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T Otto

Publications and source records attributed to T Otto.

At least 55 records · Page 3Linked to original sources

Combined lesions of perirhinal and entorhinal cortex impair rats' performance in two versions of the spatially guided radial-arm maze.

The present study examined the effects of combined lesions of the entorhinal and perirhinal cortex (PRER) on performance of two versions of the spatially guided eigh-tarm radial maze. In the first version, all arms were baited and in each session the rats were allowed to explore the maze freely until they retrieved all of the reinforcers. PRER subjects were profoundly impaired in performance of this task, making fewer correct choices and more total errors than control subjects. In the second task, a delayed nonmatching to sample version of the radial-arm maze, each daily session was separated into two phases. In the first, predelay phase, four arms were open and the remaining four arms were blocked with clear Plexiglas barriers; subjects were permitted to visit each of the four arms and retrieve the reinforcers. In the second, postdelay phase, the subject was placed on the maze with free access to all eight of the arms, but only those arms that were blocked in the predelay phase contained reinforcers. Delays of either 10 min or 30 s separated the pre- and postdelay phases. PRER subjects were significantly impaired in their performance of this task at both delays, making fewer correct choices and more errors than controls; the magnitude of this deficit was not dependent on length of delay. These data suggest that, along with the hippocampal formation, the entorhinal and perirhinal cortices actively participate in the acquisition and performance of appetitively motivated spatial memory tasks.

Analysis of Variance↗

NIR reflection measurements of hemoglobin and cytochrome aa3 in healthy tissue and tumors. Correlations to oxygen consumption: preclinical and clinical data.

OBJECTIVES: A new near infrared reflectance spectroscopy based technology (MULTISCAN OS 10/30) for non-invasive measurements of tissue oxygenation allows detection of absolute tissue hemoglobin concentration and saturation values in real time. METHODS: MULTISCAN OS 10/30 scans a tissue sector of defined geometry at 400 to 1200 nm wavelength with 0.3 nm intervals at a scan rate of up to 400 Hz in reflection mode. The newly developed algorithms are based on the entropy pattern of photons and allow the detection of absolute values of total hemoglobin (tHb), deoxy- (Hb) and oxy-hemoglobin (HbO2) in mg/ml tissue as well as tissue oxygen (saturation = tiSO2) in the range of 0 to 100% in real time. Cytochrome aa3 (Cyt) can be monitored simultaneously. RESULTS: Physiological Stimulation. Clamping experiments at the finger of volunteers, in the intestine of a pig, in the kidney of mice and rats showed a very fast, sensitive and tissue specific reaction. Changes in breathing and/or anesthesia conditions were immediately followed by corresponding changes of tissue oxygenation (brain, finger, skin). Simultaneous measurements of oxygen (HbO2), and cytochrome showed a strong correlation between both parameters. For validation purposes parallel polarographic measurements (pO2 measurements) were performed in mice. Furthermore angiographic data of patients as well as NMR/I data were compared with the NIR spectroscopy findings. Tumor Measurements. Patients with tumors of different origins showed significantly different oxygen values. The lowest level was found in glioblastoma (< 10% sat, < 1.0 mg/ml tHb), whereas renal carcinoma showed tremendously increased values (> 90% sat, > 5.0 mg/ml tHb). In contrast the surrounding healthy kidney tissue was significantly less oxygenated and perfused compared to the tumors. Oxygen Consumption Measurements. Oxygen consumption was measured in 16 patients after ligation of the blood supply (A. and V. renalis) to the kidney affected by tumor. All tumors showed a significantly lower consumption rate compared to the healthy tissue. These findings were controlled by animal experiments of human renal carcinomas on nude mice. The same results were obtained under these experimental conditions. CONCLUSION: MULTISCAN OS 10/30 is a new and useful tool for in vivo characterization of oxygen and cytochrome in healthy and tumor tissues. In many clinically relevant situations oxygen measurements can be helpful and support the clinical routine diagnostics.

Adult↗

Detection of loss of heterozygosity in the APC tumor suppressor gene in nonpapillary renal cell carcinoma by microdissection and polymerase chain reaction.

The role of the APC (adenomatous polyposis coli) tumor suppressor gene in the genesis of nonpapillary renal cell carcinoma is addressed. The frequency of allelic deletion in the APC gene was analyzed using microdissection of the tumor specimens and a PCR (polymerase chain reaction)-based assay for the detection of intragenic loss of heterozygosity (LOH). Twelve of 29 carcinomas investigated were informative (41%). In five of these (42%) LOH was detected in the APC gene, LOH did not correlate with tumor grade or stage. This high frequency of intragenic LOH suggests an implication of the APC gene or a closely linked gene in the genesis of a subset of nonpapillary renal cell carcinoma. The use of a microdissection technique allows the reliable detection of tumor-specific LOH when using a PCR-based assay.

