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Biomedical subjects

M Stöhr

Publications and source records attributed to M Stöhr.

At least 37 records · Page 2Linked to original sources

[The prognostic place of EEG in comparison with evoked potentials in severe hypoxic brain damage].

This retrospective study comprises 34 patients, who died due to the cerebral damage caused by severe anoxia, who were assessed by EEG and AEP or SEP on the same day and in whom at least one of these electrophysiological methods indicated a fatal prognosis. EEG-findings identified 76% of patients with fatal outcome, whereas SEP reliably predicted the outcome in 93% of patients, who died of the cerebral anoxia. In some patients centrally acting drugs made EEG-based but not SEP-based prognosis impossible. In some cases of fatal brain damage, however, only the EEG-findings as opposed to SEP-findings predicted the fatal outcome. Thus the combined assessment by EEG and SEP appears to be optimal in the assessment of an early prognosis. The BAEP were of less prognostic value than the EEG. BAEP findings indicating a fatal outcome were to be found mainly in final clinical stages with loss of brainstem function, whereas EEG as well as SEP identified a considerable number of fatal cases in spite of comparably favourable clinical findings. The evaluation of early electrophysiological testing done within the first 3 days after the anoxic event results in an identical estimation of the prognostic significance of EEG versus BAEP- or SEP-findings, respectively.

Adolescent↗

In vitro and clinical characterisation of a Newcastle disease virus-modified autologous tumour cell vaccine for treatment of colorectal cancer patients.

A virus-modified autologous tumour cell vaccine prepared from human colorectal cancer cells is described. After dissociation an average of 5 x 10(7) cells/g tissue were obtained from primary tumours and 9 x 10(7)/g tissue from metastases with an average viability of 72% and 51%, respectively. Following irradiation (200 Gy), inactivation of the proliferative activity of the cells was demonstrated by their degeneration in tissue culture and the absence of incorporation of 3H-labelled thymidine. One third of the cells were still metabolically active, as shown by the incorporation of 3H-uridine and a mixture of 3H-aminoacids. The dissociated cells expressed MHC class I and II antigens in a qualitatively similar way to tissue sections. Epithelium-specific antigens (detected by MAb HEA125) were expressed on an average of more than 75% cells of the suspension, while leucocyte-specific antigens (detected by MAb CD53) were expressed on an average of less than 25% cells. The vaccine was prepared by admixing the nonlytic strain Ulster of Newcastle disease virus (NDV) with the tumour cell suspension. The NDV adsorption at tumour cells was shown by electron microscopy. Clinically, the treatment with the vaccine was associated with an increased sensibilisation against autologous tumour cells, measured by DTH skin reactivity. First results in 23 patients with colorectal liver metastases who underwent "curative" liver resection followed by vaccination show a clear correlation between the induced increase of DTH skin reaction against autologous tumour cells and the recurrence-free interval. No correlation was found for DTH reaction caused by standard antigens (Mérieux test), NDV alone or autologous normal liver tissue. The results demonstrate the possibility of preparing immunogenic virus-modified autologous tumour cell vaccine from colorectal cancer tissue, which could be used for cancer therapy.

Adult↗

Sensitization of multidrug-resistant mouse ascites HD33 and Chinese hamster ovary CHRC5S3 cells by a photoreactive vinblastine derivative, NAPAVIN.

We have synthesized a new photoreactive vinblastine derivative, 3-[[[2-amino(4-azido-2-nitrophenyl)ethyl]amino] carbonyl]-O4-deacetyl-3-de-(methoxycarbonyl)-vincaleukoblastine (NAPAVIN), which absorbs light at around 450 nm. We report here its effects in vitro on multidrug-resistant mouse HD33 Ehrlich-Lettré ascites cells, on Chinese hamster ovary CHRC5S3 cells, on the corresponding drug-sensitive cells, on chemosensitive rat TMA1 mammary carcinoma, and on human SW48 colon carcinoma cells. Cells were incubated with the drug prior to activation by laser light at 457 nm. In Vinca alkaloid-sensitive cells, the short-term effects (30 to 72 h after treatment) of NAPAVIN with and without irradiation on cell proliferation are comparable to those of vinblastine. In drug-resistant cells, NAPAVIN without irradiation reduces the 50% inhibitory concentration 2- to 9-fold, compared with vinblastine. Upon irradiation with an argon laser at 457 nm, the concentration causing 50% inhibition of cell proliferation is further decreased to a total of 9- to 33-fold. Long-term effects (up to 6 wk after treatment) are seen in both sensitive and resistant cells. A single dose of the photoactivated drug causes a 6- to 9-fold larger delay (5 wk) in proliferation, compared with an equal dose of vinblastine.

