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Biomedical subjects

T Otto

Publications and source records attributed to T Otto.

At least 19 recordsLinked to original sources
PubMed2000

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↗
PubMed2000

[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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

[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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

[Neuroprotection in ischemia of the retina in an animal model].

QUESTION: The NMDA-receptorantagonist memantin is neuroprotective in retinal ischemia. Does this also apply to the NMDA-receptorantagonist cerestat and the glutamate release inhibitor riluzole? METHODS: In 50 rats ischemia was induced by elevating the IOP of one eye to 120 mmHg for 1 h. The drugs were injected before ischemia because, according to our hypothesis, a neuroprotective effect would be most evident in prophylactic preischemia treatment. Ten rats received 20 mg/kg/d memantine s.c., 10 received 16.8 mg/kg/d cerestat s.c., 10 received 16 mg/kg/d riluzole i.p. and 20 rats served as controls. Two weeks later, the ischemic damage was histologically quantified by counting the number of neurons in the ganglion cell layer of retinal whole-mounts stained with cresyl violet. RESULTS: In the memantine group 47% of the neurons survived ischemia, in the cerestat group 61%, and in the riluzole group 43%. In the control group the percentage was 28%. The differences from the control group were statistically significant (P < 0.05). CONCLUSION: Cerestat, memantine and riluzole have a neuroprotective effect--reducing excitotoxic damage of retinal neurons. The relative drug potencies cannot be directly compared, because of differences in dosage and the route of administration.

Animals↗
PubMed1999

Levels of synthetic musks; bromocyclene and PCBs in eel (Anguilla anguilla) and PCBs in sediment samples from some waters of Berlin/Germany.

The purpose of this study was to identify firstly the extent of contamination both of the aquatic biota and of sediments and secondly any regional differences in the concentrations of these compounds. In 1996, polychlorinated biphenyls (PCBs, including their coplanar congeners) were measured in 58 eel and 50 sediment samples. Furthermore, the veterinary pharmacetical bromocyclene and the nitro musks were determined in 84 (1995) and 122 (1996) eel samples. Polycyclic musk fragrances were additionally determined in analyses carried out in 1996. The mean values obtained during the two measurement periods (1995 and 1996) were 24 and 12 micrograms/kg fw. for musk xylene, 41 and 39 micrograms/kg fw. for musk ketone, 14 and 7 micrograms/kg fw. for bromocyclene and, in 1996, 592 micrograms/kg fw. for HHCB (maximum: 4131 micrograms/kg fw.). Decreasing contamination levels are seen for musk xylene and bromocylene but not for musk ketone. This tendency, and the high amounts of polycyclic musk fragrances in the edible parts of eel show that these musks are widely being used in place of nitro musks and that they reach the aquatic system via waste waters, especially those of sewage treatment plants. The mean levels of PCBs in the biota samples of a highly polluted area were 1227 micrograms/kg fw. or 119 pgTEQ/g (sediment: 203 micrograms/kg dw.) and of a slightly polluted area 340 micrograms/kg fw. or 49 TEQ/g (sediment: 47 micrograms/kg dw.).

Anguilla↗
PubMed1999

Intravesical therapy with pertussis toxin before radical cystectomy in patients with bladder cancer: a Phase I study.

OBJECTIVES: To ascertain the side effects of intravesical instillation of pertussis toxin (PTX) because it inhibits tumor cell motility in vitro and in vivo and seems to be a promising therapeutic approach against cancer. METHODS: We initiated a Phase I study and measured the effect of intravesical instillation of PTX before radical cystectomy. Study end points were PTX-related side effects. PTX was instilled at five dose levels, starting with 14 microg and continuing to 72 microg. RESULTS: Fifteen patients, with a median age of 64 years, were included in the study. Intravesical instillation of PTX was without local or systemic side effects (grade 0, according to National Cancer Institute toxicity criteria). CONCLUSIONS: Treatment with PTX was safe and well tolerated without any significant local or systemic toxicity in dosages up to 72 microg. Therefore, the influence of PTX on local tumor should be evaluated in a Phase II study.

