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Biomedical subjects

T Schenk

Publications and source records attributed to T Schenk.

At least 37 records · Page 2Linked to original sources

Time constraints improve reaching movements in an ataxic patient.

We report on a patient (AM) with a post-traumatic ataxia who has uncoordinated reaching movements to resting targets, but is able to catch moving objects. AM participated in three experiments to identify factors responsible for the favorable effect of object motion on her performance. In the first experiment, the task was to catch an object that moved away from AM. The speed of the object to be grasped (target object) varied. In experiment 2, the effect of time constraints on reaching performance was examined. AM had to reach for and grasp a stationary object and was allowed either 600 ms or 2000 ms to perform the task. In the third experiment, liquid crystal shutter glasses were used to manipulate the time that the subject was able to view the stationary target object and her reaching movements (vision-on time). While increased speed of the object, tighter time constraints, and short vision-on time hardly affected the performance of AM's unaffected left hand, they greatly improved her right-hand performance. These results are discussed in light of the hypothesis that the brain mechanisms controlling externally triggered movements differ from those controlling internally regulated movements.

Adult↗

Replication of a foamy virus mutant with a constitutively active U3 promoter and deleted accessory genes.

Foamy viruses (FVs) are complex retroviruses which require for their replication the activity of a transcriptional trans-activator (Tas) as well as Tas-responsive elements in the viral promoters. A mutant of the chimpanzee FV strain, CFV/hu (previously called human FV), genome in which most of the U3 promoter of the CFV long terminal repeat was substituted by the constitutively active human cytomegalovirus immediate early gene enhancer/promoter was constructed. This plasmid (pTS12) and a derivative (pTS13), which has a deletion in the tas gene, gave rise to replication-competent virus. Compared with parental CFV, both mutants replicated only very poorly, with retarded growth kinetics and maximal cell-free virus titres reduced by approximately three orders of magnitude. Mutation of the DD35E motif of the CFV integrase to DA35E rendered the recombinant TS virus replication-deficient. This indicated that provirus integration is probably still required for this FV derivative, which had been converted from a complex regulated retrovirus into a simple one by incorporation of a constitutively active promoter from another virus which regularly does not integrate into the host cell genome.

Animals↗

Visual motion perception after brain damage: I. Deficits in global motion perception.

We report on the test results of a group of 32 mostly unilaterally brain-damaged patients examined for global visual motion perception. Three of these patients had severely impaired visual motion perception in their contralateral visual half-field, a deficit remarkably similar to the perceptual defects found in V5-lesioned monkeys. Two of these three patients had a right-hemisphere lesion; the remaining one had a left-hemisphere lesion. We conclude that both hemispheres of the human brain contain an area, functionally equivalent to V5, which subserves visual motion perception in the contralateral visual half-field. Lesion analysis revealed that this area is located in the posterior medial temporal gyrus.

Adult↗

Visual motion perception after brain damage: II. Deficits in form-from-motion perception.

We investigated form-from-motion perception (FFM perception) in a sample of 39 patients with acquired brain damage. Pronounced FFM deficits were found in two patients (FM1 and FM2) with biparietal lesions. Both patients were able to identify the relevant figure, when it was not embedded in obstructive texture. Moreover, they could localize the figures in the FFM condition, although they could not reliably identify them. The two patients had normal motion coherence thresholds. Their performance in a static figure-ground task did not differ from that of other patients. These findings imply that the FFM deficits are not caused by impairment of basic visual motion or form perception but are the consequence of damage to a parietal brain structure involved in the combined analysis of visual motion and form information. The nature and functional role of this brain structure as well as the implications of our results for models of FFM perception are discussed.

Adult↗

Detection of chromosomal aneuploidy by interphase fluorescence in situ hybridization in bronchoscopically gained cells from lung cancer patients.

