Epicardial adipose tissue and adrenal gland volume in patients with borderline personality disorder.

Borderline personality disorder (BPD) is associated with an elevated mortality risk that is partially attributed to suicide, but few studies examined other possible causes of premature death. The present study compared epicardial adipose tissue (EAT) volume as a known early predictor of premature cardiovascular morbidity, cardiovascular risk indices, and adrenal gland volume (AGV) as an indicator for chronic hypothalamus-pituitary-adrenal (HPA) axis activation in females with borderline personality disorder (BPD), major depressive disorder (MDD) and in healthy individuals. Twenty-eight patients with BPD comorbid with MDD (BPD/MDD), 22 MDD patients and 26 healthy females (CTRL) of comparable age were included. EAT and AGV were assessed by magnetic resonance tomography; 10-year cardiovascular risk and diabetes risk were determined by PROCAM and FINDRISK score; metabolic syndrome was defined following National Cholesterol Education Adult Treatment Panel III R (NCEP/ATP III) criteria. MADRS was used to assess depression severity. After adjustment for age, body mass index (BMI), and physical activity, EAT and AGV were significantly increased in BPD/MDD compared to MDD and CTRL. EAT and AGV displayed a positive correlation. Finally, diabetes risk in BPD/MDD was elevated compared to CTRL and MDD. The present study highlights the increased cardiometabolic risk of BPD patients. We identify EAT accumulation as an early predictor and potential mediator of cardiovascular disease in BPD that appears to be driven at least in part by HPA axis dysregulation. Therefore, interventions that reduce EAT volume (i.e. exercise and diet) should be considered in the clinical management of BPD.

Do biomarkers allow a differentiation between osteonecrosis of the femoral head and osteoarthritis of the hip? - a biochemical, histological and gene expression analysis.

OBJECTIVE: Osteonecrosis of the femoral head (ONFH) is a devastating disease of the hip joint. Its early diagnosis is crucial to increase the chances of joint preserving, yet difficult due to similarities with osteoarthritis (OA) of the hip in its clinical appearance. The purpose of this study was to enhance the understanding of ONFH and its pathologic processes in contrast to OA and to identify serum biomarkers helping to improve the diagnosis of the disease. DESIGN: Bone and bone marrow samples were collected from 24 patients diagnosed with OA and 25 patients with ONFH during total hip replacement surgery. RNA was isolated, histological examination, determination of free reactive oxygen species as well as gene expression and biomarker analysis were performed. RESULTS: Histological analysis revealed differences in the structural and cellular pattern between the groups. Gene expression analysis revealed a significant upregulation for the genes ASPN, COL1A1, COL2A1 and IL6 and a significant downregulation for HIF1A in ONFH compared to OA group. Analysis of serum biomarkers showed significant differences between the groups for asporin and adiponectin. A final logistical regression model including the parameters adiponectin, asporin and HIF 1α was overall significant, explained 34.5 % of variance and classified 74.5 % of the cases correctly. CONCLUSION: The combination of adiponectin, asporin and HIF 1α as serum biomarkers revealed a classification accuracy of 74.5 %. The information provided in this study may help to enhance the understanding of pathologic processes in ONFH and to elaborate further aspects of prediction and treatment.

Increased pericardial adipose tissue and cardiometabolic risk in patients with schizophrenia versus healthy controls.

Patients with schizophrenia are at increased risk of diabetes, cardiovascular disease (CVD) and associated mortality versus the general population. Increased intra-abdominal and pericardial adipose tissue are associated with elevated CVD and mortality in the general population, but little is known about these in patients with schizophrenia. This study examined pericardial and intra-abdominal adipose tissue in schizophrenia and compared this to healthy controls. Thirty-one patients with schizophrenia (mean age 41.2 years, 76% males) and 30 healthy volunteers (CTRL) were examined in this study. The primary outcomes were the volumes of pericardial adipose tissue and intra-abdominal adipose tissue, measured using magnetic resonance imaging. Secondary outcomes included diabetes and cardiac event risk assessed by established instruments. Volumes of pericardial adipose tissue were increased in male and female patients with schizophrenia compared to healthy controls after the adjustment of age, sex and body mass index (P < 0.005). The 10-year risk of a cardiac event was significantly higher in patients with schizophrenia. Furthermore, the risk for developing type-2 diabetes mellitus was slightly increased in schizophrenia. Volumes of intra-abdominal adipose tissue were slightly increased in male and female patients with schizophrenia, albeit not statistically significant. This study demonstrates that patients with schizophrenia have increased pericardial adipose tissue versus controls. This increased fat deposit around the heart is highly relevant for understanding the comorbidity between heart disease and schizophrenia. Interventions aiming to reduce pericardial and intra-abdominal adipose tissue, such as exercise, may be essential to reduce the burden of heart disease in schizophrenia.

