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Biomedical subjects

U Maier

Publications and source records attributed to U Maier.

At least 73 records · Page 4Linked to original sources

Distribution of DNA in human Sertoli cell nucleoli.

For better understanding of nucleolar architecture, different techniques have been used to localize DNA within the dense fibrillar component (DF) or within the fibrillar centers (FC) by electron microscopy (EM). Since it still remains controversial which components contain DNA, we investigated the distribution of DNA in human Sertoli cells using various approaches. In situ hybridization (ISH) with human total genomic DNA as probe and the use of anti-DNA antibody were followed by immunogold detection. This allowed statistical evaluation of the signal density over individual components. The Feulgen-like osmium-ammine (OA) technique for the selective visualization of DNA was also applied. The anti-DNA antibodies detected DNA in mitochondria, in chromatin, and in the DF of the nucleolus. ISH using human total genomic DNA showed similar labeling patterns. The OA technique revealed DNA filaments in the FC and focal agglomerates of decondensed DNA within the DF. We conclude that (a) EM staining techniques that utilize colloidal gold appear to be less sensitive for DNA detection than the OA method, (b) the DF consists of different domains with different molecular composition, and (c) decondensed DNA is not necessarily confined to one particular nucleolar component.

Cell Nucleolus↗

Renal clearance of pyridostigmine in myasthenic patients and volunteers under the influence of ranitidine and pirenzepine.

1. To assess the contribution of tubular secretion to the renal excretion of pyridostigmine, and its modification by other cationic drugs, six volunteers were given single oral doses of 60-mg pyridostigmine bromide with and without co-administration of ranitidine or pirenzepine. Renal clearances were determined by h.p.l.c. analysis of pyridostigmine and enzymic measurement of endogenous creatinine in plasma and urine. 2. In patients with myasthenia receiving continuous pyridostigmine therapy, renal clearance values were obtained in the same manner with and without ranitidine (10 patients) or pirenzepine (nine patients) co-medication. 3. Pyridostigmine was not bound to plasma proteins. Its renal clearance averaged 6.65 ml/min per kg (350% of the creatinine clearance) in all subjects, 74% being due to net tubular secretion. 4. Mean values for pyridostigmine renal clearance and for clearance by secretion were decreased in the presence of pirenzepine, but plasma concentrations were not affected significantly. Ranitidine caused a small non-significant decrease of the pyridostigmine clearance in patients. 5. Pyridostigmine had a higher elimination (2 h-1) than the absorption rate constant (0.23 h-1) when administered orally as a non-retarded preparation. 6. The renal clearance of creatinine was slightly increased by pyridostigmine in volunteers and slightly decreased by pirenzepine in the total group of subjects.

Adolescent↗

Topical chemoprophylaxis of superficial bladder cancer with mitomycin C and adjuvant hyaluronidase.

The effect of intravesical instillation of 200,000 IU hyaluronidase in addition to mitomycin C as chemoprophylaxis of superficial bladder cancer was evaluated. Based on our result of a previous study that this approach results in a significantly reduced recurrence rate (7.1 versus 32.1%), 43 patients undergoing transurethral resection of Ta-T1 tumors were retrospectively analyzed after a mean observation period of 48.5 months. During the 2 years of prophylactic therapy, tumor recurrence was seen in 6 patients (13.9%). Of the 37 patients who remained recurrence-free under treatment, 5 (13.5%) had recurrent tumors later during a mean observation period of 24.5 (18-42) months after treatment. These values are significantly lower than those obtained previously from a group of 63 patients treated with mitomycin alone, with recurrence rates of 33.3% during chemoprophylaxis and 26.2% thereafter (mean observation period 50.4 months). It appears that additive hyaluronidase enhances the local effect of mitomycin C in the intravesical chemoprophylaxis of bladder cancer, presumably by improving diffusion into the bladder mucosa and catalyzing the breakdown of a hyaluronic acid contained in a protective halo around malignant urothelial cells.

Administration, Intravesical↗

Long-term observation after intravesical metaphylaxis with mitomycin C in patients with superficial bladder tumors.

After transurethral resection of a superficial bladder tumor 63 patients were treated by chemoprophylaxis with mitomycin C over a period of two years: 33.3 percent experienced recurrent disease under metaphylaxis and 42 patients who remained recurrence-free during instillation therapy were observed further for an average of 26.4 months. During this period 26.2 percent of the patients showed recurrences ranging between two to forty-four months after completing instillation. The majority of the patients in whom recurrent tumors developed also had recurrent tumor processes before the instillation therapy was begun. Of the 42 patients 73.8 percent stayed recurrence-free during the observation period of twelve to fifty-four months after completing instillation therapy. In conclusion, during an average observation period of 50.4 months, 52.4 percent of the patients in this study showed recurrences.