BACKGROUND: Development and progression of human malignancies involve multiple genetic changes. New techniques to distinguish neoplastic from benign diseases unequivocally with small amounts of cells as gained by bronchoscopy are needed to come closer to the goal of an early diagnosis in lung cancer. STUDY OBJECTIVE: The aim of this study was to determine whether interphase fluorescence in situ hybridization (FISH) can be used to visualize chromosomal aberrations in bronchoscopically gained cells from lung cancer patients and could eventually become a complementary technique to conventional cytology. METHODS: We examined 20 cancerous specimens (10 primary tumors, 10 malignant effusions) of 18 lung cancer patients by FISH with DNA probes specific for chromosomes 3, 8, 11, 12, 17, and 18. From five additional patients, endobronchial brushings and/or forceps biopsy specimens were subjected to interphase FISH analysis. RESULTS: In all primary tumors and malignant effusions, highly aneuploid cells were detectable by FISH. Chromosomal aberrations always consisted of gains of chromosomal signal numbers, and all chromosomes were found to be aneuploid to a similar extent. Using chromosomal aneuploidy as a marker of malignancy, material obtained by bronchoscopy was then examined for the presence of malignant cells. In all specimens, evidence for malignancy was obtained by FISH, including three specimens in which cells appeared to be normal or reactively changed by cytologic criteria. CONCLUSION: We conclude that interphase FISH is useful in detecting aneuploidy associated with malignancy in bronchoscopically gained cells that do not clearly meet the criteria of malignancy by conventional cytologic study.

Adenocarcinoma↗

Phase I/II trial of dexverapamil, epirubicin, and granulocyte-macrophage-colony stimulating factor in patients with advanced pancreatic adenocarcinoma.

BACKGROUND: The purpose of this study was to determine the maximum tolerated dose (MTD) of a cytotoxic regimen consisting of the second-generation chemosensitizer dexverapamil (DVPM), high dose epirubicin, and recombinant human granulocyte-macrophage-colony stimulating factor (GM-CSF) in pancreatic carcinoma. PATIENTS AND METHODS: Twenty-eight previously untreated patients with locally advanced or metastatic adenocarcinoma of the pancreas were studied. Treatment consisted of oral DVPM at a dose of 1000-1200 mg/day for 3 days, epirubicin administered as an intravenous bolus injection on Day 2 with an initial dose of 90 mg/m2, and a dose of GM-CSF of 400 micrograms administered subcutaneously from Day 5s through 14. Epirubicin dose escalation levels were 90, 105, 120 and 135 mg/m2. Consecutive cohorts of four to eight patients were planned at each dose level. Treatment cycles were repeated every 3 weeks. RESULTS: Hematologic toxicity, specifically granulocytopenia, constituted the dose-limiting toxicity with an MTD of 120 mg/m2 for epirubicin. Despite routine supportive therapy with GM-CSF, four, two, and five patients experienced Grade 4 granulocytopenia during their first two treatment courses at levels 105, 120, and 135 mg/m2, respectively. Grade 4 granulocytopenia was observed in two, three, and one additional patients during subsequent courses with these levels. Nonhematologic toxicity was uncommon, generally modest, and did not correlate clearly with the anthracycline dose. Dexverapamil-related cardiovascular symptoms occurred frequently, but they never resulted in serious toxicity requiring active medical intervention or permanent discontinuation of therapy. Nine of 28 patients achieved partial responses to this therapy. Stable disease was observed in nine patients, and tumor progress occurred in 10. CONCLUSION: The MTD of epirubicin for this regimen with DVPM and GM-CSF was 120 mg/m2 every 3 weeks. Though it remains uncertain whether the encouraging response activity observed in this disease-oriented Phase I study was, in fact, due to successful modulation of multidrug resistance, these results suggest that this regimen is likely to be an effective and tolerable treatment strategy for patients with pancreatic cancer, which should be evaluated further.

Adenocarcinoma↗

High-performance liquid chromatographic determination of the rhamnolipids produced by Pseudomonas aeruginosa.

The bacterial biosurfactants 3-[3'-(L-rhamnopyranosyloxy)decanoyloxy]decanoic acid (RL-1) and 3-[3'-(2"-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosyloxy) decanoyloxy]decanoic acid (RL-2) were isolated from Pseudomonas aeruginosa DSM 2659 cultures. An HPLC method was developed for the p-bromophenacyl esters of the rhamnolipids. Separation was obtained within 25 min on a RP C18 column using a linear gradient of water-acetonitrile (30:70 to 0:100) and UV detection (265 and 320 nm). Linearity of response existed for 1.2-25 microg of the RL-1 and 1.8-25 microg of the RL-2-p-bromophenacyl ester (0.9-19.2 microg RL-1 and 1.3-18.0 microg RL-2). The reproducibility of the entire analytical method (extraction, derivatisation) was tested.

