[Non-Antibiotic Strategies to Prevent the Recurrence of Uncomplicated Urinary Tract Infections in Women]. / Nicht antibiotische Strategien zur Rezidivprophylaxe von unkomplizierten Harnwegsinfektionen der Frau.

The aim of all medical treatment is "primum nihil nocere" ("First, do no harm").Restoring the integrity of intestinal microbiota and optimising the immune response in recurrent infections, especially in the urinary tract, are treatment alternatives which are closer to this target than the usual focus on antibiotic prevention of recurrence.In the future, antibiotics will continue to be recommended for the prevention of urinary tract infections on a case-by-case basis. However, the problems of an excessive use of antibiotics, e. g. resistance and long-term interference with intestinal microbiota, are forcing us to search for alternatives. The use of probiotics alone or in combination with immunotherapeutics, or the sole use of immunotherapeutics, are important treatment options, which are already routinely available in clinical practice. These therapies are focused on the pathomechanism of an infection and tackle the root cause of the problem. Phytotherapeutics or small molecules like mannose, which restricts the adherence of bacteria to the urothelium, are complementary approaches.The EAU guidelines recommend the following treatments for the long-term prevention of urinary tract infections:Oral and parenteral immunostimulants (StroVac(®)), local estrogen replacement and administration of Lactobacillus rhamnosus and Lactobacillus reuteri.

[Prophylaxis of recurrent urinary tract infections]. / Prophylaxe rezidivierender Harnwegsinfektionen.

BACKGROUND: Recurrent urinary tract infections (rUTI), defined as ≥ 3 UTIs per year, mostly affect young and postmenopausal women. Treatable predisposing factors are rare. METHODS: General recommendations to reduce rUTIs lower the recurrence rate by up to approximately two thirds. Continuous long-term prophylaxis (LP) with low dose antibiotics or single postcoital doses can reduce the recurrence rate of rUTIs to as low as 5%. According to the European Association of Urology guidelines nitrofurantoin, trimethoprim and co-trimoxazole are the first-line drugs and cephalosporins or fluoroquinolones should be restricted to specific indications. Oral and parenteral immunotherapy were found to be effective in several controlled studies for prevention of rUTIs and can be combined with acute antibiotic therapy. CONCLUSIONS: Vaginal prophylaxis with estriol has proven its positive effect without serious gynecological side effects and there is also increasing evidence that cranberries prevent rUTIs but the exact mode of this therapy remains to be defined. There are also other promising modalities, such as phytotherapeutics, mannose, urine acidification, influencing bacterial intestinal and vaginal flora and the general immune response by e.g. acupuncture and inpatient rehabilitation, the therapeutic value of which still has to be proven.

Prevention of recurrent urinary tract infections.

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year or ≥2 UTI/half year. In contrast, rUTI is rare in healthy men. On the other hand, rUTI are frequently found in female and male patients with complicating urological factors, e.g. urinary catheters, infection stones. Remediable predisposing factors in uncomplicated rUTI in women are rare. In complicated rUTI the success depends mainly on the possibility to eliminate or at leastimprove the complicating risk factors. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial "fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. Due to possible adverse events and the concern of selecting resistant pathogens, according to the guidelines of the European Association of Urology antimicrobial prophylaxis should be considered only after counselling, behavioural modification and non-antimicrobial measures have been attempted. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberry products, specific plant combinations or probiotics. The prophylaxis of catheter-associated UTI should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.

[Primary and secondary prevention of urinary tract infections]. / Primär- und Sekundärprävention von Harnwegsinfektionen.

Urinary tract infections (UTI) are among the most frequent bacterial infections in the community and health care setting. Mostly young and, to some extent, postmenopausal women are affected by recurrent UTI (rUTI) defined as ≥3 UTI/year. On the other hand rUTI are frequently found in patients with complicating urological factors, e.g. urinary catheters. Modifiable predisposing factors in uncomplicated rUTI in women are rare. Continuous antibiotic prophylaxis or postcoital prophylaxis, if there is close correlation with sexual intercourse, are most effective to prevent rUTI. Nitrofurantoin, trimethoprim (or cotrimoxazole), and fosfomycin trometamol are available as first-line drugs. Oral cephalosporins and quinolones should be restricted to specific indications. Antibiotic prophylaxis reduces the number of uropathogens in the gut and/or vaginal flora and reduces bacterial"fitness". Given the correct indication, the recurrence rate of rUTI can be reduced by about 90%. In postmenopausal patients vaginal substitution of oestriol should be started first. Oral or parenteral immunoprophylaxis is another option in patients with rUTI. Other possibilities with varying scientific evidence are prophylaxis with cranberries or probiotics. The prophylaxis of catheter-associated UTI or asymptomatic bacteriuria should employ strategies which result in a reduction of frequency and duration of catheter drainage of the urinary tract. The currently available catheter materials have only little influence on reducing catheter-associated rUTI.