Administration, Intravesical↗
PubMed1999

Automated scanning laser ophthalmoscope image montages of retinal diseases.

PURPOSE: To generate wide-field automated seamless retinal montage images. DESIGN: Prospective, observational, case series study. PARTICIPANTS: Eighteen eyes of 14 patients were studied. INTERVENTION: A digital scanning laser ophthalmoscope (SLO), the Heidelberg Retina Angiograph (HRA), was used to obtain overlapping images of the fundus during fluorescein angiograms, indocyanine green angiograms, or monochromatic retinal imaging using infrared or green light. Software was used to generate seamless montages. MAIN OUTCOME MEASURES: Ability to electronically synthesize retinal montages. Four laser wavelengths were used. The wide-field degrees, vertical and horizontal number of pixels, and diameter of the individual images were measured. RESULTS: High-resolution (pixel size, 10 microm), wide-field, typically 100 degrees to 140 degrees, digital montages of the postequatorial retina can be generated from HRA images. CONCLUSIONS: The software automatically and rapidly aligned the retinal blood vessels and synthesized a montage of the entire fundus that could then be overlaid on images taken at different times to illustrate change. These montages will allow improved ability to understand and follow retinal diseases.

Adolescent↗
PubMed1999

Mouse laparoscopy.

STUDY OBJECTIVE: To develop a technique for performing laparoscopy in the mouse. DESIGN: Controlled animal study (Canadian Task Force classification II-1). SETTING: University research laboratory. SUBJECTS: Twenty-eight CD-1 pregnant mice. INTERVENTION: Eight mice underwent anesthesia only and 20 had anesthesia plus laparoscopy at 5.5 and at 10.5 days' gestation (implantation occurs on day 4.5 and delivery on days 19-20). MEASUREMENTS AND MAIN RESULTS: Four mice in the laparoscopy group died early in the series, three due to hemorrhage and one due to anesthetic overdose. Among survivors, there were no differences between operated and control groups in number of pups delivered at term (8.7 +/- 5.1 and 8.9 +/- 3.8, respectively), frequency of pregnancy failure (18.8% and 12.5%), and presence of intraabdominal adhesions on autopsy after delivery (12. 5% and 12.5%). Intraabdominal contents could be manipulated to visualize both uterine horns in their entirety. The number of gestations could be counted accurately as early as 1 day after implantation. CONCLUSION: Given the fact that laparoscopy is not accompanied by the immunosuppression characteristic of laparotomy, this technique could prove useful for investigations requiring intraabdominal manipulations in mice when preservation of immune function is critical. The technique can be performed safely and repeatedly after an initial learning period. (J Am Assoc Gynecol Laparosc 6(2):173-177, 1999)

Animals↗
PubMed1999

Therapy of superficial bladder carcinomas.

Treatment of superficial bladder carcinoma was derived by several large randomized trials. This group of cancers is stratified by differentiation grade and stage in three groups of different risk profiles (Ta G1-2 vs. T1 G1-2 vs. Tis/T1 G3). Standard therapy is fractionated transurethral resection (TUR). Adjuvant therapy after transurethral resection is not indicated in primary Ta G1-2 tumors because there is a low recurrence rate and no risk of tumor progression. The recurrence rate can be decreased up to 15% in recurrent Ta or T1 G1-2 tumors by intravesical therapy with mitomycin C (20 mg/instillation) or adriamycin (50 mg/instillation). Therapy should be limited to early (within 24 h post-TUR) and short-term treatment (4 x weekly, 5 x monthly). Alternatively, patients can be treated by intravesical BCG (strain Connaught or strain RIVM). Maintenance therapy is advantageous according to recurrence rate. Tumors with great malignant ability (Tis or T1 G3) will be treated initially with adjuvant BCG. Patients who fail are candidates for radical cystectomy within 3-6 months after initial diagnosis. There is no need - except in clinical trials - for the administration of unverified or not admitted drugs.

Carcinoma, Transitional Cell↗