Biomedical subjects

Christian Stief

Publications and source records attributed to Christian Stief.

8 recordsLinked to original sources

PubMed2006

Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder.

Flat urothelial hyperplasias (FUHs) in patients with papillary bladder tumours frequently show deletions of chromosome 9, suggesting that FUH could be the first neoplastic step in the development of papillary bladder cancer. FGFR3 mutations are frequent in non-invasive papillary tumours with low risk of progression. Our aim was to investigate the frequency of FGFR3 mutations and deletions of chromosomes 9p/q and 8p/q in FUH. Thirty FUH and 9 simultaneous or consecutive tumours were detected by 5-ALA-based photodynamic cystoscopy. DNA was isolated from frozen sections and whole genome amplification was done by I-PEP-PCR, followed by LOH analysis on chromosomes 8p/q and 9p/q. FGFR3 mutations were detected by SNaPshot analysis. LOH analysis on FUH revealed deletions at 9p/q (11/30, 37%) and 8p/q (3/30, 10%). FGFR3 mutations were found in 7/30 FUH (23%). Only 2 FUH showed an FGFR3 mutation without deletions of chromosome 9. In contrast, 6 FUH revealed chromosome 9 deletions but wild type FGFR3 (p = 0.03). These results suggest that chromosome 9 deletions are the earliest genetic alterations in bladder cancer. The detection of FGFR3 mutations in FUH further supports the role of this lesion as precursor of papillary bladder cancer.

Adult↗

PubMed2006

Frequency and prognostic relevance of disseminated tumor cells in bone marrow of patients with metastatic renal cell carcinoma.

BACKGROUND: The prognostic relevance of disseminated cytokeratin-positive (CK+) tumor cells in the bone marrow of patients with different types of carcinoma has been demonstrated in several studies. In this prospective study, the frequency and prognostic value of CK+ tumor cells was investigated in the bone marrow of 55 consecutive patients with metastatic renal cell carcinoma (M1 RCC) in comparison with 256 M0 RCC patients from a previous study. METHODS: Aspiration of bone marrow from the anterior iliac crest was performed immediately before tumor resection in RCC patients. Cytospins were made and stained by immunocytochemistry using the APAAP (alkaline phosphatase-antialkaline phosphatase) protocol and monoclonal antibodies CK2 and A45-B/B3. Twenty-seven patients with no evidence of any malignant disease served as a control group. RESULTS: CK+ tumor cells were detected in 42% (23 of 55 patients) of the M1 patients and 25% (63 of 256 patients) of the M0 patients (P <.01). No CK+ cells (0 of 27 patients) were detected in the control group. In the M1 group, CK- patients demonstrated a trend toward a better outcome compared with CK+ patients (log-rank test, P = .19). This difference was significant when applying a higher threshold (0-2 CK+ cells vs. > or = 3 CK+ cells; P <.05). On multivariate analysis, the detection of > or = 3 CK+ cells in the bone marrow was found to be an independent prognostic factor (P <.001). CONCLUSIONS: The results of the current study indicate that disseminated CK+ cells play a role in the biology of tumor spread of RCC, and that their immunocytochemical detection can be useful in assessing the prognosis of patients with M1 disease.

Adult↗

PubMed2006

Symphysitis following transrectal biopsy of the prostate.

Transrectal ultrasound-guided needle biopsy of the prostate is a widely accepted technique to obtain prostatic tissue for histological examination. Severe complications are rarely seen. We report a case of symphysitis causing hospitalization and severe pain and discomfort of the patient. Possible etiologic factors are traumatic osseous lesions and transport of rectal bacteria to the periosseous region. Especially in small prostates, care should be taken to avoid this condition. Prolonged perioperative antibiotic prophylaxis is mandatory.

Anti-Bacterial Agents↗

PubMed2006

Integral spectrophotometric analysis of 5-aminolaevulinic acid-induced fluorescence cytology of the urinary bladder.

OBJECTIVE: To evaluate whether tumour cells can be detected in bladder lavage fluid samples by an objective spectrofluorometric method, as 5-aminolaevulinic acid (ALA)-induced fluorescence endoscopy (AFE) and cytology are promising valuable tools for detecting transitional cell carcinoma of the urinary bladder (TCCB). MATERIALS AND METHODS: After instilling ALA into the urinary bladder, lavage samples were collected and their sediments analysed spectroscopically under blue excitation at approximately 400 nm wavelength. During AFE, biopsies were taken. From 62 cases, 24 patients had a histologically confirmed TCCB (group A), 28 had a history of TCCB but no evidence of disease (group B) and 10 were negative for TCCB (group C). RESULTS: Lavage sediments of all patients fluoresced in the green spectral range, typical of cellular autofluorescence. Sediments of all patients of group A caused red fluorescence peaking at 635 nm, indicating protoporphyrin IX (PPIX). The PPIX signals derived from bleaching spectra were significantly different between benign and malignant findings (P = 0.001). There was another red fluorescence peak at approximately 620 nm; in 19 cases its intensity exceeded the intensity of the PPIX signal. CONCLUSIONS: Spectrofluorometric analysis of lavage sample sediments can be used to detect tumour-associated red fluorescence of PPIX in TCCB. Immediate significant and objective measurements are possible, which could be further automated for the rapid diagnosis of TCCB.

Adult↗

PubMed2005

Diagnosis of urothelial carcinoma of the bladder using fluorescence endoscopy.

