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Biomedical subjects

U Jonas

Publications and source records attributed to U Jonas.

At least 19 recordsLinked to original sources

CHESS classification of bladder-outflow obstruction. A consequence in the discussion of current concepts.

The present discussion on the natural history, growth rate pathophysiology, morbidity, and possible treatment of benign prostatic hyperplasia (BPH) reinforces the need to objectify mechanical BPH-induced obstruction with pressure-flow study. Different methods for the quantification of BPH-induced obstruction exist and the grade of simplification depends on their working mechanism. To review the limitations of the current concepts, 118 BPH patients were selected for computerized pressure-flow data analysis according to quadratic passive urethral resistance relation (PURR) function. The CHESS classification differs from all other concepts due to its two-dimensional character and was developed as a result of the following way of thinking: (1) the whole individual pressure-flow plot is the most accurate basis for further analysis; (2) PURR as the true low-pressure flank of the individual plot is the most favorable definition for mechanical obstruction; (3) PURR quantification requires at least two parameters, footpoint and curvature/slope, with regard to the documented missing significant correlation of both; and (4) a two-parameter-based classification is two-dimensional (CHESS classification).

Aged

Localized renal-cell carcinoma: detection of abnormal cells in peritumoral tissue. A cytophotometry and immunocytochemistry study.

To spare organ function, partial resection of early diagnosed renal-cell carcinoma (RCC) is applied for well-localized and small-volume RCC with increasing frequency, although recurrence of the tumor in the same kidney is occasionally observed. The aim of the present study was to establish objective prognostic parameters that would allow the selection of tumors suitable for an organsaving procedure. Of the 160 patients undergoing a radical nephrectomy, 67 were included in this study. In 7/45 patients with lymph-node dissection (15.6%), clinical staging revealed a false-negative lymph-node status. By means of conventional histopathology, multifocality could be demonstrated in 2/67 patients (3%); in 1/67 patients (1.5%), the ipsilateral adrenal gland was unexpectantly tumor-involved. Both tumor tissue and normal peritumoral tissue were examined for the presence of premalignant and tumor cells on the basis of DNA ploidy and of the expression of the tumor-associated G250 antigen, which is specifically expressed at the surface of renal cancer cells. In 40/67 (59.1%) peritumoral tissue specimens, cells with an abnormal DNA content could be observed using automated image analysis. In 12/67 cases (18%), cells obtained from peritumoral tissue also showed an aneuploid DNA histogram; 4/67 (6%) had a tumor-correlated DNA ploidy. Additionally, 38/67 (56.9%) of these tissues, histopathologically classified as normal, contained cells expressing the G250 antigen. These observations were independent of the stage or histological grade of the tumor. These data indicate that classic pathological parameters for tumor staging are insufficient for the detection of multifocality, occurring in more than 15% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Renal-cell carcinoma with intracaval neoplastic extension: stratification and surgical technique.

Surgical removal continues to be the mainstay in the treatment of renal-cell carcinoma with neoplastic venous extension. The steady improvement of surgical and anesthesiological techniques and the introduction of complete circulatory arrest has dramatically improved the morbidity even of patients with extensive thrombi. If ultrasound or computerized tomography (CT) scanning suggests the presence of a venous extension in a patient with renal-cell carcinoma, cavography, magnetic resonance imaging (MRI), transesophageal color-coded ultrasound, and echocardiography may be needed to resolve the questions of cranial extension and vascular wall infiltration. Surgical stratification and, thus, classification of the venous extension depend on the potential need for complete circulatory arrest. Surgical removal is done en bloc for smaller venous extensions and in a two-step procedure (radical nephrectomy followed by thrombectomy) for more extensive thrombi. In patients with infiltration of the suprahepatic inferior vena cava, the hepatic veins or atrium, pending thrombotic embolism, or large masses of suprahepatic thrombotic material, the use of cardiopulmonary bypass and complete circulatory arrest is recommended.

Aged

Porcine detrusor cyclic nucleotide phosphodiesterase isoenzymes: characterization and functional effects of various phosphodiesterase inhibitors in vitro.

