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Biomedical subjects

H Rübben

Publications and source records attributed to H Rübben.

At least 73 records · Page 4Linked to original sources
PubMed2002

Phase II study of repeated single 24-hour infusion of low-dose 5-fluorouracil for palliation in symptomatic hormone-refractory prostate cancer.

BACKGROUND: To assess the efficacy and toxicity of repeated single 24-hour infusion of low-dose 5-fluorouracil for symptomatic hormone-refractory prostate cancer using relevant endpoints of palliation and biological response. PATIENTS AND METHODS: 25 patients with histologically confirmed prostatic adenocarcinoma and symptomatic progressive disease despite one or several hormonal treatments and chemotherapy were included in the study. Treatment consisted of a single 24-hour infusion of 500 mg/m(2) 5-fluorouracil (5-FU) to be repeated on day 21. This regimen was continued until either progression or serious toxicity occurred. Response was assessed by serial measurements of serum prostate-specific antigen (PSA) as well as by health-related quality-of-life instruments (EORTC QLQ-C30 and McGill-Melzack Present Pain Intensity Scale) every 3 weeks. In 10 patients with bidimensionally measurable metastases, objective responses were assessed every 3 months. RESULTS: A mean number of four courses of repeated single 24-hour infusion of 5-FU was administered (range 2-6). Toxicity was absent or mild, and no patient had to be withdrawn from therapy. All patients required analgesics prior to treatment and only 3 patients experienced a significant reduction in pain for 9 weeks, the remaining patients experienced no deterioration for a mean duration of 12 weeks (6-18 weeks). Five patients (20%) demonstrated a biological response of a 50% or greater decrease in PSA from baseline, including 2 (12%) with a 75% or greater decline for 10 weeks (range 6-16 weeks). One partial remission was observed among 10 patients with measurable lesions lasting 12 weeks; 4 patients had stable disease with a mean duration of 12 weeks. Mean survival time from the onset of treatment with 5-FU was 7 months (2-12 months). CONCLUSIONS: Though less toxic than other 5-FU regimens, repeated single low-dose 24-hour infusion is of no significant benefit in patients with symptomatic hormone-refractory prostate cancer.

Adenocarcinoma↗
PubMed2001

[Hormone therapy of locally advanced and metastatic prostate carcinoma].

Hormonal treatment is a androgenoprive therapy. Adjuvant treatment after radical prostatectomy or radiotherapy seems to have no survival benefit. Neoadjuvant hormonal treatment before local therapy has no proven survival benefit. Hormonal treatment in metastatic disease can be initiated immediately, deferred or intermittent. Androgen-deprivation is performed by castration or LHRH-analoga and/or anti-androgens. Maximal androgen-deprivation has significant more side effect and is of only limited survival bebefit for a subgroup of patients. The onset of hormonal treatment is under discussion. An increase of PSA (> 25 ng/ml) and/or occurrence of symptoms is an indication for hormonal treatment. Intermittent androgen-deprivation is under investigation as a new concept.

Androgen Antagonists↗
PubMed2001

Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?

BACKGROUND: To test whether saw palmetto extracts, which act as alpha1-adrenoceptor antagonists in vitro, also do so in vivo in man. METHODS: In a placebo-controlled, double-blind, four-way cross-over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human alpha1-adrenoceptor subtypes. RESULTS: Saw palmetto extract treatment did not result in alpha1-adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. CONCLUSIONS: Despite their alpha1-adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause alpha1-adrenoceptor antagonism in man in vivo.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

Comparison of the malignant phenotype and genotype of the human androgen-independent cell line DU 145 and a subline derived from metastasis after orthotopic implantation in nude mice.

