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Biomedical subjects

P Zimmermann

Publications and source records attributed to P Zimmermann.

At least 55 records · Page 3Linked to original sources
PubMed1996

Modulation of P-glycoprotein mediated drug accumulation in multidrug resistant CCRF VCR-1000 cells by chemosensitisers.

P-glycoprotein (PGP) mediated transport of cytostatic drugs out of resistant cancer cells is a major cause of experimental and probably also of clinical multidrug resistance, which often leads to treatment failure during chemotherapy. The broad substrate specificity of PGP strongly restricts effective chemotherapy and diminishes the patients' prognosis. Inhibition of PGP's pumping function by chemosensitisers is one way to restore cellular responsiveness to otherwise ineffective cytostatics. Clinical trials with several chemosensitisers are under way. To date, it is not clear whether a certain chemosensitiser potentiates the action of different cytostatic drugs, transported by PGP equally well, or whether the chemosensitising potency is dependent on the cytostatic drugs used. Therefore, we compared the effects of five potent chemosensitisers on cellular accumulation using [3H]daunomycin, [3H]vincristine and rhodamine-123 as substrates for PGP. The acridonecarboxamide derivative GF 120918 was the most potent compound and a half-maximal effect was seen at concentrations ranging from 5 nM for rhodamine-123 accumulation to 14 and 19 nM for [3H]vincristine or [3H]daunomycin accumulation, respectively. The new chemosensitiser B9203-016 was slightly less effective than GF 120918 in all three test systems. Dexniguldipine was of intermediate potency with half-maximal effects at concentrations between 62 and 194 nM. The cyclic undecapeptide SDZ PSC 833 showed somewhat lower potency ranging from 151 to 331 nM. Cyclosporin A was less potent than SDZ PSC 833. Furthermore, enhancement of drug accumulation produced by each chemosensitiser was similar, regardless of which PGP substrate was measured, that is, the rank order of potency to increase accumulation was the same in each of the assays used. Our data point to similar, if not identical, mechanisms of drug transport by PGP and inhibition of drug transport by chemosensitisers at least for the substrates rhodamine-123, vincristine and daunomycin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[Spiral computed tomography for treatment planning and quality assurance in radiotherapy].

BACKGROUND: The possibilities of spiral CT for radiotherapeutic treatment planning and quality assurance have been systematically investigated. PATIENTS AND METHODS: The influence of parameters such as slice thickness, table speed and increment on geometric accuracy was studied. Ring-, spheric-, PMMA- and humanoid Alderson phantoms were used. Furthermore, patients with infradiaphragmatic irradiation of Hodgkin's disease or with mediastinal irradiation were studied using CT-angiography. Patients with carcinomas of the head and neck before HDR- and PDR-brachytherapy were examined as well. RESULTS: Spiral CT offers 3D volume data information with excellent reduction of breath and motion artefacts for virtual simulation. 2D multiplanar reconstructions with excellent local resolution may be obtained. 3D MIP (Maximum Intensity Projection), based on CT-angiographic imaging, is a good tool for infradiaphragmatic treatment planning of Hodgkin's disease, if small numbers for slice thickness, table speed and increment are used. SSD (Surface Shaded Display) offers good 3D visualization and good geometric control of intracavitary and interstitial brachytherapy applicators. High qualitative multiplanar reconstructions are useful for CT-based brachytherapy planning. CONCLUSIONS: Spiral CT is a precious tool for 3D treatment planning and virtual simulation in radiotherapy and superior to conventional CT data acquisition. Quality assurance is improved for dose-volume-histograms and for brachytherapy.

Angiography↗
PubMed1995

Computer-controlled flushing for long-term cannulation in freely moving rats.

An in vivo long-term perfusion system is presented, which is based on automated, computer-controlled high-frequency heparin (10 U/mL) flushing of the cannula inserted into the tail artery of freely moving rats. The short flushing intervals as achieved with this system guarantee stable conditions throughout an experiment of several days, and reduce blood clotting and the infiltration of fibroblasts. In addition, a specially developed software enables the periodical application of test substances into the blood stream under time-controlled conditions over long periods. The system can be used continuously to follow up blood parameters in single animals without significant elicitation of stress-sensitive plasma catecholamines for up to 12 days.

Animals↗
PubMed1995

Doppler flow velocimetry of the umbilical artery, uteroplacental arteries and fetal middle cerebral artery in prolonged pregnancy.

