Gene expressions of TRP channels in glioblastoma multiforme and relation with survival.

Glioblastoma multiforme (GBM) is one of the most lethal forms of cancer in humans, with a median survival of 10 to 12 months. Glioblastoma is highly malignant since the cells are supported by a great number of blood vessels. Although new treatments have been developed by increasing knowledge of molecular nature of the disease, surgical operation remains the standard of care. The TRP (transient receptor potential) superfamily consists of cation-selective channels that have roles in sensory physiology such as thermo- and osmosensation and in several complex diseases such as cancer, cardiovascular, and neuronal diseases. The aim of this study was to investigate the expression levels of TRP channel genes in patients with glioblastoma multiforme and to evaluate the relationship between TRP gene expressions and survival of the patients. Thirty-three patients diagnosed with glioblastoma were enrolled to the study. The expression levels of 21 TRP genes were quantified by using qRT-PCR with dynamic array 48 × 48 chip (BioMark HD System, Fluidigm, South San Francisco, CA, USA). TRPC1, TRPC6, TRPM2, TRPM3, TRPM7, TRPM8, TRPV1, and TRPV2 were found significantly higher in glioblastoma patients. Moreover, there was a significant relationship between the overexpression of TRP genes and the survival of the patients. These results demonstrate for the first time that TRP channels contribute to the progression and survival of the glioblastoma patients.

Cytomegalovirus ileocolitis in a rheumatoid arthritis patient: case report and literature review.

Rheumatoid arthritis (RA) is an autoimmune, systemic, chronic, inflammatory disease generally treated with various immunosuppressive drugs. Cytomegalovirus (CMV) is an opportunistic, viral infection that is commonly seen in immunosuppressed patients. A sixty-four-year old female diagnosed with RA and treated with immunosuppressive agents was admitted to our rheumatology outpatient service with complaints of diarrhea and abdominal pain, which had lasted longer than four weeks. The patient's colonoscopy revealed inflamed and ulcerated areas in the colon and in the terminal ileum. A biopsy showed intra-nuclear inclusion particles consistent with CMV. We started an oral valganciclovir therapy in this serum-CMV-polymerase chain reaction-positive patient. The concomitant use of immunosuppressive agents and anti-viral drugs eased the patient's complaints, and the endoscopic picture improved. Consequently, cytomegalovirus ileocolitis in immunosuppressed patients admitted with severe diarrhea must be considered in the differential diagnosis.

First pulmonary valve replacement with Freedom Solo stentless valve in an adolescent. A case report.

Tetralogy of Fallot (TOF) is a common form of cyanotic heart disease. Complete surgical correction in younger age group offers good long-term results with reasonable morbidity and improved prognosis in patients with TOF. However, following corrective surgery pulmonary valve replacement (PVR) might be required for residual pulmonary regurgitation in order to avoid irreversible right ventricular remodeling. Otherwise, residual uncorrected pulmonary regurgitation may lead to right ventricular dilatation, impaired biventricular function, ventricular arrhythmias and limited exercise capacity. We report the first case of Freedom Solo stentless valve (Sorin Group, Saluggia, Italy) implantation in the pulmonary position in an adolescent with severe pulmonary insufficiency 12 years after the repair of TOF. Pericardial stentless valves may be an alternative choice for pulmonary valve replacement to improve right ventricular contractile recovery and remodeling after PVR and may have impact on long-term survival.

High prevalence of coronary atherosclerosis in asymptomatic teenagers and young adults: evidence from intravascular ultrasound.

