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C Stephan

Publications and source records attributed to C Stephan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Receiver-operating characteristic as a tool for evaluating the diagnostic performance of prostate-specific antigen and its molecular forms--What has to be considered?

BACKGROUND: Receiver-operating characteristic (ROC) analysis is often applied as evaluation tool to compare the diagnostic validity of laboratory tests. The aim of this study was to draw attention to preconditions which should be taken into account when ROC analysis is used to assess the diagnostic performance of total prostate-specific antigen (tPSA) and its molecular forms in differential diagnosis between prostate cancer and benign prostatic hyperplasia (BPH). METHODS: Using a standard software (GraphROC for Windows), ROC analyses were performed and the areas under the curves were calculated for four hypothetical pairs of groups. Every group included 40 patients with prostate cancer and with BPH showing different tPSA concentrations (range of 2-10 microg, but similar free-to-total PSA ratios (fPSA%). RESULTS: The area under the fPSA% ROC curve showed the highest value, whereas the areas under the tPSA ROC curves were dependent on the distributions of tPSA concentrations in the patients. The ability of fPSA% to improve the differential diagnosis between prostate cancer and BPH in comparison to tPSA was not furthermore evident, if the prostate cancer group included more patients with higher tPSA concentrations than the BPH group. CONCLUSIONS: When the diagnostic performance of tPSA and its derivatives like molecular forms in patients with prostate cancer and BPH should be compared by ROC analysis, a matching procedure is recommended prior to ROC analysis to compensate the effect of possible unequal tPSA distributions in both groups. Each BPH (or PCa) patient should be matched with a PCa (or BPH) patient with nearest tPSA concentration so that an optimum of overlapping tPSA concentrations in both groups can be achieved.

Diagnosis, Differential↗
PubMed2001

Comparison of the clinical validity of free prostate-specific antigen, alpha-1 antichymotrypsin-bound prostate-specific antigen and complexed prostate-specific antigen in prostate cancer diagnosis.

OBJECTIVE: To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha-1- antichymotrypsin-bound PSA (PSA-ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: A total of 166 white men (age: 65-88 years) with a tPSA between 2 and 20 microg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA-ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA-ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany). RESULTS: For statistical analysis only patients with tPSA between 2 and 20 microg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 microg/l, BPH 4.03 microg/l; Roche: PCa 7.75, BPH 4.13), PSA-ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA-ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2-20 microg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA-ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA-ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were not significantly different. CONCLUSION: The determination of PSA-ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA-ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.

Aged↗
PubMed2001

Estradiol signaling via sequestrable surface receptors.

Estradiol (E(2))-signaling is widely considered to be exclusively mediated through the transcription-regulating intracellular estrogen receptor (ER) alpha and ERbeta. The aim of this study was to investigate transcription-independent E(2)-signaling in mouse IC-21 macrophages. E(2) and E(2)-BSA induce a rapid rise in the intracellular free Ca(2+) concentration ([Ca(2+)](i)) of Fura-2 loaded IC-21 cells as examined by spectrofluorometry. These changes in [Ca(2+)](i) can be inhibited by pertussis toxin, but not by the ER-blockers tamoxifen and raloxifene. The E(2)-signaling initiated at the plasma membrane is mediated through neither ERalpha nor ERbeta, but rather through a novel G protein-coupled membrane E(2)-receptor as revealed by RT-PCR, flow cytometry, and confocal laser scanning microscopy. A special feature of this E(2)-receptor is its sequestration upon agonist stimulation. Sequestration depends on energy and temperature, and it proceeds through a clathrin- and caveolin-independent pathway.

Animals↗
PubMed2001

Presence of Chlamydia pneumoniae DNA in the cerebral spinal fluid is a common phenomenon in a variety of neurological diseases and not restricted to multiple sclerosis.

