Biomedical subjects

Tomas Haas

Publications and source records attributed to Tomas Haas.

10 recordsLinked to original sources

PubMed2007

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.0 mg/day with reduced-dose CsA. Study 1 enrolled 237 de novo renal allograft recipients, randomizing 222 nonblack patients to either everolimus 1.5 or 3.0 mg/day, with the Neoral) dose guided by C(2) (monitoring of CsA concentration 2 h after dosing). Study 2 had a similar protocol, with basiliximab included, enrolling 256 recipients and randomizing 243 nonblack patients. In Study 1, there was a lower incidence of acute rejection in nonblack patients on 3 mg/day (16.4%) compared with 1.5 mg/day (25.9%), P = 0.08. In Study 2, the inclusion of basiliximab lowered the overall incidence of acute rejection; 14.3% of nonblack patients (3 mg/day) and 13.6% of nonblack patients (1.5 mg/day) had acute rejection by 12 months (P =0.891). Renal function was preserved throughout the study, with no differences observed between groups within studies. Everolimus was well tolerated with no significant differences between doses. Everolimus, in combination with reduced-dose Neoral), demonstrated efficacy and was well tolerated. Basiliximab allows for utilization of lower doses of everolimus with reduced dosing of Neoral).

Adult↗

PubMed2006

Oral fingolimod (FTY720) for relapsing multiple sclerosis.

BACKGROUND: Fingolimod (FTY720) is a new oral immunomodulating agent under evaluation for the treatment of relapsing multiple sclerosis. METHODS: We randomly assigned 281 patients to receive oral fingolimod, at a dose of 1.25 mg or 5.0 mg, or a placebo once daily, and we followed these patients for 6 months with magnetic resonance imaging (MRI) and clinical evaluations (core study, months 0 to 6). The primary end point was the total number of gadolinium-enhanced lesions recorded on T(1)-weighted MRI at monthly intervals for 6 months. In an extension study in which the investigators and patients remained unaware of the dose assignments (months 7 to 12), patients who received placebo underwent randomization again to one of the fingolimod doses. RESULTS: A total of 255 patients completed the core study. The median total number of gadolinium-enhanced lesions on MRI was lower with 1.25 mg of fingolimod (1 lesion, P<0.001) and 5.0 mg of fingolimod (3 lesions, P=0.006) than with placebo (5 lesions). The annualized relapse rate was 0.77 in the placebo group, as compared with 0.35 in the group given 1.25 mg of fingolimod (P=0.009) and 0.36 in the group given 5.0 mg of fingolimod (P=0.01). For the 227 patients who completed the extension study, the number of gadolinium-enhanced lesions and relapse rates remained low in the groups that received continuous fingolimod, and both measures decreased in patients who switched from placebo to fingolimod. Adverse events included nasopharyngitis, dyspnea, headache, diarrhea, and nausea. Clinically asymptomatic elevations of alanine aminotransferase levels were more frequent with fingolimod (10 to 12%, vs. 1% in the placebo group). One case of the posterior reversible encephalopathy syndrome occurred in the 5.0-mg group. Fingolimod was also associated with an initial reduction in the heart rate and a modest decrease in the forced expiratory volume in 1 second. CONCLUSIONS: In this proof-of-concept study, fingolimod reduced the number of lesions detected on MRI and clinical disease activity in patients with multiple sclerosis. Evaluation in larger, longer-term studies is warranted. (Clinicaltrials.gov numbers, NCT00333138 [core study] and NCT00235430 [ClinicalTrials.gov] [extension].).

Adolescent↗

PubMed2005

Analysis of 645 patients with primary hyperparathyroidism with special references to cholelithiasis.

UNLABELLED: OBJECTIVE The clinical picture of primary hyperparathyroidism (PHPT) has changed during the past 50 years. It is currently unknown whether or not PHPT is associated with an increased risk of cholelithiasis. PATIENTS: To determine the frequency of cholelithiasis in PHPT we analyzed 645 consecutive patients seen at Prague University Hospital from 1992 through 2002 and compared them with a of normocalcaemic control group. METHODS: We investigated 645 patients with proven PHPT (518 female and 127 males aged 20-80 years) during a period of 10 years. To determine the frequency of cholelithiasis in normal population we analyzed 2,015 patients receiving periodic health examination at an outpatient ward from January 1998 to December 1998 (1505 females and 510 males aged 24-85 years). A detailed history, physical examination, biochemical measurements and abdominal ultrasonography were done. RESULTS: Cholelithiasis was proven in 157 of 518 women (30.3%) and in 11 of 127 men (8.66%) with PHPT. Their mean age was 59.67+/-12 years in women and 56.0+/-10 years in men. In the control group 260 of 1505 women (17.27%) and 54 of the 510 men (10.58%) had cholelithiasis. The mean age was 64.55+/-13.8 years in women and 61.2+/-12.4 in men. Only in the case of women, the difference was highly statistically significant (p<0.001). There were no significant differences between the mean values for the serum calcium level, bone alkaline phosphatase, total cholesterol, urinary hydroxyproline and body mass index in hyperparathyroid patients with and without cholelithiasis. However the hyperparathyroid women with cholelithiasis had an increased concentration of parathyroid hormone (236.1+/-56 pg/ml) compared with hyperparathyroid women without cholelithiasis (179.0+/-45 pg/ml), p<0.01. CONCLUSION: The mechanism of PTH associated gallstone formation may involve inhibition of gallblader emptying, hepatic bile secretion and sphincter Oddi motility as well as modification of bile composition. While it might be difficult to prove it seems likely that the association of cholelithiasis with primary hyperparathyroidism in women with a high concentration of parathyroid hormone is more than merely coincidental and from our study it is obvious that a significant association exists.

