[The prevention of anthracycline-induced cardiomyopathy with a chelating agent (dexrazoxane = ICRF-187)].
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
H Sauer
Publications and source records attributed to H Sauer.
Effects of graft pooling of foetal rat and mouse tissue and immunosuppression in the 6-hydroxydopamine rat model of Parkinson's disease.
We employed intracerebral co-transplantation of foetal xenogeneic striatal mouse tissue and allogeneic rat substantia nigra into the adult rat brain to elucidate the effects of xenogeneic mouse graft on the function and survival of an allogeneic rat graft in 6-hydroxydopamine lesioned Sprague-Dawley rats. Foetal mouse striatum (STR) and rat substantia nigra (VM) were transplanted as non-pooled separate deposits or a pooled cell suspension with or without cyclosporin A (Cy A). Immunosuppressed recipients of pooled rat and mouse co-grafts showed a significantly better compensation of amphetamine-induced rotational behaviour compared with non-immunosuppressed animals with pooled rat and mouse co-grafts 3 and 6 weeks post-grafting. Tyrosine hydroxylase (TH) immunohistochemistry revealed a non-significant reduction in survival in pooled (1806.3+/-367.5 cells) rat and mouse co-transplants without immunosuppression compared with immunosuppressed pooled (3383.3+/-732.7 cells) animals with allo- and xenogeneic tissue and controls (3506.4+/-839.3 cells). Graft volumes were significantly reduced in pooled transplants without immunosuppression (0.1+/-0.026 mm3; ANOVA post-hoc Scheffe F-test, P<0.0001) compared with immunosuppressed recipients (0.7+/-0.1 mm3) and controls (0.6+/-0.1 mm3). In non-pooled allo- and xenogeneic grafts without immunosuppression the survival rate of the TH-immunoreactive cells and graft volumes were reduced (2359.3+/-479.5 cells; 0.2+/-0.043 mm3) compared with immunosuppressed animals (2927.3+/-946.6 cells; 0.6+/-0.2 mm3) and controls (2701.1+/-693.8 cells; 0.3+/-0.1 mm3) without reaching a level of significance. Rejection of mouse tissue was observed in all non-immunosuppressed recipients. In summary: (i) continued immunosuppression yielded significant beneficial effects on function and beneficial effects on survival of pooled grafts with an immunogenetic disparity; (ii) the rejection of a xenogeneic graft component may compromise survival and function of other, allogeneic graft components; and (iii) transplantation of non-pooled allo- and xenogeneic tissues may result in a better survival of the graft compared with pooled cell suspensions.
Animals↗
Cholescintigraphy in the evaluation of bile flow after Roux-en-Y hepatico-jejunostomy and hepatico-antrostomy in infants with choledochal cysts.
BACKGROUND: The study tests the hypothesis that stasis of bile in the Roux-en-Y hepatico-jejunostomy (RYJS) loop might facilitate biliary reflux and cause cholangitis, whereas quicker transit times in hepatico-antrostomy (HAST) might prevent cholangitis. MATERIALS AND METHODS: Cholescintigraphy was performed using Tc99m-trimethyl-Br-IDA in seven RYJS patients and in five HAST patients. RESULTS: The time to peak (Tmax) within the RYJS loop occurred between 18 and 50 min postinjection in all patients and the mean transit time (MTT) ranged between 42 and 69 min in 5/7 patients. Prolonged clearance of the tracer from the liver was seen in 2/7 RYJS patients, in whom the MTT was 77 and 240 min, respectively. In the HAST group, the Tmax within the anastomosed antrum occurred between 5 and 33 min postinjection, and the MTT ranged between 42 and 44 min in 2/5 patients. Protracted tracer uptake in the liver in one patient and localised tracer retention in the left hepatic bile ducts in 2/5 patients caused prolonged MTTs. Recurrent cholangitis and diarrhoea occurred in 4/7 RYJS patients, but in none of the HAST patients. Elevated gastrin levels after RYJS contrasted sharply to normal gastrin levels after HAST. CONCLUSION: The findings on cholescintigraphy did not differ significantly between RYJS and HAST and provided no explanation for the distinctly different postoperative clinical course of both surgical methods. Nevertheless, we consider cholescintigraphy to be an efficient and cost-effective diagnostic modality for evaluation of the surgical outcome as regards biliary flow.
Anastomosis, Roux-en-Y↗
Personality differences between patients with major depression and bipolar disorder--the impact of minor symptoms on self-ratings of personality.