Chlamydial DNA and viable organisms have been reported in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. We investigated whether this phenomenon is specific for MS and not occurring in patients with other neurological diseases (OND) or in healthy controls and whether it is caused by infected blood monocytes having crossed the blood-brain barrier. Twelve (21%) of fifty-eight MS patients and 20 (43%) of 47 OND patients had Chlamydia pneumoniae DNA in the CSF as determined by nested polymerase chain reaction. Viable organisms were cultured from one OND patient. We failed to detect C. pneumoniae in the CSF of 67 neurologically healthy persons. C. pneumoniae was detected in parallel in the blood monocytes of 2 of 6 CSF-positive MS patients and in 8 of 10 CSF-positive OND patients. Thus, chlamydial presence cannot exclusively be explained as being caused by contaminating infected monocytes that have crossed the blood-brain barrier. In peripheral blood mononuclear cell-negative patients, chlamydia have been cleared from the circulation but persist in the central nervous system (CNS), indicating the establishment of a chronic process. In summary, the presence of C. pneumoniae in patients with neurological diseases is a common phenomenon and is not restricted to MS patients. The pathogenetic relevance of a chronic chlamydial CNS infection for neurological diseases remains unclear, but the hypothesis that susceptible patients may be impaired in their ability to clear chlamydiae from the CNS requires further examination.

Adolescent↗
PubMed2000

Inhibition of cyclin-dependent kinase 4 (Cdk4) by fascaplysin, a marine natural product.

Small chemical molecules that interfere with biological proteins could be useful for gaining insight into the complex biochemical processes in mammalian cells. Cdk4 is a key protein whose activity is required not only for emergence of cells from quiescence but also at the G1/S transition in the cell cycle and which is misregulated in 60-70% of human cancers. We set out to identify chemical inhibitors of Cdk4 and discovered that, in vitro, fascaplysin specifically inhibited Cdk4. Molecular modelling based on the crystal structure of Cdk2 suggests that fascaplysin inhibits Cdk4 by binding to the ATP pocket of the kinase. Treatment of tumour (p16(-), pRb(+)) and normal (p16(+), pRb(+)) cell lines with fascaplysin caused G1 arrest and prevented pRb phosphorylation at sites implicated as being specific for Cdk4 kinase. Fascaplysin will therefore prove to be a useful tool in studying the consequence of Cdk4 inhibition, especially in cells containing inactivated p16.

3T3 Cells↗
PubMed2000

Decreased concentrations of prostate-specific antigen and human glandular kallikrein 2 in malignant versus nonmalignant prostatic tissue.

OBJECTIVES: To study quantitatively the relative expression of human glandular kallikrein 2 (hK2) and prostate-specific antigen (PSA) in paired (from the same patient) cancerous and noncancerous prostatic tissue to evaluate whether these proteins are overexpressed or underexpressed in cancer. METHODS: We studied 14 patients who underwent radical retropubic prostatectomy for prostate cancer. Cancerous and adjacent normal tissues were excised and then extracted to prepare cytosolic extracts. The extracts were analyzed for total protein, and for hK2 and PSA using sensitive and specific immunofluorometric procedures. RESULTS: PSA was present in the prostatic extracts at about 50 to 100 times higher amounts than hK2. The correlation between PSA and hK2 values was good. Both prostate kallikreins were expressed more in noncancerous than in cancerous prostatic tissue. CONCLUSIONS: Our results demonstrated that both PSA and hK2 are down-regulated in prostate cancer compared with noncancerous tissue. The degree of down-regulation was higher for PSA than for hK2. The mechanism and physiologic consequences of this down-regulation are unknown.

Aged↗
PubMed2000

[Leptospirosis after a staff outing].

HISTORY AND CLINICAL FINDINGS: Three male colleagues aged between 34 and 38 years were admitted at the same time to three different Rhein-Main area Hospitals. They presented with a variety of symptoms, including high fever (39.0 to 40.0 degrees C), chills, headache with meningismus or facial paralysis, mild hepatitis and renal involvement. About 18 days before they had been together on a boat rafting tour when the boat capsized when they had fallen into a river in high flood. INVESTIGATIONS: Laboratory tests showed elevated inflammatory parameters, signs of a mild hepatitis and renal involvement. All patients had leptospirosis antibodies, detected by immunofluorescence test. In two cases there was evidence of antibodies against Leptospira interrogans serovar bataviae in the microscopic agglutination test (MAT). TREATMENT AND COURSE: The history and clinical presentation indicated leptospirosis in all patients, in two cases confirmed by laboratory findings. Following therapy with doxycycline or ceftriaxone, symptoms resolved quickly and permanently. CONCLUSION: Leptospires of serogroup Bataviae is a known pathogen of anicteric non-Weil leptospirosis. The symptoms are non-specific and, moreover, in some cases the laboratory tests are negative, so that clinical diagnosis remains crucial. Typically there is a history of contact with contaminated water or urine. In our cases striking neurotropism was observed, which may be characteristic for this serovar.

