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Biomedical subjects

H Rübben

Publications and source records attributed to H Rübben.

At least 91 records · Page 5Linked to original sources

[Therapy of prostate carcinoma. Age, general health status and stage determine choice of therapy].

Radical prostatectomy is indicated in patients with an estimated life expectancy of 10 years and with organ defined cancer disease (T1b-T2, No, Mo). Radiotherapy is an effective alternative treatment, especially in patients with an increased comorbidity. Primary hormonal treatment is not indicated for organ-defined cancer. Prognosis of patients with locally advanced prostatic carcinoma (T3,NO,MO) is poor because of micrometastases; tumour progression will occur in 75% of patients independent of local therapy. Orchiectomy or LH-RH treatment is option of first choice in metastatic prostate cancer disease. There is no need for complete androgen deprivation. Ongoing trials measure the effect of intermittant androgen deprivation. Intention for treatment of hormone refractory cancer is improvement of quality of life. Cancer-related symptoms are pain caused by bone metastases, lymphoedemas and urinary retention. Therapeutic options are monochemotherapy, hormonal treatment, analgetic treatment besides palliative radiotherapy.

Health Status↗

[PSA-based early detection of prostate cancer].

Prevention of prostate cancer up to now is not possible, advanced stages of prostate cancer are not curable. About 13 000 men a year die of prostate cancer in Germany. PSA-based screening has been shown to be effective in detecting prostate cancer at an early, potentially curable stage; however, this tumor marker is limited by appreciable false-positive and false-negative results. Several PSA-related indexes may improve the power of PSA in early detection: As PSA density, age-adjusted PSA, and percent free PSA. These indexes can improve positive predictive value of PSA-testing, but are not able to differentiate carcinoma from benign hyperplasia on an individual basis. Men presenting for early detection have to be informed about possible overtreatment before undergoing biopsy to further investigate increased PSA above 4.0 ng/ml or suspect findings in digital rectal examination.

Biomarkers, Tumor↗

[Early detection of prostatic carcinoma in urologic practice with digital rectal examination and prostate-specific antigen. Early Detection Project Group].

For the early detection of prostate cancer, a patient should undergo digital rectal examination (DRE) and PSA investigation. Follow-up of increased PSA levels detects nearly 80% of cancers. Positive predictive value of suspicious DRE and PSA is about 50%. Whereas in the first evaluation of this case-finding trial about 70% of the patients had organ-confined cancers, nearly all of the detected cancers in the follow-up investigation were organ confined. The increased number of organ-confined cancers detected in early periodical examinations can lead to a reduction of mortality and morbidity from prostate cancer.

Adult↗

The Whitaker test, a useful tool in renal grafts?

OBJECTIVES: To evaluate the Whitaker test, a pressure flow examination, for its prognostic value in dilated renal transplants because urologic complications, such as ureteral stenosis, are significant problems after kidney transplantation. METHODS: Twenty-five patients with obstruction of the renal transplant and subsequent percutaneous nephrostomy were evaluated with a urodynamic pressure flow test (Whitaker test) in combination with antegrade pyeloureterography. The results of the Whitaker test were related to the serum creatinine values. RESULTS: The Whitaker test demonstrated normal pressure flow (less than 15 cm H(2)O) in 7 patients, pressure flow between 15 and 25 cm H(2)O in 10, and pathologic results (greater than 25 cm H(2)O) in 8 patients. After percutaneous nephrostomy, the serum creatinine level decreased in 22 of 25 patients, although the urodynamic pressure flow revealed a significant obstruction (Whitaker test greater than 25 cm H(2)O) in only 8 patients. The sensitivity of the Whitaker test to indicate the relevance of post-renal transplant stenosis in comparison to the declining serum creatinine level after successful percutaneous nephrostomy was 79%; the specificity was 50%. CONCLUSIONS: The results of our study indicate that a decreasing creatinine level in correlation with radiologic results is the leading finding in dilation of transplanted kidneys without rejection. The Whitaker test, as a pressure flow examination, provided no additional information.

