Role of mitochondrial translation in remodeling of energy metabolism in ER/PR(+) breast cancer.

Remodeling of mitochondrial energy metabolism is essential for the survival of tumor cells in limited nutrient availability and hypoxic conditions. Defects in oxidative phosphorylation (OXPHOS) and mitochondrial biogenesis also cause a switch in energy metabolism from oxidative to aerobic glycolysis contributing to the tumor heterogeneity in cancer. Specifically, the aberrant expressions of mitochondrial translation components such as ribosomal proteins (MRPs) and translation factors have been increasingly associated with many different cancers including breast cancer. The mitochondrial translation is responsible for the synthesis 13 of mitochondrial-encoded OXPHOS subunits of complexes. In this study, we investigated the contribution of mitochondrial translation in the remodeling of oxidative energy metabolism through altered expression of OXPHOS subunits in 26 ER/PR(+) breast tumors. We observed a significant correlation between the changes in the expression of mitochondrial translation-related proteins and OXPHOS subunits in the majority of the ER/PR(+) breast tumors and breast cancer cell lines. The reduced expression of OXPHOS and mitochondrial translation components also correlated well with the changes in epithelial-mesenchymal transition (EMT) markers, E-cadherin (CHD1), and vimentin (VIM) in the ER/PR(+) tumor biopsies. Data mining analysis of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) breast cancer proteome further supported the correlation between the reduced OXPHOS subunit expression and increased EMT and metastatic marker expression in the majority of the ER/PR(+) tumors. Therefore, understanding the role of MRPs in the remodeling of energy metabolism will be essential in the characterization of heterogeneity at the molecular level and serve as diagnostic and prognostic markers in breast cancer.

Intralenticular Sustained-Release Dexamethasone Implant: Is It Still Effective on Macular Edema?

PURPOSE: To report the therapeutic efficacy of an accidentally injected intralenticular sustained-release dexamethasone implant in a patient with macular edema secondary to branch retinal vein occlusion and shortly discuss the management strategy of this rare complication. METHODS: Complete ophthalmological examination and optical coherence tomography imaging were performed at each visit. RESULTS: The implant accidentally caused a posterior capsular tear during the procedure and was injected into the crystalline lens because of an involuntary head movement of the patient. Since the anterior segment was normal, and the resultant cataract and implant itself did not obscure the visual axis, the decision was made to observe the patient with intralenticular implant, preserve the therapeutic effect and avoid reinjection. The macular edema resolved within time, while visual acuity did not show significant improvement due to an increase in lens opacification. The patient underwent phacoemulsification surgery at 7 months after the injection with implantation of posterior chamber IOL into the capsular bag. CONCLUSION: Inadvertent injection of sustained-release intravitreal dexamethasone implant into the crystalline lens is an uncommon but possible complication that is mostly caused by surgeon inexperience, improper technique and uncontrolled head movement during the procedure. Once this complication occurs, early phacoemulsification and repositioning of the implant into the vitreous is the frequently preferred management strategy. However, remarkable decrease in macular edema and visual acuity improvement can also be achieved without an immediate surgical intervention.

The protective effect of single dose tadalafil in contrast-induced nephropathy: an experimental study.

OBJECTIVE: Contrast-induced nephropathy (CIN) is one of the most common causes of acute renal failure in hospitalized patients. The direct toxic effect of contrast media; ischemic damage caused by reactive oxygen species; increased perivascular hydrostatic pressure; high viscosity and changes in the activity of vasoactive substances play important roles in the pathogenesis. Tadalafil inhibits the phosphodiesterase enzyme which destroys nitric oxide. Nitric oxide causes renal vasodilatation, increases renal medullar blood flow and mediates the removal of free oxygen radicals. Drugs that increase levels of nitric oxide are expected to reduce the development of contrast nephropathy due to contrast media. We aimed to test the hypothesis that tadalafil reduces the development of contrast nephropathy due to contrast toxicity. METHODS: A total of 24 female Wistar albino rats, three groups of eight, were included in the study. After 48 hours of dehydration, contrast media (meglumine diatrozoate, 6 mL/kg) was administered to the first group, and contrast media with tadalafil (10 mg/kg) was administered to the second group. The third group served as the control group. Blood and tissue samples were taken 48 hours after this procedure. RESULTS: Serum cystatin C, serum creatinine and blood urea nitrogen (BUN) values were significantly lower in the contrast with tadalafil group compared to the group given only contrast. Serum and tissue malondialdehyde (MDA) levels were significantly lower in the contrast with tadalafil group than in the contrast only group. CONCLUSION: These results demonstrate the protective effect of tadalafil in the prevention of CIN in rats.

