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Biomedical subjects

S A Loening

Publications and source records attributed to S A Loening.

At least 19 recordsLinked to original sources

[Laparoscopic transperitoneal donor nephrectomy. Technique and results].

Living donor kidney transplantation is one possibility to meet the growing demand for organs in patients with chronic renal failure. In 1995 the first laparoscopic living donor nephrectomy (LDN) was performed in the United States. More than 100 transplant centers worldwide perform LDN. The expectations of a larger number of willing organ donors were fulfilled due to the less traumatic operation. Meanwhile, several techniques exist to retrieve a kidney laparoscopically, including the trans- or retroperitoneal, strictly laparoscopic, or hand-assisted approach. From February 1999 to September 2002, 63 strictly laparoscopic, transperitoneal LDNs were performed at the Department of Urology of the Charité University Hospital, Berlin. Warm ischemic time was 148 s (105-360) and operating time was 203 min (110-305). Intraoperative complications were due to insufficient closure of the vessels in four patients. Mean postoperative hospital stay was 5.7 days (3-9). One year after LDN, renal function as well as creatinine levels of the recipient showed no difference compared to the organs harvested via the approach at our department prior to implementation of LDN. Strictly laparoscopic transperitoneal donor nephrectomy is a safe method for kidney retrieval and ensures excellent graft function.

Adolescent↗

[Laparoscopic radical cystectomy with intracorporeal creation of a continent urinary diversion. Future or present?].

Once laparoscopic radical prostatectomy has been mastered, the step to performing a radical cystectomy is not that far. The challenge is to create the urinary diversion by laparoscopy. In this report we describe our experience with 11 laparoscopic radical cystectomies and intracorporeal construction of a continent urinary diversion (Mainz pouch II) as a treatment option in patients with muscle-invading bladder cancer. All 11 procedures could be performed successfully. A conversion to open surgery was not required in any case. The mean surgery time was 6.7 h. Except for two pouch fistulas we did not observe any intra- or postoperative complications. The functional as well as the oncological results are convincing. Less morbidity and faster recovery are the main advantages of this minimally invasive procedure. In addition, the low levels of blood loss, fluid shifts, and electrolyte loss considerably reduce cardiovascular stress. Radical cystectomy and construction of a continent urinary diversion represent the limit of technically feasible laparoscopy and should be done exclusively in specialized centers.

Aged↗

Estramustine phosphate enhances the effects of hyperthermia and induces the small heat shock protein HSP27 in the human prostate carcinoma cell line PC-3.

The antimicrotubule drug estramustine phosphate (EMP) has been shown to sensitize prostate carcinoma cells to radiation via synchronization at the G2/M phase of the cell cycle. This synchronization may also render cells more sensitive to hyperthermia, providing a rationale for multimodal treatment approaches. We have investigated the effects of EMP and hyperthermia, as well as the regulation of heat shock proteins (HSP) in the PC-3 prostatic carcinoma cell line. Cells were incubated with four doses of EMP for 48 h followed by a 1-h hyperthermia treatment ranging from 41 degrees C to 44 degrees C. Cell cycle distribution at the end of the EMP incubation was investigated by flow cytometry. Cytotoxicity was assessed by colony formation assays. HSP accumulation was investigated by Western immunoblotting. Doses of 1, 5, 10 and 15 microM EMP synchronized 27, 28, 46, and 68% of PC-3 cells at G2/M. With 5, 10 and 15 microM, a sensitizing effect of EMP was assessed at hyperthermic temperatures of 42, 43 and 44 degrees C. EMP did not alter the expression of HSP72, but substantially induced the synthesis of HSP27 in PC-3 cells. Our data show that EMP sensitizes PC-3 cells to hyperthermia induced cytotoxicity. This observation supports the rationale for multimodal treatment approaches in locally advanced prostate cancer.

Antineoplastic Agents↗

[Radical prostatectomy in clinically localized prostate carcinoma. Pro laparoscopic approach].

