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Biomedical subjects

U Jonas

Publications and source records attributed to U Jonas.

At least 91 records · Page 5Linked to original sources

Gene expression of the phosphodiesterases 3A and 5A in human corpus cavernosum penis.

OBJECTIVE: The following study was performed to evaluate the importance of phosphodiesterases 3A (PDE3A) and 5A (PDE5A) for the regulation of penile smooth muscle tone. Furthermore, indications of side effects of specific inhibitors in certain tissues as well as of a possible relation between the level of PDE3A and PDE5A gene expression and erectile dysfunction should have been deduced from the results obtained. METHODS: Total ribonucleic acid was isolated from different human tissues (urogenital tract, gastrointestinal tract, cardiovascular system and central nervous system) and subjected to RTPCR analysis and Northern blotting using primers and probes specific for PDE3A and PDE5A. RESULTS: As shown by RT-PCR and Northern blotting, PDE3A and PDE5A mRNAs exhibit a distinct distribution throughout the tissues examined but were 2-fold higher in cavernous tissue than in all other tissues investigated. However, there were no significant differences in the levels of gene expression between the two subgroups of patients. CONCLUSIONS: Very high expression levels of PDE3A and PDE5A in human cavernous tissue underscore the physiological importance of these enzymes for the regulation of penile erection, emphasizing their therapeutical and pharmacological relevance. The distribution pattern of the mRNA for the isoenzymes PDE3A and PDE5A may explain the pharmacological effects as well as the side effects of milrinone and sidenafil.

3',5'-Cyclic-AMP Phosphodiesterases↗

Congenital and acquired penile deviation treated with the essed plication method.

OBJECTIVES: To evaluate our results with the Essed procedure for the correction of penile curvature, either congenital or due to Peyronie's disease, and compare it with the data from the literature, both for the Essed and the Nesbit procedure. METHODS: From 1991 to 1996 the Essed procedure was performed in 61 patients. 65.6% (n = 40) had congenital deviation and 34.4% (n = 21) suffered from secondary deviation due to Peyronie's disease. In all patients 2-6 nonabsorbable inverting interrupted sutures were placed bringing the knot between the plicated tunica. RESULTS: Patients' ages ranged from 15 to 65 (mean 31.3) years and the mean follow-up time was 39.8 (12-75) months. The preoperative penile deviation was between 20 and 90 degrees (mean 47.4 degrees ). Eighteen patients (29.5%) had a recurrent deviation following surgery. This failure rate was higher in the patient group with Peyronie's disease (42.9%) than in the group with congenital deformation (22.5%). Postoperatively, 2 patients (3.3%) with Peyronie's disease reported de novo erectile dysfunction. Twenty patients (32.8%) complained of persistent discomfort or pain at the area of the still palpable plication sutures, but this inhibited sexual intercourse only in 1 case. 45.9% stated penile shortening after surgery but only 21.3% felt bothered by this. CONCLUSION: The results reported are in accordance with the literature showing a higher recurrence rate of the deviation with the Essed compared to the Nesbit procedure. For both methods the risk of recurrent disease is higher in patients with Peyronie's disease and with both techniques, an equally low incidence of erectile dysfunction is evident. However, since with the Essed technique one third of all patients complained of discomfort from the nonabsorbable sutures, the Nesbit procedure seems to be superior.

Adolescent↗

Historical aspects of the treatment of urinary incontinence.

Ancient reports on urinary incontinence are rather rare and mainly address cases of extraurethral incontinence, e.g. due to a fistula acquired during childbirth or overflow incontinence, e.g. in males with urinary retention or after spinal cord injury. In modern times several authors dealt with the problem of postoperative incontinence after perineal lithotomy. Surgical techniques for the cure of urinary incontinence were not introduced before the 19th century. First this was limited to fistula repair but at the turn of the century new procedures for stress incontinence were introduced and became standard clinical procedures. Other modern techniques, e.g. artificial sphincters or electrostimulation, were alternatives developed in urology during the second half of our century. This article from the history of medicine outlines early reports on urinary incontinence and reveals a more detailed review of the different treatment options including conservative therapies, incontinence devices, electrotherapy and surgical procedures, including injection therapies and artificial sphincters.

Equipment Design↗

Plasma levels of cavernous and systemic norepinephrine and epinephrine in men during different phases of penile erection.

