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K H Bichler

Publications and source records attributed to K H Bichler.

At least 19 recordsLinked to original sources
PubMed1992

Melatonin and 6-sulfatoxymelatonin circadian rhythms in serum and urine of primary prostate cancer patients: evidence for reduced pineal activity and relevance of urinary determinations.

The circadian rhythms of melatonin and 6-sulfatoxymelatonin (aMT6s) were analyzed in serum and urine of young men (YM, n = 8), of elderly patients with benign prostatic hyperplasia (BPH, n = 7) and of patients of similar age with primary prostate cancer (PC, n = 9). The data expressed as concentration and in urine also as hourly excreted quantity were analyzed chronobiologically by the single cosinor method and, subsequently submitted to linear regression analyses. Circadian rhythms were detected in all cases except for the excreted quantity of melatonin. The circadian patterns of melatonin and aMT6s in serum were very similar in the different groups and regression analyses showed close correlations between both variables. MESOR and amplitude were significantly depressed in PC (40-60%) as compared to BPH and YM indicating that the depression of serum melatonin in PC is due to a reduced pineal activity and is not caused by an enhanced metabolic degradation in the liver. Acrophases of serum melatonin occurred between 01:34 and 03:26 h and of serum aMT6s between 03:58 and 04:35 h. Circadian rhythms similar to those of serum melatonin and aMT6s were found in urine, particularly for aMT6s excretion as well as melatonin concentration; the determination of both parameters in overnight urine samples closely correlated with the nocturnal peak of circulating melatonin. These results imply that it is feasible to estimate changes in pineal function of prostate cancer patients by means of non-invasive determination using urinary melatonin and aMT6s.

Adult↗
PubMed1992

Immune modulating effects of low doses of cyclophosphamide and keyhole limpet hemocyanin on peripheral blood immune parameters in patients with metastatic renal cell carcinoma.

Assessing the peripheral blood immune status, we had found evidence of immunosuppression in metastatic renal cell carcinoma. Since immunosuppression might interfere with the outcome of immunotherapy, it was submitted to further investigation. Immunosuppression can be mediated by T suppressor cells, which for their part are inhibited by low-dose cyclophosphamide (Cy). We tested whether the immunomodulating effects of the biological response modifier keyhole limpet hemocyanin (KLH) on cellular and humoral immune parameters would be intensified by low-dose Cy. 10 patients were given 300 mg/m2 Cy i.v. 3 days before application of 1 mg KLH i.m. up to 8 times in 4-weekly intervals. Immune parameters were assayed twice pre-therapeutically, and prior to and 1 day and 1 week after each KLH injection. In contrast to the results obtained with KLH-mono-application, lymphocyte subsets-with the exception of T4 cell counts and the T4/T8 ratio-remained stable during the first 4 months of observation. There were increases in immunoglobulins and in the immunoactivation markers tumor necrosis factor, neopterin and beta 2-microglobulin. The tendencies found here differed from those found in a previous study on patients who were given KLH alone, and were similar to those found in patients with nonmetastatic disease who received KLH alone. However, the increases of the activation markers during KLH+Cy application were at best half as much as in patients with nonmetastatic disease. In conclusion, immunosuppression was influenced, but not counterbalanced by low-dose Cy. Most probably other mediators of immunosuppression than T suppressor cells, for example prostaglandin E2, must be considered as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1992

Postoperative long-term course of peripheral blood immune parameters and immunomodulating effects of keyhole limpet hemocyanin in patients with nonmetastatic renal cell carcinoma.

Therapeutic approaches to metastatic renal cell carcinoma (RCC) often focus on the application of immune modulators; the success rates, however, are not satisfactory. Up to the time of this study, no diagnostic tool has been available to select those patients who might profit from immunotherapy. Starting from this point, we have been assessing the immune status of patients suffering from RCC, intending to find markers that would characterize the more favorable prognosis. Our interest is focused not only on the metastatic but also on the nonmetastatic disease, i.e., the disease with the better prognosis. In the present study, we have assessed both the postoperative long-term course of several immune parameters of the peripheral blood and the reactivity of the immune system to immunostimulation with keyhole limpet hemocyanin (KLH) in patients with nonmetastatic RCC. In a prospectively randomized study, the verum group (n = 8) got 1 mg KLH per month up to 1 year while the control group (n = 9) got no immunostimulator after tumor nephrectomy. Both patient groups had stable or even increasing cell counts of lymphocyte subpopulations (T, B, natural killer, T4, T8 cells), and the humoral immunoactivation markers neopterin, beta 2-microglobulin and tumor necrosis factor increased considerably after tumor nephrectomy. An effect of KLH is evident 4-8 months postoperatively: here, the neopterin values in the KLH group are more than twice as high as in the control group. Thus, while patients with metastatic disease had turned out to be immunosuppressed (previous study), in patients with nonmetastatic RCC, both the long-term course indicating postoperative immunostimulation and the reactivity to KLH give evidence of immunocompetence.

