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T Otto

Publications and source records attributed to T Otto.

At least 37 records · Page 2Linked to original sources

[Treatment of metastases of urothelial carcinoma. Results of a prospective study of metastases surgery].

We initiated a prospective phase II trial to assess the outcome of complete surgical removal of metastases from bladder cancer with regard to survival and quality of life. Between 1995 and 1999, 70 patients (52 males, 18 females) with a median age of 64 years (range: 30-88 years) were treated with surgical complete resection of bladder cancer metastases. Patients with asymptomatic (n = 19) and symptomatic (n = 51) secondary metastases from bladder cancer refractory to methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) therapy were included. We removed secondary metastases in lymph nodes (63%), peritoneum (10%), skin (3%), bone (3%), lung (15%), and liver (6%) and measured survival and performance scores. The median survival time was 7 months. With a 1-year survival rate of 30% and a 2-year survival rate of 19%, the prognosis is unfavorable independent from the site of metastasis. However, 83% (42 of 51) of the patients with symptomatic secondary metastases did benefit from surgery regarding quality of life, e.g., performance score, and we assessed an improvement in the WHO performance score from 3.3 to 2.1 (p = 0.005). Surgical removal of metastases from bladder cancer refractory to systemic therapy has an impact on quality of life limited to patients with symptomatic disease.

Adult↗

Polycyclic musk fragrances in different environmental compartments in Berlin (Germany).

The aim of this study was to obtain data about the contamination of different environmental compartments (102 surface water samples, 59 sediment samples and 165 eel samples) by polycyclic musks (HHCB, AHTN, ADBI, AHMI, and ATII) within the framework of an exposure monitoring program. Results for HHCB (Galaxolide) gave the following mean values in areas strongly polluted with sewage: surface water 1.59 micrograms l-1; sediment 0.92 mg kg-1 d.w. and eel 1513 micrograms kg-1 f.w. (in the edible portion) (6471 micrograms kg-1 lipid). The following average concentrations were found in waters hardly contaminated with sewage: surface water 0.07 microgram l-1, sediment < 0.02 mg kg-1 and eel 52 micrograms kg-1 f.w. (445 micrograms kg-1 lipid). Mean concentrations of 6.85 micrograms l-1 (maximum: 13.3 micrograms/l) could be measured at sewage treatment plants' outlets. It could be shown that these polycyclics are highly suited to use as indicators of the degree of contamination of waters with organic substances originating from sewage. A mean bioconcentration factor (BCF) on wet weight of 862 (HHCB) and 1069 (AHTN) for the transfer from water to eel under natural conditions could be calculated. The corresponding BCF-values based on the lipid content of eel were 3504 (HHCB) and 5017 (AHTN).

Berlin↗

Impact of surgical resection of bladder cancer metastases refractory to systemic therapy on performance score: a phase II trial.

OBJECTIVES: To assess the outcome of complete surgical removal of metastases from bladder cancer with regard to survival, performance score, and tumor-related symptoms in a prospective Phase II trial. METHODS: Between 1995 and 1999, 70 patients (52 men and 18 women) with a median age of 64 years (range 30 to 88) were treated with complete surgical resection of bladder cancer metastases. Patients with asymptomatic (n = 19) and symptomatic (n = 51) secondary cancer from bladder cancer refractory to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy were included. We removed secondary cancer metastatic to the lymph nodes, peritoneum, skin, bone, lung, and liver and measured the survival, performance score, and tumor-related and therapy-related symptoms. RESULTS: The median survival time was 7 months. With a 1-year survival rate of 30% and a 2-year survival rate of 19%, the prognosis is unfavorable, independent of the site of metastasis. Patients who were asymptomatic complained of a reduced sense of well-being postoperatively (P = 0.007). However, 42 (83%) of the 51 patients with symptomatic secondary cancer did benefit from surgery in terms of tumor-related symptoms and performance score. The World Health Organization performance score changed from 3.3 to 2.1 (P = 0.005). CONCLUSIONS: Surgical removal of metastases from bladder cancer refractory to systemic therapy has an impact on the quality of life of patients with symptomatic disease only. Asymptomatic patients felt worse after surgery and no survival advantage appeared to be gained.

