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Biomedical subjects

M Oelke

Publications and source records attributed to M Oelke.

At least 19 recordsLinked to original sources

[Gynaecomastia and male infertility as symptoms of a nonpalpable Leydig cell tumour].

A 35-year-old man and his partner were referred for intracytoplasmic sperm injection treatment (ICSI) because of secondary infertility due to severe oligoasthenoteratospermia. Three years earlier he had presented elsewhere with left unilateral gynaecomastia. A hypertrophic mammary gland had been excised one year later. Histopathological investigation showed benign hypertrophy. One year later he developed gynaecomastia on the other side. Physical examination and incomplete hormonal screening showed no abnormalities. The couple were referred to our tertiary clinic for ICSI treatment. The patient still had unilateral gynaecomastia. Hormonal screening showed not only severe oligoasthenoteratospermia, but also an elevated serum oestrogen level. Scrotal ultrasound revealed a 17 mm mass in his right testicle. Subsequently unilateral orchidectomy was performed. Histology showed a benign Leydig cell tumour for which no further therapy was required. Four months after surgery the gynaecomastia diminished, oestrogen levels became normal and improvement in semen parameters followed. Patients with severe male infertility or gynaecomastia are at a higher risk of developing a testicular neoplasm. Besides history taking, physical examination of breasts and testicles, hormonal screening and scrotal sonography should be performed as some testicular neoplasms are not apparent on palpation.

Adult↗

[Anticholinergics for overactive bladder: does subtype selectivity play a role?].

Anticholinergics act in the treatment of overactive bladder by blocking muscarinic receptors of which five subtypes exist. Their desired effects occur via M(3) receptors, but a role for M(2) receptors is being discussed. Adverse effects such as dry mouth and constipation occur also via M(3) receptors, but M(2) and M(1) receptors can mediate side effects in the heart or on cognitive function, respectively. Therefore, an M(3)-selective drug such as darifenacin could theoretically be less effective but also have fewer cardiac or central nervous side effects. However, the limited available clinical data do not support a smaller efficacy or better general tolerability. The lack of adverse effects on cognitive function is well documented for darifenacin, but it cannot yet be determined definitively whether this discriminates it from other modern anticholinergics.

Benzofurans↗

Safety and tolerability of duloxetine in women with stress urinary incontinence.

BACKGROUND: The serotonin/noradrenaline uptake inhibitor duloxetine has been shown to be effective in the medical treatment of stress urinary incontinence (SUI) in women. AIM: To review the safety and tolerability of duloxetine with SUI. METHODS: A systematic Medline search for the key word "duloxetine" was performed, and abstracts from recent international gynaecological and urological meetings were also considered. RESULTS: Various unpleasant adverse effects exist, among which nausea is the most frequent, but is mild to moderate and transient in most cases. Dose escalation upon initiation of treatment improves the tolerability of duloxetine. The use of duloxetine appears safe as it lacks the cardiovascular adverse effects of older amine reuptake inhibitors. CONCLUSIONS: Duloxetine has an acceptable safety profile. Dose escalation combined with patient counselling on the intensity and transient nature of adverse effects may help to further improve the benefit/tolerability ratio of duloxetine in the treatment of SUI.

Adrenergic Uptake Inhibitors↗

[Medical therapy of urinary incontinence].

Urinary incontinence has a high prevalence in both men and women. Women suffer predominantly from stress urinary incontinence and men from urge incontinence. Other types of incontinence are less frequent. Stress urinary incontinence is caused by an insufficient urethral closure mechanism and urge incontinence by uninhibited detrusor contractions. Medical treatment is beside other conservative options and operations only one part of the treatment strategy in incontinence. Duloxetine, a serotonine-norepinephrine reuptake inhibitor, is used to treat stress urinary incontinence, can increase activity of the external urethral sphincter and is able to reduce incontinence episodes in up to 64%. Antagonists of muscarinic receptors can reduce urgency, frequency and urge incontinence as well as increase bladder capacity significantly. In Germany, trospium chloride, tolterodine, solifenacin, oxybutynin and propiverine are available to treat urge incontinence. Efficacy of these agents are comparable. However, tolerability is different and side effects, especially dry mouth, often limit their use. None of the agents show ideal efficacy or tolerability in all patients and, therefore, new agents and formulations are currently under clinical investigation.