Adjuvants, Immunologic↗
PubMed1992

Renal insufficiency induced by parathyroid hormone: influence of the calcium antagonist Gö 6070.

To study the pathogenesis of parathyroid-hormone-induced renal insufficiency and the influence of the new calcium channel antagonist Gö 6070 (Gödecke AG, Berlin, FRG) rats were assigned to three groups (n = 8 each): (1) control, (2) PTH, (3) PTH plus Gö 6070. PTH (30 micrograms/24 h, a nonhypercalcemic dose) was administered i.p. and Gö 6070 (1 mg/kg/24 h) p.o. for 6 days. PTH did not change plasma or urinary calcium and did not induce nephrocalcinosis. The glomerular filtration rate (GFR), however, was decreased (4.9 vs. 10.3 ml/min/kg). Concomitant administration of Gö 6070 attenuated the PTH-induced fall in GFR (6.2 ml/min/kg).

Animals↗
PubMed1991

Tumor necrosis factor in benign and malign tissue of the kidney.

The use of tumor necrosis factor (TNF) in immunotherapy of tumor diseases has attracted increasing interest. Since the direct antitumor effect of the TNF is mediated by receptor-bound TNF, we immunohistologically stained both benign and malignant tissue from 35 tumor-bearing human kidneys for TNF. Using a polyclonal anti-TNF-antiserum, paraffin sections were tested in the presence and absence of in vitro preincubation with TNF. Furthermore, all specimens were stained immunohistologically for Tamm-Horsfall protein (THP) because this renospecific glycoprotein can bind TNF in a lectin-like manner. In the absence of TNF preincubation, malignant tissue was TNF-positive in 34 specimens, as was benign tissue from the same tumor-bearing kidneys in 35 cases. In several specimens the staining was so intense that preincubation with TNF did not enhance the reaction. Whereas TNF staining in tumor tissue was relatively homogenous, that in benign tissue was intensive in distal tubuli, moderate in proximal tubuli, and negative in glomeruli. THP staining was negative in malignant kidney tissue but positive in the distal tubuli of benign tissue, i.e., in the regions in which TNF staining was most intense. These results indicate that TNF binds not only to membrane, most likely in a receptor-mediated manner, but also to THP both in vivo and in vitro. In vivo binding of TNF to THP was confirmed in animal experiments in which pigs were given injections of TNF. Immunohistological staining of the animals' kidneys revealed positive reactions for both TNF and THP at the distal tubuli, indicating TNF binding to THP after in vivo TNF administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Angiodynography (color-coded duplex sonography) in the evaluation of vasculogenic impotence.

The penile arteries of 18 men with erectile dysfunction were examined by angiodynography (color-coded duplex sonography). Blood flow velocity was measured before and after intracavernous injection of papaverine/phentolamine. The angiodynographic findings were compared to arteriography. Normal values of peak flow velocity (after injection) were obtained from 6 men with normal arteriographic findings (deep artery greater than 25 cm/s, superficial artery greater than 30 cm/s). Angiodynography enables good imaging of the four penile arteries superior to duplex sonography. A strong correlation with the arteriographic findings could be found. Thus noninvasive angiodynography may replace penile arteriography for the routine evaluation of impotence.

Adult↗
PubMed1991

[Local hyperthermia in benign prostatic hyperplasia].