The study explores whether minor symptoms of patients in recovery from a mood disorder have an impact on self-ratings of personality with special consideration of potential differences between diagnostic groups. 90 recovered DSM-III-R major unipolar depressives and 167 recovered bipolars were compared with respect to scale values of the Munich Personality Test (MPT). Major depressives showed significantly higher scores on the MPT scales Rigidity and Orientation towards Social Norms, and lower scores on Extraversion than the bipolar patients. Using a LISREL-model, psychopathology was found to have a significant impact on Neuroticism and Extraversion, but not on Rigidity and on Orientation towards Social Norms. Controlling for symptomatology, the differences in the MPT scale values of the two diagnostic groups remained significant and can hardly be sufficiently explained by residual symptomatology.
Adult↗
Lithium versus carbamazepine in the maintenance treatment of bipolar disorders--a randomised study.
In a randomised multicentre study, the prophylactic efficacy of lithium and carbamazepine was compared in 144 patients with bipolar disorder (74 vs. 70 patients; observation period: 2.5 years; lithium serum level: 0.63 +/- 0.12 mmol/l, carbamazepine dose: 621 +/- 186 mg/day). Hospitalisations, recurrences, need of psychotropic comedication and adverse effects prompting discontinuation were defined as treatment failures. Survival analyses regarding hospitalisations and recurrences showed no statistically significant differences between both drugs. Results were distinctly in favour of lithium, considering recurrences combined with comedication (P = 0.041) and/or adverse effects (P = 0.007). Whereas adverse effects prompting discontinuation were more frequent under carbamazepine (9 vs. 4, ns), lithium patients reported more often slight/moderate side effects (61% vs. 21% after 2.5 years; P = 0.0006). In completers, recurrences occurred in 28% (lithium) vs. 47% (carbamazepine) of the patients (P = 0.06). Lithium seems to be superior to carbamazepine in maintenance treatment of bipolar disorder, in particular when applying broader outcome criteria including psychotropic comedication and severe side effects.
Adult↗
5-HT brain function in affective disorder: d,l-fenfluramine-induced hormone release and clinical outcome in long-term lithium/carbamazepine prophylaxis.
Prolactin (PRL) and Cortisol (CORT) responses to d,l-fenfluramine (FEN) challenge (60 mg) were examined in patients with affective disorders on two occasions under euthymic conditions: drug-free before admission to prophylactic treatment and after about 9 months of medication with lithium or carbamazepine. Response to treatment was assessed by a complex algorithm using continuous ratings in outpatient clinic over a period of 2 years. In general, treatment resulted in a delayed and diminished CORT release (n.s.); subgroup analysis revealed an attenuated CORT response (P < 0.05) in responders, whereas nonresponders showed no change in CORT secretion pattern except an enhanced CORT baseline value (P < 0.05). Cross-sectional comparison of responders with nonresponders under medication yielded a trend for greater CORT stimulation in nonresponders. This result was not affected by FEN/NorFEN or lithium/carbamazepine serum levels, baseline CORT values, age, sex, diagnostic distribution, number of appointments to the outpatient clinic or duration of medication at the time of FEN test session. Before onset of prophylactic medication responders and nonresponders could not be discriminated significantly regarding stimulated hormone release, probably due to the small sample size (n = 17). CORT response to FEN was increased in drugfree unipolar patients compared to bipolar (P < 0.05) and to schizoaffective patients (P < 0.1). In accordance with its well-documented presynaptic 5-HT-agonistic action lithium medication resulted in a significantly greater increase in CORT release than carbamazepine (P < 0.05). Evaluation of PRL stimulation showed patterns of secretion quite similar to those of CORT, without reaching statistical significance in most cases. Perhaps due to methodological differences in assessing treatment response, these data do not confirm former results, which supposed an enhanced 5-HT net activity in long-term prophylactic lithium treatment. Because of high interindividual variances of hormone parameters, the FEN-test procedure is not a useful tool for the prediction of therapeutical outcome in terms of clinical routine use. Relations of stimulated hormone response as a marker of central serotoninergic activity and clinical outcome are discussed.
Adult↗
Quantitative magnetic resonance imaging and neuropsychological functions in dementia of the Alzheimer type.