Adult↗

PubMed2004

Everolimus and reduced-exposure cyclosporine in de novo renal-transplant recipients: a three-year phase II, randomized, multicenter, open-label study.

BACKGROUND: Everolimus and cyclosporine (CsA) exhibit synergistic immunosuppressive activity when used in combination. We explored the use of everolimus with a CsA-sparing strategy in de novo renal-transplant recipients. METHODS: A phase II, randomized, open-label 3-year study was performed in 111 patients to compare the efficacy and tolerability of everolimus (3 mg/day) in combination with basiliximab, steroids, and either full-dose Neoral (FDN) or reduced-dose Neoral (RDN) (CsA trough levels 125-250 ng/mL and 50-100 ng/mL, respectively). Efficacy failure (biopsy-proven acute rejection, death, graft loss, or loss to follow-up), safety, and renal function were evaluated at 6, 12, and 36 months. A protocol amendment allowed further reduction of CsA exposure after 12 months. RESULTS: Efficacy failure was significantly higher in FDN than in the RDN group at 6 (15.1% vs. 3.4%; P=0.046), 12 (28.3% vs. 8.6%; P=0.012), and 36 (35.8% vs. 17.2%; P=0.032) months. Mean creatinine clearance was higher in the RDN group at 6 (59.7 mL/min vs. 51.1 mL/min; P=0.009), 12 (60.9 mL/min vs. 53.5 mL/min; P=0.007), and 36 (56.6 mL/min vs. 51.7 mL/min; P=0.436) months. Discontinuations and serious adverse events were more frequent in the FDN group. Reduction of CsA exposure for 6 months during the amendment improved renal function in the FDN group. CONCLUSIONS: In de novo renal-transplant recipients, the regimen of everolimus plus RDN was well tolerated, with low efficacy failure and better renal function in comparison with everolimus plus FDN.

Adolescent↗

PubMed2004

Repeatability of noninvasive surrogates of endothelial function.

We compared the repeatability of 2 ultrasonographic methods for endothelial function assessment at brachial artery-flow-mediated dilation (FMD) and post-ischemic peak blood flow (PBF). Twenty healthy volunteers were examined twice within 10 days; coefficients of variation were 13.8% for PBF and 41.0% for FMD. PBF seems to be superior to FMD in terms of reproducibility. Consequently, smaller noninvasive studies of endothelial function can be designed utilizing PBF compared with FMD.

Adult↗

PubMed2004

Everolimus with optimized cyclosporine dosing in renal transplant recipients: 6-month safety and efficacy results of two randomized studies.

Two prospective, randomized studies evaluated everolimus 1.5 vs. 3 mg/day with steroids and low-exposure cyclosporine (CsA) (C2 monitoring) in de novo renal transplant patients. Everolimus dosing was adjusted to maintain a minimum trough level of 3 ng/mL. Study 1 (A2306; n=237) had no induction therapy; in Study 2 (A2307; n=256) basiliximab was administered (Days 0 and 4). The primary endpoint was renal function at 6 months. CsA C2 target levels, initially 1200 ng/mL in Study 1 and 600 ng/mL in Study 2, were tapered over time post-transplant. Median creatinine levels in Study 1 were 133 and 132 micromol/L at 6 months in the 1.5 and 3 mg/day groups, respectively, and 130 micromol/L in both groups in Study 2. Biopsy-proven acute rejection (BPAR) occurred in 25.0% and 15.2% of patients in the 1.5 and 3 mg/day groups in Study 1, and 13.7% and 15.1% in Study 2. Incidence of BPAR was significantly higher in patients with an everolimus trough <3 ng/mL. There were no significant between-group differences in the composite endpoint of BPAR, graft loss or death, nor any significant between-group differences in adverse events in either study. Concentration-controlled everolimus with low-exposure CsA provided effective protection against rejection with good renal function.

Adult↗

PubMed2003

Effect of atorvastatin and fenofibrate on autonomic tone in subjects with combined hyperlipidemia.

