Urea, Uric Acid, Prolactin and fT4 Concentrations in Aqueous Humor of Keratoconus Patients.

PURPOSE: Keratoconus is a noninflammatory disease of the cornea associated with progressive thinning and conical shape. Metabolic alterations in the urea cycle, with changes in collagen fibril stability, oxidative stress, thyroid hormones and prolactin with regulatory effect on biosynthesis and biomechanical stability of corneal stroma, may all play a role in keratoconus etiology. Our purpose was to determine urea, uric acid, prolactin and free thyroxin (fT4) concentrations in human aqueous humor (hAH) of keratoconus and cataract patients. METHODS: hAH was collected from 100 keratoconus (penetrating keratoplasty) (41.9 ± 14.9 years, 69 males) and 100 cataract patients (cataract surgery) (71.2 ± 12.4 years, 58 males). Urea, uric acid, prolactin and fT4 concentrations were measured by Siemens clinical chemistry or immunoassay system. For statistical analysis, a generalized linear model (GLM) was used. RESULTS: Urea concentration was 11.88 ± 3.03 mg/dl in keratoconus and 16.44 ± 6.40 mg/dl in cataract patients, uric acid 2.04 ± 0.59 mg/dl in keratoconus and 2.18 ± 0.73 mg/dl in cataract groups. Prolactin concentration was 3.18 ± 0.34 ng/ml in keratoconus and 3.33 ± 0.32 ng/ml in cataract patients, fT4 20.57 ± 4.76 pmol/l in KC and 19.06 ± 3.86 pmol/l in cataract group. Urea concentration was effected through gender (p = 0.039), age (p = 0.001) and diagnosis (p = 0.025). Uric acid concentration was not effected through any of the analyzed parameters (p > 0.056). Prolactin and fT4 concentration were effected only through diagnosis (p = 0.009 and p = 0.006). CONCLUSIONS: Urea and prolactin concentrations are decreased, fT4 concentration is increased in aqueous humor of keratoconus patients, and uric acid concentration remains unchanged. Urea concentration in aqueous humor is also increased in older and male patients. Therefore, metabolic disorder and hormonal balance may both have an impact on keratoconus development. Further studies are necessary to assess the specific impact.

Prospective comparison of three risk score models at three different surgical intensive care units.

PURPOSE: Although risk score models are of great value, their use is restricted because of the additional effort involved. The aim of this study was to compare three different score systems. Each of these requires a different degree of effort by the medical staff. One of the score systems is solely based on routine laboratory parameters. Data were collected on three different ICUs units, with each showing a large variety in patients' health conditions. METHODS: Prospective data of 588 surgical patients were collected by means of Acute Physiology and Chronic Health Evaluation II (APACHE II), Dense Laboratory Whole Blood Applied Risk Estimation (DELAWARE), and Simplified Acute Physiology Score II (SAPS II) score systems. These patients were admitted to three different intensive care units over a period of 12 months. On the day of admission, predicted hospital survival and mortality were evaluated. RESULTS: With a cutoff value of 0.6, the sensitivity of the APACHE II, DELAWARE, and SAPS II was at 0.19, 0.24, and 0.21; the specificity was at 0.98, 0.92, and 0.98; and the correct classification rate at 0.86, 0.83, and 0.86. The r(2) value was 0.35 for the APACHE II, 0.12 for the DELAWARE, and 0.21 for the SAPS II. The hospital mortality rate was overestimated in all three score systems. CONCLUSIONS: The results of this first multicenter study comparing three risk score systems indicate that it is possible to establish a general risk score for surgical intensive care patients on admission date. Such a risk score is solely based on quality-controlled, low-cost routine laboratory parameters.

Long-term comparison of a routine laboratory parameter-based severity score with APACHE II and SAPS II.