Aged↗

Detection of vital germ cell tumor cells in short-term cell cultures of primary tumors and of retroperitoneal metastasis--clinical implications.

By establishing short-term cell cultures derived from retroperitoneal metastasis after neoadjuvant chemotherapy, our aim was to improve the diagnosis and prognosis in patients with advanced testicular germ cell tumors. The histological evaluation of surgically removed metastatic tissue by retroperitoneal lymphadenectomy (RLA) is extremely complicated after previous chemotherapy, but knowledge of persistence of vital tumor cells in residual lesions is of great prognostic value and therapeutic consequence in patients with testicular germ cell tumors. We therefore investigated whether vital tumor tissue could be detected in short-term cell cultures derived from such metastatic lesions by measuring the concentration of the tumor markers beta human chorionic gonadotropin (beta HCG) and alpha-1 fetoprotein (AFP) in cell culture supernatants. We initially demonstrated the specificity of the determination in cell cultures of human transitional-cell carcinoma cell lines, human foreskin fibroblasts and normal testicular tissue. In a group of 20 patients with untreated primary testicular germ cell tumors, detection of beta HCG and AFP was increased about threefold in cell culture supernatants in comparison to the serum concentration. Finally, we prepared primary cell cultures from surgically removed retroperitoneal metastasis of 12 patients with testicular germ cell tumors after chemotherapy. The serum concentrations of beta HCG and AFP of all patients were at normal values when RLA was performed. However, pathologically increased concentrations of beta HCG (3/3) and AFP (2/3) in cell culture supernatants were found in 3 of 12 cell cultures. Interestingly, these three patients with a pathological increase in beta HCG and AFP as determined in the supernatant of the short-term cell cultures had tumor progression within a mean follow-up of 3 +/- 1 months (P < 0.01), whereas 9 of 12 patients who had no pathological increase in beta HCG and AFP as determined in the supernatant of the short-term cell culture were in complete remission (CR) after a mean follow-up of 40 +/- 11.6 months.

Adult↗

Identification of G protein-coupled receptors potently stimulating migration of human transitional-cell carcinoma cells.

The expression of G protein-coupled receptors inducing calcium mobilization and stimulating cell migration was examined in human transitional-cell carcinoma (J82) cells. Measurements of cytoplasmic Ca2+ concentration ([Ca2+]i) and phospholipase C activity indicated that these cells express several calcium-mobilizing receptors, including those for lysophosphatidic acid (LPA), thrombin, bradykinin, bombesin and histamine, of which only the LPA response was sensitive (approximately 50%) to pertussis toxin (PTX). Migration of J82 cells was strongly stimulated by LPA and thrombin, by 5- to 20-fold, whereas bradykinin, bombesin and histamine were ineffective. Migration induced by either LPA or thrombin was inhibited by the actin cytoskeleton-disrupting agent, cytochalasin B, by the Rho protein-inactivating Clostridium difficile toxin B, by preventing [Ca2+]i transients with an intracellular calcium-chelating agent, and by the phorbol ester, phorbol 12-myristate 13-acetate, which also blocked the LPA- and thrombin-induced [Ca2+]i increases. On the other hand, ADP-ribosylation of Gi type G proteins by PTX abrogated the migratory response to LPA, without affecting the thrombin effect. Similarly, raising cAMP levels inhibited, by about 50%, the LPA- but not the thrombin-induced J82 cell migration. In conclusion, human transitional-cell carcinoma (J82) cells express various G protein-coupled, calcium-mobilizing receptors, out of which only those for LPA and thrombin stimulate cell migration, indicating that phospholipase C-derived second messengers per se are not sufficient for initiating this response. The complex signal transduction processes leading to LPA- and thrombin-stimulated motility of these human carcinoma cells apparently involve several common, essential factors, such as [Ca2+]i changes and Rho protein-regulated reorganization of the cytoskeleton, as well as some distinct components, most notably distinct subtypes of heterotrimeric G proteins and apparently also distinct cAMP-sensitive targets.

Calcium↗

[Long-term results of wall stent implantation in benign prostatic hyperplasia and high risk status].