Cholinergic Antagonists↗

[The relevance of urinary bladder filling in suprapubic bladder catheterization].

Suprapubic punction of the urinary bladder (cystostomy) may cause typical, sometimes lethal injuries of pelvic organs especially in cases of an insufficient bladder filling. Some of these cases were described in the literature of legal medicine. To verify the importance of the cranial displacement of the vulnerable intestine by a filled bladder, the distances between the upper end of the symphysis and apex vesicae were measured in 76 forensic autopsies in situ and correlated with the filling volume of the urinary bladder. 69,2% of cases with a bladder filling volume up to 200 ml showed a suprapubic distance of only < or =4 cm. However, this distance collides with the preferred clinical intervention point, 2 fingers above the symphysis. In all cases with a bladder filling volume > or =300 ml, the distances were > or =5 cm. Based on our measurements, we recommend a preoperative bladder filling of > or =300 ml for an uncomplicated insertion of a suprapubic catheter.

Cadaver↗

[The prevalence of sexual problems in female medical students].

Female sexual dysfunction and even female sexual function are widely unknown. We therefore evaluated the sexual behaviour of younger and older women using a questionnaire. A total of 998 young women entered the study at Hannover Medical school. They were between 19 and 43 years old (median 24 years), and 64% answered the questionnaire. A total of 97.1% of the female students were heterosexual, 1.6% were lesbians and 1.3% were bisexual. Lack of sexual intercourse in the previous month was recorded by 21.1%, while 21.3% recorded intercourse 1-3 times a month, 46.8% 1-3 times a week and 5.5% daily. Adverse reactions to sexual situations were reported by 25% of the women, 20.5% had a negative perception for special partners or circumstances. Some 55% of the evaluated women were satisfied with their sexual life in the last month, 20% were fairly satisfied and 21% were un-satisfied. This study of a selected population of medical students shows a wide variety of sexual problems with a high prevalence of different disorders.

Adult↗

[Impact of tumor size on long-term survival of patients with organ-confined renal cell cancer].

PURPOSE: As a result of the observation that the potential biological aggressiveness of even early stage renal cell cancer (RCC) strongly correlates with tumor size, the 5th edition of the TNM system (1997), which classifies all renal tumors up to a maximum diameter of 7 cm as T1, was modified in the current classification to distinguish T1a and T1b tumors based on a cut-off of 4 cm. Only a few larger investigations supporting this cut-off are available in the literature and these are based on univariate statistical analysis. To determine whether this cut-off best reflects the correlation between aggressive potential and tumor size and thus differentiates patients at low or high risk of progression, this investigation was performed using both univariate and multivariate statistical analysis. MATERIALS AND METHODS: Between 1981 and 2000, a total of 652 patients underwent tumor nephrectomy for renal cell carcinoma. Of these, the 243 patients with local RCC not extending beyond the renal capsule were subjected to univariate (log rank test) and multivariate (Cox regression model) statistical analysis. RESULTS: It became evident that, while during univariate analysis the prognostic calue of a cut-off size of 4 cm was confirmed, multivariate analysis identified the highest relative risk of cause-specific death (2.93) in those patients with tumors larger than 5 cm maximum diameter. CONCLUSIONS: The 5 cm cut-off thus appears to best determine the clinical prognosis for patients undergoing tumor nephrectomy for early stage renal call cancer. Taking this into consideration, the present study clearly demonstrates the reed for a multivariate statistical approach when the current modification of the TNM classification system is critically reevaluated.

Adult↗

[Drug therapy of benign prostatic hyperplasia syndrome with alpha 1-receptor blockers. Basic principles and clinical results].