BACKGROUND: Risk score models predicting mortality have tremendous value, but because of the additional effort involved, their clinical use remains low. The aim of this study is to compare three different scores that each requires different levels of effort during admission and throughout treatment: the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II (SAPS II), and the Dense Laboratory Whole Blood Applied Risk Estimation (DELAWARE) score. Of the three, only the DELAWARE is based solely on routine laboratory parameters. METHODS: Prospective data of the three scores were collected for 268 surgical patients admitted to the intensive care unit over 1 year. The predicted hospital mortality and survival were evaluated for the first 14 days. RESULTS: With a cutoff value of 0.65, the sensitivity of the DELAWARE was 71.6%, the specificity, 92.5%, and the correct classification rate, 87.3%. The APACHE II and SAPS II showed values of 41.2%/96.8%/86.2% and 62.7%/87.1%/82.5%, respectively. The r2 value was 0.884 for the DELAWARE, 0.876/0.814 for the APACHE II and SAPS II. Hospital mortality rate was overestimated by 20% to 65% in all scores. The discriminatory ability of the APACHE II and SAPS II increased throughout the course of treatment. CONCLUSIONS: The routine laboratory-based DELAWARE provides a reliable, valid risk assessment of the surgical intensive care patient at admission. It also provides additional information without added effort or poor interobserver reliability, which leads to better data comparability. We have to state that until now the data have been collected in a single-center and their general validity is therefore limited. By the end of treatment, the SAPS II and APACHE II had increased discriminatory ability and are therefore useful as process parameters.

Association of nucleated red blood cells in blood and arterial oxygen partial tension.

BACKGROUND: Several studies suggest that the detection of nucleated red blood cells (NRBCs) in hospitalized patients indicates an increased risk of mortality. This study evaluates the impact of low arterial oxygen partial tension (pO2) on NRBC appearance and prognosis in NRBC positive patients. METHODS: NRBCs in blood, arterial blood gases, and other laboratory parameters were monitored daily in 234 surgical intensive care patients. pO2 was assessed in relation to mortality and the detection of NRBCs. RESULTS: NRBCs were found in 67 patients (28.6%). Mortality was significantly higher in NRBC positive patients (41.8%, 28/67) than in those that were NRBC negative (3.0%, 5/167). Multivariate logistic regression showed an increased mortality in NRBC positive patients (odds ratio 5.79; 95% confidence interval (CI) 1.07-31.33, p < 0.05). NRBC positive patients showed significantly lower pO2 levels during intensive care treatment than NRBC negative patients. Prior to the initial detection of NRBCs in the peripheral blood, pO2 levels were significantly lower in patients who died than in surviving patients. After the first appearance of NRBCs, no significant difference in pO2 between these groups was found. CONCLUSIONS: The detection of NRBCs is of prognostic significance concerning patient mortality. In NRBC positive patients, hypoxemia occurs more frequently. Low-levels of pO2 seem to precede the appearance of NRBCs, especially in those patients with high risk of mortality.

Secretion of soluble VEGF receptor 2 by microvascular endothelial cells derived by human benign prostatic hyperplasia.

Vascular endothelial growth factor (VEGF) is one of the most potent mitogenic factors stimulating both prostate endothelial and prostate epithelial cells. Recently, some studies reported on the endothelial secretion of a soluble VEGF receptor 2 (sVEGFR-2) that modifies the free VEGF concentration by binding VEGF. For the first time in this study, we report on the secretion and the regulation of the secretion of sVEGFR-2 by microvascular endothelial cells derived from the tissue of human benign prostatic hyperplasia (HPEC). HPEC were isolated and cultured from fresh prostate tissue. The prostate epithelial cell line BPH-1 was cultured with the supernatant of the HPEC cell culture (fractioned by fast protein liquid chromatography) and the VEGF concentration was subsequently measured. HPEC were incubated with VEGF or tumor necrosis factor alpha (TNF-alpha). Afterwards, the concentration of sVEGFR-2 in the supernatant of unstimulated and stimulated HPEC was measured by ELISA. HPEC showed a typical endothelial morphology. Under cell culture conditions sVEGFR-2 binds VEGF: The measured VEGF concentration in the supernatant of BPH-1 cells was reduced when the fractions of HPEC conditioned medium with the highest sVEGFR-2 concentration were incubated with the BPH-1 cells. The sVEGFR-2 secretion of HPEC was stimulated by VEGF and TNF-alpha. For the first time we report on the secretion of sVEGFR-2 by microvascular endothelial cells of prostate origin. The secretion of sVEGFR-2 by HPEC was stimulated by VEGF and TNF-alpha. Our data suggest that sVEGFR-2 secreted by prostate endothelial cells could modify the effect of VEGF on prostate endothelial and prostate epithelial cells.

Salivary cortisol and psychological mechanisms in patients with acute versus chronic low back pain.