BACKGROUND: Most of our knowledge about atherosclerosis at young ages is derived from necropsy studies, which have inherent limitations. Detailed, in vivo data on atherosclerosis in young individuals are limited. Intravascular ultrasonography provides a unique opportunity for in vivo characterization of early atherosclerosis in a clinically relevant context. METHODS AND RESULTS: Intravascular ultrasound was performed in 262 heart transplant recipients 30.9+/-13.2 days after transplantation to investigate coronary arteries in young asymptomatic subjects. The donor population consisted of 146 men and 116 women (mean age of 33.4+/-13.2 years). Extensive imaging of all possible (including distal) coronary segments was performed. Sites with the greatest and least intimal thickness in each CASS segment were measured in multiple coronary arteries. Sites with intimal thickness >/=0.5 mm were defined as atherosclerotic. A total of 2014 sites within 1477 segments in 574 coronary arteries (2.2 arteries per person) were analyzed. An atherosclerotic lesion was present in 136 patients, or 51.9%. The prevalence of atherosclerosis varied from 17% in individuals <20 years old to 85% in subjects >/=50 years old. In subjects with atherosclerosis, intimal thickness and area stenosis averaged 1.08+/-0.48 mm and 32.7+/-15.9%, respectively. For all age groups, the average intimal thickness was greater in men than women, although the prevalence of atherosclerosis was similar (52% in men and 51.7% in women). CONCLUSIONS: This study demonstrates that coronary atherosclerosis begins at a young age and that lesions are present in 1 of 6 teenagers. These findings suggest the need for intensive efforts at coronary disease prevention in young adults.

Echocardiographic evaluation of left ventricular diastolic function in chronic cor pulmonale.

In this study we hoped to understand the abnormalities of left ventricular filling dynamics in chronic cor pulmonale. Our findings showed a severe left ventricular diastolic impairment, directly related to a progressive increase in pulmonary hypertension itself, as expressed by correlation analysis between systolic pulmonary artery pressure and the following parameters: transmitral flow velocity in early/late diastole ratio (r = -0.69, p <0.001), isovolumic relaxation time (r = 0.54, p = 0.001), and transmitral flow velocity in early diastole (r = -0.59, p <0.01).

Ophthalmo-acromelic syndrome: report and review.

The ophthalmo-acromelic syndrome of Waardenburg is an autosomal recessive trait comprising eye malformations ranging from true anophthalmia to mild microphthalmia with acromelic malformations. Some 29 affected individuals have been reported since Waardenburg's first report in 1935 [Waardenburg et al., 1961]. We report on a new case with bilateral anophthalmia and typical limb malformations. The patient also was found to have interruption of the inferior vena cava with azygos continuation as an additional finding. The previous reports are reviewed to elucidate the spectrum of the syndrome.

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.

The effects of L-carnitine treatment on left ventricular function and erythrocyte superoxide dismutase activity in patients with ischemic cardiomyopathy.

We studied the effects of L-carnitine on left ventricular systolic function and the erythrocyte superoxide dismutase activity in 51 patients with ischemic cardiomyopathy. They all previously were under the treatment of angiotensin-converting enzyme inhibitor, digitalis and diuretics. Patients were randomized into two groups. In group I (n=31), 2 g/day L-carnitine was added to therapy. L-Carnitine was not given to the other 20 patients (Group II). In group I (mean age 64.3+/-7.8 years), 27 of the patients were men, and four were women. In group II (mean age 66.2+/-8.7 years), 17 of the patients were men, and three were women. Twenty age-matched healthy subjects (mean age: 60.1+/-5.3 years) constituted the control group. In each group, left ventricular ejection fraction (LVEF) by echocardiography and red cell superoxide dismutase activity by spectrophotometric method were measured initially and after 1 month of randomisation. Compared with normal healthy subjects (n=20), patients (n=51) had significantly higher red cell SOD activity (5633+/-1225 vs. 3202+/-373 U/g Hb, P<0.001). At the end of 1 month of L-carnitine therapy, red cell SOD activity showed an increase in group I (5918+/-1448 to 7218+/-1917 U/g Hb, P<0.05). In group II, red cell SOD activity showed no significant change after 1 month of randomisation (5190+/-545 to 5234+/-487 U/g Hb, P=0. 256). One month after randomisation there was a significant increase in LVEF in both groups I and II (37.8-42.3%, P<0.001 in group I; 41. 5-43.8%, P<0.001 in group II). The improvement in LVEF was more significant in the L-carnitine group (4.5% vs. 2.3%, P<0.01). We conclude that, as a sign of increased free radical production, superoxide dismutase activity was further increased in patients with L-carnitine treatment. L-Carnitine treatment in combination with other traditional pharmacological therapy might have an additive effect for the improvement of left ventricular function in ischemic cardiomyopathy.