This article reviews the structure and function of the sympathetic nervous system controlling the myogenic tone of the bladder outlet. Therefore, the sympathetic nervous system is partially responsible for urinary outflow resistance. The alpha 1-adrenoceptor antagonists alfuzosin, doxazosin, tamsulosin, or terazosin are able to reduce bladder outflow resistance, which leads to significant relief of LUTS (20-65%) and improvement of urinary flow (1-4.3 ml/s) in patients with symptomatic BPH. Alpha 1-blocker treatment works irrespective of the severity of symptoms, degree of subvesical obstruction, or prostate size. A significant reduction of residual urine was observed only occasionally, but at least alfuzosin is able to reduce the incidence of acute urinary retention. This article presents the results of 39 randomized, placebo-controlled trials with 14,924 patients as well as trials with alpha 1-blockers and plant extracts or finasteride. The results of these trials indicate that all alpha 1-blockers are equally effective. However, tolerability of alfuzosin or tamsulosin is superior to doxazosin or terazosin. Furthermore, treatment of hypertension with doxazosin or terazosin is no longer recommended due to the increased frequency of cardiovascular side effects seen in the ALLHAT Study. As alpha 1-blockers can relieve symptoms and improve urinary flow more effectively than plant extracts or finasteride, alpha 1-blockers are the treatment of first choice in patients with symptomatic BPH without or with a minor degree of subvesical obstruction.

Adrenergic alpha-1 Receptor Antagonists↗

Induction and clonal expansion of tumor-specific cytotoxic T lymphocytes from renal cell carcinoma patients after stimulation with autologous dendritic cells loaded with tumor cells.

Melanoma and renal cell carcinoma (RCC) are considered to be the most immunogenic tumors in humans. To generate conditions to induce primary T-cell responses against RCC and to allow further expansion of tumor-specific cytotoxic T lymphocytes (CTL) for adoptive transfer, peripheral blood mononuclear cells from RCC patients were stimulated with primary autologous tumor cells or monocyte-derived dendritic cells (DC) loaded with either tumor lysate (TU-LY) or apoptotic tumor cells (TU-AP). Whereas repetitive stimulation (4x) with tumor cells alone induced a predominant population of CD3(-) natural killer cells, 4 weeks of stimulation with tumor-loaded DC favored induction and expansion of CD4+ T cells (>80%). However, 2 weekly stimulation cycles with tumor-loaded DC followed by restimulation with autologous irradiated tumor cells alone were optimal for induction of tumor-specific CTL responses in vitro. Using these culture conditions a marked increase of CD4+ T cells was observed during the first 2 weeks of stimulation with tumor-loaded DC. Subsequent restimulation with autologous tumor cells alone gave rise to 500-fold expansion of CD8+ T cells. These CD8+ T cells were shown to exhibit strong major histocompatibility complex class I-restricted cytotoxic activity against the autologous tumor. Comparison of TU-LY and TU-AP as a source of tumor antigen for loading DC did not show any difference in stimulating tumor-specific CTL. Length pattern analysis of the complementary determining region 3 (CDR3) of the T-cell receptor Vbeta chain revealed expansion of oligoclonal CTL populations with outgrowth of 1 or 2 clones after prolonged stimulation with autologous tumor cells. Our study demonstrated an efficient method for generating tumor-specific CTL in vitro that may be used to identify tumor cell antigens or that can be expanded for adoptive T-cell transfer in tumor immunotherapy.

ATP-Binding Cassette Transporters↗

Trospium chloride--an effective drug in the treatment of overactive bladder and detrusor hyperreflexia.

Trospium chloride (TCL), a quaternary ammonium derivative of nortropanol, has been evaluated in a number of clinical and pharmacological studies. Selected pharmacological and clinical pharmacokinetic data are discussed as providing a basis for a better interpretation and understanding of the clinical trial results. An overview of the results of 20 clinical trials and post-marketing surveillance studies including more than 10000 patients is presented.

Benzilates↗

Functional characterization of CD8(+) antigen-specific cytotoxic T lymphocytes after enrichment based on cytokine secretion: comparison with the MHC-tetramer technology.