Carbohydrate Sequence↗

Interphase cytogenetics reveals a high incidence of aneuploidy and intra-tumour heterogeneity in breast cancer.

The occurrence of aberrations involving chromosomes 11 and 17 in malignant tissues of breast cancer patients has not yet been studied systematically. Using fluorescence in situ hybridisation (FISH) with centromere-specific probes, we determined chromosome 11 and 17 status in interphase nuclei from primary and/or metastatic breast cancer cells. In all cancerous specimens obtained from 30 patients, FISH identified cells with clonal chromosomal abnormalities, with aneuploidy rates ranging from 6% to 92% (median 59%). There was a gain of centromeric signals for chromosome 11, most likely corresponding to hyperploidy; aberrations of chromosome 17 in specimens from 26 patients (87%) were hyperploid as well; however, four cases (13%) showed loss of chromosome 17 centromeres. All specimens contained heterogeneous aneuploid cell populations with excessive gain of signals in some cases. The pattern of aneuploidy did not appear to correlate with tumour grade/stage and was comparable in primary tumours and corresponding metastatic axillary lymph nodes, indicative of genetic instability early in tumour development. Screening with a panel of FISH probes may lead to enhanced sensitivity and specificity in detecting malignant cells, as demonstrated in this study with effusions which could not be conclusively interpreted as being malignant by cytological criteria.

Adult↗

Tissue polypeptide-specific antigen (TPS) in monitoring palliative treatment response of patients with gastrointestinal tumours.

The new proliferation marker, tissue polypeptide-specific antigen (TPS), representing the specific epitope M3 of tissue polypeptide antigen, and three conventional biochemical markers, CEA, CA 19-9 and CA-195, were analysed in 69 patients with advanced gastrointestinal tumours. The aim of our study was to assess the clinical relevance of these markers and to determine whether their use in monitoring the course of the disease can reduce the need for serial imaging procedures. At baseline, pathologically elevated TPS levels occurred in 90% of patients. CEA was elevated in 73%, CA 19-9 in 59% and CA-195 in 68%. With a detection rate of > 90% in both advanced colorectal (n = 37) and pancreatic cancer (n = 20), and of 75% in gastric cancer (n = 12), TPS was the most sensitive marker in all three tumour types included in this analysis. Serial evaluations of TPS and other biochemical markers were available in 39 patients undergoing palliative systemic chemotherapy. Treatment with a fluorouracil-based regimen resulted in a partial response in 5/27 patients with colorectal cancer, whereas 2/12 patients with pancreatic cancer responded to therapy with a high-dose epirubicin combination regimen. All other patients had disease stabilisation or suffered from progressive disease. When compared with the results of serial CT scanning, the TPS correlated best with the course of the disease, the positive predictive value being 75% for a partial response, 96% for stable disease and partial response combined and 100% for progressive disease. The corresponding values for CEA were 50%, 81% and 62% and were similar to those for CA 19-9 and CA-195. In summary, TPS seems to represent a sensitive, clinically relevant and specific marker of proliferative activity in gastrointestinal cancer. According to our preliminary results in colorectal and pancreatic cancer, TPS may be considered as the primary means of monitoring treatment, and imaging reduced to confirm the response.

Adult↗

Preoperative characterization of pigmented skin lesions by epiluminescence microscopy and high-frequency ultrasound.

BACKGROUND AND DESIGN: Previous studies have referred to the value of epiluminescence microscopy in the differential diagnosis of pigmented skin lesions and to the possibility of preoperative tumor thickness measurement in malignant melanoma by high-frequency ultrasound. Both noninvasive methods have been combined in this study. The question of improved diagnostic accuracy was discussed. Previously proposed epiluminescence microscopic characteristics of 508 melanocytic lesions and sonographic characteristics of 792 skin tumors were investigated for their sensitivity and specificity. The tumor thickness of 108 malignant melanomas was measured sonographically. RESULTS: Black dots, irregular pigment network, and grayish-blue areas have been shown to be the most sensitive characteristics, whereas pseudopods, grayish-blue areas, and a whitish veil have been shown to be the most specific epiluminescence microscopic features for malignant melanoma. Sonography alone cannot reliably distinguish between different skin tumors. Preoperatively, the tumor thickness of 85% of the melanomas was assessed correctly concerning the pT stage. CONCLUSIONS: A 20-MHz ultrasound, in addition to epiluminescence microscopy, may improve the diagnostic accuracy by delivering information about depth and topographic location of skin tumors, but cannot give highly specific information about tissue dignity. It is a reliable tool for tumor thickness measurement for surgical planning.