Angiopoietin-like protein 4 and cardiovascular function in COPD.

INTRODUCTION: The coexistence of chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) is frequent and might be inter-related through inflammation-related processes reflected by specific markers. Here, we studied angiopoietin-like protein 4 (ANGPTL4), an upcoming cardiovascular marker, in stable COPD, and its relationship to cardiovascular function with respect to well-known CVD risk factors. METHODS: In a prospective COPD cohort study, we investigated serum ANGPTL4 levels, vascular status (ankle-brachial index (ABI)) and cardiac function (N-terminal pro-B-type natriuretic peptide (NT-proBNP)) as well as airflow limitation, objectively measured physical activity, the metabolic syndrome, high-sensitive C reactive protein (hs-CRP) and other CVD risk factors at 2 time points. We initially studied 74 stable COPD patients and 18 controls. For internal validation, we additionally studied 160 COPD patients of a former visit. RESULTS: ANGPTL4 was significantly elevated in COPD patients compared with controls (p=0.026). After correction for traditional CVD risk factors, including hs-CRP, higher levels of ANGPTL4 were independently associated with lower ABI (p=0.023) and higher NT-proBNP (p<0.001). These findings were confirmed in the internal validation analysis, which included echocardiographic assessments. CONCLUSIONS: Serum ANGPTL4 is independently associated with cardiovascular function in COPD and might qualify as a biomarker reflecting a pathogenic link between COPD and CVD.

Xanthochromia of the skull bone associated with HbA1c.

The color of the surface of 105 skull bones (part of the parietal bone) was determined using a portable spectral colorimeter (spectro color(®)). By this means it was possible to characterize the color objectively according to the L*a*b* color system defined by the "International Commission de l'Eclairage" (CIE). Biochemical markers of carbohydrate metabolism, HbA1c from venous blood, and glucose/lactate concentrations from vitreous humor, were also determined, for assessment of the ante-mortem plasma glucose concentration using Traub's sum formula. As biochemical markers for lipid metabolism disorder, cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were all determined from venous blood. There is a significant correlation of bone yellowing with HbA1c (p<0.001) and age (p<0.001). The literature asserts a significant correlation between diabetic condition and yellowing of the skull bone. Despite efforts to find the substance responsible for the yellowing of the bone in chronic metabolism disorder, no significant correlation was found between bone color and lipoproteins/bone extracted lipid acids.

Pericardial, intra-abdominal, and subcutaneous adipose tissue in patients with major depressive disorder.

OBJECTIVE: Major depressive disorder (MDD) is associated with an increased risk for developing coronary artery disease (CAD). Recently, pericardial adipose tissue, a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of CAD. Therefore, we investigated pericardial adipose tissue volumes in patients with MDD and compared them to healthy comparison subjects. METHOD: In this case-control study at a university medical center, 50 male and female in-patients with MDD and 25 healthy men and women were examined. The main outcome measures were the volumes of pericardial adipose tissue, intra-abdominal adipose tissue (IaAT) and subcutaneous adipose tissue (ScAT) which were measured using magnetic resonance imaging. RESULTS: The pericardial adipose tissue volumes were greater in men and women with MDD compared with the healthy comparison group following adjustments for the effects of age, weight, height, and physical activity. CONCLUSION: This study expands our knowledge about the alterations in body composition that occur in patients with MDD. The findings are highly relevant for understanding the comorbidity between heart disease and depressive disorders.