To investigate the potential genetic changes underlying the progression of human hormone-resistant prostate cancer, we related chromosomal alterations of the DU 145 cell line and a subline isolated form a metastasis in an orthotopic model to tumorigenicity, metastasis and chemoresistance. In 15 mice 1 x 10(5) DU 145 cells were injected into the dorsal prostate. From a resulting paraaortic lymphnode metastasis, we isolated a subline (DU 145 MN1), which was injected into 15 nude mice. The sulforhodamine B (SRB) assay was used to analyze cell doubling time and the IC(50) of cisplatin and 5-fluorouracil for both cell lines. Cytogenetic characterization was performed with conventional karyotype analysis and fluorescence in situ hybridization (FISH). After orthotopic implantation of DU 145 cells tumorigenicity was 100% whereas only 2 mice revealed lymphnode metastases. In contrast, the take rate after implantation of DU 145 MN1 was 100%, with lymphnode metastases in 7 mice. The SRB assay revealed a 8-fold increased IC(50) for cisplatin and a 2.5-fold increase for 5-FU in DU 145 MN1 as compared to DU 145 cells. There was gain of a chromosome 8 and only two copies of chromosome 17 in the DU 145 MN1 cells as compared to the parental cell line. The emergence of an i(9)(q10) in addition to two normal chromosome 9 homologues in the DU 145 MN1 cell line was confirmed by FISH using a chromosome 9-specific painting probe. In summary, clonal evolution of the chromosomal changes following repeated orthotopic implantation, may assist in locating the genes involved in the progression and chemoresistance of human hormone-resistant prostate cancer.

Androgens↗
PubMed2001

[Sachse internal urethrotomy. Is erectile dysfuction a possible complication?].

Erectile dysfunction is reported to be a complication of direct-vision internal urethrotomy by some authors in 2.2-10.6% of cases. It is caused by injury to the cavernous nerve by direct severance with the cutting blade, late fibrosis after extravasation and infection, or by a shunt between the corpora cavernosa and corpus spongiosum. The aim of this examination was to evaluate all internal urethrotomy patients from 1990 to 1999, regarding this kind of complication. Of 184 patients, 111 had to be excluded due to preexisting erectile dysfunction, malignancy, age over 75 years, or open surgery of the urethra before internal urethrotomy. Five patients died. Of 184,68 patients did not have erectile problems before the operation and only one complained about erectile dysfunction following direct-vision internal urethrotomy. Further examination showed an impaired arterial inflow in both arteriae penis profunda; cavernosography could not prove a shunt between the corpora cavernosa and corpus spongiosum. Erectile dysfunction is a possible complication of direct-vision internal urethrotomy. External sphincterotomy at the 3- and 9-o'clock position, urethrotomy after injury or open reconstructive surgery of the urethra, and urethrotomy of long and dense strictures as well as a dilatation over 22 Chr. are known to cause this complication. To inform the patient concerning this kind of complication is recommended before urethrotomy.

Adolescent↗
PubMed2001

[Locally advanced or metastatic bladder carcinoma. Current aspects of therapy].

The prognostic factors for infiltrating tumors established by the TNM system in 1997 include: Depth of infiltration, degree of differentiation, status of lymph nodes distant metastases. Of the additional factors investigated, only tumor size and hydronephrosis appear to be of prognostic significance. In the scope of molecular markers, the loss of expression of the epithelial cell-cell adhesion molecule E-cadherin signals an unfavorable clinical course. In cases of carcinoma of the urinary bladder without metastases (T2-4,N0,M0), radical cystectomy is the therapy of choice. A preceding neoadjuvant systemic regimen of chemotherapy with three cycles of M-VAC (methotrexate, vinblastine, adriamycin, cisplatin) significantly improves the survival rate. In patients with locally advanced urinary bladder carcinoma, however, adjuvant systemic chemotherapy with M-VAC after cystectomy and lymphadenectomy offers no advantages for survival. Quality of life in patients with metastatic bladder cancer disease is improved by new cytotoxic drugs, i.e. gemcitabine or taxanes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

[Treatment of metastases of urothelial carcinoma. Results of a prospective study of metastases surgery].