Adult↗

Investigations of the suitability of pallesthesiometry in the diagnostics of functional disturbances of the peripheral nervous system.

This contribution presents the results of fundamental investigations of the suitability of measurements of vibration sensitivity threshold (pallesthesiometry) as a method for the assessment of vibration-induced nerve impairments. Sinusoidal vibration stimuli are applied at the fingertips of the subjects in this method. The sensitivity threshold of the subjects is determined similar like the hearing threshold in audiometry and is used as a measure for possibly existing nerve disorders. Laboratory and field experiments were carried out by means of a simple to serve and inexpensive pallesthesiometer. The test results proved the suitability of the pallesthesiometry for screening purposes in principle. Concentration and cooperation of the subjects as well as the suitable selection of the investigation frequencies according to the frequency content of the vibration exposure are of essential meaning for comparable and reliable measuring results. Furthermore the rest and vibration-free position of the hand and fingers during the measurement of the thresholds are important to avoid measurement falsifications. A most extensive standardization of the investigation methodology and of the measuring equipment as well as the establishment of normative values of the sensitivity thresholds for different age groups are necessary for a broad application of the pallesthesiometry in practice.

Adult↗

Statistical analysis of vibration-induced bone and joint damages.

Vibration-induced damages to bones and joints are still occupational diseases with insufficient knowledge about causing and moderating factors and resulting damages. For a better understanding of these relationships also retrospective analyses of already acknowledged occupational diseases may be used. Already recorded detailed data for 203 in 1970 to 1979 acknowledged occupational diseases in the building industry and the building material industry of the GDR are the basis for the here described investigations. The data were gathered from the original documents of the occupational diseases and scaled in cooperation of an industrial engineer and an industrial physician. For the purposes of this investigations the data are to distinguish between data which describe the conditions of the work place (e.g. material, tools and posture), the exposure parameters (e.g. beginning of exposure and latency period) and the disease (e.g. anamnestical and radiological data). These data are treated for the use with sophisticated computerized statistical methods. The following analyses were carried out. Investigation of the connections between the several characteristics, which describe the occupational disease (health damages), including the comparison of the severity of the damages at the individual joints. Investigation of the side dependence of the damages. Investigation of the influence of the age at the beginning of the exposure and the age at the acknowledgement of the occupational disease and herewith of the exposure duration. Investigation of the effect of different occupational and exposure conditions.

Adolescent↗

Effective second line chemotherapy of advanced breast cancer with navelbine and mitomycin C.

The efficacy and toxicity of navelbine 30 mg/m2 administered intravenously (IV) over 30 minutes every 3 weeks, and mitomycin C 15 mg/m2 administered IV every 6 weeks was assessed in 34 patients with metastatic breast cancer refractory to first-line chemotherapy. An overall objective response rate of 35% was achieved (95% confidence interval, 20% to 53%), with an additional 47% of patients maintaining stable disease (SD). Four of 12 patients who responded had received previous anthracycline therapy. Median time to progression for responders and patients with SD was 6.3 months. The median survival of all patients was 8.8 months. Tolerance of this regimen was remarkable. WHO grade 3/4 side effects consisted of granulocytopenia in 12% and thrombocytopenia in 15%, and included only 1 patient each with grade 3 neurotoxicity and local toxicity due to extravasation. Delay of treatment was required for hematologic toxicity in 7 patients, and 5 required dose reductions. In conclusion, navelbine/mitomycin C is an active and well-tolerated regimen that may be considered for second-line treatment. If our results are confirmed by larger analyses of other patients studies, this combination might also warrant further exploration in combination with other active agents for front line chemotherapy of advanced breast cancer.

Adult↗

Pharmacokinetic interaction between epirubicin and the multidrug resistance reverting agent D-verapamil.

The potential for a pharmacokinetic interaction between epirubicin and the second-generation multidrug resistance modulating agent D-verapamil (DVPM) has been investigated in six patients with advanced colorectal cancer. Our results indicate that a significant interaction takes place. Enhanced distribution of epirubicin from the serum and altered disposition might, in fact, explain the increased level of myelotoxicity in this pilot as well as in other clinical phase II studies involving DVPM.

Colonic Neoplasms↗