Phenotyping and outcome on contemporary management in a German cohort of patients with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a life-threatening heart disease developing towards the end of pregnancy or in the months following delivery in previously healthy women in terms of cardiac disease. Enhanced oxidative stress and the subsequent cleavage of the nursing hormone Prolactin into an anti-angiogenic 16 kDa subfragment emerged as a potential causal factor of the disease. We established a prospective registry with confirmed PPCM present in 115 patients (mean baseline left ventricular ejection fraction, LVEF: 27 ± 9 %). Follow-up data (6 ± 3 months) showed LVEF improvement in 85 % and full recovery in 47 % while 15 % failed to recover with death in 2 % of patients. A positive family history of cardiomyopathy was present in 16.5 %. Pregnancy-associated hypertension was associated with a better outcome while a baseline LVEF ≤ 25 % was associated with a worse outcome. A high recovery rate (96 %) was observed in patients obtaining combination therapy with beta-blocker, angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor-blockers (ARBs) and bromocriptine. Increased serum levels of Cathepsin D, the enzyme that generates 16 kDa Prolactin, miR-146a, a direct target of 16 kDa Prolactin, N-terminal-pro-brain-natriuretic peptide (NT-proBNP) and asymmetric dimethylarginine (ADMA) emerged as biomarkers for PPCM. In conclusion, low baseline LVEF is a predictor for poor outcome while pregnancy-induced hypertensive disorders are associated with a better outcome in this European PPCM cohort. The high recovery rate in this collective is associated with a treatment concept using beta-blockers, ACE inhibitors/ARBs and bromocriptine. Increased levels of Cathepsin D activity, miR-146a and ADMA in serum of PPCM patients support the pathophysiological role of 16 kDa Prolactin for PPCM and may be used as a specific diagnostic marker profile.

Linking infection and inflammation in acute ischemic stroke.

Infections after ischemic stroke are known to complicate the clinical course and worsen the outcome. Neuroinflammation is one of the predominant mechanisms of secondary progression of brain injury and infection and is far from being well understood. Experimental data demonstrate that ischemic stroke patients are at a higher risk for systemic infections if they show a pronounced anti-inflammatory response after the event, which is considered an indication of a stress-mediated reduction of immune competence. Only a small number of studies describe the time course of inflammation mediators after ischemic stroke in patients with early poststroke infections. Levels of inflammation mediators after the event of stroke differ, depending on clinical severity and concomitant infectious diseases. Thus, sequential dynamics of early inflammation must be considered in the development of both mechanism-targeting anti-inflammatory and anti-infectious treatment strategies in ischemic brain damage.

The temporal profile of inflammatory markers and mediators in blood after acute ischemic stroke differs depending on stroke outcome.

BACKGROUND: Early inflammation has been suggested as an important factor contributing to unfavorable prognosis after acute ischemic stroke. The present study aimed to clarify the temporal dynamics of discrete inflammatory markers/mediators for future mechanism-targeting anti-inflammatory strategies in ischemic brain damage. METHODS: Blood samples of 69 patients with transient ischemic attack or ischemic stroke were taken upon admission and at time points 6, 12 and 24 h, as well as 3 and 7 days after symptom onset for analysis of monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin-6 (IL-6), C-reactive protein (CRP) and the brain damage marker S100B. Clinical scores (modified Rankin Scale, National Institute of Health Stroke Scale) were assessed on day 90. RESULTS: MCP-1, MMP-9, TIMP-1, IL-6, CRP and S100B showed significantly different time courses depending on stroke outcome. While the levels of IL-6, MCP-1 and MMP-9 increased already a few hours after symptom onset, CRP and S100B gradually rose commencing at 12-24 h. TIMP-1 demonstrated an extended plateau. By multiple linear regression analysis IL-6, MCP-1, TIMP-1 and S100B were determined to be independently related to clinical outcome scores at specific time points. CONCLUSIONS: Our data show important differences in the early time course of several potential markers for the complex network of inflammation and brain damage after ischemic stroke depending on stroke outcome. This must be considered for any therapeutical approach using anti-inflammatory treatment.

The role of cerebrospinal fluid S100 and lactate to predict clinically evident spinal cord ischaemia in thoraco-abdominal aortic surgery.

OBJECTIVE: Detecting spinal cord ischemia early during replacement of the thoracoabdominal aorta remains a challenge. In a high risk population, we have re-evaluated the potential impact of ischaemia/damage markers (S100, lactate) in the peripheral blood and CSF for perioperative patient management. PATIENTS AND METHODS: Thirteen patients undergoing replacement of the thoracoabdominal aorta (6 female, age 63 (27-71)) with continuous CSF pressure monitoring and drainage were entered into the study. A total of 485 CSF (C) and serum (S) samples were collected and analysed for S100, lactate and glucose. RESULTS: Two patients suffered from spinal cord injury (SCI) (15%). During and early after surgery, there was a strong correlation between C-S100 levels (r=0.79) and C-lactate levels (r=0.77) with time in patients with SCI. In patients with SCI C-lactate levels increased soon after aortic cross-clamping, whereas C-S100 levels did not become significantly elevated until 6 hours after cross-clamping. CONCLUSION: An increase of C-lactate occurs much earlier than the increase in C-S100 in patients with SCI. Both parameters may be used to adjust protective and therapeutic measures intra- and postoperatively.