Adult↗
PubMed2000

Matrix-metalloproteinases and their inhibitors in plasma and tumor tissue of patients with renal cell carcinoma.

Matrix-metalloproteinases (MMPs) are associated with invasive and metastatic behavior of several human malignant tumors. We have determined MMP-2 and MMP-9 and tissue inhibitors of MMPs (TIMP-1 and TIMP-2) in blood plasma and in renal tissue samples of patients with renal cell carcinoma (RCC) from cancerous and non-cancerous parts of the same kidney. In tumor tissue, MMP-9 and TIMP-1 were significantly higher than in normal counterparts. MMP-2 was not different between tumor tissue and normal counterparts. TIMP-2 values could not be measured. In plasma, MMP-9 concentrations were significantly higher in RCC patients than in healthy controls, MMP-2 and TIMP-2 concentrations were higher in healthy controls and TIMP-1 concentrations were not different.

Adult↗
PubMed2000

[Distal fractures of the femur].

Supracondylar femoral fractures still present a challenge to the treating surgeon. The incidence of delayed and non-unions is reduced due to the minimally invasive plating techniques, but establishing a correct axis and good function is still a problem. During the last few years new implants have been developed to allow less difficult operative techniques in minimally invasive surgery. The Less Invasive Stabilization System (LISS) is a percutaneous plating system with monocortical self-drilling screws. The screws are inserted with an aiming guide and form a stable angle with the plate. The distal femoral nail allows placement of a spiral blade in the nail, thereby enhancing the interlocking stability.

Adult↗
PubMed2000

[Molecular forms of prostate-specific antigen and human kallikrein 2 as possible indicators in prostatic carcinoma diagnosis].

Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and in the monitoring of patients with this diagnosis. Molecular forms of PSA and human kallikrein 2 (hK2) have been used to discriminate between benign prostatic hyperplasia and prostate cancer, as well as for the detection of prostate cancer within the gray zone of PSA. In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound to alpha 1-antichymotrypsin (ACT-PSA), and complexed PSA (cPSA) is given together with our own results. The ratio of fPSA/tPSA has been shown to improve both sensitivity and specificity of prostate cancer diagnosis based on tPSA measurements. The number of biopsies can be reduced in the total PSA range of 4-10 micrograms/l. Furthermore, carcinomas can be detected in patients with PSA values less than 4 micrograms/l. ACT-PSA or cPSA alone and the calculated derivatives are not superior in their discriminatory power compared with tPSA and the fPSA% value. The other molecular PSA forms and hK2 are still objects of research and their diagnostic significance needs to be evaluated in more extensive clinical trials.

Biomarkers, Tumor↗
PubMed2000

[Preoperative patient education. What is especially important?].

Any medical procedure must be legally authorized by the patient, giving informed consent. This prerequisite is based on the right to self determination. Otherwise a medical procedure is considered as physical injury. Thus, the way, how a specific procedure is performed, predominantly depends on the patient's will. The attending physician's duty is to find out this will, which is especially important when old patients and patients incapable of giving valid consent are involved. Before the procedure the physician has to have a confidential talk with the patient. He has to point out the best treatment possible considering the individual circumstances of the patient's life. The physician has to find out, weather the patient is competent to refuse or consent to treatment. Furthermore the consultation is an opportunity to diminish the patient's fear and to increase his confidence. The main problem treating old patients is that they often lack the mental ability for appreciation of the nature of the situation. One has to differentiate between the physiological mental decay and dementia or psychiatric diseases. In these cases a third party consent is necessary.