OBJECTIVES: This study was undertaken to characterize adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) phosphodiesterases (PDEs) in porcine detrusor smooth muscle and to define their possible role in tension regulation. METHODS: PDEs were isolated from porcine detrusor homogenate by Q-Sepharose anion exchange and calmodulin affinity chromatography. The effects of selective inhibitors of cAMP and cGMP PDEs were investigated on isolated PDEs and on carbachol (1 microM) precontracted detrusor strips. RESULTS: Six PDE isoenzymes were isolated by Q-Sepharose anion exchange and calmodulin affinity chromatography: one calmodulin-stimulated PDE (PDE I) which hydrolyzed mainly cGMP, one cGMP-stimulated cAMP PDE (PDE II), two cAMP-specific PDE (PDE IV alpha and IV beta), and two cGMP-specific PDE (PDE V alpha and V beta). PDE I was potently inhibited in a dose-dependent fashion by papaverine, vinpocetine, and zaprinast; the PDE IVs were potently inhibited by papaverine and rolipram; and the PDE Vs were weakly inhibited by papaverine. In organ bath studies, inhibitors of PDE III (milrinone), IV (rolipram), and V (zaprinast) caused only minor relaxations at high concentrations (200 microM), whereas papaverine and vinpocetine caused relaxations of more than 50%. CONCLUSIONS: Our findings support the involvement of cyclic nucleotide metabolism in the regulation of the detrusor smooth muscle tone in the pig and its regulation by PDEs. The weak action of PDE IV and V inhibitors in vitro may be explained by a possible intracellular compartmentalization of such PDEs and the low cyclic nucleotide turnover rate at the conditions used.

3',5'-Cyclic-AMP Phosphodiesterases

p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder.

Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those patients who develop muscle-invasive tumours or metastatic disease at recurrence do poorly clinically. In the current study 69 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, performance of instillation therapy and immunohistochemical determination of mutational inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well as immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a median follow-up of 45.8 months, 12 of 14 patients (85.7%) with more than 20% of cells positive for p53 had disease progression with muscle-invasive growth compared with only one of 55 patients (1.8%) negative for p53 (P < 0.01, chi 2 test). During univariate analysis histological grade (G1 vs G2) (P = 0.0373), positivity for PCNA (> 60% of cells) (P = 0.0033) and positivity for p53 (P < 0.001) were significant prognostic factors for disease progression (log-rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0029) (multivariate Cox regression analysis). The immunohistochemical detection of mutations of the p53 gene has been demonstrated to be a reliable, easily performed and thereby widely available technique for the investigation of fresh-frozen or paraffin-embedded tumour specimens. The results demonstrate the important role of the p53 tumour-suppressor gene protein in the development and for the progression of bladder cancer. If the high prognostic value of p53 mutations in superficial bladder cancer is confirmed in larger prospective trials, more aggressive therapeutic strategies could be discussed for patients with p53 mutations in their tumour specimens.

Aged

[Thermotherapy of benign prostatic hyperplasia].

Transurethral microwave thermotherapy (TUMT) differs from hyperthermia in the higher intraprostatic temperatures reached and in the irreversible damage it causes to intraprostatic tissue. Both subjective symptoms and objective data, such as peak flow and residual urine, are influenced differently by TUMT and by sham treatment. As expected, no improvement of the objective data was documented with TUMT, in contrast to transurethral resection of the prostate (TURP), whereas the improvement in subjective symptoms was comparable. The complication rate in terms of morbidity is clearly lower with TUMT than with TURP. TUMT can be performed as an outpatient procedure without a general anaesthetic. TUMT had a specific effect on outflow obstruction, but it was less pronounced than that achieved with TURP. Therefore, TUMT is indicated for patients with typical symptoms of BPH and a mild mechanical obstruction. In this patient group TUMT seems to be the optimal treatment, whereas TURP would constitute "overtreatment" owing to its higher complication rate and the unnecessary tissue resection. At this stage of BPH, TURP is justifiable only with reservations; it should be reserved for BPH with moderate and severe mechanical obstruction.

Follow-Up Studies

The prediction of clinical outcome from transurethral microwave thermotherapy by pressure-flow analysis: a European multicenter study.

