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Biomedical subjects

P Alken

Publications and source records attributed to P Alken.

At least 163 records · Page 9Linked to original sources

[Parameters influencing the incidence of recurrent urinary calculus after ESWL].

With extracorporeal shock wave lithotripsy, stone fragmentation and the potential creation of residual stones has become an integral part of the treatment strategy. Therefore, true recurrence, regrowth and pseudo-recurrence determine the rate of new stone formation. In nonselected series the overall recurrence rate after ESWL varies between 6% after 1 year and 20% after 4 years. The comparison between recurrence rate after ESWL and the natural recurrence rate reveals that the results of ESWL are better than expected. Lithotripsy has no specific effect on true stone recurrence, and even the pseudo-recurrence is of minor clinical significance. Nevertheless, metaphylaxis keeps its place in treatment of recurrent urolithiasis.

Follow-Up Studies↗

[Internal drainage of urine in cases of complicated urinary stasis caused by pregnancy].

In 14 women with sympthomatic hydronephrosis due to pregnancy (calyx diameter 1-2,6 cm) an internal urinary drainage was carried out during the second half of pregnancy. Retrograde stenting was placed per cystoscopy in all cases. Follow-up examinations were taken weekly for the first two weeks and further on biweekly. Primary stenting was possible in 12 out of 14 cases, and in two patients dilatation of the ureteral orifice was necessary. 11 out of 14 patients suffered from complications such as severe dysuria (9), urinary tract infection (7), persisting lumbar pain plus catheter lumen obstruction (6 each) as well as catheter migration (3). Long-term follow-up showed that urinary tract obstruction was relieved by stenting in only 6 out of 14 patients. Sufficient urinary drainage by so called double-J ureteral stents was achieved in less than half of the cases. Moreover, there was a complication rate of more than 75%. Taking these results into consideration, internal drainage of complicated pregnancy hydronephrosis needs careful evaluation.

Adult↗

The essentials of transurethral resection of bladder tumors (TUR-B).

The technique of transurethral resection of bladder tumors has to follow certain rules to guarantee that all parts of the bladder are visualized, that small tumors are completely removed and large tumors resected without complications. A second resection 6-8 weeks after the first procedure seems to be necessary for complete tumor removal even in case of low stage cancer.

Humans↗

Extracorporeal shock wave lithotripsy of ureteric stones with the Modulith SL 20.

A series of 138 patients with ureteric calculi was treated by in situ extracorporeal shock wave lithotripsy (ESWL) during the clinical introduction of the Modulith SL 20. This machine represents a newly developed lithotriptor with an electromagnetic cylinder as shock wave source and a dual localisation system consisting of in-line ultrasound and an integrated fluoroscope C-arm. During the first 2 months, 12 patients (phase 1) were treated under ultrasound localisation alone; during the next 5 months, 37 patients (phase 2) were treated using dual imaging modalities with reduced peak pressure (max. 18 kV = 800 bar); during the final 7 months, 89 patients (phase 3) were treated under ultrasonic and fluoroscopic localisation combined with an increased maximal shock wave pressure (20 kV = 1024 bar). The introduction of fluoroscopic targeting (phases 2 and 3) resulted in satisfactory localisation of calculi in the mid-ureter, previously limited by use of only coaxial ultrasound. The extension of stone localisation to the whole length of the ureter was associated with a marked decrease in treatment time, reflecting the easy handling of the dual localisation system. The rise in generator voltage (phase 3) improved the disintegration rate from 81% (phase 2) to 85%, whereas the number of impulses remained unchanged. However, the rate of auxiliary procedures following ESWL (adjuvant and curative) was reduced from 33% (phase 2) to 24.5%. Thus the Modulith SL 20 in its final design enables in situ ESWL to be the treatment of choice for all ureteric calculi, rendering special positioning techniques or multiple treatment unnecessary.

Humans↗

Penile revascularization in nonresponders to intracavernous injections using a modified microsurgical technique.