Adolescent↗

Long-term follow-up of female patients with congenital adrenal hyperplasia from 21-hydroxylase deficiency, with special emphasis on the results of vaginoplasty.

OBJECTIVE: To assess, in a long-term follow-up, female patients with congenital adrenal hyperplasia (CAH), with special emphasis on vaginal functional outcome and sexual activity after vaginoplasty. PATIENTS AND METHODS: Twenty-seven patients with CAH (aged 14-33 years; six Prader grade II, 14 grade III, six grade IV and one grade V) underwent surgery between 1972 and 1988. Three of the patients underwent clitoridectomy, 24 clitoroplasty and 25 vaginoplasty (24 with a Fortunoff flap and one a 'pull-through' procedure). In 20 patients the vaginoplasty was a one-stage procedure, undertaken at a mean (range) age of 3.6 (1-9) years, and in five patients a two-stage operation. The analysis was based on the patients' history and examination; the patients also completed a questionnaire, including a psychological profile. RESULTS: Nine of the 25 patients (36%) who underwent vaginoplasty developed intravaginal stenosis; of these nine, six were Prader grade III and three grade IV. All had undergone a single-stage procedure at a mean (range) age of 4.7 (2-9) years. Of the 16 patients who answered the questionnaire, 14 had problems with their overall body image; patients in whom vaginal stenosis was corrected were particularly anxious about sexual intercourse and had problems with orgasm. CONCLUSION: The main problem during the long-term follow-up was intravaginal stenosis; all the affected patients had undergone a single-stage procedure early in life to correct ambiguous genitalia. This high rate of vaginal stenosis suggests that vaginoplasty should be undertaken at the beginning of puberty, because higher oestrogen levels may prevent stenosis and, if necessary, dilatation can be performed by the patient. These data also underscore the importance of psychological support in the treatment of children with CAH.

Adolescent↗

Influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC3 in an orthotopic model.

OBJECTIVE: It has been demonstrated that quinoline-3-carboxamide, linomide, inhibited angiogenesis and reduced the volume of tumors grown from human hormone-resistant prostate cancer cell lines after subcutaneous implantation in mice. However, subcutaneous xenograft models may not mimic human conditions due to the absence of prostatic stromal cells at the ectopic site. Therefore, we investigated the influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC-3 in an orthotopic model. METHODS: In 30 athymic nude mice, 5x10(5) PC-3 cells were injected into the dorsal prostate after surgical exposure. After 7 days, group 1 (n = 15 mice) received linomide 100 mg/kg/day in the drinking water (per os). The other 15 mice (group 2) served as controls. All mice were sacrificed after 38 days followed by macroscopical and histological evaluation of local tumor growth and metastasis. Microvessel density was determined by immunohistochemical staining for von Willebrand factor as well as silver staining followed by morphometric analysis in an area of highest vessel density. RESULTS: In the control group, local tumorigenicity and locoregional lymph node metastasis was 100%. The mean weight of the local tumor was 894 mg (395- 1,261 mg). The mean transversal diameter of the lymph node metastases was 4.0 mm (1.5-5. 4 mm). In the treatment group, local tumor growth and lymph node metastasis was 100% with a mean local tumor weight of 869 mg (232-1, 131 mg) and a mean lymph node metastasis diameter of 4.6 mm (1.3-5.9 mm). Microvessel density of the local tumor in the control and treatment group did not differ significantly. CONCLUSION: Contrary to the results reported in subcutaneous animal models, linomide per os has no effect on net tumor growth and metastasis after orthotopic implantation of the human hormone-resistant prostate cancer cell line PC-3 in nude mice.

Angiogenesis Inhibitors↗

Keyhole limpet haemocyanin in experimental bladder cancer: literature review and own results.

