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Biomedical subjects

T Otto

Publications and source records attributed to T Otto.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Tumor cell motility. A novel therapeutic target in bladder carcinoma, experimental and clinical results.

Surgery, chemotherapy and radiotherapy are the current modalities of tumor management. However, in systemic disease, predicted patients' cure can be achieved in but a few tumor diseases. Based on previous basic research we have highlighted that the loss of cell-cell adhesion in association with an increased tumor cell motility is an essential feature of the malignant potential of bladder tumors. Thus, we have attempted therapeutical methods differing from hitherto existing treatments by focusing on a tumor cell function we call cell motility. Characterization of so-called anti-motility drugs was performed biochemically as well analyzed by in vitro by using in established bladder carcinoma cell lines. We evaluated the potential therapeutic benefit in a model of chemically induced bladder carcinoma followed by a phase I/II trial applying anti-motility drugs in patients which were chemotherapy-resistant and having metastatic bladder cancer. Both basic research as well as the results of first translational clinical trials confirmed, that advanced bladder carcinomas can be favorably affected by inhibition of tumor cell motility.

Adult↗
PubMed1998

Contributions of anterior perirhinal cortex to olfactory and contextual fear conditioning.

The present experiments examined the effects of excitotoxic lesions of anterior perirhinal cortex (PRH) on the expression of fear conditioned to an explicit olfactory CS and to the context in which CS-US pairing took place. Animals with anterior PRH lesions exhibited an attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data replicate previous findings in our laboratory examining the effects of aspirative lesions of anterior PRH, and are consistent with the notion that this cortical region comprises a critically important component of the neural system mediating the acquisition and/or expression of associations between olfactory cues and footshock.

Analysis of Variance↗
PubMed1998

Phase II trial of titanocene dichloride in advanced renal-cell carcinoma.

Titanocene dichloride was capable of inhibiting the growth of different types of human tumors in vitro. A total of 14 patients with metastatic renal-cell carcinoma (RCC) received 270 mg/m2 titanocene dichloride every 3 weeks for 6 weeks. Although the toxicities and side effects encountered were mild to moderate, no partial or complete response was detectable. In conclusion, titanocene dichloride has no advantage in the therapy of RCC.

Adult↗
PubMed1998

In prostatism patients the ratio of human glandular kallikrein to free PSA improves the discrimination between prostate cancer and benign hyperplasia within the diagnostic "gray zone" of total PSA 4 to 10 ng/mL.

OBJECTIVES: Human glandular kallikrein (hK2) possesses approximately 80% structure identity with prostate-specific antigen (PSA). Moreover, messenger ribonucleic acid for hK2 and for PSA is expressed in both benign and malignant prostatic tissue. We investigated whether the hK2 serum measurement may improve the detection of prostate cancer (PCa) in patients with total PSA of 4 to 10 ng/mL (diagnostic "gray zone"). METHODS: Blood samples were obtained from 90 consecutive male patients with lower urinary tract symptoms and total PSA values of 4 to 10 ng/mL. Eighty-one patients underwent transurethral resection of the prostate and 6 radical prostatectomy. The patients were divided into two groups: I, patients with PCa (n = 20) and II, patients with benign prostatic hyperplasia (BPH) (n = 70). An "in-house" immunofluorometric assay with analytical sensitivity of 0.01 ng/mL and the functional sensitivity of 0.05 ng/mL (at this level the mean coefficient of variation, calculated from the precision profile based on the assays of serum samples, was less than 20%) was used to determine serum hK2 concentrations. Total PSA, free PSA (ProStatus), and PSA complexed to alpha1-antichymotrypsin (PSA-ACT) were also measured. Free/total PSA, hK2/total PSA, and hK2/free PSA ratios were calculated. RESULTS: The serum hK2 could be detected in all samples and in 76 (84.4%) of 90 samples (PCa, n = 18; BPH, n = 58) at given functional sensitivity level. For these cases the median concentration of hK2 was 0.135 ng/mL in PCa and 0.09 ng/mL in BPH (P < 0.1). The median hK2/total PSA ratio was 2% for PCa and 1.6% for BPH (P < 0.2). The median free/total PSA ratio was 0.122 for PCa and 0.215 for BPH (P < 0.0008) and the hK2/free PSA ratio was 0.139 for PCa and 0.075 for BPH (P < 0.000003). At a 7.2% cutoff, the specificity of hK2/free PSA ratio was 48.2% at 100% sensitivity and increased to 60.3% at 94.4% sensitivity level (the area under the receiver operating characteristic curve was 0.86). In comparison, the free/total PSA ratio at a 25.2% cutoff had a sensitivity of 94.4% and a specificity of 27.6% (area under the curve = 0.76). CONCLUSIONS: hK2 was detected in all sera with total PSA values of 4 to 10 ng/mL. Of particular clinical interest is the finding that the hK2/free PSA ratio had a better specificity without loss of sensitivity for PCa than total PSA or the PSA free/total ratio within the range of 4 to 10 ng/mL total PSA. hK2 in combination with free PSA may offer a new diagnostic means for PCa detection.