Cell therapy with antigen-specific T cells holds promise for various diseases including cancer and viral infections. The powerful enrichment procedure based on major histocompatibility complex (MHC)-tetramers, however, is of limited applicability so far. Therefore, the recently developed cell surface affinity matrix technology that allows direct identification and enrichment of life antigen-specific T cells based on cytokine secretion was evaluated in this respect. To this end, CD8(+) T cells directed against the HLA-A(*)0201-restricted melanoma-associated peptide Melan-A (aa26-35) were generated by combining stimulation of peptide-pulsed autologous dendritic cells (DC) with antigen-independent expansion with anti-CD3/anti-CD28 monoclonal antibodies (MoAb). Antigen-specific cytotoxic T lymphocyte (CTL) were detected based on stimulation-induced interferon (IFN)-gamma and interleukin (IL)-4 secretion and enriched > 100-fold using the cell surface affinity matrix technology. The resulting IFN-gamma- and IL-4-secreting CTL lines contained > 80% and > 70% cytokine positive T cells, respectively. They exhibited a cytotoxic activity against Melan-A expressing target cells that was significantly higher as compared to nonpurified CTL. Direct staining of enriched CTL with HLA-A2-Melan-A-tetramers revealed a high correlation between the results obtained from the cell surface affinity matrix technology and those obtained from tetrameric complexes. Altogether, our study demonstrates that cytokine-driven enrichment based on the cell surface affinity matrix technology enables selective isolation of functionally active antigen-specific CTL that may be used for an adoptive T cell transfer in immunotherapy.

Antigens, Neoplasm↗

Historical aspects of the treatment of urinary incontinence.

Ancient reports on urinary incontinence are rather rare and mainly address cases of extraurethral incontinence, e.g. due to a fistula acquired during childbirth or overflow incontinence, e.g. in males with urinary retention or after spinal cord injury. In modern times several authors dealt with the problem of postoperative incontinence after perineal lithotomy. Surgical techniques for the cure of urinary incontinence were not introduced before the 19th century. First this was limited to fistula repair but at the turn of the century new procedures for stress incontinence were introduced and became standard clinical procedures. Other modern techniques, e.g. artificial sphincters or electrostimulation, were alternatives developed in urology during the second half of our century. This article from the history of medicine outlines early reports on urinary incontinence and reveals a more detailed review of the different treatment options including conservative therapies, incontinence devices, electrotherapy and surgical procedures, including injection therapies and artificial sphincters.

Equipment Design↗

Generation and purification of CD8+ melan-A-specific cytotoxic T lymphocytes for adoptive transfer in tumor immunotherapy.

Tumor antigens that might serve as potential targets for adoptive T-cell therapy have been defined in different tumor entities, especially in malignant melanoma. To generate conditions to induce primary T-cell responses against different HLA-A*0201-restricted melanoma peptides and to allow further expansion of peptide-specific T cells for adoptive transfer, CD8+-purified T cells from healthy donors were stimulated with Melan-A-pulsed autologous dendritic cells. Dendritic cells were generated in vitro from monocytes with granulocyte macrophage colony-stimulating factor, interleukin-4, and transforming growth factor-beta1. After 3-4 weekly stimulation cycles with Melan-A-pulsed DCs, we were able to induce a strong peptide-specific CTL response in vitro. MHC-peptide tetramer staining revealed a frequency of up to 3.5% CD8+/Melan-A+ T cells. Additional antigen-independent expansion with anti-CD3/anti-CD28 monoclonal antibodies together with interleukin-2 gave rise to 600-fold expansion of CD8+ CTLs that maintained Melan-A specificity and were able to efficiently lyse Melan-A-expressing melanoma cells. To enrich antigen-specific T cells in vitro, we used a recently established technology for analysis and sorting of live cells according to secreted cytokines. In the present study, we demonstrated that Melan-A-specific T cells can be purified by magnetic separation according to secreted IFN-gamma. These cells revealed a very potent monospecific CTL response, even at low E:T ratios, against Melan-A-pulsed and Melan-A-expressing target cells. Altogether, our study demonstrated that we have developed an efficient method for generating large numbers of peptide-specific T cells in vitro that may be used for adoptive T-cell transfer in tumor immunotherapy.

Adoptive Transfer↗

Petroleum jelly is an ideal contact medium for pain reduction and successful treatment with extracorporeal shock wave lithotripsy.