Administration, Intravesical↗

Fibrinolytic parameters in spermatozoas and seminal plasma.

Urokinase-type (u-PA) and tissue-type plasminogen activator antigen (t-PA) as well as plasminogen activator-inhibitor activity were determined in seminal plasma and lysates of the respective spermatozoas in 67 ejaculate of males in infertile marriage without genito urinary pathology. U-PA was determined by a competition RIA, t-PA by an ELISA and PAI by a spectrophotometric assay. 15 patients showed normozoospermia, 11 azoospermia and 41 oligoasthenoteratozoospermia (OAT-syndrome). In lysates of spermatozoas, significantly higher levels of both plasminogenactivators and PAI were found in patients with OAT syndrome as compared to those exhibiting normozoospermia. Whereas PAI was absent in the seminal plasma of normozoospermic ejaculate, patients with azoospermia (180 +/- 13 mU/ml.) and OAT-syndrome (60 +/- 5 mU/ml.) showed high PAI levels. The similarly high values of t-PA (190.8-227.8 ng./ml.) and u-PA (19.4-32 ng./ml.) in the same compartment confirm their predominantly prostatic origin and seem to have no influence on the quality of the ejaculate.

Enzyme-Linked Immunosorbent Assay↗

Value of bladder wash cytology in the follow-up of patients with bladder carcinoma receiving intravesical chemoprophylaxis with mitomycin C.

511 bladder wash cytologic findings in 121 patients receiving intravesical chemoprophylaxis with mitomycin C after transurethral resection of stage pTa to stage pT2 bladder carcinoma were retrospectively analyzed. In 42 recurrent tumors, sensitivity of detection by cytology amounted to 67% in GIII tumors, 56% in GII tumors, and 20% in GI tumors. 16% of G0 tumors were cytologically positive. 33% of a total of 30 endoscopically detected recurrent GI-GIII tumors yielded negative results at bladder wash cytology, the findings were suspicious in 27%, while only 40% of all recurrences had a positive bladder wash cytology. Positive cytologic findings combined with normal endoscopic results were obtained in 24 patients. 15 of these (62%) developed recurrences after a mean interval of 15 months (3-60 months) during or after metaphylaxis. When suspicious findings were included, 20 of 30 carcinomas were detected, while 7 of 12 G0 tumors were overgraded. Bladder wash cytology has its merits for early detection of recurrences, since almost two thirds of the patients with positive cytologic findings and negative endoscopy developed a recurrent tumor at a later date. Whether or not positive cytology combined with negative endoscopic results should lead to therapeutic consequences remains to be discussed.

Administration, Intravesical↗

Gamma-seminoprotein--a new tumour marker in prostatic cancer? Results of a pilot study.

Serum levels of gamma-seminoprotein (GSM), prostate specific antigen (PSA) and prostate specific acid phosphatase (PAP) were examined, using enzyme immunoassay, in 250 patients with prostatic disease. The results indicated that the highest specificity was obtained with GSM (94%) and the lowest with PSA (60%). In contrast, the highest sensitivity in newly detected carcinomas (n = 41) was obtained with PSA (71%), whereas that of GSM (51%) was comparable to that of PAP (44%). Of 41 patients with newly detected prostatic cancer, 35 (85%) showed a significant increase in at least 1 of the tumour markers. Five of 6 patients whose markers were within normal limits had incidental carcinomas. During follow-up, PSA was raised in 88%, GSM in 66% and PAP in 55% within 12 months prior to clinical progression. Our results suggest that the determination of GSM may be of value in the serological detection and monitoring of prostatic cancer. These findings must be confirmed by further studies with larger numbers of patients and longer follow-up.

Acid Phosphatase↗

Neuromuscular function and plasma drug levels in pyridostigmine treatment of myasthenia gravis.

In 18 patients with generalised myasthenia treated with oral pyridostigmine, muscular strength, decrement of neuromuscular transmission in the trapezius muscle on repetitive accessory nerve stimulation, and pyridostigmine plasma level were measured repeatedly during 1-3 dosing intervals. Significant correlations between pyridostigmine concentrations and functional parameters were present in three out of 11 cases in which plasma levels changed by at least 25 ng/ml during the investigational period and peak levels did not exceed 100 ng/ml. Several other observations indicated that pyridostigmine at levels above 100 ng/ml may impair neuromuscular function.