Adult↗

Patterns of Fos expression in the amygdala and ventral perirhinal cortex induced by training in an olfactory fear conditioning paradigm.

The activation of amygdaloid nuclei, the ventral perirhinal cortex (vPRh), and several other brain areas in the rat during the acquisition and expression of olfactory fear conditioning was assessed through Fos immunocytochemistry in 3 separate experiments. The results of Experiment 1 suggest that olfactory and somatosensory inputs may functionally converge in the anterior region ot the medial nucleus (aMe). The results of Experiment 2 indicate that the aMe exhibited significantly greater Fos-like immunoreactivity (FLI) in subjects acquiring conditioned stimulus-unconditioned stimulus associations than in those presented with the same olfactory and somatosensory stimuli in a manner that precluded acquisition. The results of Experiment 3 indicate that the vPRh appeared to exhibit learning-related increases in FLI during the expression of previously acquired associations. Collectively, these data suggest that the aMe and vPRh may be critically involved in different aspects of olfactory fear conditioning.

Amygdala↗

Polycyclic musk fragrances in fish samples from Berlin waterways, Germany.

The contamination of different fish species by polycyclic musks [Galaxolide (HHCB), Tonalide (AHTN), Celestolide (ADBI), Phantolide (AHMI), and Traesolide (ATII) within the frame work of an exposure monitoring programme are reported. A total of 341 fish samples were taken from three waterways in Berlin known to be contaminated to different extents with sewage. The mean levels of musk fragrance compounds reported on a whole weight basis in fish samples were as follows for the most common polycyclic compound, HHCB, in samples (taken from edible parts) of eel caught in waters strongly polluted with sewage levels were 1513 microg/kg (6471 microg/kg lipid) (AHTN: 726 microg/kg and from slightly polluted waters 52 microg/kg (445 microg/kg lipid) (AHTN: only one value above the detection limit). Median concentrations in fish samples were: perch 200 microg/kg (33.3 mg/kg lipid) common bream 1571 microg/kg (90.1 mg/kg lipid), roach 168 microg/kg (13.0 mg/kg lipid), pike 366 and 370 microg/kg (66.5 and 61.7 mg/kg lipid) and for pike perch 190 microg/kg (47.3 mg/kg lipid). ADBI, AHMI and ATII could be determined only in low concentrations (<10% of the total contents of polycyclics in eel). Clear concentration differences were seen between fish samples from waters contaminated at different levels within the programme of biomonitoring. This demonstrated that polycyclic musks are a very good indicator of the level of contamination of a waterway with sewage. Human exposure to these musk fragrances from consumption of contaminated fish was estimated to be low in comparison to direct dermal absorption from the use of fragrance products.

Animals↗

Docetaxel and ifosfamide as second line treatment for patients with advanced or metastatic urothelial cancer after failure of platinum chemotherapy: a phase 2 study.