PURPOSE: Knowledge of the functional anatomy, hemodynamics, neurophysiology and pharmacology of penile erection has improved tremendously during the last 2 decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out up until now. Therefore, we conducted a study to examine plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in the peripheral and cavernous blood of healthy men during penile flaccidity and in different phases of erection. MATERIALS AND METHODS: Blood samples were drawn simultaneously from the corpus cavernosum (CC) and the cubital vein (P) in 53 healthy volunteers with normal erectile function, in four different functional states of the cavernous erectile tissue (flaccidity = 1, tumescence = 2, rigidity = 3, detumescence = 4). Penile erections were induced by audiovisual and tactile stimulation and the plasma concentrations of NE and E were determined by means of a radioimmunoassay (RIA). RESULTS: A significant (p <0.001) reduction of NE in CC plasma was found from flaccidity (362 + or - 173 pg./ml.) to rigidity (248 + or - 122 pg./ml.), followed by an increase in the detumescence phase (336 + or - 199 pg./ml.), (p <0.001). In contrast, changes in NE levels in the peripheral plasma were less pronounced from 1P (202 + or - 102 pg./ml.) to 3P (229 + or - 118 pg./ml.), (p = 0.006) and from 3P to 4P (222 + or - 127 pg./ml.), respectively (p = 0.370). The most pronounced increase in cavernous E levels were observed from flaccidity (47 + or - 41 pg. /ml.) to tumescence (130 + or - 106 pg./ml.) (p <0.001). Cavernous E levels dropped significantly from 113 + or - 67 pg./ml. during rigidity to 76 + or - 57 pg./ml. + or - during detumescence (p <0.001). The course of peripheral plasma levels of E was similar to that in the cavernous blood. Mean peripheral E level was 69 + or - 55 pg./ml. in the state of penile flaccidity, reaching 98 + or - 78 pg./ml. in tumescence and 82 + or - 64 pg./ml. in rigidity (p <0.001), respectively, and finally decreasing to 62 + or - 46 pg./ml. in detumescence. CONCLUSION: Penile erection, based on the relaxation of cavernous and arterial smooth muscle, is accompanied by a significant reduction of NE in cavernous blood, while E levels rose in peripheral and cavernous blood during developing erection.

Adult↗

Max Brödel (1870-1941) and medical illustration in urology.

PURPOSE: Max Brödel (1870-1941) is known as one of the major medical illustrators of the turn of the last century. Some important aspects of his biography and his influence on illustration in the specialty of urology are discussed. MATERIALS AND METHODS: The German artist Brödel was invited to The Johns Hopkins Hospital, Baltimore in 1894 and soon became a well-known illustrator in gynecology. He introduced new innovative art media, such as his carbon dust and stipple board technique to reproduce vivid tissue, while developing an instructive and didactic manner of medical illustration. He is also known as an anatomist and scientist, mainly for his description of an avascular area of the kidney (Brödel's bloodless line) and an improved method of nephropexy using a suture that he designed. RESULTS: In 1911 Max Brödel became head of the first Department of Art as Applied to Medicine, establishing the profession of medical illustration. In addition to some work for Hugh Hampton Young, his most important influence on urology was through his student William P. Didusch, who was a medical illustrator at the Brady Urological Institute in Baltimore for more than 40 years. CONCLUSIONS: Brödel changed the appearance of medical illustration at the beginning of the 20th century and improved its role in medical literature. Max Brödel should be referred to as the man who put art into medicine.

Germany↗

Possible role of human growth hormone in penile erection.

PURPOSE: Treatment with recombinant human growth hormone in adult patients with growth hormone deficiency increases nitric oxide and cyclic guanosine monophosphate (cGMP). We examined the functional in vitro effects of recombinant human growth hormone on tissue tension and cyclic nucleotide levels of human corpus cavernosum and detected changes in growth hormone in the cavernous and peripheral blood during different phases of penile erection. MATERIALS AND METHODS: Relaxant responses of human corpus cavernosum were investigated using the organ bath technique. Tissue levels of cGMP were determined by a specific radioimmunoassay after dose dependent exposition of isolated human corpus cavernosum strips to recombinant human growth hormone. In 35 healthy potent volunteers blood samples were obtained simultaneously from the corpus cavernosum and cubital vein during different functional conditions of the penis, including flaccidity, tumescence, rigidity and detumescence. Penile erection was induced by audiovisual and tactile stimulation. Serum growth hormone was determined by an immunoradiometric assay. RESULTS: Recombinant human growth hormone elicited dose dependent relaxation of human corpus cavernosum strips in vitro. The relaxing potency of recombinant human growth hormone was paralleled by its ability to elevate intracellular levels of cGMP. In vivo the peripheral growth hormone serum profile of the respective penile conditions did not significantly differ from those of cavernous serum. The main increase in growth hormone to greater than 90% was determined during developing penile tumescence, followed by a transient decrease afterward. CONCLUSIONS: These results suggest that penile erection may probably be induced by growth hormone through its cGMP stimulating activity on human corpus cavernosum smooth muscle.

Adult↗

Management of the post-chemotherapy residual mass in patients with advanced stage non-seminomatous germ cell tumors (NSGCT).