BACKGROUND: The aim of the present study was to investigate neuropsychological functions in dementia of the Alzheimer type (DAT) with respect to morphological changes that were revealed by quantitative magnetic resonance imaging (MRI). METHODS: Twenty patients with DAT (NINCDS-ADRDA criteria) and 10 healthy age and sex matched controls were included. The neuropsychological function was evaluated on a test battery covering the severity of dementia, verbal and visual memory, concentration and attention, language skills and general intelligence as well as activities of daily living. 3D MRI sequences were acquired using a 1.5 T Siemens MAGNETOM. Whole brain volume, total intracranial volume (TIV), volume of the frontal and temporal lobes and volumes of the amygdalahippocampus complex (AHC) were assessed using the newly developed software NMR Win. RESULTS: Apart from TIV all morphometric parameters differed significantly between the diagnostic groups. AHC volumes discriminated best between the groups, with only a small overlap. AHC atrophy exceeded generalized atrophy. These findings were confirmed when the data were reanalysed after dividing the DAT patients into a mildly and moderately affected group. The severity of dementia was significantly correlated with the volumes of the AHC and the volumes of the temporal lobes bilaterally, but not with the whole brain volume and the volumes of the frontal lobes. CONCLUSIONS: These results underline the important role of the temporal substructures for aetiology and progression of DAT. They indicate that the volume of the AHC can be monitored by MRI and may be used to follow up the disease process.
Aged↗
DC electrical field-induced c-fos expression and growth stimulation in multicellular prostate cancer spheroids.
The effects of electrical direct current (DC) field pulses on c-fos expression, growth kinetics and vitality patterns of multicellular tumour spheroids (MCSs) were studied. Monitoring the membrane potential of MCSs by di-8-ANNEPS staining and confocal microscopy during DC electrical field treatment revealed a hyperpolarization at the anode-facing side and a depolarization at the cathode-facing side. When a single 500 V m(-1) electrical field pulse with a duration of 60 s was applied to MCSs (150-350 microm in diameter) an enhancement of the growth kinetics within a period of 6 days post pulse was observed. Whereas the volume doubling time amounted to 4-5 days in control samples, it was reduced to 1-2 days in electropulsed MCSs. At day 6 post pulse the diameter of the necrotic core was significantly smaller than the control. The critical diameter for the first appearance of central necrosis amounted to 350 +/- 50 microm in the control and 450 +/- 50 microm in the electropulsed MCSs. Coincidentally, the proliferating rim was increased to 107 +/- 11 microm in electropulsed MCSs as compared with 60 +/- 6 microm in the control. The growth stimulation may be mediated by the proto-oncogene c-fos as its expression increased by a factor of 2.5 within 2 h post pulse. c-fos expression declined towards control values within 8 h post pulse.
Buffers↗
Prior fluoridation in childhood affects dental caries and tooth wear in a south east Queensland population.
Fluoride exposure in early life has an effect on dental caries experience, but does it affect tooth wear in later life? Ninety-six South East Queensland subjects were studied. Their histories revealed three groups; a fluoride (F-) in water supply, a F- by supplement, and a non-fluoridated (non F-) group. Significantly higher caries experience was found in the non-F- group compared with F- in water group and the F- supplement group. No statistically significant difference in caries experience was found between the F- in water and F- supplement groups. Overall, tooth wear affected more sextants of the dentitions of non-fluoridated, high-caries subjects than of fluoridated low-caries subjects. Comparisons of wear patterns on sextants of the dentitions, between the fluoridated and non-fluoridated groups, revealed that in sextants where attrition was present no marked differences were discernible between the two groups. However, in most sextants where incisal, palatal, occlusal or non-occlusal erosion was found, this type of wear was commoner in non-fluoridated subjects. The exceptions were the mandibular molar sextants, where prior fluoride-exposure did not appear to protect against occlusal erosion patterns. This study showed that fluoride exposure during the first 12 years of life, which reduced dental caries in this population, may also protect teeth from wear to some extent.
Adolescent↗
Electrical fields enhance growth of cancer spheroids by reactive oxygen species and intracellular Ca2+.
A single electrical field pulse (500 V/m) with a duration of 60 s increased tumor outgrowth over a postpulse period of 24 h. RNA staining with acridine orange showed a rise in RNA content in pulsed spheroids, indicating stimulation of cell cycle activity. The electropulse induced an intracellular Ca2+ concentration ([Ca2+]i) transient that started approximately 40 s after the onset of the electrical field. Neither the presence of extracellular Ni2+ (0.5 mM) nor the absence of extracellular Ca2+ impeded the [Ca2+]i rise. It was, however, totally blocked by thapsigargin (1 microM), indicating that the initial Ca2+ response is due to Ca2+ release from intracellular stores. The [Ca2+]i transient was paralleled by an increase in reactive oxygen species (ROS), as revealed using 2',7'-dichlorofluorescein diacetate as an indicator. The radical scavengers N-acetyl-L-cysteine (NAC)(20 mM) and dehydroascorbate (5 mM) inhibited both ROS production and the [Ca2+]i transient during electrical field treatment. The mitogenic activation was dependent on the rise in [Ca2+]i because inhibition of Ca2+ release during electrical field treatment by addition of either thapsigargin or NAC to the incubation medium abolished the observed effect. We conclude that a single, direct current electrical field pulse induces production of ROS, which in turn mediate Ca2+ release from intracellular stores and activate cell cycle activity in multicellular spheroids.