Adult↗

Organ-preserving surgery in patients with urothelial tumors of the upper urinary tract.

The Austrian Urological Oncology Group reports on 55 organ-preserving operations in 52 patients with tumors of the upper urinary tract epithelium. The data were gathered from 12 urological departments in the country. There was no evidence of distant metastases in any of the patients at the time of surgery. The observation period ranged from 0.5 to 12 years. 69.2% (36 of 52) of the patients were alive and recurrence-free at the time of data collection, after a mean observation period of 41.4 months. 9.6% died for reasons other than cancer after an average of 18.8 months, and 21.2% were still alive with or had died due to recurrent tumors. The recurrence rate after open surgery was similar in tumors of the upper ureter or pelvis (15.3%) as in tumors of the lower ureter (17.6%). After endoscopic treatment 4 of 9 patients showed recurrences. 92% (22 of 24) of the patients with no compelling indication for organ-preserving therapy were alive and recurrence-free or had died due to other causes. Therefore organ-preserving surgery appears to be appropriate in tumors of the upper urinary tract epithelium.

Aged↗

Estramustine phosphate in secondary hormone-resistant carcinoma of the prostate.

In this retrospective study, 71 patients with secondary hormone-refractory prostatic carcinomas were treated with estramustine phosphate (EMP), at three different dosages (280, 560, 840 mg orally). All patients were completely followed up until cancer-induced death. In 12 cases of further progression polychemotherapy was administered. As this was not a randomized study, an analysis of statistical significance was not performed. The higher dosages of EMP caused an extended progression-free interval accompanied by an equally considerable alleviation of carcinoma-induced pain. The overall survival time was not influenced by subsequent polychemotherapy. An elevation of liver function parameters was observed in 5 patients. One of these patients died of toxic liver damage, possibly therapy-related, on the basis of a preexisting cirrhosis. Cardiovascular side effects were not observed. With regard to survival time, the positioning of polychemotherapy as a third-line treatment for prostatic cancer should be examined critically. Before administration of high-dose EMP, it is mandatory to control liver functions carefully.

Aged↗

Tamoxifen and kallikrein in therapy of oligoasthenozoospermia: results of a randomized study.

Because of the good results achieved with tamoxifen in the treatment of oligozoospermia and with kallikrein in the treatment of asthenozoospermia, a randomized study of the combined treatment of oligoasthenozoospermia suggested itself. 67 patients with idiopathic normogonadotropic oligoasthenozoospermia were treated with 30 mg tamoxifen/day (n = 33) or with 30 mg tamoxifen/day and additionally 600 IU kallikrein/day (n = 34). It was shown that, apart from a significant increase in sperm density in both groups, the combination therapy also resulted in an overall significant increase (p less than 0.02) in sperm motility. Sperm morphology and the swell test remained unaffected. After 3 months of therapy, 4 pregnancies occurred in each group. In ejaculates with a sperm density of less than 10 million/ml not even one sperm parameter was significantly affected in any of the groups, while with an initial value of more than 10 million/ml the increase in motility was more significant (p less than 0.008) in the group with additional kallikrein therapy (n = 18). In the monotherapy group, no significant therapeutic effect on sperm motility was seen even in patients with a sperm density of more than 10 million. The combination of tamoxifen and kallikrein therefore seems to constitute an improvement of the systemic therapy of male subfertility in patients with moderately severe oligoasthenozoospermia.

Adult↗

[The role of cytological studies in urology].

1100 patients with pathological findings of the prostate, urothelium and lymph-nodes underwent cytological examination with histological control. Prostatic cytology showed a sensitivity of 81% in detecting cancer. Through reassessment of originally false negative or only suspicious aspirates a specificity rate of 90% was achieved while the rate of unsatisfactory smears were doubled. In urothelial tumors evidence of lavage cytology was significantly higher than exfoliative cytology and depends on grading and staging of the tumor. Tumors with a low grade of malignancy were rarely detected cytologically. Topical chemotherapy seems to change the accuracy of cytological examinations because of the difficulty to separate malignancy associated cell changes from therapy induced cellular features. Transperitoneal aspiration cytology of retroperitoneal lymph-nodes has no evidence.