Bladder cancer is a frequent disease and represents the second most common genitourinary neoplasm. Although many aspects of the management of superficial bladder cancer are now well established, significant challenges remain, which influences patient outcome. Early detection and treatment of recurrent disease is required to optimize bladder preservation, reduce patient morbidity, and increase quality of life and survival. Fluorescence endoscopy, often referred to as 'photodynamic diagnosis' (PDD), with intravesical application of photosensitizing agents, has been developed to enhance the early detection of bladder cancer. There is growing evidence that PDD using 5-aminolaevulinic acid (ALA), hexyl-ALA ester or hypericin enhances the detection of bladder cancer, particularly of high-grade flat lesions. Furthermore, transurethral resection of bladder tumour under fluorescence guidance reduces the risk of recurrent tumours. However, the impact on the progression of disease remains unclear and must be investigated in prospective randomized trials.

Aminolevulinic Acid↗

PubMed2004

Pharmacotherapy for erectile dysfunction.

INTRODUCTION: Advances in understanding of the biochemistry and physiology of penile erection have led to breakthroughs in pharmacotherapy of erectile dysfunction. AIM: To provide recommendations/guidelines concerning state-of-the-art knowledge for the putative molecular and cellular mechanisms of action of centrally and peripherally acting drugs currently utilized in pharmacotherapy of erectile dysfunction. METHODS: An international consultation in collaboration with the major urology and sexual medicine associations assembled over 200 multidisciplinary experts from 60 countries into 17 committees. Committee members established specific objectives and scopes for various male and female sexual medicine topics. The recommendations concerning state-of-the-art knowledge in the respective sexual medicine topic represent the opinion of experts from five continents developed in a process over a two-year period. Concerning the Pharmacotherapy for Erectile Dysfunction Committee there were 25 experts from 10 countries. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation and debate. RESULTS: Selective and potent oral PDE5 inhibitors have significantly more affinity than cGMP and form broader molecular interactions with multiple amino acids, thereby blocking access to cGMP in the catalytic sites of the PDE5 enzyme. PDE5 inhibitors, which vary as to biochemical potency, selectivity and pharmacokinetics, lead to cGMP elevation and relaxation facilitation of penile corpus cavernosum smooth muscle cells following sexual stimulation. Various centrally acting drugs influence sexual behaviour. In particular, the dopaminergic substance apomorphine is a central enhancer that acts in the paraventricular nucleus of the hypothalamus as a dopamine (D2) receptor agonist, induces and increases penile erection responses via disinhibition, following sexual stimulation. CONCLUSIONS: There is a need for more research in the pharmacotherapeutic development of central and peripheral agents for safe and effective erectile dysfunction treatment.

Apomorphine↗

PubMed2003

ACE gene I/D and NOS3 G894T polymorphisms and response to sildenafil in men with erectile dysfunction.

OBJECTIVES: To examine a potential association between the response to the phosphodiesterase-5 inhibitor sildenafil and angiotensin-converting enzyme (ACE), as well as NOS3 G894T genotypes in patients with erectile dysfunction (ED). An insertion/deletion (I/D) polymorphism in the gene encoding the ACE and a single nucleotide exchange polymorphism (G894T) in the gene NOS3 encoding endothelial nitric oxide synthase have been associated with cardiovascular disorders. METHODS: The response to sildenafil in 113 men with ED was monitored according to the patients' diaries. ACE and NOS3 genotypes were determined in patients with ED and in 108 healthy male blood donors. RESULTS: Genotype distributions of ACE and NOS3 polymorphisms in the patient group were similar to those of the healthy control group. Analysis of the response to sildenafil revealed that 15 of 20 individuals homozygous for the ACE II genotype showed a positive erectile response after sildenafil use and only 46 of 93 D allele (combined DD and DI genotypes) carriers had a positive response (positive erectile response, odds ratio 3.07, 95% confidence interval 1.03 to 9.13, P = 0.04; chi-square test). Analysis of NOS3 genotypes revealed that 30 of 52 individuals homozygous for the G894 allele had a sufficient response to sildenafil and only 4 of 12 patients homozygous for the 894T allele had a sufficient erection. CONCLUSIONS: It appears that patients with elevated ACE serum concentrations, as associated with the D allele of the ACE I/D polymorphism, are less likely to respond to sildenafil.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2002

Thirteen-year, long-term efficacy of interferon 2alpha and interleukin 2-based home therapy in patients with advanced renal cell carcinoma.

BACKGROUND: The goal of the current report was to demonstrate the long-term efficacy of outpatient subcutaneous (sc) interferon alpha (IFN-alpha) and sc interleukin 2 (IL-2)-based combination regimens in patients with metastatic renal cell carcinoma. METHODS: In three consecutive clinical trials, 443 patients received combined sc IFN-alpha and sc IL-2 (n = 97 patients); combined sc IFN-alpha, sc IL-2, and intravenous (iv) 5-fluorouracil (5-FU) (n = 260 patients); or combined sc IFN-alpha, sc IL-2, and iv 5-FU with oral 13cis-retinoic acid (n = 86 patients). RESULTS: The median overall survival was 21+ months. The 2-year, 5-year, and 13-year survival rates were calculated at 45.26%, 15.96%, and 8.96%, respectively. The median time to disease progression was 6 months. The 2-year, 5-year, and 13-year progression free survival rates were 17.84%, 9.54%, and 9.20%, respectively. CONCLUSIONS: The current data suggest that combined outpatient sc IFN-alpha and sc IL-2, according to the Atzpodien regimen, achieves long-term survival benefits in a subset of patients with metastatic renal cell carcinoma, both with and without 13-cis-retinoic acid and/or 5-fluorouracil.

Administration, Oral↗