OBJECTIVES: Keyhole limpet haemocyanin (KLH) is a high-molecular-weight protein antigen collected from the haemolymph of the sea mollusk Megathura crenulata. It is a powerful non-specific immune response modifier that induces both a cell-mediated and a humoral response in animals and man. Thus, it is commonly used clinically as a measure of immune competence. In 1974, Olson studied the immune competence of bladder cancer patients by intradermal application of KLH. He later observed a significant reduction of recurrent disease in this patient group compared to another not immunized with KLH. This prompted a variety of experimental and clinical studies using KLH as an immunotherapy for recurrent bladder cancer. METHODS: Three different bladder cancer models have been used for experimental studies: intravesical transplantation of tumour cells in syngeneic mouse bladders; subcutaneous transplantation of tumour cells in syngeneic mice; direct chemical induction of bladder tumours by feeding rats with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. RESULTS: The efficacy of KLH as an immunotherapeutic agent has been compared with different immune response modifiers alone or in combination with these in 11 experimental studies. Most of the studies used different concentration and application schedules for KLH. In addition a pre-immunisation prior to inoculation of the tumour was not performed in all studies. Therefore it is not useful to compare the results of these studies. However, most of the experiments demonstrated a significant effect on tumour appearance and extension after treatment with KLH. Intralesional or systemic application of KLH seemed to be superior to intravesical treatment. Pre-immunisation with KLH several days or weeks before tumour inoculation also seems to be a key point of success. No study reported severe side-effects after application of KLH; additionally performed toxicity studies underlined the good tolerability of KLH. CONCLUSION: Based on all the experimental studies, KLH has to be judged as an effective and safe immunotherapeutic drug for the treatment of experimental bladder cancer. Prospective randomised clinical trials should evaluate the role of KLH as an immunotherapeutic alternative in the prophylaxis of recurrent bladder cancer and should determine whether the efficacy of KLH in man may be improved by systemic application.

Adjuvants, Immunologic↗

Saw palmetto extracts potently and noncompetitively inhibit human alpha1-adrenoceptors in vitro.

BACKGROUND: We wanted to test whether phytotherapeutic agents used in the treatment of lower urinary tract symptoms have alpha1-adrenoceptor antagonistic properties in vitro. METHODS: Preparations of beta-sitosterol and extracts of stinging nettle, medicinal pumpkin, and saw palmetto were obtained from several pharmaceutical companies. They were tested for their ability to inhibit [3H]tamsulosin binding to human prostatic alpha1-adrenoceptors and [3H]prazosin binding to cloned human alpha1A- and alpha1B-adrenoceptors. Inhibition of phenylephrine-stimulated [3H]inositol phosphate formation by cloned receptors was also investigated. RESULTS: Up to the highest concentration which could be tested, preparations of beta-sitosterol, stinging nettle, and medicinal pumpkin were without consistent inhibitory effect in all assays. In contrast, all tested saw palmetto extracts inhibited radioligand binding to human alpha1-adrenoceptors and agonist-induced [3H]inositol phosphate formation. Saturation binding experiments in the presence of a single saw palmetto extract concentration indicated a noncompetitive antagonism. The relationship between active concentrations in vitro and recommended therapeutic doses for the saw palmetto extracts was slightly lower than that for several chemically defined alpha1-adrenoceptor antagonists. CONCLUSIONS: Saw palmetto extracts have alpha1-adrenoceptor-inhibitory properties. If bioavailability and other pharmacokinetic properties of these ingredients are similar to those of the chemically defined alpha1-adrenoceptor antagonists, alpha1-adrenoceptor antagonism might be involved in the therapeutic effects of these extracts in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.

Adrenergic alpha-1 Receptor Antagonists↗

[Urological diagnosis in children with myelomeningocele].