Combined NT-pro-BNP and CW-Doppler ultrasound cardiac output monitoring (USCOM) in epirubicin and liposomal doxorubicin therapy.

BACKGROUND: Chemotherapy with epirubicin is approved in women with breast cancer and is associated with a certain degree of cardiotoxicity. HYPOTHESIS: Epirubicin changes stroke volume, cardiac output and systemic vascular resistance, while liposomal doxorubicin does not. METHODS: 75 patients with HER-2-positive metastatic breast cancer were continuously measured with CW-Doppler ultrasound for stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) before, during and after drug infusion in combination with NT-pro-BNP before and 10 min after drug infusion. RESULTS: Epirubicin infusion increased stroke volume significantly in low-level NT-pro-BNP (62+/-23 ml vs. 74+/-29 ml, p=0.004) and high-level NT-pro-BNP (48+/-5 ml vs. 64+/-20 ml, p=0.131), while liposomal doxorubicin infusion increased stroke volume significantly in low-level NT-pro-BNP (54+/-16 ml vs. 67+/-22 ml, p=0.001) and high-level NT-pro-BNP (65+/-22 ml vs. 82+/-27 ml, p=0.001). Cardiac output was significantly increased in epirubicin (p=0.004) by 20% (NT-pro-BNP<125 pg/ml) and not significantly 38% (NT-pro-BNP>125 pg/ml; p=0.144), while in liposomal doxorubicin cardiac output was significantly increased by 23% (NT-pro-BNP<125 pg/ml; p=0.023) and 33% (NT-pro-BNP>125 pg/ml; p=0.001). In liposomal doxorubicin cardiac index was significantly increased by 26% (NT-pro-BNP<125 pg/ml; p=0.021) and 33% (NT-pro-BNP>125 pg/ml; p=0.0001). SVR was significantly reduced during and after epirubicin therapy. CONCLUSION: Using the CW-Doppler USCOM a different hemodynamic response to epirubicin vs. liposomal doxorubicin is evident. Epirubicin leads to a significant upregulation of stroke volume and cardiac output, which is even more pronounced in the high-level NT-pro-BNP group, while liposomal doxorubicin does not change immediate hemodynamics. No deterioration of cardiac function using the real-time CW-Doppler ultrasound USCOM or an increase in NT-pro-BNP levels was evident during epirubicin or liposomal doxorubicin therapy.

Simultaneous hemodynamic and serological cardiotoxicity monitoring during immunotherapy with trastuzumab.

BACKGROUND: Immunotherapy with trastuzumab (Herceptin), a selective HER-2(ErbB2)-antibody, is associated with a certain degree of cardiotoxicity. This study sought to evaluate the immediate hemodynamic response to trastuzumab with real-time CW-Doppler depending on the level of nt-pro-BNP (brain natriuretic peptide) as a possible marker of cardiotoxicity. METHODS: 48 patients with HER-2-positive metastatic breast cancer were continuously measured with CW-Doppler ultrasound for cardiac output (CO) and systemic vascular resistance (SVR) before, during and after drug infusion in combination with nt-pro-BNP before and 10 min after drug infusion. Depending on the nt-pro-BNP-levels <125 pg/ml (group A, n=34, 51+/-11 years) vs. nt-pro-BNP >125 pg/ml (group B, n=14, 63+/-7 years) two groups have been defined. RESULTS: Trastuzumab therapy did not change nt-pro-BNP immediately before (44+/-29 pg/ml) vs. after the infusion (45+/-32 pg/ml, n.s.) in the low-level as in the high level nt-pro-BNP group (231+/-356 pg/ml prior and 240+/-377 pg/ml, n.s.). Cardiac output remained stable during trastuzumab infusion, however cardiac output was significantly increased following the end of the infusion stronger in the high-level nt-pro-BNP group. Systemic vascular resistance prior to the trastuzumab infusion was higher in the high-level nt-pro-BNP group with significant decrement during and after the infusion. CONCLUSION: Combining real-time CW-Doppler ultrasound and nt-pro-BNP monitoring is feasible to monitor the immediate hemodynamic changes during and after trastuzumab infusion.