This study was designed to explore whether the basal adrenocortical activity is related with pain-related coping, nonverbal pain behavior, depressive mood, and fatigue in patients with acute and chronic nonspecific low back pain. 19 patients with acute low back pain (ALBP) and 24 with chronic low back pain (CLBP) participated in the study. The adrenocortical activity was assessed through the cortisol awakening response. All participants provided five saliva samples (0, 15, 30, 45, and 60min after waking) on two consecutive days off work. Pain-related coping [fear-avoidance coping (FAC) and endurance coping (EC)], nonverbal pain behavior (NPB), depressive mood, and fatigue were assessed through questionnaires. Among ALPB patients, EC was negatively associated with the cortisol release, whereas fatigue was positively associated with it. Among CLBP patients, FAC, NPB, depressive mood, and fatigue were negatively associated with the cortisol awakening response, whereas EC tended to be positively associated with it. The results indicate that pain-related coping strategies which are expected to be successful appear to lower the adrenocortical activity among ALBP patients, whereas affective distress may enhance the level of cortisol in this group. Among CLBP patients, long-term maladaptive coping strategies might contribute to hypocortisolism.

The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome.

BACKGROUND: Non-thyroidal illness syndrome (NTIS) is a characteristic functional constellation of thyrotropic feedback control that frequently occurs in critically ill patients. Although this condition is associated with significantly increased morbidity and mortality, there is still controversy on whether NTIS is caused by artefacts, is a form of beneficial adaptation, or is a disorder requiring treatment. Trials investigating substitution therapy of NTIS revealed contradictory results. The comparison of heterogeneous patient cohorts may be the cause for those inconsistencies. OBJECTIVES: Primary objective of this study is the identification and differentiation of different functional states of thyrotropic feedback control in order to define relevant evaluation criteria for the prognosis of affected patients. Furthermore, we intend to assess the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent (so-called "sub-clinical") thyrotoxicosis.Secondary objective is observation of variables that quantify distinct components of NTIS in the context of independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication. DESIGN: The approach to a quantitative follow-up of non-thyroidal illness syndrome (AQUA FONTIS study) is designed as both a cross-sectional and prospective longitudinal observation trial in critically ill patients. Patients are observed in at least two evaluation points with consecutive assessments of thyroid status, physiological and clinical data in additional weekly observations up to discharge. A second part of the study investigates the neuropsychological impact of NTIS and medium-term outcomes.The study design incorporates a two-module structure that covers a reduced protocol in form of an observation trial before patients give informed consent. Additional investigations are performed if and after patients agree in participation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00591032.

Re-evaluation of established risk scores by measurement of nucleated red blood cells in blood of surgical intensive care patients.

BACKGROUND: In adults, the appearance of nucleated red blood cells (NRBC) in the peripheral blood is associated with several severe diseases. When NRBC are detected in the blood, the prognosis is poor. The purpose of this study was to identify the impact of NRBC on the clinical outcomes of surgical intensive care patients under consideration of established risk models. METHODS: In a prospective study, the detection of NRBC in the peripheral blood of surgical intensive care patients was analyzed with regard to the in- hospital mortality. NRBC were daily measured with a Sysmex XE-2100. The prognostic significance of NRBC in blood was analyzed under consideration of established risk scores for intensive care patients, i.e., the Acute Physiology and Chronic Health Evaluation (APACHE II) and the Simplified Acute Physiology Score (SAPS II). RESULTS: Two hundred seventy-one surgical intensive care patients were included in this study. The mean age was 61.3 years +/- 1.2 years (range, 18-98 years). The average APACHE II and SAPS II scores were 20.6 +/- 0.6 and 44.1 +/- 1.2, respectively. The in-hospital mortality of NRBC-positive patients was 51.7% (45 of 87). This was significantly higher (p < 0.001) than the mortality of NRBC-negative patients (12.0%, 22 of 184). The area under curve (C-statistic) was 0.77. Mortality increased with the NRBC concentration. On average, in NRBC-positive patients who died, NRBC were detected for the first time 13.3 days +/- 3.1 days (n = 45, median = 6 days) before death. Multiple logistic regression analysis under consideration of the APACHE II or the SAPS II revealed a significant association between NRBC and increased mortality, the mean odds ratio being 1.97 for each increase in the NRBC category (0/microL; 1-40/microL; 41-80/microL; 81-240/microL, >240/microL). In contrast, under consideration of the NRBC-data the mean odds ratios for the increase of one score point of the APACHE II and SAPS II were 1.10 and 1.05, respectively. Therefore, each step-up in the NRBC category is equivalent to approximately 7 APACHE II-score points and 14 SAPS II-score points, respectively. CONCLUSIONS: The daily screening for NRBC in blood of surgical intensive care patients is of prognostic power with regard to the patients' in-hospital mortality. This prognostic significance of NRBC was independent of the scores APACHE II and SAPS II, respectively. Therefore, for prognostic purposes an adjustment of these established risk models by including the NRBC-results is feasible.