Animals↗

[Cauda equina syndrome in ankylosing spondylitis].

A 55-year-old man who has had ankylosing spondylitis for over 20 years developed gradually increasing pain and sensory disorders in the legs, as well as mild foot and toe elevator weakness. There was no evidence of inflammatory activity. Clinical, neurophysiological and neuroradiological examination revealed a cauda equina syndrome as a late complication of ankylosing spondylitis. There is no known causal treatment.

Cauda Equina↗

Downregulation of T cell growth factor production by ornithine decarboxylase and its product putrescine: D,L-alpha-difluoromethylornithine suppresses general protein synthesis but augments simultaneously the production of interleukin-2.

Treatment of EL-4 lymphoma cells with tetradecanoylphorbol-acetate (TPA), a well-known activator of protein kinase C, induces the production of the T cell growth factor interleukin-2 (IL-2) and the expression of IL-2-specific mRNA within 4-8 h. This system is an ideal model for studies on the induction of a differentiated function in a homogeneous lymphoid cell population by a defined signal. TPA induces also an increase of ornithine decarboxylase (ODC) activity and elevates the intracellular concentrations of putrescine and polyamines within 4-8 h. A similar increase of intracellular putrescine and polyamine concentrations can be achieved by administration of 2 mM putrescine to the culture medium. However, putrescine cannot induce the production of IL-2 in the absence of TPA and cannot reconstitute the IL-2 production in cultures with PGE2 or cyclosporine A, i.e., two well-known immunosuppressive substances which inhibit ODC activity. Putrescine has rather a counter-regulatory effect as concluded from the observation that the TPA-induced TCGF production and IL-2-specific mRNA expression are augmented (superinduced) by the ODC inhibitor D,L-alpha-difluoromethylornithine (DFMO) and again suppressed after the administration of putrescine or polyamines to DFMO-treated cultures. The glycolytic activity, general protein synthesis [( 3H]leucine incorporation), and the cell cycle progression from G2/M to G1, in contrast, are inhibited by DFMO and reconstituted by putrescine. This demonstrates that the cells are able to sacrifice to a large extent several vital functions including their general protein synthesis and to devote themselves at the same time to a fulminant production of their functionally most relevant protein IL-2. This process is downregulated by ODC and its product putrescine. A correlation between increased IL-2 production and accumulation of cells in the G2/M phase was also observed in cultures treated with hydroxyurea or with a combination of amethopterin and adenosine.

Adjuvants, Immunologic↗

[Early prognosis in severe cranio-cerebral trauma using the Glasgow Coma Score and evoked potentials].

During 72 h following severe head injury, 103 patients in acute posttraumatic coma were assessed by clinical examinations (documented by Glasgow Coma Score) and brain stem auditory evoked potentials (BAEP) as well as short-latency somatosensory evoked potentials (SEP) following median-nerve stimulation. Patient outcomes were classified at 6 months or more according to the following categories: good recovery, severely disabled or vegetative, and brain dead. Patients who had died of systemic complications (pneumonia, septicemia, renal failure, etc.) were excluded from the study. The Glasgow Coma Score was reliable in forecasting a favorable outcome; all patients with a Score over 9 points had a good recovery. The Glasgow Coma Score was not reliable in predicting an unfavorable outcome, however; some patients with the lowest possible Glasgow Coma Score (3 points) at the early clinical examination survived with good recovery. The BAEPs were reliable predictors of an unfavorable outcome; the outcome was unfavorable when a missing wave V or more missing waves pointed toward a secondary brainstem lesion. Normal BAEPs were not reliable, however, in predicting a favorable outcome. SEP data served as a prognostic indicator of unfavorable as well as favorable outcomes. In summary, evoked potentials add valuable information to the clinical examination in assessing a patient's outcome after severe head injury.

Acute Disease↗

Relationship between the timing of DNA replication and the developmental competence in Acanthamoeba castellanii.

