Search PubMed⌕ Search

Biomedical subjects

M Covic

Publications and source records attributed to M Covic.

At least 19 recordsLinked to original sources
PubMed2003

Successful renal transplantation decreases aortic stiffness and increases vascular reactivity in dialysis patients.

BACKGROUND: Patients with end-stage renal disease on dialysis have among the highest cardiovascular event rates documented. Abnormal nitric oxide (NO)-dependent endothelial reactivity and increased arterial stiffness are commonly described in hemodialysis (HD) patients. Measures of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AGI)--have been shown to be powerful predictors of survival on hemodialysis. It is not known how these parameters interfere with successful renal transplantation. METHODS: PWV and aortic AGI (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from contour analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD patients (20 men; age, 41.8 years) and in a control group of 20 patients with essential hypertension (HTA) (10 men; age, 43.6 years). Twenty of the HD patients (10 men; age, 39.7 years) received live-related renal transplants (RTx) and were restudied (3 months after RTx, normal serum creatinine). NO-dependent and NO-independent vascular reactivity were assessed by changes in AGI after challenges with inhaled salbutamol (SAL) and sublingual nitroglycerin (NTG), respectively. RESULTS: AGI values were significantly lower in RTx patients compared with subjects on hemodialysis (15.9 +/- 13.9% vs. 27.9 +/- 11.9%, P<0.05), but similar to essential HTA controls (16.5 +/- 17%). Serial AGI measurements showed that successful renal transplantation is associated with a decrease in AGI in all cases, from a mean of 25.1 +/- 7.8% while on dialysis to 15.9 +/- 7.0% 3 months after transplantation (P<0.0001). The responsiveness to both endothelium-dependent stimuli (inhaled SAL) and endothelium-independent stimuli (sublingual NTG) was greater in transplant patients than in hemodialysis patients (SAL-induced decrease in AGI -82.3 +/- 65.7% vs. 45 +/- 72.3%, P<0.01; and NTG-induced decrease in AGI 197 +/- 108 vs. -129.0 +/- 215.5%, P<0.01). PWV values in dialysis patients (7.19 +/- 1.88 m/sec) were significantly higher than those measured in essential HTA patients (6.34 +/- 1.32 m/sec, P<0.05) with normal renal function (despite similar blood pressure levels). PWV after RTx was 6.59 +/- 1.62 m/sec, significantly different from pretransplantation (dialysis) values (P<0.05 for comparison) but similar to the control group of essential HTA patients. CONCLUSIONS: Renal transplantation is associated with marked improvements in vascular structure and function to a profile comparable to essential HTA patients.

Adult↗
PubMed2001

The enzymatic and DNA binding activity of PARP-1 are not required for NF-kappa B coactivator function.

Poly(ADP-ribose) polymerase 1 (PARP-1)-deficient mice are protected against septic shock, diabetes type I, stroke, and inflammation. We report that primary cells from PARP-1(-/-) animals are impaired in kappa B-dependent transcriptional activation induced by different stimuli involved in inflammatory and genotoxic stress signaling. PARP-1 was also required for p65-mediated transcriptional activation. PARP-1 enzymatic inhibitors did not inhibit the transcriptional activation of a kappa B-dependent reporter gene in wild type cells. Remarkably, neither the enzymatic activity nor the DNA binding activity of PARP-1 was required for kappa B-dependent transcriptional activation in PARP-1(-/-) cells complemented with different PARP-1 mutants. However, PARP-1 interacted in vitro directly with both subunits of NF-kappa B (p50 and p65), and mapping of the interaction domains revealed that both subunits bind to different PARP-1 domains. Furthermore, a PARP-1 mutant lacking the enzymatic and DNA binding activity interacted comparably to the wild type PARP-1 with p65 or p50. Finally, we showed that PARP-1 is activating the natural inducible nitric-oxide synthase and P-selectin promoter in a kappa B-dependent manner upon stimulation of the cells with inflammatory stimuli or cotransfection of p65. Our results provide evidence that neither the DNA binding nor the enzymatic activity of PARP-1 but its direct protein-protein interaction with both subunits of NF-kappa B is required for its coactivator function, thus expanding the role of PARP-1 as an essential and novel classical transcriptional coactivator for kappa B-dependent gene expression in vivo.

B-Lymphocytes↗
PubMed2000

Reduced blood pressure diurnal variability as a risk factor for progressive left ventricular dilatation in hemodialysis patients.

