Heart failure in patients is associated with downregulation of mitochondrial quality control genes.

BACKGROUND: Mitochondrial dysfunction is one of key factors causing heart failure. We performed a comprehensive analysis of expression of mitochondrial quality control (MQC) genes in heart failure. METHODS: Myocardial samples were obtained from patients with ischemic and dilated cardiomyopathy in a terminal stage of heart failure and donors without heart disease. Using quantitative real-time PCR, we analysed a total of 45 MQC genes belonging to mitochondrial biogenesis, fusion-fission balance, mitochondrial unfolded protein response (UPRmt), translocase of the inner membrane (TIM) and mitophagy. Protein expression was analysed by ELISA and immunohistochemistry. RESULTS: The following genes were downregulated in ischemic and dilated cardiomyopathy: COX1, NRF1, TFAM, SIRT1, MTOR, MFF, DNM1L, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and BECN1. Moreover, MT-ATP8, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. VDAC1 and JUN were only genes that exhibited significantly different expression between ischemic and dilated cardiomyopathy. Expression of PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 was not significantly different between control and any form of heart failure. TOMM20 and COX proteins were downregulated in ICM and DCM. CONCLUSIONS: Heart failure in patients with ischemic and dilated cardiomyopathy is associated with downregulation of large number of UPRmt, mitophagy, TIM and fusion-fission balance genes. This indicates multiple defects in MQC and represents one of potential mechanisms underlying mitochondrial dysfunction in patients with heart failure.

Drug-Eluting Balloons-A New Tool in the Treatment of Cardiac Allograft Vasculopathy: A Case Series.

Percutaneous coronary intervention in patients with cardiac allograft vasculopathy is burdened with a lot of difficulties. Although they have allowed significant progress in comparison with plain balloon angioplasty and bare metal stents, drug-eluting stents have not fully overcome problems of diffuse lesions and small-vessel disease that are so common in transplant coronary artery disease. There is growing evidence that drug-eluting balloons might be a better choice for patients with small vessel atherosclerotic coronary disease and yet there is no experience with this technology in patients with cardiac allograft vasculopathy. Herein we report a case series of successful percutaneous coronary interventions in patients with cardiac allograft vasculopathy.

Incidental extraction of a temporary epicardial pacemaker wire with right ventricular perforation during endomyocardial biopsy: a case report.

INTRODUCTION: Right ventricular perforation during endomyocardial biopsy is an unusual, although potentially life-threatening, complication caused with the tip of the bioptome. The majority of perforations in heart transplant patients can be managed without surgery owing to adhesions nearly obliterating pericardial space. CASE REPORT: We report a case of heart transplant patient who suffered right ventricular perforation as a consequence of incidental extraction of a temporary epicardial pacemaker wire during a routine endomyocardial biopsy sampling. CONCLUSIONS: The patient suffered no clinical consequences.

PPARγ and IL-6 - 174G>C gene variants in Croatian patients with ischemic stroke.

AIM: Etiology of ischemic stroke (IS) is multifactorial and includes interaction of genetic and environmental factors. Different genes, their polymorphisms, host susceptibility, and inflammation processes play a role in IS development. The aim of this study was to evaluate the effect of PPAR-γ and IL-6 gene variants on IS onset. MATERIAL AND METHODS: A total of 301 subjects (144 males, 157 females) participated in the study, 114 patients with IS and 187 healthy controls. RESULTS: Statistically significant predictors of IS were male gender (OR 7.13, 95% CI 2.92-17.39, p<0.001), hypertension (OR 7.82. 95% CI 2.53-24.19, p<0.001), lowered HDL cholesterol (OR 8.20, 95% CI 2.41-27.94, p=0.001), elevated C-reactive protein (OR 5.26, 95% CI 1.92-14.41) and IL-6 -174 GC (OR 2.44 95% CI 1.01-5.91, p=0.0048) genotype. Males, compared to females, had 7 times higher odds for stroke. IL6 -174G/C genotype increased the odds for IS for 2.4 times. PPARγ was not statistically significantly associated with stroke. CONCLUSION: We can point to the IL-6 -174G>C polymorphisms as candidate gene marker and risk factor for the prediction of ischemic stroke.

Management of heparin-induced thrombocytopenia with fondaparinux in a patient with left ventricular assist device.