In Acanthamoeba, two different cell types are known. Trophozoites are generated in the mitotic division cycle, whereas cells committed at late G2 phase of the cell cycle develop into cysts in response to starvation. In this paper we study the role of timing of DNA replication in regulating development. The investigation was performed with cultures growing in a non-defined medium (ND cells) that show a high encystation competence and with cultures that have been growing in a chemically defined medium (D cells) for several years and show a low encystation competence. Bivariate DNA/BrdUrd distributions show that ND cells progress through a cycle in which the short replication phase occurs immediately and exclusively after prior completion of mitosis. These cells arrest at late G2 phase of the cell cycle during the stationary stage. In D cells, DNA replication and mitosis seem to be uncoupled, since replication takes place before as well as after mitosis. These cells arrest within their replication phase during the stationary stage. These findings indicate that D cells do not progress into late G2 phase of the cell cycle and hence do not have the competence for commitment. The alternate timing of DNA replication and the low encystation competence of D cells can be reversed by cultivation of these cells in ND medium. Synchronization experiments reveal that late G2 phase ND cells exhibit a low capacity for BrdUrd incorporation and growth after transfer into D medium, whereas ND cells of earlier phases of the cell cycle show premitotic incorporation of BrdUrd into nuclear DNA and growth. These findings suggest on the one hand that premitotic DNA synthesis is a prerequisite for growth of cells in D medium, and that there is a dependence of the induction of premitotic DNA synthesis on the cell cycle, and on the other hand that a reciprocal relationship exists between the capacity of premitotic DNA synthesis and commitment to differentiation.

Acanthamoeba↗

Somatosensory evoked potentials following median and tibial nerve stimulation in patients with Friedreich's ataxia.

The changes in evoked potentials following median and tibial nerve stimulation in nine patients with clinically defined Friedreich's ataxia are reported and discussed. The response originating in the brachial plexus (Erb's point potential) was absent or reduced in amplitude with no prolongation of peak latency, and the response generated in the cauda equina (N18) was absent in all cases. Conduction time from the brachial plexus to cervical spine and medulla oblongata was normal, whereas the central conduction time (N13a/N20, N13b/N20) was delayed. There was moderate to marked attenuation of the primary cortical response to median nerve stimulation. In one patient N20 disappeared during the course of the disease as opposed to the persisting subsequent negative wave, the latter thus simulating a very marked delay in the primary cortical response. Accordingly the cortical response to tibial nerve stimulation, which was only present in two patients and was markedly delayed, might represent a later potential with the primary response absent. The findings are consistent with neuropathological descriptions of a dying back neuropathy with primary axonal degeneration concerning the 1st order sensory neuron. In addition there is evidence either of delayed conduction in 2nd and 3rd order sensory neurones or of abnormal synaptic transmission.

Adolescent↗

Short-latency somatosensory evoked potentials in brain death.

Simultaneous recording of somatosensory evoked potentials to median nerve stimulation above the upper and lower neck in brain-dead patients revealed that all cervical responses were preserved in 10%, whereas a marked reduction in amplitude or even loss of N 13b at the level of the C2 spinous process was observed in 90%. Of the patients, 55% revealed an additional loss of N 13a, recorded at the level of the C7 spinous process; in 15% all cortical and spinal evoked potentials were missing, but Erb's point waves were still normal. These results suggest two different origins of the main negative waves (N 13a and N 13b), recorded above the upper and lower cervical spinal cord. N 13a (C7) is supposed to arise in the dorsal horn at the C6/7 level, N 13b (C2) in the cervicomedullary junction.

Adolescent↗

The kinetics of nuclear polyploidization and tumour formation in livers of CF-1 mice exposed to dieldrin.

The kinetics of nuclear polyploidization in livers of CF-1 mice exposed to dieldrin were studied at concentrations of 0, 0.1, 1, 5 and 10 p.p.m. in the diet, in 'steady-state' situations (which are reached within a few weeks after initiation of treatment). Animals were killed at five time intervals (after 1.85, 3, 6, 9 and 14 months of exposure). The changes in the percentage of octaploid nuclei (8C) were used as an indicator of the kinetics of overall polyploidization. Polyploidization in control mice increased proportionally (linearly) with time (age). The enhancement of polyploidization by dieldrin was found to be proportional to dietary concentration. The slopes of the linear regressions of polyploidization, as a function of age, were identical in all dieldrin-treated groups and controls, indicating that there was no cumulative effect of dieldrin in time. A comparative analysis of the observed dieldrin dietary concentration: response relationship of polyploidization and of tumour formation in CF-1 mouse liver indicates that liver tumour formation is associated with a constant degree of polyploidization. Assuming that polyploidization reflects the ageing process, the data suggest that liver tumour formation is imminent at a constant biological age and that tumour promoters, such as dieldrin, could operate by advancing the biological age of mouse liver in the initial phases of treatment. The results of this study suggest that the analysis of ploidy changes may serve as an aid to perspective in evaluating risks associated with exposures to liver tumour promoters.

Aging↗

[Early prognostic assessment using evoked potentials in severe craniocerebral trauma].

