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ABSTRACT: Primary hyperparathyroidism (PHPT) is accompanied with a reduced bone mineral density (BMD) and an increased risk of fracture. Surgery is the only option for cure. It is hypothesized that in patients with PHPT bone metabolism normalizes after parathyroidectomy (PTX) and that BMD gradually increases. Fifty-two patients with PHPT who underwent surgery were prospectively followed for 1 year. Biochemical analyses were performed at baseline and 1, 4, 7 days; 6 weeks; and 3, 6, and 12 months, and BMD before and one year after surgery. Parathyroid hormone (PTH), calcium, and the bone resorption marker dropped immediately, but transiently after PTX, bone formation decreased more slowly. Osteoprotegerin (OPG) as well as cathepsin K did not show significant changes. BMD of the lumbar spine, but not of the femoral neck, increased significantly within one year after surgery. Moderate correlations existed between the changes of total calcium, ionized calcium, as well as bone-specific alkaline phosphatase and changes of the lumbar BMD. Patients who needed postoperative supplementation with calcium and vitamin D had significantly higher PTH levels. Some gender-specific differences in patients with PHPT were observed. In patients with PHPT, males appear to be more severely affected than females. Within the first year after PTX, bone metabolism normalized, and BMD of the lumbar spine increased. Patients who needed a supplementation with calcium and vitamin D after PTX preoperatively had higher serum levels of PTH.
Hormone and Metabolic Research 04/2012; 44(6):476-81. · 2.19 Impact Factor
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ABSTRACT: The aim of this study was to assess the impact of temperamental traits in alcohol dependent patients on the course of illness.
The case files of 116 alcohol dependent patients, according to ICD-10 and DSM-IV-TR, were examined retrospectively. All patients were in treatment between 02/08 and 03/09 at the Psychiatric Department of the General Hospital Vienna, either at the alcohol outpatient clinic or the psychiatric ward, which has the treatment focus on alcohol dependence. The brief TEMPS-M auto-questionnaire was used to assess the temperamental distribution. The dimensions of alcohol dependence have been assessed using the Lesch Alcoholism Typology, a computerized structured interview. The potential effect of temperamental scores on various outcomes describing the course of illness is investigated using multi-variable regression models.
Cyclothymic score was the only temperament which significantly influenced the age of onset of alcohol abuse and age of onset of alcohol dependence. Backward selection among temperaments exhibits depressive temperament as most important effect regarding the likelihood of suicide-attempts in the patient's case history and anxious temperament as most important effect regarding having psychiatric treatment focusing on alcohol dependence prior to current in- or outpatient stay.
The sample size of this study is small compared to the number of investigated outcomes and temperaments. Further, a healthy control group, matched for age and gender, was not available for comparison of the temperament sub-scores.
Dominant cyclothymic, but also depressive and anxious temperament, seem to be negative predictors for the course of illness in alcohol dependence. Regarding positive long term outcome specific evidence based medical treatment approaches are needed for these patients.
Journal of affective disorders 08/2011; 135(1-3):177-83. · 3.76 Impact Factor
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ABSTRACT: We considered that completed opiate detoxification resulted in increased life expectancy and earning capacity as compared to non-completed detoxification.
The cohort study sample included pure opioid or poly-substance addicts admitted for voluntary in-patient detoxification between 1997 and 2004. Of 404 patients, 58.7% completed the detoxification program and 41.3% did not. The Austrian Social Security Institution supplied data on survival and employment records for every single day in the individual observation period between discharge and December 2007. Statistical analyses included the calculation of standardized mortality rates for the follow-up period of up to 11 years.
The standardized mortality ratios (SMRs) were between 13.5 and 17.9 during the first five years after discharge, thereafter they fell clearly with time. Mortality did not differ statistically significantly between completers and non-completers. The median employment rate was insignificantly higher in completers (12.0%) than in non-completers (5.5%). The odds for being employed were higher in pure opioid addicts than in poly-substance addicts (p=0.003).
The assumption that completers of detoxification treatment have a better outcome than non-completers has not been confirmed. The decrease in mortality with time elapsed since detoxification is interesting. Pure opioid addicts had better employment prospects than poly-substance addicts.