At certain centers, microsurgical penile revascularization, using different surgical techniques, has gained importance throughout the past years. In general, only patients classified as intracavernous injection nonresponders are subjected to this kind of surgery. Since 1988, revascularization surgery has been performed at our clinic on 19 intracavernous injection nonresponders. The Hauri technique was carried out on the first 6 patients. The last 10 patients underwent modified anastomosis surgery. The inferior epigastric artery and the dorsal penile artery are anastomosed, one behind the other, end-to-side, to the dorsal penile vein. This results in a more simple procedure with assurance of flow. The Virag technique was performed on 3 patients. 18 patients achieved erections with or without the aid of intracavernous injections (at a mean follow-up of 13.4 months). 11 patients were capable of spontaneous erections, whereby it was particularly noted that 8 of the 10 patients undergoing the modified technique achieved spontaneous erections. The results demonstrate that intracavernous injection nonresponders benefit from revascularization surgery.

Alprostadil↗

The effect of impaired lipid metabolism on the smooth muscle cells of rabbits.

Our clinical data enabled us to demonstrate a correlation between impaired lipid metabolism and vasculogenic impotent men. Our aim was to evaluate the effect of an impaired lipid metabolism on the smooth muscle of the corpus cavernosum. A total of 16 rabbits were given a cholesterol-enriched diet for 3 months, and 8 of these received additional thromboxane A2 receptor antagonist; 10 other rabbits (control) were fed a normal diet. Subsequently, cavernous tissue biopsies were taken, and tissue lipid extractions and electron microscopic evaluation were made from 3 rabbits in each group. In the untreated high-cholesterol diet group, cholesterol levels reached approx. 2.1 micrograms/mg body weight compared with 1.07 micrograms/mg b.wt. in the thromboxane A2 receptor antagonist-treated group and elevated levels compared with control group. Similar results were found for the triglyceride and free fatty acid levels. Lecithin tissue levels in treated rabbits were distinctly elevated against those of other 2 groups. Ultramorphological examination of the control group disclosed normal smooth muscle cell (SMC) architecture with numerous sites of intercellular contacts. These findings contrasted with those of the high-cholesterol diet groups which showed significant SMC degeneration with loss of intercellular contacts. Our data imply that impaired lipid metabolism causes cavernous SMC degeneration which plays a major role in the pathogenesis of erectile dysfunction. The thromboxane A2 receptor antagonist seems to produce a protective metabolic effect on the erectile tissue which may have some consequences future treatment strategies.

Animals↗

Cross-resistance patterns related to glutathione metabolism in primary human renal cell carcinoma.

In 59 cases of primary human renal cell carcinoma (RCC), cross-resistance and collateral susceptibility patterns were determined in an MTT microculture assay. Concomitantly, the glutathione (GSH) content and the enzymatic activity of gamma-glutamyl transpeptidase (GGT) were measured as distinct resistance characteristics. Resistance or chemoresponse towards Vinca alkaloids and anthracyclines were found to be highly coincident, suggesting that the classical multidrug resistance mechanism is active in human RCC. Strong resistance to platinum complexes combined with relative sensitivity to bleomycin was significantly associated with elevated glutathione levels, providing evidence for another pathway instigating chemoresistance. In contrast, despite substantial enzymatic activity, GGT effects revealed no correlation to the chemoresistance pattern. This result implies that it is the GSH-linked binding and reduction potential rather than the GGT-associated transportation capacity that has an impact on the expression of chemoresistance in human RCC.

Antineoplastic Agents↗

Extracorporeal shock-wave lithotripsy and endoscopy: combined therapy for problematic bile duct stones.

Endoscopic treatment of bile duct stones is currently successful in 86% of patients. We prospectively studied the efficacy and complication rate of extracorporeal shock-wave lithotripsy (ESWL) of problematic bile duct stones combined with endoscopy. When stone removal was not possible, patients were subjected to ESWL. Fragmented stones were removed endoscopically. During 1 year, 220 patients presenting with choledocholithiasis were diagnosed and 188 were successfully treated endoscopically. In all, 3 subjects received alternative treatment and the remaining 29 (13%) constituted our study group; 19 (65%) were women and the mean age was 76.7 years. Overall, 22 (76%) were high-risk patients; 23 (79%) were jaundiced and 9 (31%) had cholangitis at admission. The most frequent indication for ESWL was stone size. Stone fragmentation was achieved in 80% of cases. Complications were mild and were managed conservatively. No patient died. Complete stone clearance was possible in 23 (80%) cases. The association of ESWL and endoscopy enhanced the success rate of endoscopic stone clearance from 86% to 96%. During the same period, open surgery was performed in 4 cases for residual common bile duct (CBD) stones and in 32 cases in association with simultaneous cholecystectomy.