Heparin-induced thrombocytopenia is an immune-mediated serious adverse effect of heparin therapy. It is a relatively frequent complication among patients with mechanical circulatory support. Herein, we present a patient with severe heart failure and sepsis who developed heparin-induced thrombocytopenia shortly after implantation of left ventricular assist device as a bridge to transplantation and who was successfully treated with fondaparinux.

[Current management of patients with ventricular tachycardia]. / Suvremeni pristup bolesnicima s ventrikulskom tahikardijom.

Ventricular arrhythmia has for decades been considered as a premonitory sign and risk marker of sudden death. Novel theories about arrhythmogenesis and conditions for the occurrence of sudden death, as well as evidence about proarrhythmic effect of antiarrhythmic drugs, have changed the views on the treatment of ventricular arrhythmia. Ventricular tachycardia (VT) is most often associated with structural heart disease: ischemic heart disease and previous myocardial infarction, cardiomyopathy (dilated and hypertrophic), arrhythmogenic right ventricular dysplasia, valvular heart disease (mitral valve prolapse), heart failure, condition after surgical correction of a congenital heart disease. Sometimes VT occurs without structural heart disease (congenital LQTS, Brugada syndrome, idiopathic VT). Today's standpoint is to treat only symptomatic and/or prognostically significant arrhythmias. Prognostic significance of VT mostly depends on the type and degree of structural heart disease and on global cardiac function. In patients with asymptomatic non-sustained VT and low risk for sudden death no treatment is needed or antiarrhythmics are administered. Conversely, in high risk patients implantation of automatic cardioverter-defibrillator is indicated. In the treatment of acute attack of VT the following can be used: electroconversion, cardiac pacing (overdrive), lidocaine, amiodarone, beta-blockers, and occasionally magnesium or verapamil. In the prevention of recurrent arrhythmia and sudden death we can use: amiodarone, sotalol, mexiletin, phenytoin, beta-blockers, radiofrequency ablation, implantable cardioverter-defibrillator, and in specific patients verapamil, pacemaker or left ganglion stellatum denervation.

Glutathione and glutathione S-transferases as early markers for ovarian carcinomas: case series.

AIM: To determine the activity of glutathione (GSH) and concentrations of glutathione S-transferases (GST), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type 1 (PAI-1), and to evaluate their diagnostic and prognostic value and possible correlation with clinical and histopathological prognostic factors for ovarian carcinomas. METHODS: The concentrations of GSH, uPA, PAI-1, and activity of GST were analyzed in 35 tissue samples taken from 10 normal ovaries, 10 benign, 10 primary malignant, and 5 metastatic ovarian tumors. The GSH level and GST activity were determined by spectrophotometric methods, and uPA and PAI-1 concentrations by ELISA commercial kits. RESULTS: GSH concentrations were significantly higher in primary malignant (126.3+/-12.8 nmol/mg protein) and metastatic (160.5+/-24.3 nmol/mg protein) ovarian tumor specimens than in normal ovarian tissue (48.9+/-8.1 nmol/mg protein, p<0.003 for both carcinoma groups) or benign ovarian tumor samples (35.2+/-5.0 nmol/mg protein, p=0.001). The GST activity was significantly higher in primary malignant (245.8+/-22.7 nmol/min/mg protein) and metastatic (303.7+/-48.8 nmol/min/mg protein) ovarian tumor tissues than in benign tumor specimens (105.9+/-16.2 nmol/min/mg protein, p<0.004 for both carcinoma groups) or normal ovarian tissue samples (133.2+/-32.0 nmol/min/mg protein, p<0.044 for both carcinoma groups). There were no statistical differences in uPA and PAI-1 concentrations between normal, benign, and malignant tumor samples. Concentrations of GSH, uPA and PAI-1, and activity of GST were independent from histopathological and clinical prognostic factors. CONCLUSION: Increased GSH concentration and GST activity found in primary malignant and metastatic ovarian tumor samples were independent of histopathological and clinical prognostic factors, suggesting that they could be early markers for ovarian carcinomas.

A method for the repair of vesicovaginal fistulas.