European Psychiatry 07/2010; 27(4):294-300. · 2.77 Impact Factor
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ABSTRACT: The aim of this retrospective study was to assess ultra-rapid opiate detoxification (UROD) and to estimate the retention rate in naltrexone maintenance treatment.
45 opiate-addicted male patients (DSM-IV 304.00; opiate per oral or per inhalation n=40, heroin intravenous n=5; concomitant cannabis abuse n=6) were detoxified by 6 h of naloxone infusion under general anesthesia with midazolam, propofol, clonidine and atracurium. Withdrawal signs were evaluated by the objective opiate withdrawal scale (OOWS, range 0-13) up to 24 h after awakening. After UROD, naltrexone 50 mg/day was prescribed for 9 months with assessments in 4-week intervals.
Adverse events after UROD were prolonged unconsciousness (n=1), transient confusion (n=8) and depressive mood (n=6). The total sample showed a median OOWS score of 2 (mild withdrawal syndrome). The only two extreme outliers were found only in the subgroups "intravenous" (score 8) and "cannabis" (score 11). 96% (43/45) of the patients could be discharged the day after UROD. Thirty-six patients (80%) continued naltrexone therapy for the entire 9-month observation period.
UROD and subsequently induction of naltrexone maintenance therapy can be regarded as safe and effective in patients with pure opiate addiction. Owing to cultural and economical factors our Iranian results may not correspond to European and American treatment modalities.
Pharmacopsychiatry 06/2010; 43(4):130-7. · 2.07 Impact Factor
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ABSTRACT: Recently, mutations in the filaggrin gene (FLG) have been shown to be a major predisposing factor for atopic dermatitis (AD).
In this study, we evaluated the influence of four prevalent mutations (R501X, 2282del4, R2447X and S3247X) in a large cohort of 462 Austrian and German AD patients and in 402 control individuals.
We found a strong association of the FLG mutations with AD. Subgroup analysis revealed a significantly higher proportion of patients with an early age of disease onset and significantly higher median serum IgE levels among mutation carriers. Furthermore, we observed an overrepresentation of null alleles in AD patients with concomitant asthma compared with those without this co-morbidity.
Our data confirm and extend the knowledge of the influence of FLG mutations in AD.
Journal of the European Academy of Dermatology and Venereology 10/2009; 24(5):607-10. · 2.98 Impact Factor
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ABSTRACT: Development of factor VIII inhibitors is a serious complication in haemophilia A patients. Recombinant factor VIIa (rVIIa) is clinically effective, but its effects on haemostatic system need still to be fully elucidated.
In an open controlled study, we measured thrombin generation (peak thrombin) in venous blood and prothrombin fragment F1 + 2 (F1 + 2) and D-dimer in venous and in shed blood in five haemophilia A patients with inhibitors before and after rVIIa infusion. A total of five healthy individuals who did not receive rVIIa served as controls.
At baseline, patients had lower mean (min-max) peak thrombin levels than controls [0.12 (0.0-0.6) vs. 186.9 (116.0-254.4) nM, P = 0.001]. After infusion, peak thrombin levels increased in average to 40.7 (28.3-51.6) nM, which translates into 80.2% (95% CI 65.4-88.6%) lower levels compared to that of controls. Mean (min-max) F1 + 2 levels in venous blood did not differ significantly between patients and controls [160.7 (89.8-331.3) vs. 160.8 (104.4-242.3) pmol L(-1)], but increased in average (min-max) by 39.4% (14.1-58.5%) after infusion. In blood emerging from incisions made to determine the bleeding (shed blood), F1 + 2 levels were lower in patients than controls [1383.3 (906.4-2044.6) vs. 2981.7 (1610.0-4539.6) pmol L(-1); P = 0.04], but were not affected by rVIIa; D-dimer levels were significantly higher in haemophiliacs than in controls and remained unchanged after infusion.