PURPOSE: This phase 2 trial was designed to assess the efficacy and safety of combination chemotherapy with docetaxel and ifosfamide in previously treated patients with advanced urothelial cancer. MATERIALS AND METHODS: Enrolled in our study were 22 patients with advanced urothelial cancer who failed to respond or had relapse after previous platinum based chemotherapy. Treatment consisted of 60 mg./m.2 docetaxel given during 1 hour and 2.5 gm./m.2 ifosfamide given for 24 hours every 3 weeks with 500 mg. mesna administered intravenously at the start of the ifosfamide infusion, and 4 and 8 hours later. Patients also received premedication with oral dexamethasone. RESULTS: The objective response rate in 20 evaluable patients was 25%, including 4 complete responses (20%) associated with lymph node only recurrence. Disease was stable in 5 cases. At followup 16 patients had died 1 to 11 months (median 4) after the initiation of treatment, while 6 remained alive at 4 to 14 months, including 3 who were continuously disease-free. Treatment was well tolerated. Grades 3 and 4 leukopenia developed in 17% and 4% of the cycles, respectively. Neutropenic sepsis and grade 4 thrombocytopenia developed in 1 case each. Nausea and vomiting were mild to moderate. Other nonhematological toxicities included a hypersensitivity reaction in 1 patient and paresthesias in 2. CONCLUSIONS: The combination of docetaxel and ifosfamide is active in previously treated patients with urothelial cancer, although it appears to be a reasonable treatment option only in those with lymph node dominant recurrence. The mild toxicity underlines the usefulness of the regimen in this setting. Further investigation of the combination in previously untreated patients seems warranted.

Antineoplastic Agents, Alkylating↗

Pavlovian conditioning of emotional responses to olfactory and contextual stimuli: a potential model for the development and expression of chemical intolerance.

Chemical intolerance (CI) in humans is a poorly understood phenomenon of uncertain etiology, seemingly influenced by multiple factors both within and between affected individuals. Several authors have suggested that the development of CI in some individuals may be due, at least in part, to Pavlovian conditioning processes in which the expression of overt symptoms to certain substances reflects classically conditioned responses to previously neutral olfactory and contextual stimuli. In this paper, we describe the potential relationship between olfactory and contextual conditioning in experimental animals and the development and expression of CI in humans. Furthermore, as significant advances have been made in delineating the brain areas that underlie these learned responses, we also review recent research on the contributions of the amygdala and perirhinal cortical region to olfactory and contextual fear conditioning.

Amygdala↗

Behavioral and neuropsychological foundations of olfactory fear conditioning.

Pavlovian fear conditioning procedures have been a fruitful means of exploring the neural substrates of associative learning. There is now substantial evidence suggesting that many aspects of conditioned fear depend critically upon the integrity of the amygdala and the perirhinal cortex. Recent studies in our laboratory examining the contributions of these areas to olfactory and contextual fear conditioning are reviewed; collectively the results of these studies suggest that the amygdala participates critically in the acquisition and expression of fear conditioned to both an olfactory conditioned stimulus (CS) and to the training context, while the perirhinal cortex contributes to olfactory, but not contextual, fear conditioning. Moreover, it appears that perirhinal cortex may play a prominent role in recognition of the CS following conditioning. These results are discussed in light of the extent to which they replicate and extend previous research examining the contributions of these areas to fear conditioned to auditory and visual CSs.

Animals↗

[Therapy of prostate carcinoma. Age, general health status and stage determine choice of therapy].

Radical prostatectomy is indicated in patients with an estimated life expectancy of 10 years and with organ defined cancer disease (T1b-T2, No, Mo). Radiotherapy is an effective alternative treatment, especially in patients with an increased comorbidity. Primary hormonal treatment is not indicated for organ-defined cancer. Prognosis of patients with locally advanced prostatic carcinoma (T3,NO,MO) is poor because of micrometastases; tumour progression will occur in 75% of patients independent of local therapy. Orchiectomy or LH-RH treatment is option of first choice in metastatic prostate cancer disease. There is no need for complete androgen deprivation. Ongoing trials measure the effect of intermittant androgen deprivation. Intention for treatment of hormone refractory cancer is improvement of quality of life. Cancer-related symptoms are pain caused by bone metastases, lymphoedemas and urinary retention. Therapeutic options are monochemotherapy, hormonal treatment, analgetic treatment besides palliative radiotherapy.

Health Status↗

Principal component analysis and blind separation of sources for optical imaging of intrinsic signals.