In recent years, hyperthermia has been used for the treatment of benign prostatic hyperplasia (BPH). The preliminary results reported were promising. Except for patients with total urinary retention, however, objective voiding parameters have not been reported in detail for patients with "prostatism". In a phase II study we treated 30 patients with BPH by local microwave hyperthermia (915 MHz). The prostate was heated transrectally to 42-43 degrees C in eight sessions of 60 min each. The sessions were given twice a week. To assess the results of the treatment the following parameters were determined before and 4 weeks after hyperthermia therapy: transrectal ultrasound of the prostate with volumetry, urinary flow rate, and residual volume. In all, 28 patients were evaluatable. Only 2/28 showed clinical improvement. Neither the voiding parameters nor the size of the prostate were significantly changed by hyperthermia. The success rate of 7.1% is even lower than the spontaneous temporary regression rate of BPH. Thus, to our mind, hyperthermia cannot be regarded an effective treatment comparable to TUR for BPH.

Aged↗
PubMed1991

[Local hyperthermia in prostate cancer].

We conducted a clinical trial evaluating the effects of hyperthermia in patients with carcinoma of the prostate, treating 20 patients with newly diagnosed carcinoma of the prostate with local microwave hyperthermia (915 MHz). Histological examination revealed hypoeremic effects and diffuse oedema with interstitial lymphoplasmatic cellular infiltration. However, necrotic tumour cells were not found in any of specimens. A second series consisted of 10 patients with metastasizing carcinoma of the prostate (n = 4 untreated; n = 6 hormone-resistant). For 8 weeks, epirubicin was administered once weekly, followed each time by local microwave hyperthermia 1 h later. The efficacy was evaluated according to the EORTC criteria. In 4 patients with untreated carcinoma no change was found in the size of the prostate or metastases. In 3 of the 6 patients with hormone-resistant carcinoma progressive disease was found, while the other 3 had stable disease. Only in 2 of the 10 patients did the grading of tumour regression reveal any improvement. Cytophotometric studies showed no change of DNA ploidy. Currently we consider hyperthermia unsuitable as monotherapy for carcinoma of the prostate, and the combination of epirubicin and hyperthermia is no more favourable than monotherapy with epirubicin alone. Further studies are necessary to evaluate other cytotoxic regimens and various patterns of application for hyperthermia.

Adenocarcinoma↗
PubMed1990

Damaging effects of high energy shock waves on cultured Madin Darby canine kidney (MDCK) cells.

Shock wave lithotripsy (ESWL) has become an almost non-invasive standard treatment modality for urolithiasis. Several investigations, however, demonstrated that ESWL is not completely free of side effects. Among others alteration of renal tubular function has been reported. To study the effect of shock waves on tubular cells directly an in-vitro model with cultured Madin Darby Canine Kidney (MDCK) cells was established. Suspensions of MDCK cells (7 groups of 6 containers each) were exposed to 0, 16, 32, 64, 128, 256 shock waves (Dornier HM4, 18 kV). Before and 0, 1, 3, 6, 9, 12, 24 h after ESWL the following parameters were measured in the nutrient medium: lactate dehydroxygenase (LDH), glutamate oxalacetate transaminase (GOT), electrolytes. LDH and GOT increased depending on the number of shock waves indicating a membrane damage of MDCK cells. The MDCK model seems suitable for further studies on the effect of shock waves on renal tubular cells.

Animals↗
PubMed1990

Alveolar echinococcosis with involvement of the ureter and testis.

Alveolar echinococcosis is a rare disease of the liver, and occasionally of the lungs and brain, that is endemic across areas of Central Europe, the Soviet Union and Alaska. We describe a case of alveolar echinococcosis with involvement of the ureter and testis overshadowing the liver manifestation. The unusual presentation and nondemonstrable exposure to the organism caused misinterpretation of the histological findings and an initial misdiagnosis of tuberculosis.

Adult↗
PubMed1990

Local microwave hyperthermia of benign prostatic hyperplasia.

Recently, hyperthermia has been used for treatment of benign prostatic hyperplasia. The preliminary results reported were promising. However, apart from patients with total urinary retention, objective voiding parameters have not been reported in detail for patients with prostatism. In a phase II study we treated 30 patients with benign prostatic hyperplasia by local microwave hyperthermia (915 MHz.). The prostate was heated transrectally to 42 to 43C, with the treatment consisting of 8 sessions of 60 minutes each given twice a week. To assess the results of treatment several parameters were determined before and 4 weeks after hyperthermia therapy, including transrectal ultrasound of the prostate with volumetry, urinary flow rate and residual volume. Of the patients 28 could be evaluated and only 2 showed a relevant improvement. Neither the voiding parameters nor the size of the prostate could be changed significantly by hyperthermia. The success rate of 7.1% is even lower than the spontaneous temporary regression rate of benign prostatic hyperplasia. Thus, we believe that hyperthermia cannot be regarded as an effective treatment for benign prostatic hyperplasia comparable to transurethral resection.