103 patients in acute posttraumatic coma were assessed during 72 hours following severe head injury by clinical examinations (documented with a modified Glasgow-Coma-Score and a brain-stem-score and brainstem auditory evoked potentials (BAEP) as well as short latency somatosensory evoked potentials (SEP). Patient outcomes were classified at 6 months or more, according to the following categories: good recovery, severely disabled or vegetative, and brain dead. Patients who had died by systemic complications were excluded from the study. The Glasgow-Coma-Score was reliable in forecasting a favorable outcome, but tended to produce false-pessimistic predictions. The brainstemscore and the BAEPs were reliable predictors of an unfavorable but not a favorable outcome. SEP data however, performed well as a prognostic indicant in predicting an unfavorable as well as a favorable outcome. Using the BAEP, the amplitude ratio Wave V/Wave I is more sensitive to detect a lesion than the interpeak-latency Wave I-Wave V, and--using the SEP--the amplitude ratio N20/N13b (over C2) is more sensitive than the central conduction time (N13a (over C7)--N20).

Adolescent↗

[Significance of somatosensory evoked potentials in determining brain death].

Electrophysiological examinations are useful to confirm the clinical diagnosis of brain death and to substantiate the loss of brain function and of brain stem function. In addition to the EEG, which has been an useful ancillary test for many years to diagnose brain death, auditory and somatosensory evoked potentials are other electrophysiological techniques that give useful information on the assessment of brain death. In this study, short-latency somatosensory evoked potentials following median nerve stimulation were recorded in 20 patients who fulfilled the clinical criteria of brain death. The primary cortical responses N 20/P 25 recorded above the somatosensory cortex disappeared in all patients. Furthermore, except in two patients, there was a loss of the N 13 b component recorded above the spinous process C2 (N 13 b is assumed to originate in the cervicomedullary junction). Nine patients in whom brain death had occurred exhibited additionally changes of N 13 a - recorded above the spinous process C7 - a potential generated in the lower cervical cord. These data point to the occasional involvement of the cervical cord in the loss of function in patients in whom brain death had become manifest.

Adolescent↗

[Significance of early acoustic evoked potentials in the diagnosis of brain death].

Tests of early acoustic evoked potentials in 49 patients in whom clinical and EEG criteria indicated brain death demonstrated a bilateral loss of brainstem-generated components III to V in 12.6%, a loss of the components II-V in 16.8% and a loss of all early acoustic evoked potentials in 47.4%. This method, practicable in an intensive care unit, seems thus suitable for demonstrating loss of brainstem function as demanded for diagnosis of brain death.

Brain Death↗

[Evoked potentials. Indications and diagnostic significance].

Visual, auditory and somatosensory evoked potentials are useful in the detection and localization of demyelinating lesions, which mainly cause a slowing of conduction and therefore a latency increase in the evoked potential. Primarily amplitude reductions or loss of the response are seen in partial or complete impulse conduction blocks due to a tumor e.g. Acoustic nerve tumors can be detected by AEP, orbit tumors or processes of the chiasm by VEP and spinal cord tumors by SEP. The use of evoked potentials for the evaluation of ophthalmologic disorders, for audiometry in children and for monitoring head-injured patients with coma have become a valuable aid to the physician too.

Brain Diseases↗

Anthracycline resistance and consequences of the in situ-in vitro transfer.

Adriamycin-resistant and normal cells of the sarcoma 180 of the mouse undergo qualitatively different deflections from the in situ state when prepared for an experiment. Resistant cells perform a fast reactive decline in the proliferative activity. They are capable of quiescence as defined by the time needed for the induction of the proliferation. Sensitive cells seem to be unable to quiesce and are only slowed down. These facts must be taken into account in interpretation of similar results. Differences in experiments need not necessarily imply differences in situ. Such in vitro appearing differences between sensitive and adriamycin-resistant cells of the murine sarcoma 180 include the retention of the mitochondria-specific stain rhodamine 123 and the uptake of anthracyclines, both being reduced in resistant cells. After labeling sensitive cells with thymidine in vivo and sorting them according to their rhodamine 123-derived fluorescence, the label was only found in the major, highly fluorescing fraction. A small low-fluorescing fraction remained unlabeled. We were able to demonstrate similar results with labeled anthracyclines applied to both the sensitive and the resistant cells in a short period between the removal of the cells from the ascites and the cell sorting. The adriamycin resistance seems to be joined with the ability of the cells to reduce their proliferative activity following changes to unfavorable conditions in vitro. Quiescent cells of the resistant line demonstrate the "anthracycline pump." Substances which are known to increase the sensitivity of anthracycline-resistant cells (TWEEN, verapamil) also shift the cells from low to high rhodamine 123-fluorescence.

Animals↗