A laboratory-based risk score for medical intensive care patients.

BACKGROUND: Established general risk score models for intensive care patients incorporate several clinical and laboratory data. However, the collection, documentation and classification of clinical data are time-consuming, incur labor-related costs, and are dependent on the experience of the examiner. Therefore, in the present study a general score for medical intensive care patients based solely on routine laboratory parameters is presented. METHODS: Parameter selection was performed using stepwise logistic regression analysis. The maximum likelihood estimate of variable influence on mortality provided a relative weighting for each variable. The new score was compared to two established risk models (Acute Physiology And Chronic Health Evaluation II, APACHE II; and Simplified Acute Physiology Score II, SAPS II). RESULTS: The study included 528 medical intensive care patients with a mean age of 65.4+/-0.7 years. The in-hospital mortality was 16.5% (87/528). Multiple logistic regression analysis revealed eight parameters with significant prognostic power: alanine aminotransferase, cholesterol, creatinine, leukocytes, sodium, thrombocytes, urea, and age. These parameters were used to build a new laboratory score called Critical Risk Evaluation by Early Keys (CREEK). The area under the receiver operating characteristics curve was 0.857 (0.814-0.900). Pearson correlation analysis showed significant correlation between CREEK and APACHE II (r=0.550) and SAPS II (r=0.516; p<0.001; n=387). The areas under curve of the APACHE II and the SAPS II were 0.869 and 0.874, respectively. CONCLUSIONS: We show that a general risk score for medical intensive care patients on admission based solely on routine laboratory parameters is feasible. The quality of risk estimation using CREEK is comparable to established risk models. Furthermore, this new score is based on quality controlled low-cost laboratory parameters that are routinely measured on admission to the intensive care unit. Therefore, no additional costs are involved.

Effectiveness of CT-guided percutaneous biopsies of the spine: an analysis of 202 examinations.

RATIONALE AND OBJECTIVES: The study goal was to retrospectively evaluate the effectiveness of computed tomography (CT)-guided spinal biopsies. MATERIAL AND METHODS: Two hundred two CT-guided vertebral biopsies performed between May 1999 and June 2004 in 187 patients were retrospectively analyzed. Patient characteristics (age, sex, antibiotic therapy), technical parameters (depth and number of biopsies, needle approach), lesion features (spinal level, osteolysis, fluid collections, soft tissue tumor), and complications were documented. Furthermore, histopathological and microbiological diagnoses were considered. RESULTS: There were two focal hematomas in our study group (complication rate: 1%). Histopathological diagnosis was established in 74% of examinations with spondylitis (41% of cases) being most common. In spinal tumors (27% of cases), malignant lesions were found in 52 of 54 examinations (96%). Osteolysis was diagnosed in 98% of patients with spondylitis and in 87% of patients with tumors (P < .01). Spinal tumors were most commonly seen in the sacrum (53%, P < .001), whereas spondylitis typically occurred in the lumbar spine (55%, P = .001). Neither patient age nor sex, needle approach, needle depth, or vertebral abnormalities showed a significant impact on diagnostic accuracy. Microbiological tests were performed in 98 patients (49%); 62 of 98 patients (65%) received antibiotic therapy. In 12 of 62 patients (19%) with antibiotic therapy and in 9 of 36 patients (25%) without antibiotic treatment, microbiological tests were positive (P = .153). Staphylococcus aureus was found in 9 of 21 examinations (43%). CONCLUSIONS: CT-guided vertebral biopsy is a safe and effective procedure to establish final diagnosis in spinal lesions of unclear origin. Patient characteristics, lesions features, and technical considerations did not influence sample quality. In spondylitis, which was commonly caused by Staphylococcus aureus, microbiological yield was low regardless of antibiotic therapy.

Nucleated red blood cells in the blood of medical intensive care patients indicate increased mortality risk: a prospective cohort study.