Effects of combined supplementation with B vitamins and antioxidants on plasma levels of asymmetric dimethylarginine (ADMA) in subjects with elevated risk for cardiovascular disease.

Elevated plasma asymmetric dimethylarginine (ADMA) concentrations have been suggested as a potential risk factor for cardiovascular disease (CVD). Studies indicate a linkage between hyperhomocysteinemia, oxidative stress and ADMA metabolism. We tested the hypothesis that combined supplementation of B vitamins and antioxidants reduces ADMA concentrations in subjects with at least two CVD risk factors. A total of 123 men and women (58+/-8.1 years) were randomly assigned to take either a preparation including B vitamins and antioxidants (verum) or placebo for 6 months in a double-blind design. Blood concentrations of ADMA, symmetric dimethylarginine (SDMA), L-arginine, B vitamins, total homocysteine (tHcy), alpha-tocopherol, antioxidant capacity (TEAC), and oxLDL were measured pre- and post-intervention. Treatment with verum significantly decreased tHcy (-2.14 micromol/L; P<0.001) and significantly increased TEAC values (+39.3 microM; P<0.022), but no effect on ADMA was observed. OxLDL was significantly reduced in verum (-7.3 U/L; P=0.001) and placebo (-9.2U/L; P<0.001). At baseline, significant correlations were found only between ADMA and SDMA (r=0.281; P=0.002), L-arginine/ADMA and SDMA (r=-0.294; P<0.001), L-arginine/ADMA and oxLDL (r=-0.281; P=0.016), and L-arginine/ADMA and age (r=-0.231; P=0.010). Our results indicate that combined supplementation of B vitamins and antioxidants is not an adequate strategy to reduce ADMA plasma levels in subjects with elevated CVD risk.

Physicochemical compatibility of nebulizable drug mixtures containing dornase alfa and ipratropium and/or albuterol.

Patients suffering from cystic fibrosis (CF) often need to inhale multiple doses of different nebulizable drugs per day. Patients attempt to shorten the time consuming administration procedure by mixing drug solutions/suspensions for simultaneous inhalation. The objective of this experimental study was to determine whether mixtures of Pulmozyme inhalation solution with Atrovent or Sultano are physicochemically compatible. Drug combinations were prepared in accordance with the product information and clinical practice by mixing the content of one respule Pulmozyme with 2 mL Atrovent LS and 0.5 mL Sultanol Inhalationslösung (inhalation solution) or with one respule of either Atrovent 500 microg/2 mL Fertiginhalat (unit dose formulation) or Sultanol forte Fertiginhalat. Test solutions were stored at room temperature and exposed to light. Dornase alfa activity was determined by a kinetic colorimetric DNase activity assay. Ipratropium bromide and albuterol concentrations were investigated by a stability-indicating HPLC assay with ultraviolet detection. Physical compatibility was determined by visual inspection and measurements of pH and osmolality. Ipratropium bromide and albuterol concentrations were not affected by mixing the drug products. Dornase alfa activity is affected by benzalkonium chloride, used as excipient in Atrovent"LS and Sultanol'Inhalationsl6öung, and disodium edetate used as an excipient in AtroventfLS. Patients should be advised not to mix Pulmozymelwith Atrovent1LS and/or Sultanol"Inhalationsldöung, because of the incompatibility reaction. Mixtures of Pulmozyme with Atrovent 500 microg/2 mL Fertiginhalat or Sultanol forte Fertiginhalat can be designated as compatible for a limited period of time.

Effects of a cinnamon extract on plasma glucose, HbA, and serum lipids in diabetes mellitus type 2.