Calcium↗
Measuring treatment outcome by the Beck Depression Inventory.
The construct validity of the Beck Depression Inventory (BDI) in measuring treatment outcome is assessed in 103 psychiatric inpatients. In this context, construct validity means that the BDI measures the same construct in repeated measurement and that the change scores can be explained by treatment effects. In confirmatory factor analyses, only the first factor proved to be stable. In accordance with other studies, the sensitivity to therapeutic change in long-term intervals of several weeks could be confirmed. Significant changes in a short-term interval of 1 day in the non-endogenously depressed patients indicate an overreactivity of the BDI to change which cannot be explained by treatment effects or mood changes.
Adjustment Disorders↗
Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease.
Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neurons in vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenerative process seen in Parkinson's disease. GDNF injected close to the substantia nigra provided near-complete protection and persistent survival of the lesioned nigral neurons for at least 4 months after discontinuation of GDNF treatment. Long-term rescue of the nigral cells, however, was not accompanied by any significant reinnervation of the lesioned striatal target or any signs of functional recovery in either drug-induced or spontaneous motor behaviors. We conclude that not only preservation of the nigral DA neurons but also restoration of striatal DA function is necessary for functional recovery in the rat Parkinson model.
Amphetamine↗
Comparative efficacy of lithium and amitriptyline in the maintenance treatment of recurrent unipolar depression: a randomised study.
The present study, including 81 depressive patients, compares the prophylactic efficacy of lithium and amitriptyline in recurrent unipolar depression over a treatment period of 2.5 years in a randomised multicentre design. Hospitalisation, re-emergence of depressive or subdepressive recurrences, unwanted side-effects and need of concomitant psychotropic medication were considered to indicate treatment failures. Average dosage for amitriptyline was 98 +/- 37 mg/day, average lithium blood level was 0.59 +/- 0.12 mmol/l. Survival analyses demonstrated a significant superiority of lithium (P = 0.015) regarding the outcome criteria 'recurrences and/or subclinical recurrences' and non-significantly better results of lithium compared to amitriptyline concerning 'recurrence' (P = 0.059) or 'recurrence and/or concomitant medication' (P = 0.066).
Adolescent↗
Internal consistency of dipole localizations for the human movement-evoked magnetic field component 1 (MEF 1).
The present magnetoencephalographic study was conducted in order to assess the accuracy of dipole localizations for the movement-evoked field component 1 (MEF 1). Three male subjects were requested to perform self-paced flexions of their index finger and thumb in repeated sessions of 60 trials while the neuromagnetic field was recorded by a 31 channel system. Single moving dipole localizations were performed for the MEF 1. The error within single sessions was calculated by split-half reliability and window-homogeneity in a total of 61 sessions. The mean spatial deviation between both halves amounted to 3.8 mm. The window-homogeneity was found to be 2 mm deviation/10 ms.
Adult↗
Renal and neuronal abnormalities in mice lacking GDNF.
Glial cell-line derived neurotrophic factor (GDNF) is a potent survival factor for embryonic midbrain dopaminergic, spinal motor, cranial sensory, sympathetic, and hindbrain noradrenergic neurons, and is available to these cells in vivo. It is therefore considered a physiological trophic factor and a potential therapeutic agent for Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Here we show that at postnatal day 0 (P0), GDNF-deficient mice have deficits in dorsal root ganglion, sympathetic and nodose neurons, but not in hindbrain noradrenergic or midbrain dopaminergic neurons. These mice completely lack the enteric nervous system (ENS), ureters and kidneys. Thus GDNF is important for the development and/or survival of enteric, sympathetic and sensory neurons and the renal system, but is not essential for catecholaminergic neurons in the central nervous system (CNS).
Animals↗
Immunoglobulin G galactosylation deficiency determined by isoelectric focusing and lectin affinoblotting in differential diagnosis of rheumatoid arthritis.