Cardiovascular mortality places a considerable burden on chronic renal replacement therapy programs. Left ventricular hypertrophy (LVH) increases the risk for cardiovascular mortality. Risk factors for LVH in the dialysis population are numerous and include arterial distensibility, hypertension, anemia, arteriovenous fistula, and hyperparathyroidism. An important factor to consider in the diagnosis and evaluation of hypertension in this clinical setting is blood pressure (BP) level variation, only accessible using ambulatory BP monitoring (ABPM). In uremic patients, a relative elevation of BP during sleep periods leading to an increased 24-hour BP load is frequently described. Whether this additional BP burden is pathophysiologically significant has not been resolved. This study is designed to examine the effect on echocardiographically derived measurements of the left ventricle in 60 stable chronic hemodialysis patients of abnormal (reduced) diurnal BP variability, measuring ambulatory BP on three occasions and performing echocardiography twice over a 12-month period. First, we found that most dialysis patients (76%) had consistent diurnal BP rhythms over a 12-month period, and second, those patients with persistently reduced diurnal BP rhythm tended to develop a dilated left ventricle and left atrium in the absence of other known and/or relevant risk factors (persistently increased sleep BP group; n = 36; LV end-diastolic diameter, 38.2 +/- 2.5 mm/m(2) versus persistently normal sleep BP group; n = 10; LV end-diastolic diameter, 30.6 +/- 3. 3 mm/m(2); P < 0.05). These results suggest that persistent abnormal BP variability is a risk factor for a dilated heart on dialysis, independent of the BP level.

Adult↗
PubMed2000

Analysis of the effect of hemodialysis on peripheral and central arterial pressure waveforms.

BACKGROUND: Arterial stiffening is very pronounced in renal patients. Carotid artery stiffening is a powerful predictor of future cardiovascular mortality, and measures of arterial compliance correlate much better with left ventricular mass (LVM) in dialysis patients than does brachial artery blood pressure (BP). The aim of our study was to describe the influence of a hemodialysis (HD) session on arterial cushioning function and to correlate the potential different types of behavior with echocardiographic derived parameters. METHODS: Radial artery pressure waveforms were measured and recorded noninvasively by applanation tonometry in 51 healthy patients on regular three times weekly HD. The data were then converted into aortic pressure waveforms using a regression equation (SphymoCortrade mark apparatus). Measurements were done pre- and post-HD in order to ascertain the effect of a single HD session on arterial hemodynamics. The augmentation index (AGI; the difference between early and late pressure peaks divided by the pulse pressure amplitude) was used as an index for vascular compliance. Reproducibility was assessed in 20 young healthy subjects by determining the aortic pulse wave augmentation index twice from radial artery BP measurements one minute apart. Intraobserver error was 2.4%. For 10 dialysis patients similarly studied, the intraobserver error was 1.6%. RESULTS: AGI was correlated with subjects' height (r = -0.37, P = 0.009), weight (r = -0.41, P = 0.002), and BP levels: radial systolic BP (r = 0.33, P = 0.018), radial diastolic BP (r = 0.29, P = 0.036), and central systolic BP (r = 0.51, P < 0.001). Comparing the pre- with the post-HD AGI values, four patterns of evolution became apparent: (1) The AGI was negative before the HD session and became even more negative afterward (N = 3 out of 51). (2) The AGI was positive before the HD session but became negative after dialysis (N = 19 out of 51). (3) The AGI was positive before the HD session and, although diminished afterward, remained positive (N = 23 out of 51). (4) The AGI was positive before the HD session and increased afterward (N = 6 out of 51). We also found that in some patients, AGI remained at lower than predialysis levels for at least 24 hours. Significant relationships between echocardiographic parameters and pulse wave contour (PWC) variables included pre-HD AGI and LVM (r = 0.47, P < 0. 001). There was better correlation between LVM and derived predialysis aortic systolic BP (r = 0.56, P < 0.001) than measured brachial (peripheral) systolic BP (r = 0.35, P = 0.04). Patients whose waveform remained abnormal (AGI remained positive) after HD had a more dilated LV (LV-EDD = 52.07 +/- 3.48 mm) than did those patients for whom HD restored "normal" arterial hemodynamics (LV-EDD 46.86 +/- 4.06 mm, P < 0.05). CONCLUSIONS: A standard HD session profoundly affected aortic BP waveform characteristics, with a reduction in wave reflection in 88% of patients. However, restoration by HD of a normal aortic waveform was unusual. Patients whose waveform remained abnormal after HD had larger more dilated LV chambers than did those patients for whom HD restored "normal" arterial hemodynamics.

Adult↗
PubMed1999

Hepatitis virus infection in haemodialysis patients from Moldavia.