Systematic development of laparoscopy during the last decade has led to establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On the basis of extensive experience at our center, the advantages of the minimally invasive method are described as well as the problems still in existence. Reduced trauma caused by laparoscopic access in combination with clearly reduced blood loss has resulted in less morbidity after laparoscopic procedures. This is reflected in a shorter postoperative stay in hospital and faster convalescence. LRP as an ambitious and complex procedure has an average complication rate of 12%, which shows that the method has surpassed the stage of experimental surgery. By direct comparison, the costs of LRP are higher than for the open surgical procedure, but on the whole this is economically balanced by the lower morbidity, shorter hospital stay, and faster convalescence. The progress in technology to be expected in the field of laparoscopy will further increase quality, precision, and safety of LRP and thus contribute to the establishment of laparoscopic radical prostatectomy as a surgical method of choice.

Adult↗

The novel synthetic inhibitor of matrix metalloproteinases Ro 28-2653 induces apoptosis in Dunning tumor cells.

The effect of synthetic inhibitors of matrix metalloproteinases (MMP) has been shown against a variety of tumors in preclinical models. Ro 28-2653, a novel synthetic MMP inhibitor, is able to reduce tumor growth in orthotopic prostatic cancer in rats (R3327 Dunning tumor). However, at present this inhibitory mechanism in tumor inhibition in vivo can only be partly explained by the inhibition of the catalytic activity of MMPs overexpressed in cancereous tissue. Using the flow cytometric method, we have investigated the effect of various concentrations of Ro 28-2653 on the Dunning tumor cells with regard to the staining of F-actin and DNA as markers of apoptosis. In combination with fluorescence microscopy we detected the loss of F-actin and the degradation of internucleosomal DNA. This effect of Ro 28-2653 on apoptosis was dose- and time-dependent increasing with concentration between 10 and 100 microg/ml as well as with time of treatment between 24 and 48 h.

Actins↗

Tissue inhibitors of metalloproteinases 1 and 2 in human seminal plasma and their association with spermatozoa.

A 24-kDa heparin binding protein recently identified as tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in bovine seminal fluid was suggested to play an important role in bull fertility. As no data are present for men, the concentrations of tissue inhibitors of metalloproteinases 1 (TIMP-1) and TIMP-2 were quantified in human seminal plasma of normozoospermic and azoospermic men using enzyme-linked immunosorbent assay methods. TIMP-1 and 2 were not significantly different in both groups and there were no relationships between the concentrations of both TIMPs and other sperm characteristics. It is assumed that TIMPs are released from accessory sex glands.

Enzyme-Linked Immunosorbent Assay↗

Quantitative differences in matrix metalloproteinase (MMP)-2, but not in MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 or TIMP-2, in seminal plasma of normozoospermic and azoospermic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), have been detected in reproductive tissues and seminal plasma. The purpose of this study was to quantify MMP-2, MMP-9, TIMP-1 and TIMP-2 in human seminal plasma and to evaluate their association with sperm. METHODS: Seminal plasma was analysed using ELISA assays for all four analytes in 12 normozoospermic and 12 azoospermic patients and then for MMP-2 only in another 114 men with azoospermia (n = 16), after vasectomy (n = 20) and with sperm counts within the following ranges: 0.3-19 x 10(6)/ml (n = 20), 20-23 x 10(6)/ml (n = 11), 49-57 x 10(6)/ml (n = 12), 96-110 x 10(6)/ml (n = 12), 139-161 x 10(6)/ml (n = 12) and 215-346 x 10(6)/ml (n = 11). Additional zymographic analyses using SDS-PAGE were performed. RESULTS: All investigated MMPs and TIMPs were detected. MMP-9, TIMP-1 and TIMP-2 were not significantly different in normozoospermia and azoospermia. Only the MMP-2 concentration was significantly decreased in azoospermic compared with normozoospermic patients (mean +/- SD: 650.6 +/- 288.9 versus 1677 +/- 910.4 ng/ml respectively; P = 0.0002) and significantly correlated with the number of sperm (r = 0.54; P < 0.0001). CONCLUSION: MMP-2 in seminal plasma was strongly correlated to the sperm count in a linear fashion. Its origin and potential function remain to be elucidated.