OBJECTIVE: To determine the efficacy of the sliding layers method for repairing vesicovaginal fistulas caused by surgical trauma. METHOD: Twenty one women suffering from vesicovaginal fistulas after surgical trauma, operated on between 1990 and 1995 using the sliding layers method, were included in an uncontrolled prospective study and followed 24 months after the procedure. Patient outcome was assessed according to subjective estimation, gynecological examination and objectively by instillation of diluted methylene blue to the urinary bladder. RESULTS: Sixteen out of 21 patients suffered vesicovaginal fistulas after being subjected to abdominal hysterectomy and five patients after vaginal surgery. Fourteen fistulas were located 5 to 10 mm over the interureteric edge, five fistulas were in the trigone and two fistulas were in the bladder neck region. Fistula size ranged from 5 to 35 mm in diameter but 72.1% of patient fistulas were less than 10 mm in diameter. Only one patient had a large bladder defect of 35 mm in diameter. According to subjective estimation and objective assessment the overall success rate of the procedure after 2 years was 95.2%. Only one patient had to be subjected to a second successful attempt for fistula closure. CONCLUSION: The sliding layers method is a safe and reliable vaginal surgical approach for the repair of vesicovaginal fistulas after surgical trauma.

Determination of rates of cerebral blood flow during the gestation period under 33 weeks colour doppler pulse study

No disponible

Plasminogen activator inhibitor type 2: potential prognostic factor for endometrial carcinomas.

The clinical determination of proteases which are involved in carcinogenesis, invasion and metastasis may contribute to the detection of the early stage of disease, and to the prognostic assessment of patients with the cancer. The aim of the present study was to determine the level of urokinase plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1) and plasminogen activator inhibitor type 2 (PAI-2) in normal and malignant tissues of corpus uteri and to evaluate the possible correlation with clinical and histopathological prognostic factors. UPA, PA-I and PAI-2 were determined by the ELISA assay in tissue cytosol of matched pair samples from 27 patients with endometrial carcinoma. Results show that significantly higher levels of these proteins were found in malignant than in normal tissue samples (uPA: 1.266 versus 0.633 ng/mg protein, PAI-1:4.468 versus 1.958 ng/mg protein, and PAI-2:3.428 versus 0.483 ng/ml protein). The levels of uPA and PAI-1 did not correlate with clinical staging or pathohistological grading. However, in tumor tissues with clinical stages II and III, myometrial invasion > 50%, and lymphovascular invasion, increased levels of PAI-2 were determined. Our results indicate that components of the plasminogen activation cascade are up-regulated in endometrial cancer and suggest the role of PAI-2 in determining invasive potential of endometrial carcinomas.

Clinical variability and molecular diagnosis in a four-generation family with X-linked Emery-Dreifuss muscular dystrophy.

AIM: To describe the clinical variability of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) with cardiac involvement in a four-generation family with a novel mutation in the STA gene. METHODS: Clinical data were provided for 4 affected males and a female carrier. The Western blot analysis of emerin was performed on lymphoblastoid cell lines and followed by sequencing of the emerin gene. RESULTS: A thymine insertion at nucleotide 417 in exon 2, resulting in a frameshift with a premature stop codon at position 62 and absence of functional protein, was found in one of the three available patients. In ten-year-old proband's dizygotic twin-nephews the intermittent first-degree A-V block, atrial and ventricular ectopy, atrial runs, and exit sinus block were found, although the echocardiographic findings were normal. One of the twins also had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm. CONCLUSION: Cardiac abnormalities in the proband's ten-year-old dizygotic twins without evident clinical features suggestive of EDMD were remarkable in contrast to the oldest patient in the family, who lived to the age of 63 without a pacemaker, and to the proband who had a very early onset of muscle wasting and weakness, and a pacemaker implantation at the age of 27. This striking intra-familial variability in cardiac involvement associated with specific null mutation (417 ins T) has practical early diagnostic and possibly preventive implications. It also points at genetic and environmental factors as causes of clinical features in X-EDMD.

Intravesically administered ketoprofen in treatment of detrusor instability: cross-over study.