[Capillary electrophoresis coupled to mass spectrometry for proteome analysis. An innovative diagnostic method for prostate and bladder cancer]. / Kapillarelektrophorese gekoppelte Massenspektrometrie zur Proteomanalyse. Eine innovative diagnostische Methode bei Prostata- und Blasenkrebs.

We developed a proteomics-based technology for the non-invasive detection of urothelial and prostate carcinoma. Using capillary electrophoresis coupled to mass spectrometry, disease-specific changes in the urinary proteome were detected and subsequently relevant polypeptides were employed as disease-specific biomarkers. Here we report the results of various studies including approximately 1,000 patients with different diseases and healthy volunteers. The results of these studies revealed that prostate and urothelial carcinoma can be detected by using disease-specific polypeptide patterns. Preliminary results also indicate that the tumour stage of an urothelial carcinoma can be estimated by this approach. In conclusion, this new and non-invasive application might help to improve the diagnostic methods already available.

[European Association of Urology guidelines on urinary and male genital tract infections]. / Synoptische Leitlinie der sexuell übertragbaren Erkrankungen (STD) mit Primärsymptomen im männlichen Genitale (S1). Leitinien der Deutschen Gesellschaft für Urologie.

Today, the classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis, chancroid and inguinal granuloma, only account for a small proportion of all known sexually transmitted diseases (STDs). Other bacteria and viruses as well as yeasts, protozoa and epizoa must also be regarded as causative organisms of STD. Taken together, all sexually transmitted infections comprise more than 30 relevant STD pathogens. However, not all pathogens that can be sexually transmitted manifest diseases in the genitals and not all infections of the genitals are exclusively sexually transmitted. Concise information and tables summarising the diagnostic and therapeutic management of STDs in the field of urology allow a synoptic overview, and are in agreement with the recent international guidelines of other specialist areas. Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and recommended regimens are presented.

Immunostimulation by bacterial components: II. Efficacy studies and meta-analysis of the bacterial extract OM-89.

The bacterial extract OM-89 (Uro-Vaxom) consisting of immunostimulating components derived from 18 Escherichia coli strains is used for the treatment of recurrent urinary tract infections. We investigated in the mouse the immunogenicity of the bacterial extract after oral administration. After repeated administration of OM-89, a specific serum IgG and IgA response against a number of bacterial strains was obtained. Supernatants of cell cultures prepared from the urogenital tract of immunized mice also contained increased levels of strain specific IgG and IgA. We could show a bias towards a Th1 type immune response as indicated by increased IgG2a levels in sera, and increased IFNgamma levels in supernatants of spleen cells. These findings may contribute to an understanding of the therapeutic effect of Uro-Vaxom: the metaanalysis of several clinical studies confirmed that Uro-Vaxom constitutes an effective prophylaxis for urinary tract infections.

Oxaceprol is as effective as diclofenac in the therapy of osteoarthritis of the knee and hip.

In this multicentre (five centres in Germany), randomised, double-blind, comparative study, 150 patients with painful degenerative joint disease according to EULAR criteria received either oxaceprol (200 mg three times daily) or diclofenac (25 mg three times daily) for 20 days. Joint function, the primary variable, assessed according to Lequesne's indices, improved equally in both treatment groups to a clinically relevant degree. Joint mobility improved by approximately 60% in both groups. By the end of therapy in both groups, the period of pain-free walking time had more than doubled and subjectively evaluated pain perception (VAS) was reduced by almost 50% without any significant differences between the treatments. The incidence of adverse drug reactions was similar in both groups but oxaceprol induced milder symptoms. Oxaceprol is as effective and better tolerated than diclofenac in the treatment of osteoarthritis.

Psychoneuroimmunological correlates of persisting sciatic pain in patients who underwent discectomy.

Patients suffering from persisting sciatic pain 8 weeks following discectomy were compared with patients displaying low complaints and healthy, pain-free volunteers regarding their interleukin-6 (IL-6) levels, morning cortisol levels and degree of psychological distress. Whereas serum concentrations of IL-6 were measured by collecting blood samples between 0945 and 2400 h in intervals of 45 min, morning cortisol levels were obtained by sampling saliva on five ensuing measurements, beginning immediately after awakening. In addition, questionnaires aimed at measuring depressive mood, somatic symptoms, coping and chronic stress were filled out by the subjects. The patients with ongoing pain displayed significantly elevated IL-6 levels and an attenuated elevation of cortisol secretion after awakening compared to the two other groups. Patients with persisting pain were also suffering more frequently from depressive mood and ongoing work-related strains. In addition, maladaptive coping strategies were favoured by these patients. The presented data support the hypothesis that the persistence of pain in many of the concerned patients may significantly be related to dysfunctional reciprocal relations between neural, endocrine and immune function.

Recombinant interferon alfa-2a with or without vinblastine in metastatic renal cell carcinoma: results of a European multi-center phase III study.