Aged↗

[Success and failure with double J ureteral stent. Analysis of 107 cases].

An internal urinary diversion of the upper urinary tract was planned in 107 patients with acute, stone-related or chronic tumor-induced ureteral obstruction. Acute ureteral obstruction (n = 34, group I): in 30 of 32 cases (94.1%), successful placement of an indwelling stent resulted in complete drainage in 28 of 30 patients (93.7%). In 2 cases, no satisfactory urine diversion was possible, despite several catheter changes and confirmed clearway through the installed catheters. Chronic ureteral obstruction (n = 73, group II): successful placement of the indwelling stent was possible in 63 of 73 (86.3%) cases. Complete urine diversion was achieved in only 25 patients (39.7%). Hydronephrosis was diminished in 28 patients (44.4%) and persisted or increased in 10 cases (15.9%), despite orthotopic positioning of the catheter and numerous stent changes. Complete urine drainage was achieved with an internal urine diversion in only 4 of 10 cases with chronic hydronephrosis. It is assumed that the reason for the high failure rate lies in the catheter construction and, with respect to chronic hydronephrosis, the reduced or non-existent contractility of the upper urinary tract in combination with the inevitable pressure connection between the upper and lower urinary tract.

Acute Disease↗

Chemosensitivity testing of primary human renal cell carcinoma by a tetrazolium based microculture assay (MTT).

MTT staining procedures have been used in chemosensitivity testing of established cell lines of human and other sources as well as of human leukaemias, but only limited information on its application in primary solid human tumors is presently available. We have evaluated MTT staining in primary human Renal Cell Carcinomas (RCCs), studied various factors interfering with the optimal use, and finally applied it in subsequent chemosensitivity testing. The method depends on the conversion of a water-soluble tetrazolium salt (MTT) to a purple colored formazan precipitate, a reaction effected by enzymes active only in living cells. Single cell suspensions of RCCs were obtained either by enzymatic dispersion or by mechanical dissagregation, filtered through gauze, and purified by Ficoll density centrifugation. Tests were carried out in 96-well microculture plates. 10(4) viable tumor cells per well at 4 h incubation time with 20 micrograms MTT/100 microliters total medium volume yielded best results. Formazan crystals were dissolved with DMSO, and the plates were immediately measured on a microculture plate reader at 540 nm. Under these criteria, linearity of the system could be demonstrated. For chemosensitivity testing, cells were continuously exposed to a number of drugs prior to the MTT staining procedure. Reproducibility of results was assessed and confirmed by culturing RCCs in flasks additionally, resubmitting them after 1, 2, and 4 weeks to the MTT assay. We conclude that the semiautomated MTT assay offers a valid, rapid, reliable and simple method to determine the degree of chemoresistance in primary human RCCs.

Antineoplastic Agents↗

P-170 glycoprotein, glutathione and associated enzymes in relation to chemoresistance of primary human renal cell carcinomas.

High intrinsic chemoresistance contributes to the dismal outcome of patients with disseminated renal cell carcinoma (RCC). In experimental cell lines, two defined defence mechanisms, P-170 glycoprotein and glutathione metabolism, have been established in multidrug resistance, a cross-resistance to cytotoxic compounds without functional or structural similarities. In 21 primary human RCCs, P-170 expression was examined, glutathione content and activities of related enzymes determined and the results were correlated to the degree of in vitro chemoresistance. P-170 was found in 10 of 17 resistant tumors but in none of the sensitive cases. The glutathione content was significantly higher and the related enzyme distinctively enhanced in resistant RCCs. Both mechanisms occurred independently and may well explain the multidrug resistance of RCC. Therefore, reversal of one or both systems may have a clinical impact on the chemotherapy of RCCs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Modulith SL 10/20--experimental introduction and first clinical experience with a new interdisciplinary lithotriptor.