Aged↗
PubMed1990

Immune status and immune therapy of renal cell carcinoma.

At present, no sufficient therapy for metastatic renal cell carcinoma is available. Several immunotherapeutical protocols have been studied, success rates, however, were inconsistent. The purpose of this study was to assess the pretherapeutic immunological status of 13 patients with metastatic and 16 patients with nonmetastatic renal cell carcinoma and of 15 healthy volunteers. Determined were differential blood counts, lymphocyte subpopulations, beta 2-microglobulin, tumor necrosis factor (TNF), neopterin, immunoglobulin, fibronectin and ferritin. Additionally, these parameters were recorded for monitoring an immunotherapeutical approach with the xenogeneic biological response modifier Keyhole limpet hemocyanine (KLH) in 10 patients with metastatic and in 5 patients with nonmetastatic disease. The pretherapeutic immunological status of patients with metastatic disease was characterized by significantly reduced T4-, T8- and B-cell counts. Significantly increased were granulocyte counts, beta 2-microglobulin, neopterin and TNF. In patients who did not suffer from metastases, only beta 2-microglobulin and neopterin were increased significantly. During immunotherapy, in patients with metastases, there was a decline of lymphocyte subsets and of the T4/T8-ratio, which correlated with progress of the disease. Humoral immune parameters showed no changes compared to pretherapeutic values. In patients who did not suffer from metastases, cellular immune parameters showed stable values during immunotherapy; neopterin, beta 2-microglobulin and TNF increased considerably. These findings indicate immunosuppression in patients with metastatic renal cell carcinoma, increasing with progression of the disease and possibly impairing the immunostimulating effects of biological response modifiers during immunotherapy. In conclusion, the clinical response of metastatic renal cell carcinoma to immunotherapy might be improved if the immunostimulant is combined with agents suitable to overcome immunosuppression, i.e. low doses of cyclophosphamide or inhibitors of prostaglandin synthesis. In addition, assessment of immune parameters for monitoring the actual immune status of a patient and the immunological effects of therapy was found to be a necessary part of immunotherapy.

Adjuvants, Immunologic↗
PubMed1989

[Paraneoplastic syndrome in kidney cancer].

In a prospective study 60 patients suffering from histologically confirmed renal cell carcinoma were examined on paraneoplastic alterations. The following parameters were determined: Stauffer-syndrome (BSG, total protein with serum electrophoresis, alcaline phosphatase, gamma-GT, Quick values), total and ionized calcium, parathormone, calcitonin, hemoglobin, thrombocytes, LDH, IgE and arterial blood pressure. Compared to the findings obtained by other authors, we saw paraneoplastic syndromes only rarely. There was no correlation found to the stage of the tumor or to prognosis. In only four out of 60 patients paraneoplastic led to the diagnosis "renal carcinoma". With the exception of BGS, which was raised in 75% of the patients, paraneoplastic parameters are not suitable for the screening or the early diagnosis of renal carcinomas.

Adult↗
PubMed1989

An immunohistochemical technique for localization and semiquantitation of estramustine-binding protein (EMBP) in rat and human prostate.

An immunohistochemical technique for determination of "estramustine-binding protein" (EMBP) in rat prostate is described. The localization and staining intensity of this protein were correlated to prostatic morphological structures in intact animals and at different time intervals after androgen deprivation by castration. EMBP was found almost exclusively in epithelial cells, while the fibromuscular stroma seemed to be negative. Intracellularly, immunostaining was confined to the cytoplasm, but was absent in nuclei. In intact rats, acinar lumina demonstrated heavy immunostaining, indicating secretion of EMBP. Orchiectomy caused a diminution of EMBP expression as well as secretion, suggesting that EMBP synthesis is under androgenic regulation. Human benign hyperplastic and cancerous prostatic specimens were also examined. All human specimens examined so far exhibited positive epithelial staining although of varying intensity. Therefore, this immunohistochemical technique may be used for studying the correlation of EMBP with tumor malignancy grade and for clinical investigations of how various treatments affect EMBP expression in prostatic carcinomas.

Animals↗
PubMed1989

Effect of treatment on the expression of estramustine-binding protein (EMBP) in prostatic cancer patients: an immunohistochemical study.