Since it is difficult to predict the probability of persistent teratoma or of a viable tumor in patients with normalized tumor markers and a normal CT scan following chemotherapy for advanced stage testis cancer, recommendations regarding adjunctive surgery have ranged from observation to surgical exploration for all patients. Suggested variables for patients in whom surgery can be omitted safely, include normal post-chemotherapy CT scans, residual abdominal masses of less than 1.5 cm, a 90% or greater decrease in the volume of the retroperitoneal mass with chemotherapy and no teratomatous elements in the orchiectomy specimen. In contrast, during several investigations, the application of the above mentioned criteria resulted in a false-negative prediction of approximately 20%. However, recognizing the morbidity of the operative procedure itself in addition to the fact that only 2-4% of patients will develop recurrent tumor confined to the retroperitoneal space that can then be managed surgically or by administration of further chemotherapy, secondary surgery should be avoided if a sufficient follow-up after chemotherapy is guaranteed. The extent of adjunctive surgery in patients revealing a residual tumor mass after first-line chemotherapy remains a subject of ongoing discussions. It has been indicated that extensive retroperitoneal surgery after chemotherapy is associated with significant clinical morbidity. A limitation of post-chemotherapy surgery to a resection of the residual mass with or without an additional modified template dissection appears to result in an acceptable frequency of retroperitoneal recurrences and a decreased complication rate.

Antineoplastic Agents↗

Molecular biological characterization of phosphodiesterase 3A from human corpus cavernosum.

The hydrolysis of the second messenger cyclic AMP (cAMP) by phosphodiesterase 3 (PDE3) is known to play an important regulatory role in the context of relaxation of cavernous smooth muscle of the penis. Thus, we investigated the PDE3A isoform from penile cavernous tissues of male patients with and without symptoms of erectile dysfunction at the molecular biological level. As revealed by reverse transcriptase polymerase chain reaction, of all tissues of the urogenital tract analyzed the expression of the PDE3A gene was highest in the corpus cavernosum. However, significant differences in the levels of gene expression were not found between the two subgroups of patients. Also, the determined nucleotide sequences of the cloned penile PDE3A cDNAs of all patients were absolutely identical. Surprisingly, some deviations could be detected in the cDNA sequences of PDE3A from human myocard and platelets. The data obtained indicate that neither the expression levels nor the sequence deviations of PDE3A are the main reasons for erectile dysfunction in men.

3',5'-Cyclic-AMP Phosphodiesterases↗

Increased levels of human papillomavirus type 16 DNA in a subset of prostate cancers.

Whether oncogenic human papilloma viruses (HPVs) are involved in the pathogenesis of prostate cancers has been a subject of great controversy. To clarify the contradictory results of investigations, with the aim of detecting viral nucleic acids in prostate cancers, we have carried out a comparative quantitation of the HPV16-E6 sequence in 84 prostate specimens. Using single-tube quantitative competitive PCR, we characterized 47 prostate cancers and 37 control tissues of benign prostatic hyperplasia. A subgroup of the prostate tumors (10 of 47; 21%) was detected as having significantly higher copy numbers of HPV16-E6 sequences when compared to the control tissue (1 of 37; 3%), using a cutoff value of 300 copies per 12,500 diploid cells (two-sided Fisher's exact test, P = 0.02). Our results indicate that the oncogenic HPV16 might contribute to the development of a subset of prostate tumors.

Aged↗

[Extracorporeal shock wave therapy for delayed union of long bone fractures - preliminary results of a prospective cohort study].

Extracorporal shock wave therapy (ESWT) has been postulated as an additional therapeutic option in nonunion after fracture treatment. We have reexamined patients with nonunions treated at our institution to evaluate the efficacy of the method. In a prospective nonrandomized study patients were investigated with a minimum duration of nonunion of 6 months. Following 2 cycles of ESWT with 2000 impulses/18 kV, the reevaluation was performed at 1, 3 and 6 months after treatment. A total of 27 pseudarthroses was reevaluated, in 11 one or more reosteosyntheses had been performed prior to ESWT. Following ESWT we found a success rate of 41 % (n = 11). The clinical evidence of subjective, clinical improvement was found in 5 of these patients within 1 month, in all of these patients within a period of 3 months. Radiologic evidence of improvement occurred in none of these patients within 1 month, in all of these patients within 6 months. ESWT appears to represent an additional treatment option in patients with longstanding nonunion. If no improvement occurs, the maximum delay of reosteosynthesis is three months.

Adolescent↗

[New aspects on the identification of genetic alterations and prognostically important biological parameters in renal cell cancer].