Quantitation of Doppler color flow jet areas for mitral regurgitation in children: angiographic correlation.

Eighteen patients with chronic isolated rheumatic mitral regurgitation aged between 7 and 19 years (mean age +/-SD, 12.69+/-3.47 years) were analyzed with color Doppler imaging. Sixteen patients were performed cardiac catheterization within 24 h. Jets were classified as eccentric and central. Regurgitant jet area and its ratio to left atrial area and body surface area were measured by Doppler color flow imaging. Regurgitant volume and regurgitant fractions were calculated with angiography. There was a good correlation between regurgitant jet area and angiographic grade of mitral regurgitation (P<0.01). The correlation between regurgitant jet area/left atrial area ratios and angiographic grade of mitral regurgitation was limited (P<0.01). There was excellent correlation between regurgitant jet area/body surface area and angiographic regurgitant fraction (r = 0.85; P<0.001). There was also a good correlation between regurgitant jet area and regurgitant fraction (r = 0.82; P<0.001). However, the relation of regurgitant jet area/left atrial area to regurgitant fraction was weak (r = 0.72; P<0.01). In conclusion, the measurement of regurgitant fraction and its ratios to left atrial area and body surface area by color Doppler flow imaging can predict the angiographic severity in children who have even eccentric regurgitant jets.

Left atrial appendage function in patients with different pacing modes.

Many studies suggest that patients who receive a ventricular pacemaker have a higher incidence of systemic thromboembolism compared to patients receiving a physiological pacemaker. However, the exact mechanism regarding the etiology of thromboembolism remains unclear. We evaluated the left atrial appendage (LAA) functions, using multiplane transesophageal echocardiography (TEE), in patients with different pacing modes. In order to evaluate the ejection fraction (EF), peak emptying (V(E)) and filling (V(F)) flow velocities of the LAA by TEE, we studied 31 patients (mean age 63+/-18.5 years) who had been paced for 5.0+/-2.9 years. Patients with atrial fibrillation, left ventricular dysfunction and mitral valve disease were excluded. The pacing indications were complete atrioventricular block (AVB) in 19 patients (9 VVI, 10 VDD or DDD) and sick sinus syndrome (SSS) in 12 patients (5 VVI, 7 DDD). Mean EF, V(E) and V(F) of the LAA were significantly lower in all patients with ventricular pacing (25.5+/-15.6%, 30.4+/-15.6 cm/s and 29. 1+/-19.2 cm/s, respectively) compared to those with physiologic pacing (48.5+/-16.9%, 59.6+/-16.3 cm/s, 57.9+/-18.5 cm/s, respectively) (P<0.01 in all). When patients were further classified with respect to underlying heart disease whether they had SSS or AVB, all measurements of the LAA (EF, V(E) and V(F)) in both subgroup of patients with SSS and AVB were found significantly lower in those with ventricular pacing than in those with physiologic pacing (Tables 3 and 4). This decrease, especially in LAA flow, was much greater in those with SSS (Mean V(E) and V(F) <20 cm/s). In a patient paced with VVI for SSS, a thrombus was detected within the LAA cavity. In conclusion, these results suggest that the pacing modality appeared to influence the LAA functions in paced patients. Patients with asynchronous ventricular pacing modes had a significantly higher incidence of depressed LAA functions than did patients with physiological pacing, especially more marked in patients with sick sinus syndrome. This may be a factor responsible for increased risk of thrombus formation and thromboembolic events in this patient population.

Exercise performance in patients with dilated cardiomyopathy: relationship to resting left ventricular function.