Aged↗
PubMed2000

ACT-PSA and complexed PSA elimination kinetics in serum after radical retropubic prostatectomy: proof of new complex forming of PSA after release into circulation.

OBJECTIVES: To study the elimination kinetics of alpha(1)-antichymotrypsin (ACT)-prostate-specific antigen (PSA) and complexed PSA (cPSA) in comparison to the biexponential decrease of total PSA and free PSA after radical prostatectomy. METHODS: Serum total PSA, free PSA, ACT-PSA, and cPSA values and the corresponding ratios were determined in venous blood from 12 patients with prostate cancer. The samples were taken before surgery, immediately after surgery, 1, 2, 3, 4, 5, and 6 hours after surgery, and then once daily for the next 10 days. Total PSA and cPSA were analyzed by using Immuno 1 PSA assays (Bayer Corporation); free PSA was measured using the AxSym test kit (Abbott Diagnostics). For ACT-PSA, the ES analyzer system was used (Roche Diagnostics). Statistical calculations were performed with the analysis of variance and Wilcoxon tests. RESULTS: During the first 6 hours after radical retropubic prostatectomy, we found nearly constant levels of ACT-PSA and cPSA, in contrast to the rapid elimination of free PSA and significant decrease in total PSA. From days 1 to 10, a continuous and nearly identical decrease of ACT-PSA and cPSA occurred compared with total PSA; free PSA was eliminated more rapidly. CONCLUSIONS: In addition to the opinion that the first PSA decrease might be an effect of the operation itself or caused by renal elimination alone, our findings indicate that the initial rapid decrease of free PSA immediately after surgery could be caused by new complex forming of PSA with ACT and other serum protease inhibitors.

Aged↗
PubMed2000

Evidence for the existence of two soluble NAD(+) kinase isoenzymes in Euglena gracilis Z.

Two soluble NAD(+) kinase isoenzymes (isoenzymes 1 and 2) from Euglena gracilis were separated by preparative electrophoresis and characterized. They display several similar properties: both have an identical apparent molecular weight of 68 kDa and their activities are independent on calmodulin, insensitive to 2-mercaptoethanol but inhibited by p-chloromercurybenzoate, 5, 5'-dithiobis(2-nitrobenzoate) and, surprisingly, by low dithiothreitol concentrations, the inhibition by dithiothreitol being irreversible for isoenzyme 1 but reversible for isoenzyme 2. Nevertheless, the two isoenzymes mainly differ by their specificities towards triphosphate nucleotides and their catalytic mechanisms. Isoenzyme 1 is as active in the presence of ATP as of GTP and acts by a ping-pong mechanism with a k(M) for NAD(+) of 0.26 mM and a k(M) for low MgATP(2-)concentrations of 0.03 mM. Isoenzyme 2 is three-fold more active in the presence of GTP than of ATP and operates by a sequential mechanism with k(M)s for NAD(+) and MgGTP(2-) of 1.03 and 0.20 mM, respectively. This study shows the evidence for the existence of two structurally similar but catalytically different NAD(+) kinase isoenzymes in E. gracilis. One resembles the enzyme previously described in bacteria. The other displays a catalytic mechanism identical to that of NAD(+) kinase from other organisms but remains unique among all the NAD(+) kinases studied to-date regarding its specificity towards GTP.

Adenosine Triphosphate↗
PubMed2000

Elimination of serum complexed prostate-specific antigen after radical retropubic prostatectomy.

Total prostate-specific antigen (PSA) and complexed PSA were determined in venous blood from 12 patients with prostate cancer before and after radical prostatectomy by using Immuno 1 PSA assays. The elimination kinetics of complexed PSA were compared with that of total PSA. Nearly constant concentrations of complexed PSA were found during the first six hours after surgery, in contrast to the rapid elimination of free PSA and the significant decrease of total PSA. From day one to ten there was a continuous and nearly identical decrease of complexed PSA compared to total PSA. Our findings suggest that the initial rapid decrease of free PSA immediately after operation could be caused by formation of new PSA-complex.

Humans↗