We initiated a prospective phase II trial to assess the outcome of complete surgical removal of metastases from bladder cancer with regard to survival and quality of life. Between 1995 and 1999, 70 patients (52 males, 18 females) with a median age of 64 years (range: 30-88 years) were treated with surgical complete resection of bladder cancer metastases. Patients with asymptomatic (n = 19) and symptomatic (n = 51) secondary metastases from bladder cancer refractory to methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) therapy were included. We removed secondary metastases in lymph nodes (63%), peritoneum (10%), skin (3%), bone (3%), lung (15%), and liver (6%) and measured survival and performance scores. The median survival time was 7 months. With a 1-year survival rate of 30% and a 2-year survival rate of 19%, the prognosis is unfavorable independent from the site of metastasis. However, 83% (42 of 51) of the patients with symptomatic secondary metastases did benefit from surgery regarding quality of life, e.g., performance score, and we assessed an improvement in the WHO performance score from 3.3 to 2.1 (p = 0.005). Surgical removal of metastases from bladder cancer refractory to systemic therapy has an impact on quality of life limited to patients with symptomatic disease.

Adult↗
PubMed2001

Impact of surgical resection of bladder cancer metastases refractory to systemic therapy on performance score: a phase II trial.

OBJECTIVES: To assess the outcome of complete surgical removal of metastases from bladder cancer with regard to survival, performance score, and tumor-related symptoms in a prospective Phase II trial. METHODS: Between 1995 and 1999, 70 patients (52 men and 18 women) with a median age of 64 years (range 30 to 88) were treated with complete surgical resection of bladder cancer metastases. Patients with asymptomatic (n = 19) and symptomatic (n = 51) secondary cancer from bladder cancer refractory to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy were included. We removed secondary cancer metastatic to the lymph nodes, peritoneum, skin, bone, lung, and liver and measured the survival, performance score, and tumor-related and therapy-related symptoms. RESULTS: The median survival time was 7 months. With a 1-year survival rate of 30% and a 2-year survival rate of 19%, the prognosis is unfavorable, independent of the site of metastasis. Patients who were asymptomatic complained of a reduced sense of well-being postoperatively (P = 0.007). However, 42 (83%) of the 51 patients with symptomatic secondary cancer did benefit from surgery in terms of tumor-related symptoms and performance score. The World Health Organization performance score changed from 3.3 to 2.1 (P = 0.005). CONCLUSIONS: Surgical removal of metastases from bladder cancer refractory to systemic therapy has an impact on the quality of life of patients with symptomatic disease only. Asymptomatic patients felt worse after surgery and no survival advantage appeared to be gained.

Adult↗
PubMed2001

Does penile size in younger men cause problems in condom use? a prospective measurement of penile dimensions in 111 young and 32 older men.

OBJECTIVES: Young men often complain about problems with condom use, but very little information exists about the influence of men's age on penile dimensions and therefore on possible problems in the use of the most important means of contraception in the young. METHODS: We performed a prospective measurement of penile dimensions in 111 men,18 to 19 years old (group A), and in 32 men, 40 to 68 years old (group B). We measured penile length and width in the flaccid state and after visual and manual self-stimulation in group A and after intracavernous injection of prostaglandin E(1) in group B. RESULTS: The mean flaccid length in group A (8.60 cm) and group B (9.22 cm) was significantly different. The mean erect length in group A (14.48 cm) and group B (14.18 cm) was not significantly different. The mean flaccid width at the base was significantly different between group A (3.08 cm) and group B (2.87cm), but the mean flaccid width at the glans was not (group A, 3.02 cm; group B, 3.01 cm). The mean erect width at the base (group A, 3.95 cm; group B, 3.50 cm) and the erect width of the glans (group A, 3.49 cm; group B, 3.32 cm) were significantly different. CONCLUSIONS: Our assumption that the problems young men experience with condom use may be because of smaller penises could not be proved. To address the problems in condom use in younger men, a larger variety of condom sizes and better information about condom use may be useful.

Adult↗
PubMed2001

A 6-month large-scale study into the safety of tamsulosin.