Haemophilia A patients with factor VIII inhibitors have low thrombin generation. After rVIIa, the extent of coagulation activation as measured by levels of F1 + 2 is increased, but thrombin generation is restored to only 20%. Peak thrombin levels could reflect the effects of rVIIa on coagulation mechanisms, and their relevance with regard to the clinical coagulation defect of haemophilia A patients with factor VIII inhibitors might be evaluated.
European Journal of Clinical Investigation 06/2009; 39(8):707-13. · 3.02 Impact Factor
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ABSTRACT: Osteoporosis is one of the most common conditions associated with aging. It is based on an excess of bone resorption over bone formation, leading to an imbalance of bone turnover. The receptor activator of nuclear factor kappaB ligand (RANKL) is an important regulator of bone metabolism.
The aim of this investigation was to evaluate potential age- and gender-related changes in free RANKL and total RANKL (free RANKL+RANKL/osteoprotegerin complexes).
Two hundred and forty volunteers with a median age of 48 years were included in the study. Serum levels of free RANKL and total RANKL were evaluated.
On average, men have a 1.77-fold higher free RANKL level and a 2.12-fold higher free/total RANKL ratio than women of the same age. On average, the RANKL levels decrease by approximately 13% every five years.
This study showed that serum levels of free RANKL and total RANKL decrease with age, and also revealed some gender-related differences.
Experimental and Clinical Endocrinology & Diabetes 01/2008; 116(8):491-5. · 1.69 Impact Factor
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ABSTRACT: Cisplatin-based chemotherapy predisposes cancer patients to thromboembolic events.
To investigate whether endothelial damage, via formation of procoagulant endothelial microparticles (EMPs), contributes to cisplatin-related hypercoagulability.
Cell viability and caspase-3/7 activities were assessed in two endothelial cell (EC) lines [human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (HMVEC-Ls)] after exposure to cisplatin (1, 2.5, 5, 10 and 20 microm) for up to 120 h. Counts and procoagulant activity of EMPs were measured by flow cytometry and a thrombin generation assay, respectively. Tissue factor (TF) antigen and TF-dependent procoagulant activity of EMP were determined by enzyme-linked immunosorbent assay and a novel functional assay.
By inducing apoptosis, cisplatin dose- and time-dependently decreased the viability of confluent HUVECs and HMVEC-Ls. Progression of EC death was accompanied by an increased release of EMPs (relative increase at 20 microm cisplatin for 48 h vs. control: HUVECs 6.5-fold, P < 0.001; HMVEC-Ls 18.4-fold, P < 0.001). EMPs were highly procoagulant (relative increase at 20 microm cisplatin for 48 h vs. control: HUVECs 2.5-fold, P < 0.001; HMVEC-Ls 5.9-fold, P < 0.001). EMP-driven thrombin generation, however, was not dependent on TF: TF expression and TF procoagulant activity levels on microparticles were only marginal and EMP-associated thrombin generation remained unchanged when the extrinsic pathway was blocked by omission of factor VIIa and/or incubation with an anti-human TF antibody. In contrast, blocking of phospholipids by annexin V markedly diminished EMP-associated procoagulant activity.
In vitro, cisplatin induced the release of EMPs that showed TF-independent procoagulant activity.
Journal of Thrombosis and Haemostasis 12/2007; 5(12):2445-52. · 5.73 Impact Factor
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ABSTRACT: In a randomised study, 28 patients with a mean age of 62.2 years (32 to 81) with osteoarthritis or avascular necrosis of the hip received either a ceramic-on-ceramic or a metal-on-metal total hip replacement. Apart from the liners the acetabular and femoral components were made of Ti-Al-Nb alloy. The serum aluminium and cobalt levels were measured before, and at one year after surgery. The 15 patients in the ceramic-on-ceramic group had a median pre-operative aluminium level of 1.3 microg/l (0.25 to 8.4) and a cobalt level below the detection limit. At one year the aluminium level was 1.1 microg/l (0.25 to 2.3) and the cobalt level was 0.4 microg/l (0.15 to 0.7). The 13 patients in the metal-on-metal group had a median pre-operative aluminium level of 1.9 microg/l (0.25 to 4.4) and a cobalt level below the detection limit. At one year the median aluminium level was 0.9 microg/l (0.25 to 3.9) whereas the cobalt level was 1.4 microg/l (0.5 to 10.5). This increase in the cobalt level at one year was significant (p < 0.001). Our findings indicate that ceramic-on-ceramic bearings do not cause elevated levels of serum aluminium in the first post-operative year.