Aged↗
PubMed1998

Excitotoxic lesions of the hippocampus disrupt runway but not consummatory contrast.

Rats shifted from a 12-pellet to a 1-pellet reward for running in a straight runway showed a decrease in start, run, and goal speed to levels below rats that received only the 1-pellet reward throughout training (a negative contrast effect). Contrast was greatest in the goal region of the runway. Rats with damage to the hippocampus produced by the excitotoxin ibotenic acid failed to show a negative contrast effect under these conditions. The same lesioned rats tested in a consummatory, contrast procedure following a shift from 32% to 4% sucrose showed a negative contrast effect equivalent to sham-lesioned rats. These data suggest that the hippocampus is necessary for behavioral outcomes based on encoding or comparison that affect approach behavior, but not for such outcomes that affect consummatory behavior.

Analysis of Variance↗
PubMed1998

Both pre- and posttraining excitotoxic lesions of the basolateral amygdala abolish the expression of olfactory and contextual fear conditioning.

The present study examined whether the basolateral amygdaloid complex (BLA) participates in the expression of fear conditioned to both an olfactory conditioned stimulus (CS) and the training context. In Experiment 1, pretraining excitotoxic lesions of the BLA abolished immediate postshock freezing, conditioned freezing to an olfactory CS, and conditioned freezing to the training context. Control experiments indicated that lesioned and sham-lesioned subjects did not differ in locomotor activity or in acquisition of a successive-cue odor discrimination task, suggesting that deficits in freezing behavior exhibited by BLA subjects were not due to an impairment in primary aspects of olfaction or to a general enhancement of locomotor activity. In Experiment 2, excitotoxic lesions of the BLA produced either 1 day or 15 days after olfactory fear conditioning abolished both odor-elicited and contextual freezing. Collectively, these data support the notion that the BLA participates in an enduring manner in the expression of conditioned freezing behavior elicited by both olfactory and contextual stimuli.

Amygdala↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor and interferon-alpha 2B in patients with advanced renal cell carcinoma.

OBJECTIVE: Biological response modifiers such as interferon-alpha2B (IFN-alpha2B) have well-known clinical activities against renal cell carcinoma (RCC). Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has antitumorigenic effects both in vitro and in vivo. Therefore, a phase-I/II trial of IFN-alpha2B and GM-CSF was performed in patients with metastatic RCC. METHODS: 21 patients in groups of 3 patients received GM-CSF at 7 different dose levels (15-300 microg) subcutaneously in combination with IFN-alpha2B at a fixed dose of 10 x 10(6) IU s.c. three times weekly for 12 weeks. RESULTS: Two complete remissions have been observed, both with lung metastases only. With increasing dose levels of GM-CSF a slight tendency to more toxicity was detectable. Due to grade-3 toxicities 5 patients (24%) dropped out of the treatment schedule. Increases in WBC, neutrophils, lymphocytes, and monocytes were noted but were not related to the dose levels of GM-CSF. CONCLUSIONS: Results demonstrate that simultaneous administration of GM-CSF and IFN-alpha2B is tolerated up to doses of 120-150 microg GM-CSF three times weekly. But there is no additional antitumorigenic effect of GM-CSF because the overall response rate of the combined administration of GM-CSF/IFN-alpha2B is similar to IFN-alpha2B alone and there is no obvious dose relationship between increasing doses of GM-CSF and the responses.