AIMS: Tamsulosin is an alpha1-adrenoceptor antagonist for the treatment of symptomatic benign prostatic hyperplasia with a tolerability similar to that of placebo in short-term, placebo-controlled studies with limited patient numbers. The present study was designed to test the safety of tamsulosin treatment in a large cohort of men during a prolonged period of time, particularly with regard to comedications. METHODS: A multicentre, open-label phase IIIb study with 1784 patients receiving 0.4 mg o.d. tamsulosin for 6 months was performed according to good clinical practice guidelines. The analysis was performed on an intention-to-treat basis and powered to detect adverse events (AE) occurring in 0.15% of patients with 95% confidence. RESULTS: During a total drug exposure time of 811 patient years, 386 AE were recorded in 253 patients (14.2%; 95% confidence intervals [CI] 12.0-15.2%). Twenty-nine patients suffered 44 serious AE including five fatal events (CI 0.12-0.73%) due to myocardial infarction (n = 3) and to pneumonia and a car accident (one each), but all deaths were judged to be unlikely to be related to study medication. The frequency of AE in patients without any comedication (n = 1095) was 13.0% (CI 11.3-14.9%). In a logistic regression analysis beta-adrenoceptor blockers, converting enzyme inhibitors, antidiabetics and diuretics did not significantly affect the odds ratio for having AE. However, concomitant alpha-adrenoceptor antagonists (a protocol violation) and treatment with verapamil (which also has alpha-adrenoceptor antagonist activity) significantly enhanced the odds ratio for having AE to 3.87 (CI 1.52-9.85) and 3.17 (CI 1.52-6.58), respectively. Minor increases in the odds ratio, which did not reach statistical significance, were also observed for Ca2+ antagonists other than verapamil and for nitrates. CONCLUSIONS: We conclude that tamsulosin has a good safety profile relative to AE rates in the placebo arms of previous studies on tamsulosin even in the presence of most potentially complicating comedications. No major unexpected severe AE were recorded during our 6 months study.

Adrenergic alpha-Antagonists↗
PubMed2001

Male-to-female transsexualism: a technique, results and long-term follow-up in 66 patients.

OBJECTIVE: To report experience of a new surgical technique in male-to-female transsexual patients, the complications, and the functional and psychosocial long-term results. PATIENTS AND METHODS: From April 1995 to July 2000, 66 male patients underwent gender-transforming surgery at our institution and were registered prospectively. The operation should result in a normal appearing introitus, a vaginoplasty allowing for sexual intercourse and a sensitive clitoris. This was achieved by preserving the neurovascular bundle. The glans was transformed into a clitoris, the phallic cylinder used as a vagina and labia were formed from the scrotal folds. RESULTS: Major complications during, immediately and some time after surgery occurred in nine of the 66 patients (14%), including severe wound infections in six, a rectal lesion in three, necrosis of the glans in three and necrosis of the distal urethra in one. Minor complications, e.g. meatal stenosis in seven patients, occurred in 24 (36%) of patients. Ten patients with insufficient penile skin had the phallic cylinder augmented with a free-skin mesh graft, but in three of these patients an ileal augmentation was finally constructed because scarring occurred at the suture line between the penile skin and the augmented graft. A long-term follow-up questionnaire about the functional and psychosocial aspects was completed by 31 patients. More than 90% of the patients were satisfied with the cosmetic result and capacity for orgasm; 58% reported having sexual intercourse. CONCLUSION: Male-to-female surgery can achieve excellent cosmetic and functional results. Although the operative technique is partly standardized, surgery remains challenging because of several possible complications. None of the present patients claimed to regret their decision to undergo gender-transforming surgery.

Adult↗
PubMed2001

Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study.