Journal of Bone and Joint Surgery - British Volume 08/2006; 88(8):1003-5. · 2.83 Impact Factor
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D Heintel,
D Kienle,
M Shehata,
A Kröber,
E Kroemer,
I Schwarzinger,
D Mitteregger,
T Le, A Gleiss,
C Mannhalter,
A Chott,
J Schwarzmeier,
C Fonatsch,
A Gaiger,
H Döhner,
S Stilgenbauer,
U Jäger
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ABSTRACT: We investigated the pattern of lipoprotein lipase (LPL) expression in B-cell chronic lymphocytic leukemia (B-CLL) and assessed its prognostic relevance. Expression of LPL mRNA as well as protein was highly restricted to leukemic B cells. The intensity of intracellular immunoreactivity of LPL was higher in samples of patients with unmutated immunoglobulin heavy-chain variable region genes (IGV(H)) compared to those with mutated IGV(H) genes. LPL mRNA levels in peripheral blood mononuclear cells (PBMNC) from 104 CLL patients differed by 1.5 orders of magnitude between cases with mutated (N=51) or unmutated (N=53) IGV(H) (median: 1.33 vs 45.22 compared to normal PBMNC). LPL expression correlated strongly with IGV(H) mutational status (R=0.614; P<0.0001). High LPL expression predicted unmutated IGV(H) status with an odds ratio of 25.90 (P<0.0001) and discriminated between mutated and unmutated cases in 87 of 104 patients (84%). LPL expression was higher in patients with poor risk cytogenetics. High LPL expression was associated with a shorter treatment-free survival (median 40 vs 96 months, P=0.001) and a trend for a shorter median overall survival (105 months vs not reached). Our data establish LPL as a prognostic marker and suggest functional consequences of LPL overexpression in patients with B-CLL.
Leukemia 08/2005; 19(7):1216-23. · 9.56 Impact Factor
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ABSTRACT: Ghrelin stimulates GH release and causes weight gain through increased food intake and reduced fat utilization. Ghrelin levels were shown to rise in the preprandial period and decrease shortly after meal consumption, suggesting a role as a possible meal initiator. However, ghrelin secretion in fasting subjects has not yet been studied in detail.
24-h ghrelin profiles were studied in six healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m(2)) and compared with GH, insulin and glucose levels.
Blood samples were taken every 20 min during a 24-h fasting period and total ghrelin levels were measured by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin secretion and pulsatility (Cluster analysis) were evaluated.
An increase and spontaneous decrease in ghrelin were seen at the timepoints of customary meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24 h. An overall decrease in ghrelin levels was observed during the study period. There was no correlation of ghrelin with GH, insulin or blood glucose levels.
This pilot study indicates that fasting ghrelin profiles display a circadian pattern similar to that described in people eating three times per day. In a fasting condition, GH, insulin and glucose do not appear to be involved in ghrelin regulation. In addition, we found that ghrelin is secreted in a pulsatile pattern. The variation in ghrelin independently of meals in fasting subjects supports previous observations that it is the brain that is primarily involved in the regulation of meal initiation.
European Journal of Endocrinology 07/2005; 152(6):845-50. · 3.42 Impact Factor
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ABSTRACT: European chub Leuciscus cephalus collected from five localities in the lowland and subalpine regions of Austria were analysed for oestrogenic effects of endocrine-disrupting chemicals and the presence of the plerocercoid of the tapeworm Ligula intestinalis. Of 1494 chub analysed, only seven (six males, one female) were found to be infected with single, but large plerocercoids up to 15 cm in length. Ligula-infected fish showed comparatively immature gonads, as demonstrated by the gonadosomatic index and gamete developmental stages. Plasma levels of the egg precursor protein vitellogenin also showed concentrations ranging below the detection limit. The present results indicate that chub infected with L. intestinalis and exposed to exogenous oestrogenic compounds can result in reduced gonadal maturation and produce false oestrogen-positive diagnoses in male fish. For plasma vitellogenin levels, L. intestinalis infections can result in false oestrogen-negative diagnoses in male and female fish.