The analysis of data sets from optical imaging of intrinsic signals requires the separation of signals, which accurately reflect stimulated neuronal activity (mapping signal), from signals related to background activity. Here we show that blind separation of sources by extended spatial decorrelation (ESD) is a powerful method for the extraction of the mapping signal from the total recorded signal. ESD is based on the assumptions (i) that each signal component varies smoothly across space and (ii) that every component has zero cross-correlation functions with the other components. In contrast to the standard analysis of optical imaging data, the proposed method (i) is applicable to nonorthogonal stimulus-conditions, (ii) can remove the global signal, blood-vessel patterns, and movement artifacts, (iii) works without ad hoc assumptions about the data structure in the frequency domain, and (iv) provides a confidence measure for the signals (Z score). We first demonstrate on orientation maps from cat and ferret visual cortex, that principal component analysis, which acts as a preprocessing step to ESD, can already remove global signals from image stacks, as long as data stacks for at least two-not necessarily orthogonal-stimulus conditions are available. We then show that the full ESD analysis can further reduce global signal components and-finally-concentrate the mapping signal within a single component both for differential image stacks and for image stacks recorded during presentation of a single stimulus.

Animals↗

N-methyl-D-aspartate receptor subunit mRNA expression in human retinal ganglion cells.

PURPOSE: To determine the expression of mRNA coding for different N-methyl-D-aspartate receptor (NR) subunits in the human retina. METHODS: In five human eyes the distribution of NR subunit mRNA was determined by in situ hybridization using 35S-labeled cRNA probes. In 100 consecutive retinal ganglion cells of each eye the level of mRNA expression of the different NR subunits was qualitatively graded. RESULTS: Ninety-three percent of retinal ganglion cells expressed mRNA coding for NR1, 9% for NR2A, 28% for NR2B, 86% for NR2C, and 84% for NR2D. The pattern of expression did not vary among the five eyes. CONCLUSION: These data establish distinct expression profiles of NR subunits in human retinal ganglion cells and suggest the development of specific NR ligands to reduce excitotoxic retinal ganglion cell loss.

Adult↗

Influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC3 in an orthotopic model.

OBJECTIVE: It has been demonstrated that quinoline-3-carboxamide, linomide, inhibited angiogenesis and reduced the volume of tumors grown from human hormone-resistant prostate cancer cell lines after subcutaneous implantation in mice. However, subcutaneous xenograft models may not mimic human conditions due to the absence of prostatic stromal cells at the ectopic site. Therefore, we investigated the influence of linomide on local tumor growth and metastasis of the human hormone-resistant prostate cancer cell line PC-3 in an orthotopic model. METHODS: In 30 athymic nude mice, 5x10(5) PC-3 cells were injected into the dorsal prostate after surgical exposure. After 7 days, group 1 (n = 15 mice) received linomide 100 mg/kg/day in the drinking water (per os). The other 15 mice (group 2) served as controls. All mice were sacrificed after 38 days followed by macroscopical and histological evaluation of local tumor growth and metastasis. Microvessel density was determined by immunohistochemical staining for von Willebrand factor as well as silver staining followed by morphometric analysis in an area of highest vessel density. RESULTS: In the control group, local tumorigenicity and locoregional lymph node metastasis was 100%. The mean weight of the local tumor was 894 mg (395- 1,261 mg). The mean transversal diameter of the lymph node metastases was 4.0 mm (1.5-5. 4 mm). In the treatment group, local tumor growth and lymph node metastasis was 100% with a mean local tumor weight of 869 mg (232-1, 131 mg) and a mean lymph node metastasis diameter of 4.6 mm (1.3-5.9 mm). Microvessel density of the local tumor in the control and treatment group did not differ significantly. CONCLUSION: Contrary to the results reported in subcutaneous animal models, linomide per os has no effect on net tumor growth and metastasis after orthotopic implantation of the human hormone-resistant prostate cancer cell line PC-3 in nude mice.