The observation of extremely variable clinical courses for patients with renal cell carcinomas of an identical pathological stage as well as a comparable histological differentiation resp. growth pattern strongly indicates the existence of tumors harboring different biological aggressiveness. Currently available histopathological classification systems do not predict the biological behaviour of renal cell cancer as sufficiently as the establishment of a therapeutical strategy adjusted to the individual patient would require. The need for a more refined characterization of the biological potential of the individual tumor results from the introduction of modified operative strategies as organ-preserving surgery, for example, as well as from the recently suggested application of an adjuvant systemic therapy adapted to the individual risk for tumor recurrence resp. the development of progressive disease. Therefore, the clinically orientated basic scientist and the basic scientifically orientated clinician intensively try to determine prognostically important biological variables which would allow to better predict the biological aggressiveness of a single tumor in addition to "classical" prognostic parameters (T-stage, histological grading, growth patterns). In this context, several biological parameters including the identification of alterations on the DNA-, RNA- and protein level have been discussed as possible biological prognostic markers for renal cell cancer. The present review tries to reflect currently available biological characteristics of RCC which might gain clinical importance with regard to an individualized therapy in the near future.

Biomarkers, Tumor↗

[Therapy for kidney cell carcinoma with cava thrombus. Importance of extracorporeal circulation and prognostic value of cranial tumor extension].

In approximately 4-10 % of patients presenting with renal cell cancer the transluminal propagation of a tumor thrombus into the vena cava inferior or the right atrium comes to diagnosis. Recent investigations have indicated that the presence of neoplastic extension into the venous system does not reveal independent prognostic value regarding the clinical course of the disease. Although the complete surgical removal of vena cava thrombosis in patients without simultaneously occurring regional lymph node or distant metastases has become a well established treatment modality, several questions concerning this surgical strategy still remain the subject of ongoing discussions. In the present investigation that included 92 patients with renal cell cancer and intracaval neoplastic extension it was clearly demonstrated that the use of cardiopulmonary bypass, deep hypothermia and circulatory arrest preferably during the removal of intracaval thrombosis extending into the right atrium does not result in a substantially increased treatment-related intra- or postoperative mortality. However, in contrast to a previously reported observation this treatment option did not reveal any substantial impact on the long-term survival of the patients following surgical therapy. Accordingly, the cranial extension of intracaval thrombosis was not identified as a biological variable of any prognostic importance for renal cell cancer patients.

Adult↗

The need for microdissectional tumor cell preparation during the molecular genetic analysis of prostate cancer.

For clinically localized prostate cancer, recent studies strongly indicate that the determination of p53 inactivation allows the identification of a highly aggressive subgroup of prostatic tumors associated with decreased recurrence-free and long-term survival following radical prostatectomy. However, several questions regarding the determination of p53 alterations in prostate cancer, such as the poor correlation between immunohistochemistry and molecular genetic analysis, remain to be clarified. On the DNA level, p53 gene alterations have been identified in only up to 64% of tumors exhibiting immunohistochemically detected overexpression of the p53 oncoprotein. This discrepancy can be explained either by the genetic microheterogeneity of prostate cancer or by stabilization of the wild-type protein due to posttranslational events. In the present study we tried to determine the concordance between an immunohistochemically detected p53 overexpression and the result of molecular genetic analysis. Therefore, tumor tissue obtained by microdissection from 40 prostate cancer specimens was subjected to DNA-sequence analysis. Microdissection was based either only on histopathologic criteria or on the result of the immunohistochemical staining reaction. In 8 of 14 (57%) tumors a positive immunohistochemical reaction could be confirmed by DNA sequencing, which revealed a missense point mutation at the p53 gene locus, mainly in the form of G-->A transversion in exon 5 of the p53 gene. Following the micropreparation of tumor cells exhibiting p53 oncoprotein overexpression, missense point mutation could be detected in an additional 4 cases. Following a microscopically guided tumor cell dissection according to the result of immunohistochemistry, DNA sequencing confirmed an immunohistochemically detected p53 overexpression in 86% of cases investigated. This result indicates that a microdissectional tumor cell preparation is recommended for molecular genetic analysis of histologically heterogeneous tissue specimens such as prostate cancer and should be performed according to and in addition to the result of immunohistochemistry when an immunohistochemical approach is available.

Adenocarcinoma↗

Urodynamics in the anatomical work of Leonardo da Vinci (1452-1519).

Leonardo da Vinci (1452-1519) incorporates the symbiosis of art and medicine and can be addressed as the founder of medical illustration in the time of the Renaissance. His anatomy studies were not published in his time, which explains why Leonardo's outstanding knowledge of anatomy, physiology, and medicine had no impact on his scientific contemporaries and is therefore primarily of retrospective importance in the history of medicine. The collection of anatomical illustrations remained unknown until their rediscovery in the eighteenth century and their wide publication at the beginning of our century. This article systematically reviews Leonardo's genitourinary drawings with regard to urodynamic aspects of the upper and lower urinary tract, highlighting topics such as vesicoureteral reflux and urinary sphincter mechanisms.

Anatomy, Artistic↗