Journal of Helminthology 04/2005; 79(1):91-4. · 1.38 Impact Factor
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ABSTRACT: The multidrug transporter P-glycoprotein is suspected of contributing to pharmacoresistance in temporal lobe epilepsy (TLE). To assess the role of functional variations in its coding gene (ABCB1) the authors genotyped 210 patients with TLE who were stratified according to their degree of drug resistance. They identified a common haplotype that when present in the homozygous state significantly increased the risk for pharmacoresistance.
Neurology 10/2004; 63(6):1087-9. · 8.31 Impact Factor
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ABSTRACT: The prognostic value of the detection of peripheral blood (PB) and/or bone marrow (BM) involvement by polymerase chain reaction (PCR) amplification of rearranged immunoglobulin heavy chain (IgH) and immunoglobulin kappa light chain (Igkappa) genes was evaluated in 155 patients with diffuse large B-cell lymphomas (DLBCL). Immunoglobulin gene rearrangements (IgR) were detected in 35/155 (23%) patients. The presence of IgR in PB/BM was related to clinical stage (CS I-III vs CS IV; P<0.001), histopathological detection of BM involvement (P<0.001), and the International Prognostic Index (P<0.001). IgR-positive cases had a significantly lower complete remission (CR) rate (18/35, 51%) than IgR-negative patients (85/120, 71%; P=0.042), and a significantly poorer overall survival (OAS) at 5 years (25 vs 66%; P<0.001). There was a significant difference in the estimated OAS at 5 years between patients with negative BM histology and negative PCR results (66%), patients with negative BM histology but positive IgR (37%), and patients with positive BM histology (12%). Our results indicate that molecular methods improve the accuracy of staging in patients with DLBCL and define a group of patients with normal bone marrow histology who have a significantly poorer OAS due to molecular detection of PB/BM involvement.
Leukemia 06/2004; 18(6):1102-7. · 9.56 Impact Factor
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D Heintel,
E Kroemer,
D Kienle,
I Schwarzinger, A Gleiss,
J Schwarzmeier,
R Marculescu,
T Le,
C Mannhalter,
A Gaiger,
S Stilgenbauer,
H Döhner,
C Fonatsch,
U Jäger
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ABSTRACT: Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation of B-cells. We investigated the expression of AID mRNA by real-time polymerase chain reaction (PCR) in peripheral blood mononuclear cells of 80 patients with B-CLL. AID expression was detected in 45 of 80 patients (56%) at various levels, but was undetectable in 35 patients (44%). AID PCR positivity was associated with unmutated IGV(H) gene status (22 of 25 patients; P=0.002) and unfavourable cytogenetics (18 of 23 patients with deletion in 11q or loss of p53; P=0.040). Using a threshold level of 0.01-fold expression compared to Ramos control cells, even more significant associations were observed (P=0.001 for IGVH; P=0.002 for cytogenetics). A correlation was observed between individual AID levels and the percentage of V(H) homology (R=0.41; P=0.001). AID positivity predicted unmutated IGV(H) status with an odds ratio of 8.31 (P=0.003) and poor risk cytogenetics with an odds ratio of 3.46 (P=0.032). Significance was retained after adjustment for Binet or Rai stages. AID mRNA levels were stable over time. These data suggest a potential role of AID as a prognostic marker in B-CLL.
Leukemia 05/2004; 18(4):756-62. · 9.56 Impact Factor
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A Weltermann,
C Fonatsch,
O A Haas,
H T Greinix,
P Kahls,
G Mitterbauer,
U Jäger,
B Kainz,
K Geissler,
P Valent,
W R Sperr,
P Knöbl,
I Schwarzinger, A Gleiss,
K Lechner
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ABSTRACT: Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.
Leukemia 03/2004; 18(2):293-302. · 9.56 Impact Factor