The implantation of a Wallstent prosthesis is a minimally invasive alternative to conventional TUR-P for the treatment of infravesical obstruction owing to benign prostatic hyperplasia. We report on the long-term follow-up of 37 patients with a high-risk status for TUR-P who have been implanted since May 1990. The ASA status was: ASA I: 0, ASA II: 2, ASA III: 17 and ASA IV: 18 patients. The median follow-up is now 38.5 months. Directly after implantation, a medium increase in the maximum flow-rate from 7.5 ml/s to 16.9 ml/s was documented. Residual urine was reduced from 120 to 24.2 ml on average. After 12, 18, 24 and 36 months, average maximum flow rates of 16.1, 16.7, 12.0 and 11.6 ml/s were evaluated. The corresponding residual urine was 50.3, 121.1, 56.8 and 65 ml, respectively. Also, micturition frequency decreased from 12.4 preoperatively to 8.3, 7.6, 8.0, and 8.4 per day on average. Nearly all patients reported perineal discomfort in the 1st weeks after implantation. For this reason, the stent had to be removed in 1 patient on the 45th postoperative day. In addition, a dislocated stent had to be replaced in 2 patients. Six of 15 retention patients presented with persisting detrusor dysfunction after implantation and were therefore discharged with a suprapubic tube. Endoscopic controls showed complete urothelial coverage in 78% of our patients after 6 months. After 18 months all stents were completely covered. Long-term follow-up showed reobstruction in 6 of 37 patients (16.7%) and signs of incontinence in 4 of 37 (10.8%). The late complication rate is therefore calculated at 27.5%. Stent-related deaths could not be found. We conclude that Wallstent implantation into the prostatic urethra is an alternative to TUR-P for patients at high risk from surgery. The good postoperative results also remain stable during long-term follow-up.

Aged↗

[Treatment and follow-up of patients with squamous epithelial carcinoma of the penis].

Since squamous cell carcinoma of the penis is rare, prospective trials do not exist. Therefore, new treatment strategies have to be developed. Based on our experience with the treatment of 22 patients with penile squamous cell carcinoma, we describe our therapeutic approaches. Ten patients with superficial disease (T1-2N0M0) were treated with partial penectomy. The 3-year survival rate amounted to 90%. In patients with extensive disease (T3-4 or N1-3) a partial or total penectomy was performed. After initial antibiotic therapy for 4 weeks, patients underwent inguinal lymph-node dissection and if the nodes were positive, additional pelvic lymph-node dissection. In patients with ulcerous inguinal lymph-node metastases surgical resection was performed, covering the wound with a musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n = 1). The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67% and with T3-4N1-3 (n = 8) 25%. Patients with distant metastases received inductive systemic chemotherapy with cisplatin, methotrexate and bleomycin. Objective responses occurred in 22% (1 CR, 1 PR) of 9 patients. These results suggest that immediate radical surgery with lymph-node dissection is the best treatment for squamous cell carcinoma of the penis.

Adult↗

[Therapy with mitomycin C, folic acid and 5-fluorouracil in treatment of metastatic, refractory urinary bladder carcinoma--phase II study].

We performed a phase II trial with second-line chemotherapy in patients with refractory, metastatic cancer of the bladder. Second-line therapy consists of 2.6 cycles of mitomycin-C, 5-fluorouracil and folic acid. Two patients suffered from WHO grade III side effects (nephrotoxicity, leukocytopenia). We did not find any complete or partial remission. Four patients had a stable disease; 3.3 months after therapy, patients developed tumor progression with a median survival of 9 months. Four patients reported an improvement in quality of life. Since all patients received supportive care, improvement in quality of life cannot be related to chemotherapy alone. In conclusion, second-line chemotherapy with mitomycin-C, 5-fluorouracil and folic acid has no effect on refractory, metastatic cancer of the bladder and is no alternative for cisplatin and methotrexate-based chemotherapy.

Aged↗

[Long-term outcome of surgical therapy of metastatic non-seminomatous germ cell tumor in advanced tumor stages].

We present long-term results (minimum follow-up 5 years) in 145 patients with advanced non-seminomatous germ cell tumours, who underwent radical retroperitoneal lymphadenectomy (RPLA) after chemotherapy. We correlated patients' outcomes (death of disease) to different kinds of chemotherapy and to intraoperative findings. We found that patients who were treated by a modified Einhorn scheme with cisplatin, etoposide and bleomycin have a good prognosis. In all, 90% showed no evidence of disease (NED). The NED rate was significantly lower in patients who were treated by sequential alternative chemotherapy (DOD = 37%). We determined the following prognostic factors which predict a poor outcome: salvage RPLA in the case of progressive disease or tumour marker increase during chemotherapy (DOD = 89%, P < 0.0001) residual tumour in multiple-organ systems (DOD = 41%, P = 0.0006) vital tumour in RPLA specimen (DOD = 53%, P < 0.0001) residual tumour mass > 5 cm (DOD = 41%, P = 0.0188). We found that histopathological findings of the primary tumour and tumour stage IIc-IIIc according to the Lugano classification have no prognostic significance for death of disease.