A total of 178 patients with metastatic renal cell cancer were randomized to receive interferon alfa-2a (rIFN alfa-2a) or interferon alfa-2a+vinblastine (VLB). IFN alfa-2a was injected intramuscularly at a dose of 18 MIU 3 times a week and VLB was given intravenously at a dose of 0.1 mg/kg once every 3 weeks. The response rate was 11% for patients on monotherapy and 24% for those on combination treatment. The 5-year survival for 145 eligible patients was 9%, independently from the treatment arm. The performance status was significantly related to long-term prognosis, and 13% of the patients with performance status 0 were alive at 5 years, as compared to 6% and 0% for patients with a WHO grade of 1 and 2, respectively. The most frequent adverse events in both treatment arms were flu-like symptoms (95%), fatigue (70%) and gastrointestinal disturbances (68%). Leukopenia was observed more frequently with combination treatment (53%) than with IFN alfa-2a alone (30%). In conclusion, rIFN alfa-2a monotherapy at this dose and schedule has modest antitumor activity in metastatic renal cell cancer. The combination of rIFN alfa-2a+VLB results in a doubling of the response rate, but this does not translate into prolonged survival. Toxicity (except leukopenia) and tolerance were similar in both treatment arms.

[Benign prostatic hyperplasia]. / Benigne Prostatahyperplasie (BPH).

More than 40% of men, aged 50 years and more, develop a benign prostatic hyperplasia. There is some evidence that a disturbance of the testosterone and estrogene metabolism within the prostate is involved in the pathogenesis. In relation to the symptoms, either a conservative therapy or a surgical treatment and resection of the prostate is performed. Retrograde ejaculation is a frequent consequence of surgical treatment.

Seminoma testis with elevated serum beta-HCG--a category of germ-cell cancer between seminoma and nonseminoma.

Serum beta-HCG was elevated in 10 of 83 consecutive patients with histologically pure seminoma (12%). Six patients with diagnostic stage I were successfully treated by radiation therapy. One patient with state IIc suffered a mediastinal relapse following retroperitoneal radiotherapy. Two other patients with high tumour burden achieved complete remission after induction chemotherapy followed by surgery and radiotherapy, respectively. One patient with retroperitoneal bulky disease reached permanent complete remission after radiation therapy alone. Beta-HCG-positive seminomas constitute a distinct category of germ-cell tumours on the basis of morphological and clinical features. Corresponding to the intermediate histological position between seminoma and nonseminoma, safe treatment of beta-HCG-positive seminoma can be achieved by radiotherapy in stage I, by retroperitoneal lymphadenectomy plus adjuvant chemotherapy in stages IIa, b and by induction chemotherapy in stages IIc and III.

Evaluation of the cytotoxic activity of diethylstilbestrol and its mono- and diphosphate towards prostatic carcinoma cells.

To evaluate a possible direct cytotoxic effect of diethylstilbestrol diphosphate (DESDP) in the treatment of prostate cancer we exposed three prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3), 2 nonprostatic neoplastic cell lines (KB and EJ), and one nontransformed cell line (MRC-5) to diethylstilbestrol (DES), diethylstilbestrol monophosphate, and DESDP at levels occurring in patients' sera during p.o. DES therapy (2 to 5 ng/ml) or DESDP infusions (1 to 20 micrograms/ml), respectively. With 5 ng/ml of DES no effect was seen in LNCaP cells, even after 14 days of exposure. In contrast, drug levels attained during DESDP infusions showed marked, dose-dependent cytotoxicity towards all cell lines under study. Prostatic cells were not exceptionally sensitive. High-dose DES slightly stimulated the synthesis of prostatic acid phosphatase in LNCaP cells. Formation of foci of polygonal cells was induced by 5 micrograms/ml of DES in cultures of MRC-5 fibroblasts. We conclude that, at high doses, DES liberated from DESDP acts upon a regulatory or metabolic mechanism common to many if not all human cells. Preferential sensitivity of prostate cancer cells in vivo may be due to high local phosphatase activity and/or DES accumulation in prostatic tissue.

Acid phosphatase, alkaline phosphatase and prostate-specific antigen--usefulness in the diagnosis of metastatic disease and follow-up.

PSA and PAP are effective immunohistologic markers for prostatic cancer metastases. PSA seems to be more sensitive than PAP for diagnosing metastatic prostatic cancer. Simultaneous determination of PSA and PAP yields an additive clinical value in diagnosing and follow-up of prostatic cancer. The prognostic reliability for disease progression (recurrence and treatment response) seems to be PSA greater than PAP greater than AcidP greater than Alkal. P.

Simultaneous bilateral testicular germ cell tumors with dissimilar histology. Case report and review of the literature.

A 32-year-old male presented with simultaneous bilateral germ cell tumors of the testicles. Histological examination revealed dissimilar histology in both testes showing pure seminoma in the left side and mature teratoma with malignant transformation in the right testicle. A survey of the literature revealed a total of 151 previously described cases of synchronous bilateral germ cell tumors, the majority of which presenting as bilateral seminoma. Treatment of synchronous bilateral germ cell tumors with dissimilar histology should consist of bilateral orchiectomy and bilateral retroperitoneal lymph node dissection.