INTRODUCTION: In critically ill patients, the appearance of nucleated red blood cells (NRBCs) in blood is associated with a variety of severe diseases. Generally, when NRBCs are detected in the patients' blood, the prognosis is poor. METHODS: In a prospective study, the detection of NRBCs was used for a daily monitoring of 383 medical intensive care patients. RESULTS: The incidence of NRBCs in medical intensive care patients was 17.5% (67/383). The mortality of NRBC-positive patients was 50.7% (34/67); this was significantly higher (p < 0.001) than the mortality of NRBC-negative patients (9.8%, 31/316). Mortality increased with increasing NRBC concentration. Seventy-eight point six percent of the patients with NRBCs of more than 200/microl died. The detection of NRBCs is highly predictive of death, the odds ratio after adjustment for other laboratory and clinical prognostic indicators being 1.987 (p < 0.01) for each increase in the NRBC category (0/microl, 1 to 100/microl, 101 to 200/microl, and more than 200/microl). Each step-up in the NRBC category increased the mortality risk as much as an increase in APACHE II (Acute Physiology and Chronic Health Evaluation II) score of approximately 4 points. The mortality of patients who were NRBC-positive on the day of relocation from the intensive care unit to a peripheral ward was 27.6% (8/27). This was significantly higher than the mortality of patients who were NRBC-negative on the relocation day (8.6%, 28/325; p < 0.01). On average, NRBCs were detected for the first time 14 days (median, 3 days) before death. CONCLUSION: The routine analysis of NRBCs in blood is of high prognostic power with regard to mortality of critically ill patients. Therefore, this parameter may serve as a daily indicator of patients at high mortality risk. Furthermore, NRBC-positive intensive care patients should not be relocated to a normal ward but should obtain ongoing intensive care treatment.

Poor prognosis indicated by nucleated red blood cells in peripheral blood is not associated with organ failure of the liver or kidney.

BACKGROUND: The appearance of nucleated red blood cells (NRBCs) in peripheral blood is associated with a variety of severe diseases. When NRBCs are detected in blood, this is generally associated with increased mortality. METHODS: In a prospective study, NRBCs and other laboratory parameters were measured daily in the peripheral blood of surgical intensive care patients. The appearance of NRBCs was analyzed in relation to laboratory indicators of organ injury. RESULTS: A total of 284 surgical intensive care patients were included in this study. The mortality of NRBC-positive patients was 44.0% (40/91). This was significantly higher (p<0.001) than the mortality of NRBC-negative patients (4.2%, 8/193). Mortality increased with the NRBC concentration and the length of the NRBC-positive period. Multiple logistic regression analysis of several other clinical and laboratory risk indicators revealed a significant association between NRBCs and increased mortality, with an odds ratio of 1.95 (95% CI 1.35-2.82; p<0.001) for each increment in NRBC category (0, 1-40, 41-80, 81-240 and >240 NRBC/microL). After the initial detection of NRBCs in blood, there were no significant increases in creatinine concentrations or alanine aminotransferase activity. However, the appearance of NRBCs coincided with increasing C-reactive protein and thrombocyte concentrations. CONCLUSIONS: The detection of NRBCs in blood of surgical intensive care patients is of prognostic power with regard to patient mortality. This prognostic significance of NRBCs was independent of some clinical and other laboratory risk parameters. The appearance of NRBCs in blood was not associated with kidney failure or lesion of the liver.

Daily monitoring of nucleated red blood cells in the blood of surgical intensive care patients.

BACKGROUND: In intensive care patients the appearance of nucleated red blood cells (NRBC) in blood is associated with a variety of severe diseases. Generally, when NRBCs are detected in the patients' blood the prognosis is poor. MATERIAL AND METHODS: In the present study the detection of NRBCs was used for a day-to-day monitoring of 284 surgical intensive care patients. RESULTS: NRBCs were found at least once in 32.0% of all patients. The mortality of NRBC-positive patients was 44.0% (40/91); this was significantly higher (P<0.001) than the mortality of NRBC-negative patients (4.2%, 8/193). With regard to intensive care mortality, NRBCs in blood showed sensitivity and specificity of 83.3% and 78.9%, respectively. The area under curve (C-statistic) was 0.86. Mortality increased with increasing NRBC concentration. All patients with more than 2000 NRBCs/microl died. Moreover, mortality increased with increasing frequency of occurrence. When after first detection of NRBCs in blood, during the further course of intensive care treatment the NRBCs have disappeared from the circulation, the mortality again decreased to values of NRBC-negative patients. The detection of NRBCs is associated with an increased mortality rate, the odds ratio after adjustment for other laboratory prognostic indicators being 1.8 (P<0.001) for each increase in the NRBC category (1-40/microl; 41-80/microl; 81-240/microl, >240/microl). NRBCs were detected for the first time, on average, 9 days (median 5 days) before death. CONCLUSIONS: The routine analysis of NRBC in blood is of potential prognostic power with regard to mortality of critically ill patients. Therefore, this parameter could possibly serve as a daily indicator of patients at high mortality risk.

