[On the practice of therapy decision in locally limited prostate cancer: surgery vs. radiation-who benefits? : Allocation and results of a monocentric, cumulative long-term study]. / Zur Praxis der Therapieentscheidung beim lokal begrenzten Prostatakarzinom: Operation vs. Bestrahlung ­ wer profitiert? : Allokation und Ergebnisse einer unizentrischen, kumulativen Langzeitstudie.

AIM: The goal of this two-armed observational study was to map the clinical therapy effectiveness of radical prostatovesiculectomy (RPVE) and external beam radiation therapy (EBRT) in locally limited prostate cancer (PCA) in direct comparison over 20 years under clinical conditions. Retrospectively, the various variables and predictors for the individual therapy decision were identified, and the preference was to compared with studies on survival and recurrence characteristics. The presentation of toxicity was not the focus of this work. METHODOLOGY: In all, 743 patients from a single center were enrolled according to biopsy/staging chronologically in the sequence of the initial consultation after clarification and informed consent: 494 patients were in the RPVE arm and 249 patients in the EBRT arm. We used retrospective data analysis with univariate and multivariate comparisons in the alternative therapy arms. Multivariate logical regression models were developed to objectify the allocation process. Univariate processing of survival analyses, the comparison of tumor- and comorbidity-specific mortality rates was co-founded. RESULTS: Predictive variables for RPVE vs. EBRT therapy decision are significantly age, Gleason score, D'Amico index, Charlson index, prostate-specific antigen (PSA), and prostate volume. There was no significance level for the biopsy score. The age gap was in the median 67 (RPVE) and 73 (EBRT) years. Overall survival (n = 734, 20 years, all risks) in the RPVE arm was 56.8% (95% confidence interval [CI] 45.1-67.0%) and in the EBRT arm 19.2% (95%CI 9.2-31.8%). Comorbid risk was highly significantly (p < 0.0001) different (27.1% [95%CI 18.0-36.1%] in the RPVE arm, and 60.4% [95%CI 47.3-73.5%] in the EBRT arm). The risk of tumor-specific death at 16.2% (95%CI 8.1-24.4%) after RPVE and 20.5% (95%CI 11.7-29.3%) after EBRT was not significantly different (p = 0.2122, overlapping 95%CI). After stratification, a clear advantage can be demonstrated for the high-risk tumors after allocation to the RPVE arm. CONCLUSIONS: The complexity of the predictive variables of the PCA further complicates the individual therapy decision. According to our data, the higher D'Amico score, the rather low Charlson index, a high Gleason score and a higher organ volume speak for a valid therapy for RPVE.

[Modern nephrolithiasis in the complex setting of metaphylaxis : Latest epidemiological data and a nationwide survey in private practices]. / Die Nephrolithiasis im komplexen Metaphylaxesystem heute : Epidemiologische Daten zur Prävalenz und Resultate einer deutschlandweiten Praxisumfrage.

The focus of this work is on aspects of the current management of recurrent nephrolithiasis in private practices and outpatient departments in Germany. We wanted to make a contribution to the epidemiological discourse as well as for an instrument for the self-reflection and complex classification of urolithiasis in everyday practice by a first-time determination of population-based, age- and gender-based data based on the full recording of urological diagnoses and treatments in the federal accounting setting. The analysis of the taken positions in this representative practice survey prove to some extent information and experience deficits in the handling of complicated nephrolithiasis. Therefor more than 90% of the interviewees demand a structured practical training initiative. In this context, nearly 65% of practices also support the establishment of regional consultation hours. A majority strongly welcomes the establishment of a National Register of Urolithiasis, but nearly 40% are skeptical about defining pending framework conditions.

[Development and treatment of localized/systemic BCGitis : Retrospective studies in direct comparison to mitomycin C]. / Zur urogenitalen Klinik der lokalisierten/systemischen BCGitis : Retrospektive Untersuchungen im direkten Vergleich zu Mitomycin C.

Adjuvant therapy with different bacillus Calmette-Guérin (BCG) preparations is a well-established guideline-endorsed treatment for nonmuscle invasive bladder cancer (NMIBC). Our observational study demonstrates equality between BCG and mitomycin C (MMC) treatment based on the oncological outcome. However, there were significant toxicity differences with higher rates in the BCG treatment group. The potential adverse effects of BCG in terms of a BCGitis are controversially discussed regarding their occurrence. As such, we sought to retrospectively evaluate the incidence in 106 consecutive patients. The BCG group demonstrated minor adverse effects in 78.4% and major adverse effects in 43.3%-partially coincident. Moreover, the parallel MMC group showed in 34.7% respectively 1.4% adverse events-as expected distinctly lower. In the context of this clinical discussion, we refer to alternative treatment concepts. Our data show a high clinical relevance of the patient's primary comorbidity.

Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study.

Retrospective histologic analyses of bone biopsies and of post mortem samples from normal persons of different age groups, and of bone biopsies of age- and sex-matched groups of patients with primary osteoporosis and aplastic anemia show characteristic age dependent as well as pathologic changes including atrophy of osseous trabeculae and of hematopoiesis, and changes in the sinusoidal and arterial capillary compartments. These results indicate the possible role of a microvascular defect in the pathogenesis of osteoporosis and aplastic anemia.

DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection.

We tested the efficiency of induction of immune responses to the small hepatitis B surface antigen (HBsAg) in mice by intramuscular DNA immunization using different vector constructs that allow high levels of HBsAg expression in mouse cells. The HBsAg-specific responses of class I-restricted cytotoxic T lymphocytes (CTL) and of B cells (serum antibody titers) were measured. Following the intramuscular inoculation of 'naked' DNA, five different vector constructs of 4-8 kb, that contained or did not contain an intron and/or the neo gene, in which HBsAg expression was driven by promoter sequences derived from the immediate early region of HCMV, the SV40 enhancer/promoter region, or a retroviral 3' LTR efficiently primed responses of class I-restricted CD8+ CTL precursors. In contrast, the constructs in which HBsAg expression was driven by HCMV-derived promoter sequences stimulated significantly higher levels of HBsAg-specific serum antibody titers after intramuscular DNA injection than the SV40 or MPSV vector constructs. Large (15 kb) episomal vector constructs did not stimulate CTL or antibody responses. The data demonstrate that: (i) intramuscular DNA immunization represents an efficient technique for priming CTL and antibody responses to HBsAg; (ii) many vectors can be constructed that express an immunogenic product after intramuscular inoculation of 'naked' DNA; (iii) the efficiency of the tested vector constructs to prime after DNA immunization, either a CTL response, or an antibody response, differs.

SiMa, a new neuroblastoma cell line combining poor prognostic cytogenetic markers with high adrenergic differentiation.

We describe the establishment and characterization of a new neuroblastoma (Nb) cell line, SiMa, carrying the major recurrent chromosome changes associated with poor prognosis Nb, including amplification of N-MYC by formation of double minutes (dmin), der(1)t(1;17)(p35;q12) and der(22)t(17;22)(q22;p13), and loss of chromosome 11, documented at both initiation and late passage. In contrast to these cytogenetic stigmata of poor prognosis, analysis of catecholamine synthesis by high pressure liquid chromatography (HPLC) measurement revealed an advanced degree of adrenergic differentiation with high rates of 3,4-Dihydroxyphenylalanine (DOPA), noradrenaline, homovanillic acid (HVA), and vanillylmandelic acid (VMA) production. Contrastingly advanced differentiation and poor prognostic genetic markers combine to render SiMa a unique instrument for investigating the pathology and therapy of Nb.

Ascorbic acid stimulates DOPA synthesis and tyrosine hydroxylase gene expression in the human neuroblastoma cell line SK-N-SH.

Ascorbic acid is well known to induce noradrenaline synthesis in sympathetic nervous cells. In a series of experiments we found that incubation of the neuroblastoma cell line SK-N-SH with ascorbic acid (100-500 microM) for 2 h results in a significantly enhanced synthesis of 3,4-dihydroxyphenylalanine (DOPA) and dopamine. Additionally, cDNA-polymerase chain reaction (cDNA-PCR) analysis of relative mRNA levels corresponding to the enzymes involved in catecholamine synthesis revealed a 3-fold increase of tyrosine hydroxylase gene expression after 5 days of incubation with ascorbic acid (200 microM), whereas expression of dopamine-beta-hydroxylase was found to be unaltered. In summary the data give evidence that ascorbic acid leads to enhanced DOPA production in SK-N-SH cells by two different mechanisms: at the metabolic level after short-term incubation and by increasing the tyrosine hydroxylase gene expression after long-term incubation. Based on these data we suppose that enhancement of DOPA synthesis by ascorbic acid may be useful in the treatment of early Parkinson's disease.

Intraperitoneal regional chemotherapy with mitroxantrone.

Pharmacokinetic considerations and tests with cell lines and individual cell suspensions from metastatic human solid tumor biopsies suggested testing the efficacy of mitoxantrone (NOV) in intraperitoneal regional chemotherapy (IPRC). Twenty-seven patients with intraperitoneal metastatic disease of various solid tumors received cyclic IPRC with NOV for treatment of malignant ascites (N = 16) or of peritoneal carcinomatosis (N = 11) at a NOV instillate concentration of 10 micrograms/ml. A total of 125 cycles (1-5 per patient) were applied. Response and toxicity were registered according to WHO criteria. The response rate (CR+PR) was 56 percent in malignant ascites, 45 percent in peritoneal carcinomatosis, and 52 percent overall. There were no systemic toxicities. Regional side effects were bacteriemia (4 of 125 cycles), pain (2 of 125 cycles), small bowel stricture (1 of 27 patients), and small bowel perforation (1 of 27 patients). From these results we can conclude that NOV appears to be effective in IPRC for malignant ascites and peritoneal carcinomatosis at tolerable toxicities.

On the 5-hydroxytryptamine transport across the plasma membrane of rabbit platelets and its inhibition by imipramine.