AIM: To evaluate the therapeutic efficacy of intravesically administered ketoprofen in patients with urodynamically verified detrusor instability. METHODS: This double-blind randomized placebo-controlled cross-over study included 30 patients with urodynamically verified detrusor instability. Their mean age was 44+/-3.6 years (range 37-49) and the median of the parity was 2 years (1-3). The mean duration of symptoms was 18.3+/-3.1 months (range 14-23). After a 6-week screening, patients were randomized to receive ketoprofen or placebo once a day for 4 weeks. Out of 30 patients, 16 started with ketoprofen, and 14 received placebo. After a week of washing period, 16 patients received placebo, and 14 received ketoprofen. The solution for intravesical application was 50 mL of saline with 2 mL (100 mg) of ketoprofen warmed to 37 degrees C. The placebo solution contained 2 mL of distilled water instead of ketoprofen. The assessment including micturition diaries, cystometric measurements, and bacteriological analysis of urine specimens was performed at the beginning of the study and after the treatment. RESULTS: The subjective cure rate was 18/30 after ketoprofen. The instability index was lower after ketoprofen than before treatment or after placebo (p<0.001). Maximal cystometric capacity and the urinary bladder volume at which the patients felt urgency to void were larger after ketoprofen than before it (p<0.001) or after placebo (p<0.001). The number of patients with uninhibited bladder contractions decreased significantly after ketoprofen, but not after placebo (p<0.001). No side effects were observed. CONCLUSION: Intravesically administrated ketoprofen is a feasible and effective treatment for detrusor instability.

[Atrio-biventricular electrostimulation in the treatment of congestive heart failure. Case report]. / Atrio-biventrikulska elektrostimulacija u lijecenju kongestivnog zatajivanja srca. Prikaz bolesnika.

Over the past few years, indications for permanent cardiac pacing have been broadened. Accordingly, American Heart Association and American College of Cardiology included dilated cardiomyopathy, hypertrophic obstructive cardiomyopathy and pacing for prevention of atrial fibrillation into indications for permanent cardiac pacing. Studies have described favourable effect of dual chamber cardiac pacing in congestive heart failure in dilated cardiomyopathy, regardless of etiology. In the past two years, even more beneficial effect was associated with multisite, biventricular cardiac pacing. On the basis of the reported results, a multisite pacemaker InSync was implanted to a patient with dilated cardiomyopathy (NYHA class IV), who was also on the list for heart transplantation, and who fulfilled other criteria for implantation of multisite pacemaker. During the eleven-month follow-up, functional improvement, better 6-minute walking test and enhanced quality of life of the patient were observed, which is in accordance with the literature data.

Prognostic factors in squamous cell carcinoma of the larynx.

Sixty-three patients with squamous cell carcinoma of the larynx were included in a retrospective study examining the influence of the following prognostic indicators: localization, size of primary tumor, presence or absence of neck metastases, disease stage and histologic grade of differentiation. Flow cytometric analysis of the cell cycle, DNA ploidy and proliferative activity as direct prognostic indicators of tumor aggression was performed on paraffin-embedded blocks of specimens taken from 36 patients. Supraglottic tumor localization (p = 0.008), greater tumor size (p = 0.0064), local neck metastases (p = 0.00009), higher clinical disease stage (p = 0.0030), DNA aneuploidy (p = 0.0091), higher overall activity (p = 0.0001), and higher overall proliferative activity of diploid tumors (p = 0.0017) were found to be significant single unfavorable prognostic indicators of overall survival, whereas the histological grade of differentiation was not found to be a reliable prognostic indicator (p = 0.988). Only a higher overall proliferative activity of tumor cells was confirmed by the multivariate analysis as a reliable unfavorable prognostic indicator (p = 0.013). Cellular DNA content (ploidy, overall proliferative activity and overall proliferative activity of diploid tumors) correlated significantly with primary localization and size of the tumor, the presence of local metastases in the neck and the disease stage.

Prognostic factors in carcinoma of the larynx: relevance of DNA ploidy, S-fractions and localization of the tumour.

The influence of the cell cycle profile and the site of the primary tumour on the overall survival were examined in 36 patients with squamous cell carcinoma of the larynx. DNA ploidy (p = 0.0091), the overall proliferative activity (p = 0.0001), the overall proliferative activity of diploid tumour cells (p = 0.0017) and primary tumour site (p = 0.0008) were found to be significant single prognostic factors of the overall survival. Multivariate analysis showed that only the overall proliferative activity was prognostically significant (p = 0.013). The results of the study show that the supraglottic site of the tumours correlates significantly with DNA ploidy (p = 0.0334) and the overall proliferative activity of tumour cells (p = 0.0159), whereas the correlation with proliferative activity of diploid tumour cells (p = 0.1416) has not been confirmed by this study. Glottic tumours showed a prognostically significant correlation with the overall proliferative activity (p = 0.0037) and proliferative activity of diploid tumour (p = 0.0054). Such a prognostic correlation was not found for DNA ploidy (p = 0.6542).