This randomized open-label trial investigated whether autonomic cardiovascular control is altered in middle-aged men with combined hyperlipidemia and whether such alterations are affected by short-term, lipid-lowering therapy with atorvastatin and/or fenofibrate. Compared with normolipidemic subjects, untreated subjects with combined hyperlipidemia had several abnormalities of autonomic tone, indicating increased sympathetic tone and decreased baroreflex sensitivity. The alterations in autonomic cardiovascular control were partially reversible by each of the lipid-lowering drugs.

Adult↗

PubMed2003

Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine.

BACKGROUND: An elevated total plasma homocysteine (tHcy) level is considered to be an independent risk factor for atherosclerosis. It has been reported that lipid-lowering therapy with fibric acid derivatives (fibrates) increases tHcy and total plasma cysteine (tCys) levels. The aim of this study was to determine whether therapy with folic acid, a potent tHcy-lowering agent, could modify the fenofibrate-induced elevation of plasma aminothiols. METHODS: Patients with combined hyperlipidemia (n = 37) were randomized to receive 9 weeks of treatment with micronized fenofibrate 200 mg/day (F group) or fenofibrate 200 mg/day plus folic acid 10 mg/every other day (F+F group). tCys and tHcy levels were determined before and after the therapy with high performance liquid chromatography. RESULTS: The tHcy level increased significantly in the F group by 51.3% and in the F+F group by 14.6% (between-group difference P =.001). Total plasma cysteine (tCys) increased similarly after both treatments (P =.72). The serum creatinine level increased in the F group by 20.7% and in F+F group only by 9.8% (P =.04). The increase of tHcy level in F group correlated with an increase of tCys and creatinine levels (r = 0.74 and 0.64, respectively). The effects on the lipid profile did not differ by treatment group. CONCLUSIONS: Folic acid effectively reduces the fenofibrate-induced elevation of tHcy and creatinine, but it does not affect the elevation of the tCys. Folic acid has neutral effect on the lipid-lowering action of fenofibrate. Clinical efficacy of fenofibrate might be improved by folic acid coadministration.

Cholesterol↗

PubMed2003

Intima-media thickness of the common carotid artery is the significant predictor of angiographically proven coronary artery disease.

BACKGROUND: Previous studies have shown a relationship between intima-media thickness (IMT) of the common carotid artery and coronary artery disease (CAD). The role of IMT in the prediction of significant CAD has not been established. OBJECTIVES: To investigate the diagnostic accuracy of IMT measurement and the detection of carotid plaques in relation to cardiovascular risk factors in the prediction of significant CAD. PATIENTS AND METHODS: One hundred and seventy patients (121 men and 49 women; average age 58 +/- 11 years) undergoing selective coronary angiography were examined by carotid ultrasound. IMT was measured. Plasma lipid concentrations and other risk factors were determined. RESULTS: Angiographically proven significant CAD was found in 138 (81%) of all patients. Carotid plaques were detected in 98 (58%) of all patients. Presence of carotid plaques in common carotid artery (P<0.001) and male sex (P<0.005) were found to be categorical risk factors for significant CAD but in multiple regression analysis only age (P=0.15), IMT (P<0.01), high density lipoprotein (HDL) cholesterol (P=0.02) and, less significantly, total cholesterol (P=0.09) were found to be independent parameters for the prediction of significant CAD. IMT of 0.75 mm was determined as a cut-off point for the detection of significant CAD (sensitivity 78%, specificity 79%, positive predictive value 95%, negative predictive value 41%, odds ratio 12.9, 95% CI 3.5 to 47.6). CONCLUSION: The increase in IMT is the significant positive predictor of angiographically proven CAD; other predictors are high age, low HDL cholesterol and, less significantly, high total cholesterol. Presence of carotid plaques and male sex do not add any new information for the prediction of CAD once the predictors are considered.

Age Factors↗

PubMed2002

Soluble leptin receptor levels in patients with anorexia nervosa.

OBJECTIVE: To examine whether changes of serum soluble leptin receptor levels (S-LEPR) can modify leptin half-life and its tissue effects. The aim of our study was to measure S-LEPR levels in patients with anorexia nervosa (AN) before and 6 weeks after partial refeeding. METHODS: Anthropometric variables, serum leptin, S-LEPR, insulin, cortisol and TNF-alpha were measured in 15 AN patients before and after partial refeeding and 15 healthy control women. RESULTS: S-LEPR levels in AN patients were significantly higher than in healthy subjects (26.8 +/- 8.1 vs. 16.36+/-2.6U/mL, p < 0.01) and were not affected by partial refeeding (26.8 +/- 8.1 vs. 24.2 +/- 6.1 U/mL). In contrast, body mass index (BMI), body fat content, and serum leptin levels in AN patients increased significantly after partial refeeding. Except for the inverse relationship of S-LEPR levels to BMI and body fat content no clear relationship of this parameter to serum leptin, cortisol, insulin or TNF-alpha was found. CONCLUSION: S-LEPR levels are significantly increased in AN patients and this increase is unaffected by partial refeeding. The possibility of etiological role of increased S-LEPR levels in AN patients by affecting leptin central and/or peripherial effects should be further elucidated.

Adipose Tissue↗