Angiogenesis Inhibitors↗

Regeneration of olfactory receptor neurons following chemical lesion: time course and enhancement with growth factor administration.

Although it has been known for over 50 years that olfactory receptor neuron (ORN) neurogenesis and subsequent reinnervation of the olfactory bulb (OB) occurs following ORN injury, the precise intrinsic and extrinsic factors that regulate this dynamic process have not yet been fully identified. In the first of two experiments, we characterized the time course of anatomical recovery following zinc sulfate (ZnSO(4)) lesion of ORNs in adult male Sprague-Dawley rats. ZnSO(4) produced a near complete deafferentation of OB within 3 days following intranasal administration. A time-dependent increase in ORN reinnervation of OB was observed following 10, 20, and 30 day recovery intervals. Given the evidence that bFGF, EGF, and TGF-alpha have mitogenic effects on ORNs in vitro, a second experiment examined the extent to which these growth factors (GFs) might enhance ORN regeneration and subsequent reinnervation of OB in vivo. Rats received intranasal infusions of ZnSO(4) on day 0, followed by subcutaneous injections of either bFGF (5, 10, or 50 microgram/kg), EGF (5, 10, or 50 microgram/kg), or TGF-alpha (5 or 10 microgram/kg) on days 3-6. Horseradish peroxidase (HRP) histochemistry of OB following a 10-day recovery period revealed a dose-related enhancement in reinnervation of OB for each of the three growth factors examined, with the greatest enhancement produced by TGF-alpha. These data suggest that GFs may regulate ORN mitogenesis in vivo in a way similar to that which has been characterized in vitro.

Animals↗

[Lymphatic metastases in bladder carcinoma. Is radical cystectomy indicated?].

Bladder carcinomas with lymph node metastases are a systemic disease with a poor long term survival (< 10%). Surgery has no proven impact on patients survival. Outcome depends on the extent of lymph node disease. Surgery combined with systemic chemotherapy is controversially discussed. Neoadjuvant chemotherapy has no proven survival impact. Adjuvant chemotherapy is under investigation in prospective randomized phase III trials. Lymph node metastases are no exclusion criteria for orthotopic bladder replacement. Extended lymph node dissection is not superior to lymph node dissection limited to the fossa obturatoria. Despite excellent long term results of radical cystectomy and lymphadenectomy in selected patients with node positive disease, surgery seems to be an individual approach, without no proven impact on patients survival and quality of life.

Chemotherapy, Adjuvant↗

Influence of interferon-alpha2b (IFN-alpha2b) on the prevention of locally advanced bladder carcinoma in mice.

In the model of chemically induced bladder carcinoma in mice following application of betahydroxylbutylnitrosamine (BBN) we could not detect a therapeutic influence of systemic treatment with intraperitoneal injection of interferon-alpha2b (10x3x10(5) IU IFN-alpha2b) on the rate of locally advanced bladder carcinoma (IFN-alpha2b 37% versus control 41%) nor on the development of tumor precursors (severe dysplasia 100% in both groups).

Animals↗

The need for further reproductive medical advice after vasectomy reversal.

The aim of this study was to determine the motivation of patients (n = 73) who had undergone microsurgical refertilization for further treatment (assisted reproduction) and the demand for medical counseling. By an interview, 57/73 patients could be evaluated for motivation, further demand for medical counseling, and the postoperative outcome (patency rate). In all, 60% of the patients who failed the treatment and 33% with a patent anastomosis mentioned interest for further counseling, especially for assisted reproduction. The satisfaction rate after the refertilization was nearly identical in the two groups (67%/64%). Following microscopical vasovasostomies the patency was 92%, which was significantly different from that observed after macroscopical refertilization (55%). In conclusion, the standard for refertilization is the microsurgical technique. Furthermore, there is a strong need for counseling that involves urological-andrological advice given by the same work group, including advisement on the techniques of assisted reproduction that might be necessary following the operative treatment.

Counseling↗