IgG galactosylation deficiency in patients with rheumatoid arthritis (RA) can be detected by isoelectric focusing (IEF)/lectin affinoblotting. We analyzed IgG glycosylation in patients with early arthritis (n = 50) and healthy controls in order to determine the clinical value of this parameter in differential diagnosis of RA. A significant correlation between the IgG galactosylation defect at disease onset and the diagnosis of RA during the follow-up was observed. Involvement of other clinical parameters (erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor) did not improve the predictive value of IgG galactosylation changes.
Arthritis, Rheumatoid↗
Dopaminergic neuronal degeneration and motor impairments following axon terminal lesion by instrastriatal 6-hydroxydopamine in the rat.
6-Hydroxydopamine-induced nerve terminal lesion of the nigrostriatal system may provide a partial lesion model of Parkinson's disease useful for the assessment of neuroprotective treatments and behavioral recovery after therapeutic intervention. The aim of the present study was to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra and the associated behavioral and neurochemical consequences of intrastriatal injections of 6-hydroxydopamine in young adult rats. Four groups of rats were stereotaxically injected in the right striatum with graded doses of 6-hydroxydopamine ranging from 0 to 20 mu g. Structural and functional deficits were quantified by tyrosine hydroxylase-immunoreactive nigral cell numbers, striatal dopamine content, skilled paw use, and drug-induced rotation. The results show that striatal 6-hydroxydopamine lesions produce dose-dependent decreases in striatal dopamine levels and tyrosine hydroxylase-immunoreactive cell numbers in the ipsilateral substantia nigra, accompanied by a significant long-lasting atrophy of the remaining dopaminergic neurons. Paw reaching test scores on the side contralateral to the lesion were non-linearly correlated with dopaminergic neuronal cell loss and exhibited a clear symptomatic threshold such that impaired paw use appeared only after >50% loss of nigral dopamine neurons or a reduction of 60-80% of striatal dopamine levels. The behavioral, cellular, and neurochemical effects of the nerve terminal lesion thus bear some resemblance to the early stages of Parkinson's disease, where the severity of motor impairment is correlated with the loss of dopamine in the striatum and dopaminergic neuronal loss in the substantia nigra. Rats with intrastriatal 6-hydroxydopamine lesions thus provide a model of progressive dopamine neuron degeneration useful not only for the exploration of neuroprotective therapeutic intervention but also for the study of mechanisms of functional and structural recovery after subtotal damage of the nigrostriatal dopamine system.
Animals↗
P-glycoprotein expression in patients with acute leukemia-clinical relevance.
P-glycoprotein (P-gp) is a crucial factor in the development of chemotherapy resistance in malignant disorders. Between 1989 and 1995, P-gp expression was studied in bone marrow blast cells of 322 (239 AML; 83 ALL) acute leukemia patients. 166 AML patients with the AML-6 protocol (EORTC), containing daunorubicin, vincristine and conventional-dose cytarabine (ara-C), and 63 AML patients treated with intermediate-does Ara-C plus amsacrine. Further 71 ALL patients were treated according to a German standard polychemotherapy protocol (BMFT04/1989). P-gp was determined by using monoclonal antibodies C219 and 4E3, and the cutoff point for P-gp overexpression was set at >/= 10%. A significant (P < 0.06) difference in P-gp overexpression was demonstrated between AML (21.6%) and ALL (10.2%) patients at primary diagnosis and between primary diagnosis and relapse/refractoriness in AML (21.6%; 51.0%) and ALL (10.2%; 27.2%) patients. According to FAB classification P-gp overexpression was detected in AML patients significantly (P < 0.05) more frequently in classes M4, M5a and M5b and less frequently in M3, as compared to other types. For AML patients with P-gp overexpression at primary diagnosis or early relapse/refractoriness, the predictive value for nonresponse to the AML-6 protocol was 91 and 95%, respectively, while late-relapsed AML patients with P-gp overexpression had a significantly (P < 0.05) lower predictive value of 73% for nonresponse. Additionally, in refractory and late-relapsed P-gp--overexpressing AML patients treated with intermediate-dose ara-C plus amsacrine the predictive values for nonresponse were 44 and 39%, respectively, significantly (P < 0.05) lower as compared to AML-6 protocol-treated refractory or late-relapsed AML patients. In P-gp-overexpressing treated ALL patients the predictive values of 50 and 55% for non-response were calculated at primary diagnosis and late relapse, respectively. We conclude that P-gp overexpression is a common phenomenon in AML patients at primary diagnosis or relapse, has an inverse influence on AML-6 treatment outcome and should be taken into consideration in the development of new therapy strategies.
ATP Binding Cassette Transporter, Subfamily B, Mem↗