Neurogenic bladder dysfunction in childhood is mostly caused by spinal dysraphism. The urologic diagnostic procedure tries to evaluate the underlying form of neurogenic bladder, dysfunction the associated disturbances at the upper tract and the development of changes by body growth. Therapeutic main aim is the conservation and protection of the kidney function and, secondly, the development of social dryness and a form of bladder emptying, that is related to the individual situation and associated disabilities. We report here about the diagnostic procedure and result of a group of 190 patients, that have been seen in our department since birth and for more than ten years continuously. Developmental changes of neurogenic bladder dysfunction has been found in more than 25% of the children. This figure shows the need of life-long close urodynamic follow-up.

Child↗

[Detrusor myectomy (autoaugmentation) in the treatment of hyper-reflexive low compliance bladder].

After unsuccessful medical treatment of a neurogenic hyperreflexive bladder dysfunction further treatment options are the ileal bladder augmentation, the detrusor-myectomy (bladder auto-augmentation) and the sacral root deafferentation. All techniques lead to a low-pressure bladder with enlarged storage volume. The authors here report about their personal experience with the detrusor myectomy in 62 patients with hyperreflexive neurogenic bladder dysfunction from 1989 until 1998. Indication, surgical technique, and long-time results are presented.

Adult↗

[Secondary erectile dysfunction. Is oral medication in the diagnostic phase indicated?].

For patients with erectile dysfunction oral medication seems to be the most comfortable form of application. This can also be seen in the expectations looking forward to Sildenafil and other drugs in development. We present a prospective examination with the oral medication of 100 mg acecarbamol, 30 mg extract of cortex quebracho and 33 mg tocopherol acetate (Afrodor) in 100 patients complaining secondary erectile dysfunction. The patients were treated unselected with 3 x 1 tablet/day during the diagnostic schedule. 14% of the patients were able to perform satisfying sexual intercourse after 4 weeks of medication and another 15% showed an increased libido. Therefore we suggest, that the application of an oral medication, might be useful, especially during the time of diagnostics. Especially for those patients who gain without invasive diagnostic tools as intracavernous injection.

Administration, Oral↗

[Early recognition of prostate carcinoma. Initial results of a prospective multicenter study in Germany. Project Group for Early Detection DGU-BDU Laboratory diagnosis Professional Circle].

To compare the efficacy of digital rectal examination (DRE) and serum prostate specific antigen (PSA) in early detection of prostate cancer, we initiated a prospective multicenter screening trial. In 12,542 men choosen at random with a mean age of 62 (+/- 7.5) a suspect DRE or a PSA level > 4.0 ng/ml was found in 2343 (20%). Of the presently performed 744 biopsies, 157 revealed diagnosis of prostate cancer. Although further biopsies as well as the follow up of the 12,542 men are still missing, combination of DRE and PSA value > 4.0 ng/ml appears to be superior to DRE alone with a positive predictive value of 50% versus 19% in early detection of prostate cancer.

Aged↗

[Sildenafil (Viagra). Tolerance, contraindications, drug interactions].

Placebo-controlled studies have clearly demonstrated the efficacy of sildenafil in the treatment of erectile dysfunction. It's tolerability cannot yet be judged definitively based on the available information. Some findings indicate that in addition to established contraindications (allergy against the active ingredient, concomitant nitrate and NO-donor treatment, retinitis pigmentosa) factors such as coronary heart disease, advanced age, impaired liver function and drug interactions require special attention by the prescribing physician to secure drug safety.

Adverse Drug Reaction Reporting Systems↗

[Effectiveness and tolerance of 1 dosage forms (subcutaneous and intramuscular) of decapeptyl depot in patients with advanced prostate carcinoma].