PURPOSE: Various minimally invasive approaches to reduce pain during extracorporeal shock wave lithotripsy (ESWL) have been described. We compared petroleum jelly (Vaselinet) and ultrasound gel in vitro as a contact medium based on the stone fragmentation rate. The analgesic effect of cutaneous petroleum jelly was tested against eutectic mixture of local anesthesia. We also evaluated the outcome of ESWL in a large group of patients treated with petroleum jelly. MATERIALS AND METHODS: In vitro 3 artificial stones were completely fragmented with a MFL 5000* lithotriptor using petroleum jelly or ultrasound gel as a contact medium. A total of 110 patients (group 1) received petroleum jelly before treatment with the same lithotriptor. After retrospective analysis of group 1 we matched 32 patients (group 2) receiving cutaneous eutectic mixture of local anesthesia. Because of the favorable results with petroleum jelly, we used it in another 148 patients, for a total of 258 patients (group V). Treatment dependent pain was scored using a questionnaire as 1--no, 2--minor, 3--tolerable and 4--intolerable. ESWL without additional analgesics had a pain score of 1 to 3. RESULTS: In vitro petroleum jelly had a superior fragmentation rate compared to ultrasound gel. Our long-term experience with the lithotriptor indicated that only 30% of patients required no additional analgesics with cutaneous ultrasound gel. In contrast, no additional analgesics were needed in only 38% of group 2 compared to 81.8% of group V. The stone fragmentation rate did not differ statistically between groups. CONCLUSIONS: Cutaneous petroleum jelly offers a noninvasive, highly effective, inexpensive treatment modality with no side effects and significant reduction in pain. This ointment is our contact medium of choice.

Anesthetics, Local↗

[Percutaneous bladder neck suspension with osseous fixation. Surgical technique and initial results in 26 patients].

A modification of percutaneous needle suspension using a bone anchor system for fixation of the suture to the pubic bone is presented. After a follow-up of 3-11 months (mean 6,8) the postoperative success-rate in 26 patients is 73.1% (n = 19). A removal of bone anchor and suture was necessary in 2 patients because of bacterial infection or soft tissue granuloma. We can not reinforce the very optimistic results of the first reports published in the recent years. Therefore it is still questionable whether percutaneous needle bladder neck suspension should be a first line procedure for the treatment of female urinary stress incontinence.

Adult↗

Does bone anchor fixation improve the outcome of percutaneous bladder neck suspension in female stress urinary incontinence?

OBJECTIVE: To evaluate the outcome of a new modification of percutaneous needle suspension, using a bone anchor system for fixing the suture at the public bone, and to compare the results with those published previously. PATIENTS AND METHODS: From March 1996, 37 patients with stress urinary incontinence (> 2 years) were treated using a bone anchor system. On each side the suture was attached to the pubocervical fascia and the vaginal wall via a broad 'Z'-stitch. A urodynamic investigation performed preoperatively in all patients confirmed stress incontinence and excluded detrusor instability. The outcome was assessed by either by a clinical follow-up investigation or using a standardized questionnaire, over a mean follow-up of 11 months (range 6-18). RESULTS: In the 37 patients, the procedure was successful in 25 (68%), with 16 (43%) of the patients completely dry and nine (24%) significantly improved. Removal of the bone anchor and suture was necessary in two patients, because of unilateral bacterial infection in one and a bilateral soft tissue granuloma in the other. One bone anchor became dislocated in a third patient. In two cases where the treatment failed, new detrusor instability was documented urodynamically. Minor complications were prolonged wound pain in 10 (26%) and transient urinary retention or residual urine in 12 patients (32%). CONCLUSION: The poor success rate in the study corresponds with the long-term results of conventional or modified needle suspension procedures and does not reinforce the optimistic results of bone anchoring published recently. Because of the poorer long-term results from percutaneous needle suspension than from other techniques of open retropubic bladder neck suspension, it remains questionable whether percutaneous needle suspension should be considered a first-line procedure for the treatment of female stress urinary incontinence.

Adult↗