Brachiocephalic artery cannulation in proximal aortic surgery that requires circulatory arrest.

The brachiocephalic artery is an alternative cannulation site in the repair of ascending aortic lesions that require circulatory arrest. We evaluate the effectiveness and safety of this technique. Proximal aortic surgery was performed in 32 patients from 2006 through 2012 via brachiocephalic artery cannulation and circulatory arrest. Twenty-four (75%) of the patients were men. The mean age was 48.69 ± 9.43 years (range, 30-68 yr). Twelve had type I dissection, 2 had type II dissection, and 18 had true aneurysms of the ascending aorta. All operations were performed through a median sternotomy. The arterial cannula was inserted through an 8-mm vascular graft anastomosed to the brachiocephalic artery in an end-to-side fashion. In dissections, the distal anastomosis was performed without clamping the aorta. The patients were cooled to 24 °C, and circulatory arrest was established. The brachiocephalic and left carotid arteries were clamped, and antegrade cerebral perfusion was started at a rate of 10 mL/kg/min. Cardiopulmonary bypass was resumed after completion of the distal anastomosis and the initiation of rewarming. The proximal anastomosis was then performed. None of the patients sustained a major neurologic deficit, but 5 patients experienced transient postoperative agitation (<24 hr). There were 2 early deaths (6.25%), on the 3rd and the 11th postoperative days, both unrelated to the cannulation technique. Brachiocephalic artery cannulation through a graft can be a safe and effective technique in proximal aortic surgical procedures that require circulatory arrest.

Sodium bicarbonate versus isotonic saline for the prevention of contrast-induced nephropathy in patients with diabetes mellitus undergoing coronary angiography and/or intervention: a multicenter prospective randomized study.

INTRODUCTION: Contrast-induced nephropathy (CIN) is a leading cause of acute renal failure and affects mortality and morbidity. Although the incidence of CIN is quite low in the general population, CIN incidence is significantly increased in patients with diabetes mellitus (DM). OBJECTIVES: We compared the efficacy of prophylactic use consisting of a saline infusion or a sodium bicarbonate infusion for the prevention of CIN in patients with DM. MATERIALS AND METHODS: A total of 195 DM patients who had unselected renal function were randomized into 2 groups: 101 patients were assigned to saline infusion, and 94 patients were assigned to bicarbonate infusion. The primary end point was the maximum increase in the serum creatinine (SCr) level, whereas the secondary end point was the development of CIN after the procedure. RESULTS: The maximum increase in SCr levels was significantly lower in the saline group than in the bicarbonate group: -0.03 mg/dL (IQR, -0.09 to 0.10 mg/dL) versus 0.02 mg/dL (IQR, -0.09 to 0.13 mg/dL) (P = 0.014). The rate of CIN was significantly lower in the saline group than in the bicarbonate group (5.9% vs 16%, P = 0.024). In the subset of study participants with a baseline creatinine clearance of less than 60 mL/min, the maximum increase in SCr levels was significantly lower, -0.08 mg/dL (IQR, -0.13 to -0.04 mg/dL), in the saline group than in the bicarbonate group, 0.03 mg/dL (IQR, -0.13 to 0.12 mg/dL) (P = 0.004). CONCLUSIONS: The use of prophylactic hydration with isotonic saline before coronary procedures may decrease SCr levels and reduce the incidence of CIN in patients with DM with unselected renal functions to a greater extent than sodium bicarbonate can.

The evaluation of doxorubicin-induced cardiotoxicity: comparison of Doppler and tissue Doppler-derived myocardial performance index.

