS: Pentacam measurements of 45 eyes of 25 (15 females and 10 males) patients (12 with OHT, 13 with POAG) before and after SLT were obtained. Measurements were taken before and 1 and 3mo after SLT. Pentacam parameters were compared between OHT and POAG patients, and age groups (60y and older, and younger than 60y).RESULTS: The mean age of the patients was 57.8±13.9 (range 20-77y). Twelve patients (48%) were younger than 60y, while 13 patients (52%) were 60y and older. Measurements of pre-SLT and post-SLT 1mo were significantly different for the parameters of central corneal thickness (CCT) and anterior chamber volume (ACV) (P<0.05). These parameters returned back to pre-SLT values at post-SLT 3mo. Decrease of ACV at post-SLT 1mo was significantly higher in younger than 60y group than 60y and older group. There was no statistically significant difference in Pentacam parameters between OHT and POAG patients at pre- and post-treatment measurements (P>0.05).CONCLUSION:SLT leads to significant increase in CCT and decrease in ACV at the 1^st month of the procedure. Effects of SLT on these anterior segment parameters, especially for CCT that interferes IOP measurement, should be considered to ensure accurate clinical interpretation.