The intramuscular (i.m.) administration of Decapeptyl Depot has been approved in Germany for the treatment of advanced hormone dependent prostate cancer since July 1990. In this study a reformulated Decapeptyl Depot, administered as a first-line endocrine therapy, was injected intramuscularly (i.m.) or subcutaneously (s.c.) every 28 days for 6 months. At 12 different hospitals, 52 prostate cancer patients were treated, whereby 25 patients received a s.c. injection and 27 patients a i.m. injection. Testosterone was measured as the main parameter: after 28 days, both the s.c. and the i.m. application form of Decapeptyl Depot successfully reduced initial testosterone levels of at least 2.3 ng/ml to steady-state castration levels below 1.2 ng/ml, maintaining this complete suppression for the entire length of the trial (168 days). Decapeptyl Depot was well tolerated and very acceptable to the patients in both groups. Side effects were few and predictable, being largely associated with decreased testosterone concentrations. No cumulation in triptorelin serum levels was observed within the 6 months of treatment. Decapeptyl Depot, administered subcutaneously or intramuscularly was effective and safe in the treatment of patients with advanced prostate cancer.

Antineoplastic Agents, Hormonal↗

[Lymphatic metastases in bladder carcinoma. Is radical cystectomy indicated?].

Bladder carcinomas with lymph node metastases are a systemic disease with a poor long term survival (< 10%). Surgery has no proven impact on patients survival. Outcome depends on the extent of lymph node disease. Surgery combined with systemic chemotherapy is controversially discussed. Neoadjuvant chemotherapy has no proven survival impact. Adjuvant chemotherapy is under investigation in prospective randomized phase III trials. Lymph node metastases are no exclusion criteria for orthotopic bladder replacement. Extended lymph node dissection is not superior to lymph node dissection limited to the fossa obturatoria. Despite excellent long term results of radical cystectomy and lymphadenectomy in selected patients with node positive disease, surgery seems to be an individual approach, without no proven impact on patients survival and quality of life.

Chemotherapy, Adjuvant↗

The G protein beta3 subunit splice variant Gbeta3-s causes enhanced chemotaxis of human neutrophils in response to interleukin-8.

A C825T polymorphism was recently described in GNB3, the gene encoding the Gbeta3 subunit of heterotrimeric G proteins. The 825T allele is associated with the expression of a shorter splice variant (Gbeta3-s) and enhanced signal transduction via pertussis toxin (PTX)-sensitive G proteins. Given the pivotal role of G protein betagamma dimers in chemotaxis, we related the genotype at the GNB3 locus as a marker for Gbeta3-s expression to chemotaxis of human neutrophils in response to stimulation with interleukin-8 (IL-8). IL-8, which activates a CXC receptor coupled to PTX-sensitive G proteins, induced at 10 nM an enhanced maximum chemotaxis of neutrophils from individuals with TC/TT genotype compared to CC genotype. Furthermore, migration of neutrophils from 825T allele carriers was 2.5-fold higher at 0.1 nM and 1 nM IL-8. At these concentrations of IL-8, no significant chemotaxis was observed in neutrophils from homozygous C825 allele carriers, indicating a genotype-dependent, different potency of IL-8 to chemoattract neutrophils. In contrast, IL-8-induced Ca2+ signals and O2- generation were independent of genotype. The role of Gbeta3-s in enhanced chemotaxis could be confirmed by determination of chemotaxis of COS-7 cells following transfection with either Gbeta3-s or "wild-type" Gbeta3. Upon stimulation of the transfected cells with the chemoattractant lysophosphatidic acid (LPA), we observed an enhanced chemotactic response of Gbeta3-s-transfected compared to Gbeta3-transfected COS-7 cells, confirming that Gbeta3-s actually causes enhanced chemotaxis.

Alleles↗

Influence of interferon-alpha2b (IFN-alpha2b) on the prevention of locally advanced bladder carcinoma in mice.

In the model of chemically induced bladder carcinoma in mice following application of betahydroxylbutylnitrosamine (BBN) we could not detect a therapeutic influence of systemic treatment with intraperitoneal injection of interferon-alpha2b (10x3x10(5) IU IFN-alpha2b) on the rate of locally advanced bladder carcinoma (IFN-alpha2b 37% versus control 41%) nor on the development of tumor precursors (severe dysplasia 100% in both groups).

Animals↗