BACKGROUND: Doxorubicin is a chemotherapeutic agent used in a wide spectrum of cancers. However, cardiotoxic effects have limited its clinical use. The early detection of doxorubicin-induced cardiotoxicity is crucial. The purpose of our study was to assess values of Doppler and tissue Doppler imaging (TDI)-derived myocardial performance index (MPI) in adult cancer patients receiving doxorubicin treatment. METHODS: A total of 45 patients underwent echocardiographic examinations before any doxorubicin had been administered and then after doxorubicin. Doppler and TDI-derived MPI of left ventricular (LV) were determined in the evaluation of cardiotoxicity. Additionally, TDI-derived MPI of right ventricular (RV) was determined. RESULTS: All patients underwent control echocardiographic examination after mean 5 ± 1.7 months. The LV MPI obtained by both Doppler and TDI were increased after doxorubicin treatment (0.56 ± 0.11, 0.61 ± 0.10, p = 0,005 vs 0.51 ± 0.09, 0.59 ± 0.09, p = 0.001, respectively). There was no correlation between Doppler-derived MPI and cumulative doxorubicin dose (coefficient of correlation 0.11, p = 0.6). TDI-derived MPI was correlated with cumulative doxorubicin dose (coefficient of correlation 0.35, p = 0.015), but this correlation is weak (r = 0.38). The study population was divided into two groups according to doxorubicin dose (below and above 300 mg level). There was a moderate correlation between TDI-derived MPI and less than 300 mg of doxorubicin dose (coefficient of correlation 0.51, p = 0.028). However, Doppler-derived MPI was not correlated with less than 300 mg of doxorubicin dose (coefficient of correlation 0.38, p = 0.123). Also, there was no significant change in the TDI-derived RV-MPI (0.49 ± 0.14, 0.50 ± 0.12, p = 0.56). CONCLUSIONS: TDI-derived MPI is a useful parameter and an early indicator compared with Doppler-derived MPI in the detection of cardiotoxicity during the early stages. Also, doxorubicin administration does not affect RV function.

Does nebivolol prevent contrast-induced nephropathy in humans?

BACKGROUND: An experimental study showed that nebivolol is an effective agent in contrast-induced nephropathy (CIN) prophylaxis. HYPOTHESIS: We hypothesized that prophylactic nebivolol use had protective effects on renal function in human beings subjected to iodinated contrast agent since it has vasodilatory effect and antioxidant properties. METHODS: The present study enrolled 120 patients scheduled for coronary angiography and ventriculography. All patients were hydrated with intravenous isotonic saline. The patients in group I received 600 mg N-acetylcysteine every 12 hours for 4 days. The patients in group II received 5 mg nebivolol every 24 hours for 4 days. The patients in group III were only hydrated. The primary endpoint was the occurrence of CIN. The secondary endpoint was the change in serum creatinine (Cr) levels at 2 days and 5 days after the contrast exposure. RESULTS: Nine (22.5%) patients in group I developed CIN, as did 8 patients (20.0%) in group II and 11 patients (27.5%) in group III (P = 0.72). Changes in mean Cr level from baseline to day 2 were not statistically significant in all groups. However, we detected a statistically significant increase in mean Cr levels at day 5 compared with baseline levels in group I and group III (from 1.42 ± 0.13 to 1.52 ± 0.26, p2 = 0.02; and from 1.43 ± 0.14 to 1.55 ± 0.30, p2 = 0.01, respectively). Although an increase was detected in mean Cr level from baseline to the 5-day Cr level in group II, this did not reach statistical significance (from 1.40 ± 0.12 to 1.48 ± 0.23, P = 0.06). CONCLUSIONS: Pretreatment with nebivolol is protective against nephrotoxic effects of contrast media.

The effect of adenotonsillectomy on right ventricle function and pulmonary artery pressure in children with adenotonsillar hypertrophy.

OBJECTIVES: Adenotonsillar hypertrophy (ATH) is the most common cause of upper airway obstruction in children. Severe upper airway obstruction may have an effect on chronic alveolar hypoventilation, which consequently may lead to right ventricle (RV) dysfunction induced by hypoxemic pulmonary vasoconstriction. The investigators aimed to study RV function and mean pulmonary artery pressure (mPAP) in patients with ATH who were undergoing adenotonsillectomy by using tissue Doppler echocardiography (TDE). METHODS: The study examined 27 children with ATH who had a mean age of 8 ± 2 years. The subjects were comprised 17 (63%) males and 10 (37%) females. Hypertrophy of the tonsils was graded according to the Brodsky scale. Children having either grade 3 or 4 hypertrophied adenotonsils were recruited for the study. Adenotonsillectomy was performed on all subjects in the study group and echocardiographic examination was repeated 3 months postoperatively. RESULTS: Tricuspid Em significantly increased after adenotonsillectomy (17.7 ± 3.6 vs. 19.1 ± 5.5, p=0.04). The RV myocardial performance index (MPI) and mPAP significantly decreased after adenotonsillectomy (RV MPI: 0.57 ± 0.13 vs. 0.40 ± 0.12, p<0.001 and mPAP (mmHg): 31 ± 9 vs. 25 ± 7, p=0.001). CONCLUSION: The results of this study, evaluated with the results of previous studies, demonstrated that adenotonsillectomy improved RV performance and reduced mPAP in children with ATH.

Intravenous N-acetylcysteine plus high-dose hydration versus high-dose hydration and standard hydration for the prevention of contrast-induced nephropathy: CASIS--a multicenter prospective controlled trial.