Adult↗

Molecular forms of prostate-specific antigen in serum with concentrations of total prostate-specific antigen <4 microg/L: are they useful tools for early detection and screening of prostate cancer?

Molecular forms of prostate-specific antigen (PSA) improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) in men with total PSA concentrations between 4 and 10 microg/l. To evaluate the diagnostic utility of free PSA (fPSA) and complexed PSA forms for identification of men with PCa in the low PSA range of <4 microg/l, total PSA (tPSA), alpha(1)-antichymotrypsin complexed PSA (PSA-ACT) and fPSA (Roche Elecsys [ES] system) as well as tPSA and complexed PSA (cPSA) (Bayer Immuno 1 system) were measured in archival serum samples from 31 untreated patients with PCa, 66 patients with BPH, and 90 men without prostatic disease. The median ratios of fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were significantly different between patients with BPH and PCa (27.2 vs. 19.4%, 64 vs. 88%, 77.2 vs. 88.2%, p < 0.05). No associations between PSA forms and tumor stage and grade were found. Analysis of the receiver operating characteristic curves showed that these ratios could discriminate better between BPH and PCa patients than determination of the analytes tPSA, fPSA, cPSA and PSA-ACT alone. The use of one of the ratios would have eliminated roughly half of the unnecessary biopsies in this study. The ratios should be considered as potential tools to increase the selectivity of PCa detection at low PSA concentration. The ratios fPSA/tPSA and cPSA/tPSA can be determined using commercially available assays so that one of these ratios could be preferred instead of PSA-ACT determination. The ratios could be useful in assessing the risk of PCa in the individual and therefore in deciding on prostate biopsy for final diagnosis.

Aged↗

A multicenter clinical trial on the use of alpha1-antichymotrypsin-prostate-specific antigen in prostate cancer diagnosis.

BACKGROUND: The aim was to evaluate the clinical performance of alpha(1)-antichymotrypsin prostate-specific antigen (PSA-ACT) for early diagnosis of prostate cancer (PCa) in a multicenter trial. METHODS: Three hundred sixty-seven white men with PCa and 290 with benign prostatic hyperplasia (BPH) with tPSA concentrations between 2 and 20 microg/L were analyzed. The Elecsys system 2010 (Roche Diagnostics, Germany) was used for determination of total PSA (tPSA) and free PSA (fPSA). The PSA-ACT test was a prototype assay used on the ES system (Roche Diagnostics). RESULTS: The median concentrations of tPSA (PCa: 8.43 microg/L vs. BPH: 6.60 microg/L) and PSA-ACT (8.30 microg/L vs. 6.46 microg/L) were significantly different, respectively. The median ratios of fPSA/tPSA (PCa: 12% vs. BPH: 16%) and PSA-ACT/tPSA (98% vs. 95%) were significantly different. Receiver operating characteristics (ROC) analysis for discrimination between PCa and BPH (tPSA between 2 and 20 microg/L) was performed with 252 matched pairs and showed that the area under the curve (AUC) of the ratio fPSA/tPSA (0.66) was significantly different from tPSA (0.50) and PSA-ACT (0.52). PSA-ACT alone or the ratio PSA-ACT/tPSA (0.56) were not significantly different from tPSA. For tPSA between 4 and 10 microg/L (n = 145 pairs), the AUC of the ratio fPSA/tPSA (0.65) was significantly higher than tPSA (0.50) and PSA-ACT (0.54). Significant differences between tPSA and PSA-ACT or PSA-ACT/tPSA (0.56) were not found. CONCLUSIONS: The determination of PSA-ACT as well as the PSA-ACT/tPSA ratio did not improve the diagnostic impact in patients undergoing evaluation for PCa compared to fPSA/tPSA ratio.

Adult↗

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↗