Adult↗

[Reproducibility of the pattern electroretinogram].

The pattern ERG (PERG) is used as an indicator of retinal ganglion cell function. Up to now, reports on the reproducibility of the PERG have been contradictory. We investigated the reproducibility under the conditions of the forthcoming ISCEV guidelines for the PERG. We simultaneously recorded the PERG and VEP in 42 eyes of 21 subjects to phase-reversing checkerboard stimuli with DTL electrodes. Both transient (2 rps) and steady-state (16 rps) stimulation was employed. The check sizes were 0.4 degree, 0.8 degree and 16 degrees, the mean luminance 45 cd/m2, the contrast 98%, and the field size 32 degrees x 27 degrees. Measurements were repeated at the same time of day after 1 week. In addition, we compared two different electrode positions in 16 eyes: (1) across the cornea along the lower lid; and deep in the conjunctival sac. With position (1) the amplitudes were found to be higher by 20% than (2). We calculated the coefficient of variation (CV) of amplitude as a measure of reproducibility. CV was 7 +/- 1% for the steady-state PERG, 9 +/- 1% for the transient PERG, 12 +/- 2% for the steady-state VEP and 14 +/- 3% for the transient VEP. For the latency of the PERG, the intersession CV was found to be 1.5%. Amplitude reproducibility was somewhat higher under steady-state as compared to transient stimulation; we attribute this to the high noise rejection of the Fourier analysis. Altogether, the amplitude reproducibility of the PERG is somewhat higher than that of the VEP.

Adult↗

Management of neurogenic fecal incontinence in myelodysplastic children by a modified continent appendiceal stoma and antegrade colonic enema.

OBJECTIVES: Antegrade colonic enemas for neurogenic fecal incontinence via reverse reimplanted appendices (Mitrofanoff principle) have been primarily reported by Malone and coworkers in 1990. We used a modification of the described surgical technique and treated the first 10 patients with neurogenic fecal incontinence due to spina bifida. The surgical procedure and the results are reported. METHODS: Since November 1991, we have used a surgical procedure similar to the appendiceal continence mechanism in urinary diversion to establish a continent colonic cutaneous stoma for antegrade enemas in 10 myelodysplastic patients (4 females, 6 males; median age 13.2 years [range 6 to 26]) with severe neurogenic fecal incontinence. The average follow-up is now 26.4 months (range 12.5 to 50). All patients had neurogenic bladder dysfunction successfully managed by clean intermittent catheterization, anticholinergic drugs, or artificial sphincter implantation. The surgical technique for fecal incontinence included the partial orthotopic submucosal imbedding of the appendix into a cecal tenia and the fixation of the ileocecal region at the inner side of the abdominal wall after creation of an appendicocutaneous catheterizable stoma. RESULTS: All patients reached fecal continence for at least 38 hours (median 45.3) by using antegrade colonic enemas with 1.5% saline solution (n = 9) or GoLYTELY solution (n = 1), 0.5 to 1.5 L every 2 to 3 days. All other therapies (diet, oral medication, rectal purgative, or enema) to reach fecal continence had previously failed. There were only two complications seen at the follow-up. One boy with an artificial urinary sphincter presented with infection of the sphincter system, which led to explantation. Another boy presented 15 months after creation of the colonic appendiceal stoma with saline intoxication possibly due to a homemade saline solution. CONCLUSIONS: We conclude that the antegrade colonic enema via an orthotopic continent appendiceal stoma is a safe and highly effective treatment modality for fecal incontinence in patients with neurogenic bowel dysfunction if nonsurgical management has failed.

Adolescent↗

Rhinal cortex lesions impair simultaneous olfactory discrimination learning in rats.

Previous studies have found that combined lesions of the perirhinal and entorhinal (PRER) cortical areas do not impair, and in fact may facilitate, acquisition of successive olfactory discriminations. The present study sought to determine the effect of PRER lesions on the acquisition of simultaneous olfactory discriminations. Rats (N = 24; 9 PRER-lesioned, 15 sham-operated controls) were trained on a single simultaneous olfactory discrimination; PRER-lesioned animals were dramatically and persistently impaired in acquisition of the discrimination relative to sham-operated subjects. These data are consistent with the view that, in concert with the hippocampus, these cortical regions participate in the encoding of relations among multiple extant stimuli.