Association between nucleated red blood cells in blood and the levels of erythropoietin, interleukin 3, interleukin 6, and interleukin 12p70.

The appearance of nucleated red blood cells (NRBC) in the circulation is associated with a variety of severe diseases, and indicates a relatively poor prognosis. Whether a malfunction of the bone marrow leads to this phenomenon is as unknown as the possible role that cytokines could play in this process. We analyzed erythropoietin, interleukin (IL)-3, IL-6, and IL-12p70 in the blood of 301 patients with circulating NRBCs. Two hundred fifty NRBC-negative patients served as controls. Multiple logistic regression revealed a significant association between the appearance of NRBCs in the blood and erythropoietin (odds ratio, 1.017; 95% confidence limits, 1.007-1.027; P < 0.001), IL-3 (odds ratio, 1.293; 95% confidence limits, 1.180-1.417; P < 0.001), IL-6 (odds ratio, 1.138; 95% confidence limits, 1.016-1.275; P < 0.05), and age (odds ratio, 1.019; 95% confidence limits, 1.009-1.030; P < 0.001), respectively. Gender and IL-12p70 were not significantly associated with the appearance of NRBC in the blood. To estimate the RBC production in the bone marrow, the increase in the reticulocyte concentration in blood was measured. The reticulocyte concentration in NRBC-positive patients was 69 +/- 2/nL, which was significantly higher than in NRBC-negative patients (60 +/- 2/nL; P < 0.01). Taken together, NRBC could be a marker that sums up hypoxic and inflammatory injuries. Thus, generally, the appearance of NRBC in blood is a valid parameter to identify patients at high mortal risk. Moreover, the increased number of reticulocytes in the blood of NRBC-positive patients may indicate that the appearance of NRBC is not associated with disturbed bone marrow function as far as the erythropoiesis is concerned.

CD14 expression on monocytes and soluble CD14 plasma levels in correlation to the promotor polymorphism of the endotoxin receptor CD14 gene in patients with inactive Crohn's disease.

BACKGROUND/AIMS: The association of the single nucleotide polymorphism in the promotor of the lipopolysaccharide receptor CD14 gene (T/C at position -159) with Crohn's disease has recently been demonstrated. This CD14 polymorphism is a potential predisposition factor responsible for inter-individual differing inflammatory reactions involving the CD14 receptor. We studied the correlation between the CD14 genotype (CC, CT, TT) and the membrane-bound CD14 monocyte expression and soluble CD14 in patients with inactive Crohn's disease. METHODOLOGY: In 23 patients and 29 healthy volunteers the membrane-bound CD14 density on unstimulated monocytes and soluble CD14 plasma levels were examined using quantitative flow cytometry and enzyme-linked immunosorbent assay. RESULTS: In normal controls membrane-bound CD14 monocyte density did not differ significantly between the genotypes CC, CT, or TT. In contrast, patients with inactive Crohn's disease and genotype TT showed a significantly lower membrane-bound CD14 density on monocytes compared to patients with genotype CC. Soluble CD14 plasma levels were significantly higher in patients with inactive Crohn's disease compared to the same genotype of healthy controls, but there was no significant difference between the genotypes CC, CT, and TT. CONCLUSIONS: Our data show that the membrane-bound CD14 monocyte expression and the soluble CD14 plasma levels in patients with inactive Crohn's disease completely differ from that in healthy individuals. In order to develop individualized therapy strategies further studies should be carried out to evaluate whether the TT genotype is associated with differences in the clinical course of Crohn's disease and in the response to antibacterial treatment.

Prognostic significance of erythroblasts in burns.