Carcinoma, Transitional Cell↗

[Systemic therapy of male subfertility].

Almost 90% of subfertile patients show no specific aetiological condition to account for their pathological spermiogram and therefore have to be subjected to non-causal systemic therapy. The retrospective analysis of 212 patients who were treated with 30 mg tamoxifen daily because of oligozoospermia showed a significant (p less than 0.001) increase in sperm density without influencing other ejaculate parameters. The gravidity rate amounted to 32% after 6 months of therapy, on average. 147 patients with isolated asthenozoospermia treated by means of 600 IU kallikrein daily showed a resultant significant elevation (p less than 0.002) in sperm motility only. Endocrine profiles showed no statistical changes. The gravidity rate was 37%. Combination therapy with tamoxifen and kallikrein resulted in a significant increase in both sperm density and motility in males with oligoasthenoteratozoospermia (OAT-syndrome) provided pretherapeutic levels were above 10 million sperms/ml. The problems encountered in the systemic therapy of male subfertility are discussed.

Adolescent↗

Metaphylactic effect of mitomycin C with and without hyaluronidase after transurethral resection of bladder cancer: randomized trial.

In a randomized trial 2 groups of 28 patients who had undergone transurethral resection of bladder tumors were treated with 20 mg. mitomycin C alone or with 200,000 units hyaluronidase to determine whether adjuvant hyaluronidase would improve tumor recurrence rates. Patient groups were comparable statistically. In the group receiving additive hyaluronidase the percentage of tumor recurrences was decreased significantly (p less than 0.05). Side effects were not increased. Thus, adjuvant hyaluronidase appears to have a role in the metaphylaxis of bladder tumors. The potential reduction of the hyaluronidase dose without loss of protective action and the role of additive hyaluronidase in the systemic treatment of metastatic urothelial tumors remain to be investigated.

Adult↗

[Prostatic cancer in the male under age 60].

Staging, therapy and course of disease in 32 patients with carcinoma of prostate less than 60 years old were evaluated retrospectively, 87.5% of the men showed metastases before commencement of therapy. Not one case of cancer was detected during preventive check up; all patients come to urological examination because of characteristic symptoms.33.3% of carcinomas were primarily hormone-resistant. Under pure androgen deprivation (n = 21) 81% of the patients showed progression within a mean period of 9.2 months, whereas in the small group primarily given combined contrasexual cytostatic therapy (n = 5) progression occurred after a time span of 39 months on average. The importance of preventive urological examination and the possibility of primary cytostatic therapy in combination with androgen deprivation in young patients with metastatic cancer of the prostate is stressed.

Adult↗

[Value of an abbreviated intravenous urogram].

92% of patients (n = 250) were correctly diagnosed following retrospective evaluation of the plain film and one film taken 20 minutes after administration of an increased quantity of contrast medium (250 ml 30% contrast medium instead of 50 ml 58% contrast medium) for intravenous pyelography. In the remaining 8% of cases, additional information was provided by subsequent films--in 90% (of these 8%) by way of "delayed films" and only in 10% (of the 8%) by way of "early films". If information provided by 20-minute films is insufficient further films have to be obtained in any case and, thus, the patient does not escape diagnosis. In 99.2% of cases shortened intravenous urograms provided relevant information. Hence, 50% of all routinely obtained films for intravenous urograms are unnecessary if a sufficient quantity of contrast medium is administered. It appears mandatory, therefore, to change our outlook regarding this issue.

Humans↗

[Therapy of prostatic cancer with cyproterone acetate].

45 patients with recently detected prostatic cancer were treated with cyproterone acetate (CPA) at a dosage of 100 mg/die. 25 patients underwent primary orchiectomy and consecutive treatment with 200 mg CPA/die. In 44.4% of the 45 patients who underwent monotherapy with 100 mg CPA/die progression of cancer was observed 10.8 months after beginning of treatment on average 55.6% of these patients showed a remission or stabilisation. 7 patients died, 4 certainly due to prostatic cancer. In the 25 patients who underwent orchiectomy and treatment with 200 mg CPA/die, 92% showed a remission. One patient of this group died, but not as a result of cancer. Based on the present data it may be concluded that treatment of inoperable prostatic cancer with 100 mg CPA as monotherapy is not indicated in patients with poorly differentiated tumours. Combination therapy--in addition to other possibilities of contrasexual therapy in prostatic cancer--seems to be of high efficacy.

Aged↗