Estramustine-binding protein (EMBP) was determined immunohistochemically in prostatic cancer (PC) specimens taken from patients before and after therapy. The EMBP staining intensity was correlated with the tumor malignancy grade in untreated PCs. The effect of various treatments (i.e., androgen-withdrawal therapy, treatment with estramustine phosphate or radiation) on the expression of EMBP was also investigated. Although a rabbit polyclonal antiserum raised against rat EMBP was used all through the study, all untreated PCs (n = 53) examined so far displayed a positive immunoreaction. The staining intensity was higher in moderately and poorly differentiated than in well-differentiated tumors. Furthermore, two types of staining patterns were observed, that is, a diffuse type in about 70% and a focal in the remaining cases, which might reflect the multifocal appearance of PCs. The prognostic significance of these staining patterns is discussed. Irrespective of the treatment used, EMBP staining was reduced to lower or undetectable levels in PCs where cytological as well as clinical regression were indicated after 6-30 months of therapy. In nonresponders or patients with refractory disease, however, EMBP expression reappeared and returned to pretreatment levels. In a short-term follow-up, the diminuation of EMBP was evident as early as 10 days after androgen-withdrawal therapy and persisted as long as the patient responded to therapy. When estramustine phosphate was given as secondary treatment to hormone refractory PCs, EMBP decreased to undetectable levels in 3/4 of the specimens, suggesting response to therapy. In conclusion, a decreased EMBP staining was well correlated with favorable cytological regression as well as with clinical regression, whereas unchanged staining intensity was indicative of clinical progression and a poor cytological regression grade. The high levels of EMBP in moderately and poorly differentiated tumors as well as in relapsing PCs, despite continued androgen withdrawal, strongly support a regulation of EMBP that is not under androgenic control. Based on the present findings, we suggest the use of EMBP as a therapy marker. Provided that immunohistochemical measurements can be performed on fine-needle aspirates, EMBP analysis may be a direct and early means to distinguish between responding patients and nonresponders.

Carrier Proteins↗
PubMed1989

Combination of hyperthermia and cytostatics in the treatment of bladder cancer.

The intravenous administration of cytostatics in cases of locally extended carcinomas of the bladder seems to promise success. As concomitant disadvantage however we have to mention that the drugs in high concentrations needed for this treatment give rise to systemic toxic effects limiting the rational use of the drug. A further rise of cytostatic tissue concentration seems possible by performing a synchronous tumor injection of cytostatics and microspheres. An additional anticancer effect and the synergistic activation of cytostatic effectivity must be assumed by a following local transurethral high-frequency hyperthermia of the bladder. Our first urological experiences with this integrated therapy in six locoregional (T3-4N0M0) and six advanced metastasizing (T3-4N1M0-1) bladder cancers are presented consisting of a combined intraarterial cytostatic microspheres carcinoma infusion (CMCI) and scheduled adjunctive transurethral high-frequency hyperthermia (TUHH). In the case of locoregional tumor the aim was cancer destruction or debulking and in the case of metastasizing tumor palliation of local disease. Mechanisms of action, methodical procedures, indications, results as well as side effects of the intraarterial CMCI and TUHH treatment as developed by our department are presented and discussed.

Carcinoma, Transitional Cell↗
PubMed1989

[Studies of calcium metabolism in normal persons and patients with hypercalciuria in relation to therapy with the dietary fiber preparation Farnolith].

Farnolith (a dietary fibre preparation) was given to normal patients (n = 6) with absorptive hypercalciuria type I (n = 6) and to one patient with renal hypercalciuria. Farnolith binds calcium and reduces calcium absorption in the intestines. In normal subjects, the urine and serum parameters of calcium metabolism (total and ionized calcium, 1.25-dihydroxy-vitamin D) were unchanged. In absorptive hypercalciuria type I, a significant decrease in calcium excretion was achieved; oxalate excretion decreased as well. Low PTH values normalized; vitamin-D metabolites were not affected. In renal hypercalciuria, PTH and 1.25 DHCC were increased, whereas hypercalciuria persisted. Our investigations show that Farnolith is a reasonable treatment for absorptive hypercalciuria. Calcium homeostasis is rendered normal by Farnolith without producing secondary hyperoxaluria as sodium cellulose phosphate. Patients with primary renal calcium leakage and secondary hyperparathyroidism should not be treated with Farnolith.

Calcitriol↗