A total of 100 patients treated with a single session of microwave thermotherapy at 4 European centers was stratified according to 2 different types of obstruction (constrictive and compressive) and compared to clinical outcome at 6 months. Patients had a Madsen-Iversen score of 8 or more, maximum flow rate of 15 ml. per second or less and residual urine volume of 300 ml. or less at entry. The change in Madsen-Iversen score was the same in the 2 groups. Maximum flow rate increased from 8.71 +/- 2.62 to 14.73 +/- 4.04 ml. per second in the constrictive group, and from 8.54 +/- 2.26 to 10.41 +/- 4.52 in the compressive group (p < or = 0.0001). Residual urine decreased from 96.00 +/- 72.85 to 40.34 +/- 56.33 ml. in the constrictive group and from 109.86 +/- 67.09 to 84.65 +/- 81.45 ml. in the compressive group (p < or = 0.0001). Success, as defined by an increase of 50% or more in maximum flow rate and Madsen-Iversen score, was noted in 68% of the constrictive but only 15% of the compressive groups (p < or = 0.0001 chi-square test for trend). Selection by pressure-flow criteria for patients being considered for thermotherapy should improve the overall clinical results.

Diathermy

[Value of the proliferation status (PCNA) and p53 immunohistochemistry as a prognostic factor for the clinical course of superficial cancer of the urinary bladder].

Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those of them who have tumours invading muscle or metastatic disease will have a poor clinical prognosis. In the current study, 41 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, previous instillation therapy, immunohistochemical determination of mutational inactivation of p53 tumour suppressor gene (monoclonal antibody pAb 1801) and proliferation rate determined immunohistochemically by staining for PCNA (proliferating cell nuclear antigen; monoclonal antibody PC 10). After a median follow-up of 54 months 7 of 8 patients (87.5%) with more than 20% of cells positive for p53 had disease recurrence, as against only 1 of 33 patients (3%) negative for p53 detection (P < 0.01; Chi-square test). During univariate analysis histological grade (G1 vs G2; P = 0.007), positivity for PCNA (> 60% of cells; P = 0.003) and positivity for p53 (P = 0.001) were significant prognostic factors for disease progression (log rank test), while during multivariate analysis only positivity for p53 was a significant predictor for relapse of bladder cancer (P = 0.0035; multivariate Cox regression analysis).

Aged

Activation of human peripheral monocytes by angiotensin II.

This study has investigated the ability of the vasoconstrictor peptide angiotensin II to activate human peripheral blood monocytes. Activation was monitored by measuring both the release of tumor necrosis factor alpha from monocytes and their adhesion to monolayers of human endothelial cells. Angiotensin II-elicited activation of monocytes was dose-dependent (half-maximally effective concentration approximately 0.2 nM), saturable (maximally effective concentration approximately 5 nM), and sensitive to inhibition by the angiotensin type 1 receptor antagonist ZD 7155. Such direct actions imply that angiotensin II is an important candidate stimulus for the subendothelial infiltration of monocytes observed in atherogenesis and hypertension.

Angiotensin II

Effects of magnesium citrate and phytin on reducing urinary calcium excretion in rats.

The aim of this study was to determine and compare the effects of both magnesium citrate and phytin on reducing urinary calcium excretion under high-calcium-diet conditions during single and combined treatments. An animal experiment was carried out over a period of 4 weeks in 35 male rats. Urinary calcium excretion was reduced significantly by magnesium citrate and/or phytin in rats fed on high-calcium diets. The hypocalciuric effect of magnesium citrate was more evident than that of phytin. Urinary magnesium excretion was high in all experimental groups. However, the urinary magnesium/calcium ratios showed a consistent increase only in the groups treated with magnesium citrate. Urinary citrate excretion showed a relative increase with the introduction of magnesium citrate plus phytin; however, in both the high-calcium-diet group and the magnesium-citrate group this was found to be reduced. Urinary phosphate excretion was slightly higher in the groups treated with phytin. There was no definite difference in urinary oxalate concentration between the groups. No significant change was noted in the serum concentration of calcium, magnesium, or phosphate.

Animals

Detection of P53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications.