BACKGROUND: Contrast-induced nephropathy (CIN) is a leading cause of acute renal failure and affects mortality and morbidity. We investigated the efficacy of prophylactic intravenous (IV) N-acetylcysteine (NAC) and hydration for the prevention of CIN in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and/or percutaneous coronary intervention (PCI). METHODS: A total of 220 patients who had mild to moderate renal dysfunction with serum creatinine (SCr) ≥ 1.1mg/dL or creatinine clearance ≤ 60 mL/min were randomized in 3 groups: 80 patients were assigned to IV NAC plus high-dose hydration with normal saline, 80 patients to only high-dose hydration with normal saline and 60 patients to standard hydration with normal saline (control group). The primary end point was the alteration of SCr level. The secondary end point was the development of CIN after the procedure. RESULTS: SCr levels changed the least in the NAC plus high-hydration group (P=0.004). The rate of the CIN in the NAC plus high-dose hydration group was also lower than the high-dose hydration group (P=0.006). No significant differences in the primary and secondary end points were found between high-dose hydration and control group. CONCLUSION: The results of this study suggest that NAC plus high-dose hydration was superior to high-dose hydration alone as well as standard hydration for the protection of renal functions in patients with mild to moderate renal dysfunction who are undergoing coronary angiography and/or PCI. High-dose hydration without NAC was not better than standard hydration alone.

Frequency of fragmented QRS on ECG is increased in patients with rheumatoid arthritis without cardiovascular disease: a pilot study.

Myocardial fibrosis causes the fragmentation of QRS complexes (fQRS) on ECGs. We hypothesized that the frequency of fQRS could be more common in patients with rheumatoid arthritis (RA) than in control subjects. A total of 56 patients with RA were compared with 35 age- and gender-matched fibromyalgia subjects for fQRS. The fQRS was defined as the presence of an additional R wave, or notching of the R or S wave, or the presence of fragmentation in 2 contiguous leads corresponding to the territory of a major coronary artery. Patients with bundle block on ECG and cardiovascular disease were excluded. Twenty-one patients (37.5%) in the RA group had fQRS, while two patients in the control group (5.7%) had fQRS (p = 0.001). No differences were found between the groups in terms of age, gender, or drug use. Duration of disease--years (interquartile range [IQR])--was 10 (8) in the fQRS (+) group, while it was 5 (2) in the fQRS (-) group (p < 0.001). Multivariate logistic regression analysis revealed that duration of disease was associated with the presence of fQRS (B = 1.5, odds ratio = 4.5, p = 0.004, 95% confidence interval = 1.6-12.7). We found that fQRS on ECG was more common in patients with RA without cardiovascular disease than in age- and gender-matched control subjects.

[The relationship between coronary collateral circulation and blood high-sensitivity C-reactive protein levels]. / Koroner kolateral dolasim ile serum yüksek duyarlikli C-reaktif protein düzeyleri arasindaki iliski.

OBJECTIVES: We evaluated the relationship between coronary collateral circulation (CCC) and blood high-sensitivity C-reactive protein (hs-CRP) levels in patients with chronic stable coronary artery disease. STUDY DESIGN: The study included 104 patients who underwent coronary angiography at least one month after acute coronary event and were found to have total coronary occlusion in at least one major coronary artery. Patients with the diagnosis of acute coronary syndrome within the past month, severe valve disease, systemic disease, systemic inflammatory disease, or a history of coronary surgery or percutaneous coronary intervention were excluded. Collateral circulation was graded according to the Rentrop classification. Grades 0 and 1 were defined as poor, grades 2 and 3 were defined as good CCC. Blood hs-CRP levels were measured 1 to 7 days before coronary angiography. RESULTS: According to the Rentrop classification, CCC was graded as 0 in 10 patients, 1 in 26 patients, 2 in 29 patients, and 3 in 39 patients. Sixty-eight patients (65.4%) had a good CCC, and 36 patients (34.6%) had a poor CCC. The two groups were similar with respect to age, sex, risk factors, medications, localization of the occluded coronary artery, and the number of occluded arteries. However, hs-CRP levels were significantly higher in patients with a poor CCC (median 5.42 mg/dl; range 2.3-9.8 mg/dl) compared to those with a good CCC (median 3.36 mg/dl; range 2.2-9.7 mg/dl, p=0.003). Logistic regression analysis showed that hs-CRP level was a significant predictor exerting an adverse effect on collateral development (ß=-320; odds ratio= 0.725; 95% confidence interval 0.587-0.894; p=0.003). CONCLUSION: Our findings suggest that high hs-CRP level is a significant predictor of poor collateral development in patients with chronic stable coronary artery disease.