Relationship between maximal exercise tolerance and resting indexes of left ventricular systolic and diastolic function were evaluated in 35 men, aged 55.1 +/- 10.4 years, with dilated cardiomyopathy. Clinical diagnosis of dilated cardiomyopathy was confirmed with M-mode echocardiography (M-mode echocardiographic end-diastolic dimension >55 mm, fractional shortening <25%, increased E point septal separation). Coronary angiography was considered mandatory for exclusion of patients with coronary artery disease. Patients with mitral regurgitation (> or =grade 2) and rhythm other than sinus were excluded. According to the functional classification of New York Heart Association 6 patients were in class I, 11 in class II, 12 in class III and 6 in class IV. Left ventricular ejection fraction (LVEF), stroke volume (SV) and left ventricular end-diastolic pressure (LVEDP) were measured with contrast angiography. Peak early (VE) and late (VA) transmitral filling velocities and their ratio (E/A), isovolumetric relaxation time (IRT) and deceleration time (DT) were computed from pulsed wave Doppler echocardiograms. On completion of all resting measurements, patients underwent symptom limited upright treadmill exercise testing using a modified Naughton protocol and maximal exercise performance metabolic equivalent work load (NETS) was calculated from the speed, incline and length of time at the stage using standard tables to make interpatient comparisons. Significant correlation has been found between NYHA class and METS (r= -0.77, P<0.001). However NYHA class II and NYHA class III patients were found to have similar METS (P=0.317). Patients were further divided into two groups on the basis of exercise data. Group I consisted of 22 patients with relatively preserved exercise tolerance (> or =4 METS) and Group II included 13 patients with impaired exercise tolerance (> or =4 METS). This arbitrary classification was based upon previously described survival differences in these two groups. There were no differences between two groups in terms of age, gender distribution (all were male), heart rate and arterial blood pressure. LVEF, LVEDP, stroke volume, VE, VA, E/A, IRT and DT were also similar between two groups. Strong positive correlation was observed between LVEDP and VE (r=0.74) while IRT and VA negatively correlated with LVEDP (r= -0.77 and r= -0.81 respectively) but neither of resting indexes of left ventricular systolic and diastolic function showed significant correlation with METS and exercise duration.

A case of type IV dual left anterior descending artery associated with anomalous origin of the left circumflex artery in the presence of coronary atherosclerosis.

Double origin of the left anterior descending coronary artery (LAD) from the left and right coronary arteries (type IV dual LAD) is a rare coronary anomaly. We report an unusual case of type IV dual LAD associated with anomalous origin of the left circumflex artery from the right coronary artery in a patient with a recent history of myocardial infarction. The first diagonal branch originating from the short LAD demonstrated 70-80% stenosis and the posterior descending artery was totally occluded. We believe that this unusual variance of the coronary arteries in association with atherosclerosis has not been previously reported.

Antistreptococcal response is exaggerated in children with familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder. Although the pathogenesis of the disease is not yet completely understood, enhanced acute-phase responsiveness is considered to be one of the most important mechanisms. The presence of high levels of antistreptolysin O (ASO) antibodies and streptococcus-associated diseases, such as acute poststreptococcal glomerulonephritis (AGN) and acute rheumatic fever (ARF), has been reported in patients with FMF. In order to better understand the effect of FMF on antistreptococcal antibody response, we measured ASO and antideoxyribonuclease B (anti-DNAse B) levels in patients with FMF and compared them with those in healthy controls. The study consisted of two parts. In the first step, antistreptococcal antibody levels were analysed in 44 patients with FMF and 165 healthy children who had no history or clinical evidence of upper respiratory tract infection (URTI) for the last 4 months. In the second step, antistreptococcal antibody levels were measured in 15 patients with FMF and 22 healthy controls in response to documented group A beta-haemolytic streptococcal pharyngitis. In the first part of the study, ASO and anti-DNAse B levels in patients with FMF were found to be significantly higher than those in healthy controls (P<0.001). In the second part, ASO and anti-DNAse B titres were found to be significantly higher in patients with FMF than in controls (P<0.001 and <0.05, respectively) 4 weeks after a positive throat culture. We concluded that patients with FMF have an exaggerated response to streptococcal antigens and might be prone to poststreptococcal non-suppurative complications, such as ARF.