A total of 153 pregnant women, of at least 287 days' menstrual age, were studied in a prospectively designed cross-sectional trial. In addition to the non-stress test, contraction stress test, sonographic estimate of amniotic fluid and grade of placental maturation, Doppler measurements of the resistance index (RI) were taken in the umbilical artery, the uteroplacental arteries in the region of placental implantation and the fetal middle cerebral artery. Data were analyzed with regard to asphyxia and otherwise complicated fetal outcome. Furthermore, a possible relationship between grade of placental maturation, Doppler flow velocity waveforms and fetal outcome was investigated. Doppler resistance indices in the umbilical artery, uteroplacental arteries in the region of placental implantation and fetal middle cerebral artery did not change significantly with increasing gestation from 41 to 43 weeks. The grade of placental maturation on ultrasound examination was not related to fetal outcome or Doppler indices in the first two vessels. In all vessels examined in this study, the majority of Doppler measurements in pregnancies with subsequent asphyxia or otherwise complicated fetal outcome were within the 95% prediction interval for patients with normal fetal outcome. None of the patients showed absent diastolic flow in the umbilical artery. With the use of a cut-off value of RI = 0.62 in the umbilical artery, asphyxia could be predicted with 37% sensitivity and 75% specificity. Oligohydramnios and antpartum cardiotocography predicted asphyxia with 16% and 8% sensitivity and 95% and 96% specificity, respectively. Sensitivity for prediction of otherwise complicated fetal outcome by umbilical artery Doppler was only 7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1995

Vibrameter testing facilitates the diagnosis of uremic and alcoholic polyneuropathy.

The diagnostic sensitivity of Vibrameter and tuning fork examination towards uremic and alcoholic neuropathy was tested in 75 patients. In 40 uremic and 35 alcoholic patients, we compared the sensitivity of neurological examination, nerve conduction studies (NCS) and vibration thresholds assessed at the malleoli by means of Vibrameter and scaled tuning fork. Vibrameter results were correlated with NCS. Polyneuropathy was diagnosed in 52 patients, but in 16 patients diagnosis depended upon inclusion of Vibrameter testing in the examination protocol. In uremic patients, Vibrameter (47.5%) showed abnormalities as often as NCS (45%), and more often than clinical (32.5%) or tuning fork examination (2.5%). In alcoholic patients, Vibrameter revealed abnormalities more often (60%) than NCS (34.3%) or tuning fork (14.3%). Correlations between NCS and vibratory thresholds were low (-0.52 < or = Rs < or = -0.35). Vibrameter studies are far more sensitive than tuning fork tests. The technique complements NCS and refines the diagnosis of uremic and alcoholic neuropathies.

Adult↗
PubMed1995

Thermal threshold determination in alcoholic polyneuropathy: an improvement of diagnosis.

Reports on the incidence of alcoholic polyneuropathies are variable depending on diagnostic tools. In this study, 50 chronic alcoholics with positive MALT (Munich Alcoholism Test) and greater than seven years history of excessive alcohol abuse were examined neurologically. Tibial and peroneal motor and sural nerve conduction velocities (NCV) were studied. Warm and cold perception was evaluated in the area behind the internal malleolus using a Somedic-Thermotest. Thresholds were determined by the method of limits. The effect of a slow, medium and fast temperature change rate on thermal perception was tested. Thirty-eight patients (76%) showed signs of neuropathy. Thermal perception was more often abnormal (62%) than NCV (42%) and clinical examination (56%). A medium temperature change rate of 2.0-2.5 degrees C/s was the most sensitive index of small fiber neuropathy. Thermal threshold measurement proved to be a reliable, sensitive and easy to perform method that should become standard in the examination of polyneuropathies.

Adult↗
PubMed1994

Incomplete split-brain syndrome in a patient with chronic Marchiafava-Bignami disease.

A 40-year-old male patient is presented who survived Marchiafava-Bignami disease and recovered sufficiently to be assessed neurologically and neuropsychologically in some detail. Besides dementia, lack of initiative, and psychomotor retardation here ascribed to extracallosal damage, he showed a number of symptoms of hemispheric disconnection such as left-sided apraxia, poor bimanual coordination in specific laboratory tests, and deficits in the interhemispheric transfer of somaesthetic information. Other commissural functions, such as interhemispheric transfer of tactile, visual and auditory information as well as bilateral coordination in previously overlearned tasks, were nearly intact. The observed dysarthria could be meaningfully discussed in relationship to postcallosotomy mutism. It is concluded, that the partial interhemispheric disconnection syndrome in Marchiafava-Bignami disease lacks functional compensation which is different from the usual course in partial commissural section.