More than 20 second-generation lithotriptors have been introduced for extracorporeal shock-wave lithotripsy. Despite great technical progress, each machine still has its specific short-comings. In cooperation, Storz Medical (Kreuzlingen, Switzerland) and the Department of Urology (Klinikum Mannheim, FRG), have developed a new lithotriptor designed to overcome these drawbacks. Energy source: Electromagnetic cylinder with paraboloid reflector (40 cm) for focusing, providing a wide range of pressure (190-1,000 bar) and a focal zone of 28 x 6 mm. The focal depth is maximally 15 cm. Coupling and positioning: Water cushion with patient lying on a specially designed 'acoustic cradle' consisting of an impedance-adapted foil. This is integrated in either a manually or automatically operated table. Localization: Coaxial ultrasound probe for real-time scanning and integrated C arm with pulsed fluoroscopy using a virtual focus (moved along x-axis) for stone localization. In 1989, we commenced with the first treatment based on our own in vitro and in vivo studies to determine the range of energy required for safe application. We treated 137 stones (100 caliceal, 19 pelvic and 18 ureteral) in 88 patients. The mean generator voltage was 16 kV (10-18 kV). Successful disintegration was achieved in 83 patients (95%) employing an average of 2,359 impulses (940-3,500). Thirteen percent of the treatments were performed without any anesthesia on lower generator voltage (10-15 kV), whereas the majority of calculi were treated under intravenous analgesia. The 5 failure cases included 2 stones in a caliceal diverticulum. Moreover, 12 patients with biliary calculi (11 gallstones and 1 bile duct stone) were successfully treated; 1 of these cases required a second treatment session.

Animals↗

[Role of calcium antagonists in the treatment of chemoresistant cancer of the kidney].

In experimental cell lines and in some human tumors, calcium antagonists reversed multidrug resistance in vitro. So far, clinical trials have not been very rewarding as intrinsic cardiovascular activities of these compounds impeded a sufficient dosage. Renal cell carcinomas are considered to be good models for the evaluation of this new therapeutic concept. In 35 primary human renal cell carcinomas, the potency of 7 different calcium antagonists in combination with vinblastine monotherapy was examined in a tetrazolium-based microculture assay (MTT test) in order to circumvent chemoresistance. Substances derived from piperazine (flunarizine) showed only minor effects in this respect. The calcium antagonists of the papaverine type such as Verapamil etc. revealed the strongest reversal of chemo-resistance. Derivatives of benzothiazepine (diltiazem) or of dihydropyridine (nifedipine etc.) acted similarly and reached about 70% of the Verapamil activity. All calcium antagonists tested lead to significant enhancement of vinblastine cytotoxicity. In particular, the new stereoisomer R-Verapamil, which showed strong reversal of resistance but which exerts 10 times lower cardiovascular side effects than racemic Verapamil, seems to be suitable for further evaluation with regard to the clinical application.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[The Mainz-pouch. 6 years of clinical experience].

The surgical technique for creation of the Mainz-pouch uses 12 cm of cecum and ascending colon and 2 ileal loops of the same length for construction of an urinary reservoir, which has proven applicable for bladder augmentation, bladder substitution as well as for continent urinary diversion. For the creation of a continent nipple in urinary diversion 6 cm of ileum in addition are necessary. As a modification we use the non-infected submucosal imbedded appendix as continence mechanism. Since 1986 a total of 247 patients underwent a Mainz-pouch procedure: 54 for bladder augmentation, 27 for bladder substitution and 166 for continent diversion. The appendix as continence mechanism was used in 30. Postoperative mortality rested under 1%, early complications have been observed in 4.4% and late complications in 13.7% (mean follow-up of 35 months). In the bladder augmentation group 52 patients are completely dry, 2 patients have urge and frequency and 5 patients are on intermittent self catheterisation to avoid residual urine. In the bladder substitution group all patient are continent at daytime. At nighttime 3 patients have leakage if they don't empty their bladder all 4 hours. In the urinary diversion group all but 3 are completely dry and are on intermittent catheterisation. The main problem of our initial series was prolapse of the continent nipple which has been solved by stable fixation of the nipple to the bowel wall and to the ileocecal valve or by using the submucosal imbedded appendix.

Bioprosthesis↗