PURPOSE: This phase 2 trial was designed to assess the efficacy and safety of combination chemotherapy with docetaxel and ifosfamide in previously treated patients with advanced urothelial cancer. MATERIALS AND METHODS: Enrolled in our study were 22 patients with advanced urothelial cancer who failed to respond or had relapse after previous platinum based chemotherapy. Treatment consisted of 60 mg./m.2 docetaxel given during 1 hour and 2.5 gm./m.2 ifosfamide given for 24 hours every 3 weeks with 500 mg. mesna administered intravenously at the start of the ifosfamide infusion, and 4 and 8 hours later. Patients also received premedication with oral dexamethasone. RESULTS: The objective response rate in 20 evaluable patients was 25%, including 4 complete responses (20%) associated with lymph node only recurrence. Disease was stable in 5 cases. At followup 16 patients had died 1 to 11 months (median 4) after the initiation of treatment, while 6 remained alive at 4 to 14 months, including 3 who were continuously disease-free. Treatment was well tolerated. Grades 3 and 4 leukopenia developed in 17% and 4% of the cycles, respectively. Neutropenic sepsis and grade 4 thrombocytopenia developed in 1 case each. Nausea and vomiting were mild to moderate. Other nonhematological toxicities included a hypersensitivity reaction in 1 patient and paresthesias in 2. CONCLUSIONS: The combination of docetaxel and ifosfamide is active in previously treated patients with urothelial cancer, although it appears to be a reasonable treatment option only in those with lymph node dominant recurrence. The mild toxicity underlines the usefulness of the regimen in this setting. Further investigation of the combination in previously untreated patients seems warranted.

Antineoplastic Agents, Alkylating↗
PubMed2001

Clinical usefulness of free PSA in early detection of prostate cancer.

OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) is widely used as an aid in early detection of prostate cancer. Most patients with prostate cancer and a PSA level less than 10.0 ng/ml have early-stage disease. Thus, the detection of prostate cancer in its potentially curable stages requires the use of low PSA cutoffs, inevitably leading to many unnecessary biopsies. The combined use of free PSA and total PSA increases specificity of early detection. To develop risk assessment guidelines and a cutoff value of ratio of free (f) to total (t) PSA with a high predictive value for prostate cancer in men to whom the test would be applied in real life practice, a multicenter early detection trial was initiated. PATIENTS AND METHODS: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years by digital rectal examination (DRE) and prostate-specific antigen with 4.0 ng/ml as cutoff. Data of physical examination were collected by questionnaire. At this time participants were not aware of their PSA values. Suspicious findings were further investigated with sextant biopsy. Prostate volume was determined with transrectal ultrasound (TRUS). Different cutoff levels were correlated to age and detection rate. RESULTS: From1,115 biopsied men, the data of 633 men fulfilled the criteria DRE-negative, TRUS-estimated volume, and PSA 4.0-10.0 ng/ml. In that cohort 91 cancers were detected. Percentage of fPSA was significantly more predictive of cancer than tPSA (p < 0.001). The area under the ROC curve was 0.72 for percent fPSA (% fPSA) and 0.62 for total PSA. The cancer risk nearly doubled using a cutoff of 10% fPSA, the median %PSA level of the detected cancers. A better discrimination of cancer and noncancer especially in the age group above 70 years is possible. Using a cutoff of 16% fPSA increases positive predictive value (PPV) to 25% missing only 4% of cancers. Nearly 45% of the biopsies could be avoided. In the age group 45-69 years, a cutoff of 20% fPSA leads to PPV of 15%, missing 6% of cancers. Unnecessary biopsies could be avoided in 12%. CONCLUSIONS: Using % fPSA in early detection of prostate cancer reduces the number of unnecessary biopsies, especially in men with negative rectal examination in the PSA range of 4.0-10.0 ng/ml. In order to diminish biopsy rate in men 70 years or older a cutoff of 16% fPSA should be used. A cutoff of 20% fPSA in men younger than 70 years is recommended to increase sensitivity in that age group.

Aged↗
PubMed2001

Early detection of prostate cancer in Germany: a study using digital rectal examination and 4.0 ng/ml prostate-specific antigen as cutoff.