Animals↗

Odor-guided fear conditioning in rats: 2. Lesions of the anterior perirhinal cortex disrupt fear conditioned to the explicit conditioned stimulus but not to the training context.

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS-unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning.

Animals↗

Protein kinase C isoenzymes in rat and human cardiovascular tissues.

1. We have compared the expression of protein kinase C (PKC) activity and immuno-detectable isoenzymes in cytosolic and membrane extracts of rat and human cardiovascular tissues (heart, kidney, aorta, saphenous vein). Experiments were performed in raw extracts and upon combined diethylaminoethylcellulose (DEAE) and phenylsepharose column chromatography. 2. PKC activity that bound to DEAE mostly eluted with 200 mM NaCl. DEAE-purified PKC from all tissues except rat kidney bound almost quantitatively to phenylsepharose and eluted with 0.5-0 M NaCl. 3. Immunoblots with an antibody against classical PKCs and the activator profile for phosphatidylserine, diolein and Ca2+ revealed that the PKC from rat kidney, which did not bind to phenylsepharose, was most probably due to a proteolytically-generated, constitutively active PKC which is not under the control of a regulatory subunit. 4. Studies in the reference tissue, rat brain, demonstrated that all PKC isoenzymes investigated (classical PKCs alpha, beta, gamma, new PKCs delta, epsilon, eta, theta, and atypical PKCs zeta, lambda, iota) have similar DEAE and phenylsepharose chromatography elution profiles. In the functional assay an inhibitor of all known PKC isoenzymes, bisindolylmaleimide, and a specific inhibitor of classical PKCs, Gö 6976, both inhibited PKC from rat brain completely and with high potency indicating that the functional assay preferentially detects classical PKC isoenzymes. 5. Each PKC isoenzyme had a tissue-specific expression profile which was similar in rat and man. The classical PKC alpha, the new PKCs delta and epsilon and all atypical PKCs were detectable in most tissues, whereas the PKC beta and PKC gamma were not detected in any pheripheral tissue; PKC eta and PKC theta were found in some tissues. 6. We conclude that combined DEAE and phenylsepharose chromatography is useful to enrich and detect PKC isoenzymes; no major species differences in tissues-specific expression patterns appear to exist between rat and man.

Animals↗

Phase II study: adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

OBJECTIVE: Though para-aortal and ipsilateral iliacal radiation is the established adjuvant treatment for clinical stage I seminoma, promising results have been reported on adjuvant single-agent carboplatin therapy. PATIENTS AND METHODS: We treated 43 patients with clinical stage I seminoma according to this option. They received 2 courses of single-agent carboplatin (400 mg/m2) at an intervall of 3 weeks. Therapy could be performed on an outpatient basis within 2 h. RESULTS: Therapy was well tolerated. Apart from minor gastrointestinal disorders and mild myelosuppression, no adverse reactions were observed. The median follow-up is 28 months. Up to now no recurrences have been noted. CONCLUSIONS: If the recurrence rate remains as low as after adjuvant radiotherapy, which should be proved in a phase III study, single-agent carboplatin therapy will be an alternative adjuvant approach for clinical stage I seminoma.

Adult↗

Improved prognosis assessment for patients with bladder carcinoma.

Urothelial carcinomas are heterogeneous diseases with an aggressive clinical potential. To date, the most used prognostic factors for bladder carcinomas are grade and stage, which are based on histopathological parameters that are often not reliable in predicting a clinical outcome. Here, we evaluated the clinical outcome of 100 patients with urothelial carcinomas with follow-up information for more than 2 years after surgery in relation to the expression of two cell surface antigens, ie, E-cadherin and autocrine motility factor receptor (AMF-R, gp78). Frozen bladder tissues were serially cut, stained either with hematoxylin and eosin for grading, with the anti-gp78 antibodies, or with anti-E-cadherin antibodies to determine level of expression. Of 63 patients presented at the time of diagnosis with pathological loss of E-cadherin associated with increased gp78 expression, 39 (62%) succumbed to tumor progression or death. Of 37 patients with normal E-cadherin and gp78 expression positive and negative, respectively, 36 (97%) had favorable disease outcomes (P < 0.0001). The results suggest that in bladder carcinomas abnormal expression of both E-cadherin and gp78 results in a poor disease outcome, independent of tumor stage and grade.

Age Factors↗

Odor-guided fear conditioning in rats: 1. Acquisition, retention, and latent inhibition.

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)-unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS-US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more at any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning.

Animals↗