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.

Congenital isolated apical ventricular septal defects.

The diagnosis of apical ventricular septal defects (VSDs) is difficult and the ratio of spontaneous closure is not well known. At the Ankara University Pediatric Cardiology Department, between the years 1992 and 1997, 33 patients were identified by color-flow Doppler (CFD) imaging as having a small defect at the apical portion of the ventricular septum. The age range was 1 day to 13 years. All patients were asymptomatic with normal telecardiograms and electrocardiograms. There were grade 2-3/6, pansystolic murmurs at the apex or closer to the apex in 19 patients. In 30 patients, narrow and short colored jets were seen at the apex of the heart, distal to the moderator band. The jets were wide in three patients. These defects were difficult to image and required specific angulation of the transducer. Of the 23 patients who had follow-up examinations, at 3 months to 3.5 years, there was spontaneous closure in ten (43.5%). To the authors' knowledge, this report is the largest series of isolated apical trabecular ventricular septal defects (t-VSDs). In their experience, color-flow imaging is more sensitive in detecting a small apical VSD. They conclude that although the closure of apical VSD is not the rule, the prognosis is excellent.

Congenital complete atrioventricular block in an infant with long QT syndrome.

A three months old patient with congenital complete atrioventricular block and prolonged QT interval syndrome is presented. Before admission she had had two syncopal attacks. During hospitalization she had an episode of torsade de pointes which was followed by ventricular fibrillation. After a successful cardiopulmonary resuscitation, a permanent epicardial ventricular pacemaker was implanted and she was discharged on propranolol therapy. She is now free of symptoms and doing well, 16 months after discharge.

Cutaneous fixed drug eruption to paclitaxel; a case report.

The aim of this report was to investigate an adverse effect of paclitaxel. Cutaneous fixed drug eruption against paclitaxel--which is rarely seen--is explained. A 70-year-old caucasian woman experienced three operations for ovarian carcinoma and finally a paclitaxel-based chemotherapy regimen was initiated as adjuvant chemotherapy. Following the administration of the first dose of paclitaxel, the patient had a cutaneous reaction that was clinically consistent with "fixed drug eruption". Lesions regressed with a topical steroid dressing. Histopathological examination of the lesion confirmed clinical diagnosis. It is interesting that such a reaction could occur despite the use of premedication with systemic corticosteroid antihistaminic prophylaxis yet heal rapidly with topical corticosteroid therapy. Thus we recommend careful observation for cutaneous side-effects in patients who receive paclitaxel or other taxanes, even with premedication prophylaxis.

Effect of verapamil and lidocaine on TRPM and NaV1.9 gene expressions in renal ischemia-reperfusion.

BACKGROUND: To determine effects on calcium and sodium channels of Ca(2+) and Na(+) channel blockers in the present study, expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, TRPM8, and NaV1.9 genes were evaluated in kidney tissues after induced ischemia-reperfusion. MATERIAL AND METHODS: Forty albino Wistar male rats were equally divided into 4 groups as follows: group I: control group (n = 10), group II: ischemia group (60 minutes of ischemia + 48 hours of reperfusion; n = 10), group III: ischemia (60 minutes of ischemia + 48 hours of reperfusion) + calcium channel blocker (n = 8), group IV: ischemia (60 minutes of ischemia + 48 hours of reperfusion) + sodium channel blocker (n = 8). RESULTS: When compared to ischemia group expression levels of TRPM2, TRPM4, TRPM6, and NaV1.9 in Ca(2+) and Na(+) channel blocker groups were increased, whereas that of TRPM7 was decreased. However, expression levels of TRPM1, TRPM3, TRPM5, and TRPM8 were not determined in kidney tissue. Histologically, the Ca(2+) channel blocker verapamil and the Na(+) channel blocker lidocaine inhibited the cell death in kidney tissue compared to control. CONCLUSION: Our study suggested that verapamil and lidocaine significantly reduce the degree of ischemia-reperfusion injury due to effects to TRPM and Nav1.9 genes.