OBJECTIVE: While international screening studies for prostate cancer are by now almost reaching the estimated number of recruitments mandatory for the necessary power to investigate an effect on mortality of prostate cancer, no statistical figures on the detection of prostate cancer in Germany - apart from historical data before the use of prostate-specific antigen (PSA) are available. In order to generate a database and to investigate the diagnostic efficacy of the primarily practice-based urological care system, a case finding study designed as a nationwide longitudinal early detection trial was initiated. METHODS: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years of age by digital rectal examination (DRE) and PSA with 4.0 ng/ml as cutoff. Data of family history and physical examination were collected by questionnaire. At this time participants were not aware of their PSA value. PSA was determined in the study center. Indication for sextant biopsy was a PSA value above 4.0 ng/ml or a suspicious lesion on DRE. Any indicated biopsy not performed had to be clarified. In a second questionnaire results of prostate biopsy, treatment and tumor status were documented. RESULTS: The mean age of the study population was 62 years (median 62). The PSA median was 1.4 ng/ml with 82.8% presenting with < 4.0 ng/ml, 12.8% with 4-10 ng/ml and 4.4% with >10 ng/ml. From 1,115 men (47.7%) biopsied, 262 cancers were detected resulting in a detection rate of 23.5%. While 399 men refused biopsy, further investigation was not recommended in 387 men by their urologist, because prostatitis or benign hyperplasia was thought to be the cause for elevated PSA. From the 143 patients undergoing radical prostatectomy, 93 (65%) cancers were organ confined. T(1c) cancers with elevated PSA > 10 ng/ml could be treated with curative intent in 44% only. The positive predictive value (PPV) was estimated to be 16% for DRE alone (14/90), 17% for PSA alone (143/819) and 51% for the combination of both (105/206). In that cohort, use of age-adjusted PSA values and PSA density increased the PPV of PSA testing nonsignificantly. CONCLUSIONS: Significant higher PPV indicated that utilizing a combination of both DRE and PSA is most effective in the early detection of prostate cancer. Unnecessary biopsies can be avoided using either age-adjusted PSA value or PSA density, but the PPV is not significantly changed and potentially curable cancer is missed in up to 25%. Given the substantial variability of the diagnostic approach despite the study design, uniform guidelines are necessary to ensure countrywide sufficient screening.

Aged↗
PubMed2000

Cryptorchidism: fowler-stephens procedure or autotransplantation-a new experimental model.

OBJECTIVES: To investigate the effect of different operative procedures on testicular development in cryptorchidism. METHODS: One hundred ten postpubertal Wistar-WU rats were divided into four groups. Group 1 (35 rats) underwent microsurgical autotransplantation of the right testis with end-to-end anastomosis of the testicular vessels. Group 2 (35 rats) underwent the Fowler-Stephens maneuver with intra-abdominal fixation of the testis. To determine the influence of temperature on testicular development, group 3 (35 rats) underwent the Fowler-Stephens maneuver with scrotal replacement of the testis. Group 4 (5 rats) was a control group without operative treatment. To assess the early and late changes of testicular ischemia and reperfusion, groups 1 to 3 were divided into seven subgroups (5 rats each) with defined postoperative intervals (0.5 hour, 2 hours, 4 hours, 8 hours, 16 hours, 14 days, and 60 days). Testicular development, sperm density, pH value, tissue lactate concentration, and tubular diameter were the parameters used to determine success or failure. RESULTS: After autotransplantation, testicular development exhibited an atrophy rate of less than 50% and a significant decrease in groups 2 and 3 after 60 days. The sperm density was significantly different between groups 2 and 4 (control). The pH value was significantly different after 2 hours in groups 2 and 3. The tissue lactate concentration revealed no significant differences. The tubular diameters were significantly diminished in group 2 after 60 days. CONCLUSIONS: The smaller atrophy rate of the testes suggests that we successfully established a model in the rat to compare the operative outcome after autotransplantation and the Fowler-Stephens procedure in cryptorchidism. The significant difference in the tubular diameters for the intra-abdominally placed testes might be caused by the exposure of the testis to a higher temperature.

Anastomosis, Surgical↗