BACKGROUND: Although the epidemiology of hepatitis B (HBV) and C (HCV) now seems well established for Western European countries, in Central and Eastern Europe < 50% of all dialysis centres routinely test for hepatitis C antibodies since testing is not available or is not applied to all patients. This study describes the prevalence, risk factors and clinical significance of HBV and HCV infection for the haemodialysis population of the North Eastern region of Romania, Moldavia. METHODS: The presence of HBV antigens was determined with an ELISA kit (Wellcome, Abbot) and HCV antibodies with the ELISA-3 Ortho-HCV, third generation test. The following individual data were collected: gender, age, duration of dialysis, rural/urban domicile, actual and previous HBV status, actual HCV status, known acute, clinically evident hepatitis episodes in the last 3 years, monthly alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) levels, complete biochemical hepatic assessment at the time of the study, transfusions for the past 3 years and family history. RESULTS: HBV and HCV prevalences were 17% (stable over the last 3 years) and 75%, respectively; co-infection was seen in 10% of the subjects. Hospitalization (nosocomial infection) for HBV, blood transfusions and duration on dialysis for HCV, emerged as the main risk factors for hepatitis infection. Socio-economic conditions appear to be equally important for HCV infection, since the prevalence was significantly higher among patients from rural, underdeveloped areas than urban areas (80.8 vs 60.3%), and infection was already present in a large proportion of patients (47%) before starting dialysis, without being related to previous disease duration or blood transfusions. HBV and/or HCV was not associated with a worse clinical or biochemical profile at the time of the study. However, infected patients had significantly more previous cytolytic episodes, with higher, transient increases in ALAT and ASAT levels. CONCLUSIONS: HCV infection is endemic among dialysis centres in Moldavia. Apart from previously well-known risk factors for hepatitis infection, our study demonstrates the negative impact of socio-economic underdevelopment. Simple measures such as enforced general asepsia rules, careful disinfection and equipment sterilization, routine testing of patients from economically disadvantaged areas and monthly, serial determination of hepatic enzymes should be the common practice in dialysis centres in Romania.

Adult↗
PubMed1998

Rifampicin-induced acute renal failure: a series of 60 patients.

BACKGROUND: Since 1971, 55 case-reports of rifampicin-induced ARF have been published, but systematic data on this condition are not available, in view of the disparate nature of the observations. METHODS: We retrospectively assessed prevalence, clinical and biochemical features, and prognostic factors of 60 consecutive cases (41 males/19 females, age 22-68 years), who were admitted to the Iasi Dialysis Centre from 1987 to 1995 for acute renal failure (ARF) following re-treatment with rifampicin. RESULTS: The clinical appearance consisted mainly of gastrointestinal and 'flu-like' symptoms and clinical signs of intravascular haemolysis (the latter in 17% of cases). Frequent laboratory findings were anaemia (96% of cases), leukocytosis (63%), and thrombocytopenia (50%). Severe anaemia was associated with marked haemolysis (25% cases), thrombocytopenia, longer anuria, and slower rate of renal function recovery. Signs of hepatic injury were found in 25% of patients, but it did not seem to affect the outcome of renal function. Prognostic factors in post-rifampicin ARF proved to be the following: the duration of the anuric phase (correlated with the number of dialysis sessions and with the rate of decrease of azotaemia) and the severity of the immunological abnormalities and inflammatory syndrome (haemolysis, leukocytosis, hypergammaglobulinaemia). Post-rifampicin ARF accounted for 16.6% of all ARF cases hospitalized in our Centre during the studied period. Its clinical course was favourable; the mortality rate was only 1.6% (1 case), compared to a 20% general mortality rate among all ARF patients. Full recovery of renal function was achieved in 40% and 96% of patients, 30 and 90 days respectively from onset. CONCLUSIONS: ARF after treatment with rifampicin is not an uncommon condition, especially when tuberculosis prevalence is high, but renal prognosis is usually favourable. Thrombocytopenia, immune haemolytic anaemia, and intravascular haemolysis are frequent complications which are associated with a more severe renal injury.

Acute Kidney Injury↗
PubMed1995

[Secondary hyperparathyroidism].

Secondary (renal) hyperparathyroidism appears in chronic renal failure, sometimes in patients on chronic dialysis. Other causes includes rickets and osteomalacia. These diseases are associated with poor calcium and vitamin D absorbtion from the small bowel. Two patients with chronic renal failure maintained on chronic haemodialysis from two and three years, respectively underwent subtotal parathyroidectomy: removal of three glands and preserving a half of a gland in situ. The diagnosis and surgical indication was made upon clinical (bone pain and severe itching), radiological (demineralisation, ectopic calcifications) and biochemical (hypercalcemia, hyperphosphoremia, increased values of alkaline phosphatases) arguments. Postoperatively the improvement is defined by a return to normal in the clinical, laboratory and radiological parametres. The most appropriate operation for secondary hyperparathyroidism is still unresolved one of two techniques is performed according to the preference of the surgeon: subtotal parathyroidectomy or total parathyroidectomy with autotransplantation of parathyroid fragments into forearm muscle.

Adult↗
PubMed1978

[Diagnostic and therapeutic problems in a clinical case of oculoauricular dysplasia associated with mandibule-facial dysostosis (Franceschetti-Goldenhar syndrome)].

The authors present a case of oculo-auricular dysplasia (type Goldenhar) associated with France-schetti's syndrome (mandibulo-facial dysostosis) and complicated by paralytic strabismus and genital malformations. Complete investigation failed to establish a precise aetiology; one suggests an external disturbance in the course of the organogenesis of the branchial arches. Aesthetic improvement was undertaken--removal of epibulbar dermoids, correction of the squint, and ablation of the preauricular appendages; functional orthodontic treatment continues.

Adult↗