1. The carrier-mediated uptake of labelled 5-hydroxytryptamine (3H-5-HT) in rabbit platelets (defined as the difference between uptake observed in the absence and presence of 10 mumol l-1 imipramine) was studied after inhibition of monoamine oxidase and after a 1:13 dilution of the platelet-rich plasma (PRP) with Tris-containing buffer. 2. Irrespective of whether the rabbits were pretreated with reserpine or not, initial rates of 3H-5-HT uptake were maintained for at least 15 s. 3. Analysis of the saturation kinetics of 3H-5-HT uptake using Hill's equation yielded Km, Vmax and nH values of 130 nmol l-1, 116 pmol 10(8) platelets-1 min-1 and 1.40, respectively. Pretreatment of the animals with reserpine did not affect any of these kinetic parameters, but depleted more than 99% of the platelets' 5-HT stores. 4. The nH value remained greater than unity when the duration of incubation with 3H-5-HT was extended from 15 to 30 s and when the uptake of 3H-5-HT was inhibited by the presence of imipramine (10-40 nmol l-1). However, it was reduced to unity (with a consequential increase in Km) when 300 nmol l-1 ketanserin was present. This concentration of ketanserin did not affect 3H-5-HT uptake at substrate concentrations far below Km. 5. Imipramine inhibited 3H-5-HT uptake by increasing the Km for 3H-5-HT without changing Vmax. The Ki for this interaction was 18 nmol l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA-Based Vaccination Primes Tumor-Rejecting T-Cell Responses.

DNA-based vaccination efficiently primes MHC-restricted T-cell responses. This technique specifically stimulates MHC-II-restricted CD4(+) T-cell responses and MHC-I-restricted CD8(+) T-cell responses against "strong" (immunodominant) or "weak" (subdominant or cryptic) epitopes of intracellular, secreted or membrane-associated protein antigens. In many experimental systems, T-cell-mediated effector functions have the potential to control tumor growth. In particular MHC-I-restricted cytotoxic T lymphocytes (CTL) can reject tumors. This has been shown using either defined tumor-associated antigens (TAA), or viral antigens containing well-defined, MHC-binding and CTL-stimulating epitopes that are expressed by transfected tumor cells.

[Drug permeation through artificial lipid membranes. 17. The mechanism of ion pair transport]. / Arzneimittelpermeation durch künstliche Lipoidmembranen. 17. Mitteilung: Zum Mechanismus der lonenpaarpermeation.

The transport of ionized drugs across lipoid membranes can be increased considerable by lipophilic counter ions. This is caused by an increased lipophilicity of the ion pair which is formed between the ionized drugs and the lipophilic counterion. Caused by their very strong solubility in the membrane the lipophilic counterions accumulate and act like a carrier for the ionized drugs. Then the necessary compensation of the charges can take place by protons or other suitable ions of the used solution.

[Combination hormone-chemotherapy versus hormone therapy alone in the initial treatment of advanced prostate carcinoma--a prospective cooperative study]. / Kombinierte Hormon-Chemotherapie versus alleinige Hormontherapie in der Initialbehandlung des fortgeschrittenen Prostatakarzinoms--eine prospektive Kooperativstudie

The effectiveness of orchiectomy plus an antigonadotropic therapy alone (ethinylestradiol sulfonate), of orchiectomy plus a combined hormone and chemotherapy (ethinylestradiol sulfonate plus vincristine/vinblastine, cyclophosphamide, methotrexate) and of orchiectomy plus chemotherapy (vincristine/vinblastine, cyclophosphamide, methotrexate) alone for the initial treatment of advanced (stage IV) carcinoma of the prostate was compared. The cumulative 4-year survival rate was better after combined hormone and chemotherapy. Our results do not justify the administration of combined hormone and chemotherapy in previously untreated advanced carcinoma of the prostate.

[Current status of classification, diagnosis and therapy of the preliminary and early stages of cervix carcinoma]. / Zum gegenwärtigen Stand der Klassifizierung, Diagnostik und Therapie der Vorstufen und Frühstadien des Carcinoma cervicis uteri

The present state of classification, diagnostics and therapy of preinvasive and early stages of cervical carcinoma has been demonstrated by means of literature and own experiences. In order to avoid damages caused by treatment the necessity of differenciated therapy is proved. A clear classification and the subtil histological investigation performed by a pathologist experienced in gynecological histology has to be regarded as an indispensible precondition in this neccessary differentiated treatment in early cases of cervical cancer.

[Luteoma of the ovary during pregnancy (author's transl)]. / Der Luteinzelltumor des Ovars bei Gravidität.

The tumor of lutein cells of the ovary during pregnancy was first described by Sternberg (1963) as "luteoma of pregnancy". Up to 1973/74 66 cases were published. This benign tumor occurring only during pregnancy probably arises under stimulation of chorionic gonadotropin and may cause a virilization of the mother and female infant. After birth the ovarian tumors regress spontaneouly. Lutein cell tumors are usally discovered incidentally at laparotomy (cesarean section) in late pregnancy and require no radical surgical treatment. The feature of these tumors and some related questions are discussed on the basis of on own observation being, to our knowledge, the first case of this type in Central Europe.