A tinnitus objectivization: how we do it.

The medical therapy of tinnitus should be oriented by objective measurement of the disorder. Preferably, it should be qualitative, indicating the exact neural mechanism to be neuromodulated by neuroprotective medication. The neurophysiological approach in objectivization of tinnitus is presented by means of auditory brainstem response and middle latency response. These tests could be applied in functional follow-up of medical therapy, as these are more sensitive and harmless methods as compared to standard morphological methods.

[Acute renal insufficiency in children]. / Akutna renalna insuficijencija kod djece.

Acute renal failure (ARF) is not rare in hospitalized children, especially in newborns and infants. Sudden disorganization of a glomerular and tubular function is the most often transitory and require a quick make of diagnosis and early therapy in order to obtain a adequate kidney function recovery and to reduce mortality. In this article 51 children with ARF were included from newborn period to 16 years of age (25 female: 26 male). We described the most often causes of ARF, diagnosis procedures and nondialytic treatments. The diagnosis was made by history, physical examination, laboratory and radiology findings. Causes of ARF were divided on prerenal, renal and postrenal. The treatment of ARF in all cases was conservative with good success in 45 patients and in 6 children followed death because of the nature of primary diseases. The results of study show that the accent is on the prevention, early diagnosis and early therapy of diseases which lead to ARF. We conclude that a multidisciplinary therapeutic approach is imperative for successful management of ARF.

[Remission of nephrotic syndrome in children treated with corticosteroids and other immunosuppressive therapy]. / Remisija nefrotskog sindroma kod djece lijecene kortikosteroidima i drugom imunosupresivnom terapijom.

Hypoproteinaemia, proteinuria and edema are the main features of Nephrotic syndrome (NS) and are the result of greater permeability of glomerular basal membrane for proteins. It is difficult to predict course of disease and outcome. During 1989-1998 year 18 children were followed up, 9 boys and 9 girls, at the age of 2 to 14 years and diagnosis of NS. Therapy with pronison was initiated in all children according to the protocol of ISKDC. Children were then divided in two groups, depending on success of therapy. In the first group (13 patients, 72.22%) were the patients that had remission, and the second group consisted of 5 patients that did not have remission. In the first group relapses occurred in 7 patients (53.84%), because of side effect of pronison therapy was discontinued in 3 patients. Those 3 patients along with 5 patients from second group were then turned to immuno-suppressive therapy. One patient responded well to cyclophosphamide, rest of them with regular follow up. Two years latter two of them had relapse but responded well on pronisone therapy in the full dose. Biopsies that were done showed that 2 had minimal changes, 2 had focal segmental sclerosis and one membranous proliferative glomerulonephritis. One patient developed chronic renal insufficiency. We conclude that our experience shows that if there is not favorable effect of corticosteroid therapy cyclosporine A is the first choice in NS, without regarding of the patho-hystological findings.

Influence of nasal fontanel receptors on the regulation of tracheobronchal vagal tone.

AIM: To test the hypothesis according that the receptors located in the nasal fontanels influence the regulation of the tracheobronchial tree vagus tone. METHODS: Changes in respiratory parameters (forced expiratory volume in the first second- FEV1 and total resistance- Rt) occurring consequentially to light mechanical nasal stimulation were determined in healthy volunteer, non-smokers using spirometric and body plethysmographic measurements. The parameters were measured before and at 15 and 60 min after mechanical stimulation with cotton pledge. RESULTS: In subjects in whom the middle nasal meatus was stimulated by a cotton pledge soaked in saline, FEV1 decreased (p=0.01) and Rt increased (p=0.03). In subjects in whom the middle nasal meatus was stimulated by a cotton pledge soaked in 5% cocaine solution, no change was observed. In the control group of subjects, in whom the inferior nasal concha was stimulated by a cotton pledge soaked in saline, only a statistically significant decrease for FEV1 (p=0.04) was found. CONCLUSION: There is a reflex communication between the nasal fontanel receptors and lungs, which is regulating the tracheobronchial vagal tone and resistance in lung airways. Further studies of this important physiologic relation are needed.