Assessment of atrial conduction time in patients with sarcoidosis.

OBJECTIVES: Sarcoidosis is an inflammatory granulomatous disease of unknown cause that involves multiple organ systems. Myocardial involvement is usually associated with poor prognosis, but diagnosis of cardiac sarcoidosis is frequently difficult. The aim of this study was to investigate the atrial conduction time in patients with sarcoidosis by using high-usefulness tissue Doppler echocardiography. METHODS: The study population included 49 patients with sarcoidosis (19 men; mean age, 40.5 ± 9.8 years; mean disease duration, 35.7 ± 15.3 months) and 45 healthy control subjects (17 men; mean age, 40.7 ± 7.2 years). From the 12-lead electrocardiogram, P wave dispersion (PWD) was calculated. The timing of atrial contractions (PA) was measured as the intervals between the onset of P wave on electrocardiogram and the beginning of A-wave on TDI, and atrial electromechanical delay (EMD) was calculated from the lateral (PA lateral) and septal (PA septal) mitral annulus and lateral tricuspid annulus (PA tricuspid). RESULTS: Both PA lateral and PA septal were significantly longer in patients with sarcoidosis than control subjects (67.9 ± 16.1 vs 56.3 ± 13.1, P < 0.001; and 54.8 ± 15.2 vs 45.1 ± 14.2 ms, P = 0.002, respectively). Intra-atrial (PA septal-PA tricuspid) and interatrial (PA lateral-PA tricuspid) EMD were significantly higher in sarcoidosis groups (12.6 ± 7.5 vs 8.0 ± 7.1, P = 0.003; and 25.7 ± 9.8 vs 19.3 ± 7.7 ms, P = 0.001, respectively). Similarly, maximum P-wave duration and PWD were significantly longer in patients with sarcoidosis than control subjects (105.2 ± 11.8 vs 96.7 ± 15.4, P = 0.004 and 24.7 ± 5.6 vs 19.7 ± 7.1 ms, P = 0.001, respectively). There were significant positive correlations between the disease duration and interatrial EMD (r = 0.56, P < 0.001) and intra-atrial EMD (r = 0.66, P < 0.001). Positive correlation also was present between the disease duration and PWD (r = .62, P < 0.001). CONCLUSIONS: Atrial EMD was found prolonged in patients with sarcoidosis. We also have demonstrated that PWD, interatrial and intra-atrial EMD were significantly correlated with disease duration. This study calls attention to measurement of atrial conduction time that may be clinically helpful in the recognition of cardiac involvement.

Hemolysis and infective endocarditis in a mitral prosthetic valve.

Traumatic intravascular hemolysis after heart valve replacement can be a serious problem. It is commonly associated with either structural deterioration or paravalvular leaks. A 63-year-old woman with a six-year history of surgery for mitral stenosis presented with complaints of weakness and dyspnea. She received treatment at other centers three times in the past six months for dyspnea and anemia requiring transfusion of red blood cells. Transthoracic echocardiography showed a normally functioning mitral mechanic prosthesis. Laboratory findings were abnormal for hemoglobin, hematocrit, white blood cell count, C-reactive protein, serum haptoglobin, and lactate dehydrogenase. Peripheral blood smear showed marked schistocytes, indicative of mechanical erythrocyte destruction. Transesophageal echocardiography demonstrated severe paravalvular leak and a large (9x13 mm) vegetation adhering to the prosthetic valve, protruding into the left atrium. Enterococcus faecalis was isolated from blood cultures. Surgery was planned because of large vegetation, repeated hemolysis, and severe paravalvular regurgitation, but the patient refused surgical treatment.

Acute coronary embolism without valve thrombosis in a patient with a prosthetic mitral valve--successful percutaneous coronary intervention: a case report.

We present a 44-year-old female patient with anterior myocardial infarction caused by embolization from mitral valve prosthesis due to inadequate anticoagulation. The patient underwent a cardiac catheterization within the 1st hour of arrival. The angiography showed total occlusion of the left anterior descending coronary artery after the second diagonal branch. Percutaneous transluminal coronary angioplasty and stenting were performed, and coronary artery perfusion was restored. The pain disappeared completely immediately after this intervention. Transthoracic echocardiography shortly after this intervention showed normal prosthetic valve function and no thrombus. Transesophageal echocardiography performed 2 days later revealed no thrombus at the prosthetic valve. In conclusion, this case demonstrated that coronary embolism may occur even without prosthetic valve thrombus or dysfunction with suboptimal International Normalized Ratio levels, and can be successfully treated with percutaneous transluminal coronary angioplasty and stenting.