BACKGROUND: According to previous studies, cinnamon may have a positive effect on the glycaemic control and the lipid profile in patients with diabetes mellitus type 2. The aim of this trial was to determine whether an aqueous cinnamon purified extract improves glycated haemoglobin A1c (HbA1c), fasting plasma glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triacylglycerol concentrations in patients with type 2 diabetes. METHODS: A total of 79 patients with diagnosed diabetes mellitus type 2 not on insulin therapy but treated with oral antidiabetics or diet were randomly assigned to take either a cinnamon extract or a placebo capsule three times a day for 4 months in a double-blind study. The amount of aqueous cinnamon extract corresponded to 3 g of cinnamon powder per day. RESULTS: The mean absolute and percentage differences between the pre- and post-intervention fasting plasma glucose level of the cinnamon and placebo groups were significantly different. There was a significantly higher reduction in the cinnamon group (10.3%) than in the placebo group (3.4%). No significant intragroup or intergroup differences were observed regarding HbA1c, lipid profiles or differences between the pre- and postintervention levels of these variables. The decrease in plasma glucose correlated significantly with the baseline concentrations, indicating that subjects with a higher initial plasma glucose level may benefit more from cinnamon intake. No adverse effects were observed. CONCLUSIONS: The cinnamon extract seems to have a moderate effect in reducing fasting plasma glucose concentrations in diabetic patients with poor glycaemic control.

Oncofoetal fibronectin--a tumour-specific marker in detecting minimal residual disease in differentiated thyroid carcinoma.

Supposedly, thyrocyte-specific transcripts such as thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) were proposed to be useful for the diagnosis of circulating tumour cells in patients suffering from differentiated thyroid carcinoma (DTC). However, several research groups reported blood-borne Tg transcripts in healthy individuals. This study determines in particular the origin of Tg mRNA in nucleated blood cells and analyses whether other tumour-associated sequences are absent in leukocytes, but widely expressed in DTC. Therefore, expression analyses for Tg, TSH-R, cytokeratin 19 (CK 19), human telomerase reverse transcriptase (hTERT) and oncofoetal fibronectin (onfFN) were carried out using cDNAs derived from (1) leukocyte fractions, (2) 18 follicular thyroid carcinomas (FTCs) and 48 papillary thyroid carcinomas (PTCs), and (3) leukocytes of two thyrocyte-depleted individuals treated for C-cell carcinoma of the thyroid. Expression of onfFN was additionally analysed by semiquantitative RT-PCR and by quantitative fluorescence-based real-time PCR. Tg and TSH-R expression was demonstrated not only in both athyroid individuals, but in all leukocyte subgroups tested, while hTERT was absent in resting CD4+ cells and only weakly expressed in the CD8+ group. CK 19 was notable in each leukocyte population except for resting CD14(+), as well as for activated and resting CD19+ cells. All blood cell fractions proved negative for onfFN mRNA, whereas its presence in thyroid carcinoma was 78/98% (FTC/PTC). Threshold cycle values were calculated at: porphobilinogen deaminase (PBGD) = 25.95+/-0.73 (FTC)/24.55+/-5.43 (PTC) (P = 0.2878); onfFN = 25.48+/-3.15 (FTC)/21.44+/-3.44 (PTC) (*P = 0.0001). Finally, onfFN transcripts were detected in blood samples of six out of nine patients with known DTC metastases, demonstrating a reliable assay functionality. We propose that real-time RT-PCR of onfFN mRNA is superior to other markers in monitoring minimal residual disease in DTC with regard to both assay sensitivity and specificity.

Blood specimen collection methods influence the concentration and the diagnostic validity of matrix metalloproteinase 9 in blood.

BACKGROUND: Matrix metalloproteinases (MMP) in blood are promising new diagnostic tools. It was shown that the blood sampling process resulted in different blood concentrations of MMPs. To clarify whether the sampling process also influences the diagnostic validity of MMPs, MMP-9 measurements were performed in plasma and serum samples of patients with prostate carcinoma and renal cell cancer. METHODS: MMP-9 ELISAs were performed in samples of heparin plasma and serum collected in blood tubes with and without clot accelerator. Measurements were undertaken in 78 healthy persons, 33 patients with prostate carcinoma and 33 patients with renal cell carcinoma. RESULTS: MMP-9 showed higher concentrations in serum samples than in heparin plasma and was about threefold higher in serum samples collected in tubes with clot activator than in native serum samples. Both patient groups had lower MMP-9 concentrations in serum, whereas in plasma, patients with renal cell carcinoma had higher, but patients with prostate cancer unchanged MMP-9 concentrations. 13 of 33 patients with renal cell carcinoma had increased MMP-9 plasma values but no patient had increased serum concentrations. CONCLUSIONS: To optimise the diagnostic validity of the MMP-9 in blood, measurements should be performed in heparin plasma but not in serum.