For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumor-suppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (Ta) tumors to 83.3% of muscle-invasive (T3/T4) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G1 tumors to 75% of G3 tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T1) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Characterization of cyclic nucleotide phosphodiesterase isoenzymes in the human ureter and their functional role in vitro.

An increase in cyclic nucleotide monophosphate levels is suggested to play a prominent role in mediating smooth-muscle relaxation. Cyclic nucleotide phosphodiesterase (PDE) influences smooth-muscle tone by decreasing the level of cyclic nucleotides. At present, five different families of isoenzymes of PDE exist that show a distinct species- and organ-specific distribution. Our study was done to evaluate the existence of specific PDE isoenzymes and its functional role in human ureteral tissue. Normal ureteral tissue was homogenized and centrifuged and the supernatant fraction was separated using anioin-exchange diethylaminoethyl (DEAE)-Sephacel chromatography. A PDE assay was then performed and the peak fractions were added to different specific PDE activators and inhibitors. In vitro, longitudinal ureteral strips were precontracted and different selective and non-selective PDE inhibitors were added incremently. Three different PDE isoenzymes were characterized: PDE I (calmodulin-sensitive), PDE II (cGMP-stimulated), and PDE IV (cAMP-specific). All PDE inhibitors relaxed the strips dose-dependently, with the 50% effective concentrations (EC50) being 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low-level effect on the systemic circulatory parameters, may open the possibility of using selective PDE IV-inhibitors in the treatment of ureteral colics or for ureteral stone passage.

3',5'-Cyclic-AMP Phosphodiesterases

Single potential analysis of cavernous electrical activity in spinal cord injury patients.

Introduced in 1988, cavernous electromyography and its evolution, single potential analysis of cavernous electrical activity (SPACE), seem to be promising diagnostic methods in the evaluation of erectile dysfunction. The aim of our study was to determine the influence of a centrally disturbed autonomic supply on SPACE recordings. SPACE was performed in 35 male patients with complete and 2 with incomplete spinal cord lesions at a cervical or thoracic level. Simultaneous recording was done with concentric needle electrodes in both cavernous bodies with a frequency range of 0.5 to 100 Hz. All patients underwent a full neurological and urological evaluation, including cystometry. The lesion was cervical in 12 patients and thoracic in 22. Three patients underwent sacral deafferentation and bladder pacemaker implantation. One of 12 patients with cervical and 10 of 22 with thoracic lesions reported full rigid reflexogenic erections, while 3 of 12 patients with cervical lesions were not evaluable due to grounding failure. Of these patients 31 were eligible for our study. No patient had an entirely normal SPACE. Four of 9 patients with cervical and 19 of 22 with thoracic lesions had a normal, silent basic electric (less than 5 mu v.) oscillation, while the remainder had a baseline oscillation of up to 100 mu v. Normal potentials were found in 2 of 9 and 10 of 22 patients, respectively. Low frequency, high amplitude potentials were found in 6 of 9 and 21 of 22 patients, respectively, while low frequency, low amplitude potentials occurred in 8 and 8, respectively, and high frequency potentials occurred in 5 and 1, respectively. Our results show that abnormal autonomic input induces abnormal SPACE findings in patients with (presumably) normal cavernous tissue.

Action Potentials

Prognostic factors for the postoperative outcome of penile venous surgery for venogenic erectile dysfunction.

Since penile venous surgery is usually associated with a poor postoperative outcome, a study was done to evaluate possible prognostic factors for this procedure. A total of 77 patients with erectile dysfunction underwent ligation of all dorsal penile veins and resection of the deep dorsal penile vein for venous incompetence. In all patients a comprehensive evaluation was done preoperatively. All patients did not respond to pharmacotherapy and had a venous leak. After a followup of 6 months, patients were classified as having full spontaneous erections, failure and response to pharmacotherapy. Of the 77 patients 31 (40.3%) had full spontaneous erections, 8 (10.3%) were currently responding to pharmacotherapy and 38 (49.4%) failed. The maintenance flow was 75 +/- 45 ml. per minute in the group with spontaneous erections and 103 +/- 60 ml. per minute in the failure group (p = 0.20). Mean patient age was 49.8 +/- 11.7 and 49.1 +/- 10.2 years, respectively (p = 0.23). Of the 41 patients wih normal single potential analysis of cavernous electrical activity 28 had full erections postoperatively, 5 responded to pharmacotherapy and 8 failed, compared to 3, 3 and 30, respectively, of the 36 patients with abnormal single potential analysis of cavernous electrical activity. After a mean followup of 21 months (range 6 to 47 months), 4 patients with full erections at 6 months postoperatively currently require intracavernous pharmacotherapy. Our results indicate that single potential analysis of cavernous electrical activity seems to be an important prognostic factor for the postoperative outcome of penile venous surgery for venogenic impotence.