Adult↗
PubMed1997

Paclitaxel-based second-line therapy for patients with advanced chemotherapy-resistant bladder carcinoma (M1): a clinical Phase II study.

BACKGROUND: In a previous clinical trial, the authors disclosed that the expression of tumor cell motility factor gp78hAMFR correlates with tumor progression in patients with bladder carcinoma. This study was initiated to evaluate whether the combination of cytostatic drugs with an antimotility factor has an effect on chemotherapy-resistant bladder carcinoma. METHODS: In a Phase II trial, the authors evaluated the influence of paclitaxel, carboplatin, and an antimotility factor (acellular pertussis vaccine [APV]) in 18 patients with cisplatin- and methotrexate-resistant metastatic bladder carcinoma. Intramuscular injection of APV 3 times in the first week, on Days 1, 4, and 7, was followed by paclitaxel 135 mg/m2 and carboplatin 400 mg/m2. After an interval of 1 week APV was given again on Days 15 and 19. Each cycle lasted 3 weeks. On Day 22 the cycle was repeated. RESULTS: Four of 18 patients had objective responses (2 had complete remissions and 2 had partial remissions). After a median number of 2.5 cycles, side effects did not exceed World Health Organization Grade 4. CONCLUSIONS: The results of this clinical Phase II study demonstrate that the combination of paclitaxel-based therapy causes complete remissions previously not obtained with second-line chemotherapy, although no conclusions can be drawn as to the effectiveness of the individual substances. Further trials have to be evaluated with regard to the individual components.

Adult↗
PubMed1997

Memory representation within the parahippocampal region.

The activity of 378 single neurons was recorded from areas of the parahippocampal region (PHR), including the perirhinal and lateral entorhinal cortex, as well as the subiculum, in rats performing an odor-guided delayed nonmatching-to-sample task. Nearly every neuron fired in association with some trial event, and every identifiable trial event or behavior was encoded by neuronal activity in the PHR. The greatest proportion of cells was active during odor sampling, and for many cells, activity during this period was odor selective. In addition, odor memory coding was reflected in two general ways. First, a substantial proportion of cells showed odor-selective activity throughout or at the end of the memory delay period. Second, odor-responsive cells showed odor-selective enhancement or suppression of activity during stimulus repetition in the recognition phase of the task. These data, combined with evidence that the PHR is critical for maintaining odor memories in animals performing the same task, indicate that this cortical region mediates the encoding of specific memory cues, maintains stimulus representations, and supports specific match-nonmatch judgments critical to recognition memory. By contrast, hippocampal neurons do not demonstrate evoked or maintained stimulus-specific codings, and hippocampal damage results in little if any decrement in performance on this task. Thus it becomes increasingly clear that the parahippocampal cortex can support recognition memory independent of the distinct memory functions of the hippocampus itself.

Animals↗
PubMed1997

Deletion analysis at the DEL-27, APC and MTS1 loci in bladder cancer: LOH at the DEL-27 locus on 5p13-12 is a prognostic marker of tumor progression.

Inactivation of relevant tumor-suppressor genes by allelic or homozygous deletion is a characteristic event in tumor cells. Here, the prognostic value of allelic deletions on 5p13-12 at the putative del-27 tumor-suppressor locus and in the APC tumor-suppressor gene on 5q21, as well as homozygous deletions of the MTS1 (p16INK4, CDKN 2) tumor-suppressor gene on 9p21 was assessed in 87 bladder cancers using microdissection and PCR-based assays. Tumor-specific LOH was detected in 10 of 38 (26%, del-27), and 15 of 30 (50%, APC) informative specimens. Homozygous deletion of the MTS1 gene was detected in 33% of 84 tumors investigated. These deletion frequencies implicate the 3 tumor-suppressor regions in the genesis of transitional-cell carcinoma. In contrast to deletions of the APC or MTS1 genes, LOH at the del-27 locus correlated with tumor progression. This suggests that loss of the putative tumor-suppressor gene DEL-27 is involved in an aggressive behavior of the tumor cells and appears to be a prognostic marker for the clinical outcome of patients with transitional-cell carcinoma.

Carcinoma, Transitional Cell↗
PubMed1997

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↗