Changes in hematopoiesis that occur in humans after a burn injury may have important effects on morbidity and mortality. In patients with a variety of severe diseases, the presence of erythroblasts in peripheral blood is known to be indicative of a poor prognosis. However, the prognostic significance of erythroblasts in peripheral blood of burn patients has not yet been estimated. This study included 464 consecutive burn patients, of whom 81 did not survive their injuries (17.5 percent). Together with erythroblasts in blood, data on age, sex, total burn surface area, third-degree burn, inhalation trauma, white blood cell count, C-reactive protein, and hemoglobin were studied. The mortality rate of patients with erythroblasts in peripheral blood (n = 53) amounted to 56.6 percent (n = 30; total burn surface area, 39 percent), which is significantly higher (p < 0.001) than the mortality rate of patients without erythroblasts (12.4 percent, n = 51; total burn surface area, 18.69 percent). None of the 10 patients with more than 1000 erythroblasts x 10/liter survived. The detection of erythroblasts in the peripheral blood of burn patients is highly predictive of death, with the odds ratio after adjustment for the other known prognostic factors being 8.3 (95 percent confidence interval, 4.5 to 15.3). Erythroblasts were detected for the first time on average 10 +/- 4 days (median, 6 days) after admission and 13 +/- 6 days (median, 7 days) before death. Detection of erythroblasts in burn patients is of high prognostic power with regard to in-hospital mortality, providing physicians with a strong prognostic method with which to identify seriously threatened patients. It seems attractive to think about an incorporation of erythroblasts into further refinements of burn scores.

The secretion of endothelin-1 by microvascular endothelial cells from human benign prostatic hyperplasia is inhibited by vascular endothelial growth factor.

Prostate growth seems to be influenced by paracrine factors like endothelin-1 (ET-1), originating from the microvascular endothelium. Recently, we reported on the first isolation and primary culture of microvascular endothelial cells (HPEC) derived from tissue of human benign prostatic hyperplasia (BPH). Therefore, direct investigation of growth factor secretion by HPEC is now possible. BPH tissue was cut into small cubes and gently squeezed after incubation with dispase. HPEC were cultured from the resulting cell suspension after a stepwise selection by use of superparamagnetic beads coated with antibodies against endothelial specific antigens. HPEC were characterized by flow cytometry. After the incubation of HPEC either with vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-alpha), or adenosine triphosphate (ATP), the secretion of ET-1 was measured by ELISA. HPEC showed a typical endothelial morphology. They were positive for von Willebrand factor and CD31. The ET-1 secretion of HPEC was inhibited by VEGF, but was unaffected by TNF-alpha or ATP. Furthermore, histochemistry revealed that in vivo microvascular endothelial cells were negative for ET-1. Because of the suppression by the widespread VEGF, it is unlikely that ET-1 from the microvascular endothelium acts as a growth factor in human BPH.

High in-hospital mortality of intensive care patients with nucleated red blood cells in blood.

The detection of nucleated red blood cells (NRBCs) in blood of patients suffering from a variety of severe diseases is known to be highly associated with increased mortality. Blood analyzers to routinely measure NRBC concentrations are now available. However, the diagnostic and prognostic significance of this parameter for intensive care patients has not been evaluated. Using a Sysmex XE-2100 analyzer, NRBC concentrations were determined in blood samples from 421 patients treated in intensive care units (general and accident surgery, cardiothoracic surgery, and internal medicine) of a university hospital. NRBCs were found at least once in 19.2% of all patients. The mortality of NRBC-positive patients (n=81) was 42.0% (n=34); this was significantly higher (p<0.001) than the mortality of NRBC-negative patients (5.9%, n=340). The NRBC concentration was 115+/-4x10(6)/l (median 40x10(6)/l; range 20-2930x10(6)/l) at initial detection of NRBCs in the blood. Mortality increased with increasing NRBC concentration and increasing frequency of occurrence. With regard to in-hospital mortality, NRBCs in blood showed sensitivity and specificity of 63.0% and 87.2%, respectively. The detection of NRBCs is highly predictive of death, the odds ratio after adjustment for other laboratory prognostic indicators being 1.01 (p<0.01) for each increase in the NRBC concentration of +1x10(6)/l. NRBCs were detected for the first time, on average, 13 days (median 8 days) before death. The routine analysis of NRBCs in blood is of high prognostic power with regard to in-hospital mortality of critically ill patients. Therefore, this parameter may serve as an early indicator for patients at increased mortality risk.