Adult

Role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the diagnosis and treatment of erectile dysfunction.

OBJECTIVES: Recently, nitric oxide was shown to be a mediator of penile erection in men and the nitric oxide donor linsidomine chlorhydrate (SIN-1) was introduced as a novel treatment option in patients with erectile dysfunction. We now present our follow-up results with the intracavernous application of SIN-1. METHODS: One hundred thirteen patients with erectile dysfunction of various etiologies and 10 normal control subjects underwent intracavernous pharmacotesting with 1 mg SIN-1. Of the 113 patients, 71 (62.8%) underwent additional pharmacotesting with a mixture of papaverine (15 mg/mL) and phentolamine (0.5 mg/mL) (P/P). Forty-eight responders to SIN-1 were enrolled in an autoinjection program with this substance. RESULTS: All normal control subjects had full rigid erections lasting 40 to 70 minutes. Of 113 patients, 78 (69%) had responses sufficient for intercourse with SIN-1, and the other 35 patients (31%) demonstrated inadequate responses. All 44 responders to SIN-1 who also received P/P had erections sufficient for intercourse with P/P in doses of 0.25 to 2 mL (mean, 0.6 +/- 0.3 mL). Six patients (13.6%) had prolonged erections with minimal to moderate doses of P/P. From the total of 27 patients who had erections insufficient for intercourse with SIN-1, 20 (74.1%) had good responses with 0.25 to 2.0 mL P/P (mean, 1.5 +/- 0.5 mL). One patient (4%) had a prolonged erection with 1.0 mL P/P: After 10 to 150 injections/patient (total of 1160 injections; mean, 24.1 injections), no significant side effects were noted with SIN-1. CONCLUSIONS: Our data suggest that intracavernous SIN-1 is safe and efficacious in the majority of patients with erectile dysfunction; however, it has a lower smooth muscle relaxing effect than a combination of P/P. The absence of severe side effects, including priapisms, may be explained by the use of a physiologic pathway for induction of the erectile response and the rapid intracavernous decomposition of SIN-1.

Adult

Overexpression of the p53 oncoprotein in carcinoma in situ of the testis.

Carcinoma in situ (CIS) is regarded as the precursor lesion of testicular germ cell tumors. In adults CIS cells have also been described within the normal testicular tissue adjacent to mature teratomas with a frequency of 52-88%. These CIS-cells can be identified by immunohistochemical staining for "placental like alkaline phosphatase" (PLAP). In four of eight patients with mature teratomas CIS was identified by immunohistochemistry for "PLAP" in atrophic testicular tubules adjacent to the tumors. In three of these patients cells of CIS were positive for the p53 oncoprotein, indicating a mutational inactivation of the p53 tumor suppressor gene. The malignant potential of mature teratomas, which do occur without histological signs of malignancy, may therefore be associated with the occurrence of CIS within the histologically normal appearing testicular tissue adjacent to the mature tumor. Immunohistochemical positivity for the p53 protein in CIS cells of some patients may indicate that the mutational inactivation of the p53 tumor suppressor gene could be involved early in the development of testicular germ cell tumors.

Adult

Orchitis following mumps vaccination in an adult.

An acute epididymo-orchitis, followed by a viral arthritis of the left hand, occurred as complications of a mumps vaccination. In the last 17 years 4 certain cases of orchitis following vaccination have been published in Germany. We describe an additional case and discuss the possible consequences.

Adult