Adult↗
PubMed1994

Is heat hypoalgesia a useful parameter in quantitative thermal testing of alcoholic polyneuropathy?

Detection of thermal hypoaesthesia, hyperalgesia, and paradoxical sensation significantly contribute to the diagnosis of polyneuropathy (PNP). There is controversy about the clinical usefulness of detected heat hypoalgesia. In 50 chronic alcoholic patients we compared the prevalence and diagnostic value of heat hypoalgesia (HPT) to that of cold (CT) and warm (WT) hypoaesthesia using a "Marstock" thermotest. Clinical examination revealed PNP in 56%, cold hypoaesthesia was present in 62%, warm hypoaesthesia in 24%, paradoxical thermal sensation in 10%, cold and heat hyperalgesia in 12%, and heat hypoalgesia in 22%. Only 1 patient (2%) presented with heat hypoalgesia but normal warm and cold thresholds; he reported paradoxical thermal sensation and had PNP. One patient suffered first degree burn injury from heat pain examination. Heat hypoalgesia contributed least to the diagnosis of polyneuropathy (HPT versus CT: P < 0.001). In patients with sensory loss, testing heat hypoalgesia bears some risk of burn injury. In contrast to thermal hypoaesthesia and hyperalgesia, it does not significantly enrich the diagnostic workup of alcoholic polyneuropathies.

Adult↗
PubMed1994

Different mechanisms underly shifting set on external and internal cues in Parkinson's disease.

A set shifting task consisting of the comparison of two digits according to their numerical value or their form guided by an explicit (external cue) or implicit (internal cue) rule was performed by 8 untreated and 19 treated patients suffering from Parkinson's disease (PD) and 15 control subjects. The subjects could not predict the number of trials for a given target. The treated PD patient group exhibited increased post-shift error rates under the internal cue condition. In the external cue condition, only the untreated patients produced more errors when shifting to a new response criterion. Reaction times were prolonged in treated PD patients, irrespective of type of cue. Large interindividual variability within the patient groups is considered as meaningful and indicates individual differences in the neuropsychological impairment and/or the neurotransmission deficit. Pathophysiological and neuropsychological impairments underlying these findings are discussed on the basis of the models of Penney and Young (1983/1986) and Norman and Shallice (1980/1986).

Aged↗
PubMed1994

Doppler flow velocimetry of the uterine and uteroplacental circulation in pregnancies complicated by insulin-dependent diabetes mellitus.

UNLABELLED: In forty-three pregnancies complicated by insulin-dependent diabetes mellitus, 16 classified White B, 11 White C, 8 White D and 8 White R or F, the resistance-index (PR index) in the main part of the uterine artery and arcuate uterine arteries was measured by duplex-pulsed wave Doppler ultrasound. Recordings of 24 hours' blood glucose profile and glycosylated hemoglobin were parameters of glycemic control. Vascular resistance in the main uterine artery decreased with proceeding gestation as a non-diabetic pregnancy. The uterine artery supplying the placental had lower resistance than the opposite side, with a mean PR index of 0.559 (SD 0.117) and 0.622 (SD 0.133), respectively. The mean difference between both sides was 0.062 (SD 0.102) (p < 0.001). The uterine artery PR index was slightly higher in the presence of evident morphological vasculopathy, with a mean PR index of 0.591 (SD 0.104) in White D*/R/F diabetics and 0.545 (SD 0.063) in White B/C/D#, respectively (p = 0.148). Additionally more than half of the diabetics without manifest complications (B/C/D#) showed a persistent notch. Long- and short-term glycemic control was unrelated to vascular resistance in the uterine artery, with correlation coefficients of 0.027 (p = 0.746) and 0.051 (p = 0.537) for glucose and HbA1C, respectively. Doppler velocimetry could not predict diabetic specific fetal mobidity. Vascular resistance in the uterine arcuate arteries was significantly lower in the subplacental region, with a mean PR index of 0.367 (SD 0.056) compared to 0.427 (SD 0.064) in areas distant to the placenta (p < 0.0005). It was not related to vasculopathy elsewhere. IN CONCLUSION: in patients with diabetic vasculopathy the uterine artery is also affected, but there is no relationship with long- or short-term parameters of glycemic control. Doppler flow velocimetry of the uterine artery is a poor predictor of diabetes-specific fetal morbidity; if normal ranges of non-diabetic pregnancies are used for reference. Because of significantly different vascular resistance in the two main uterine arteries, mean values of both-side measurements should be used for analysis, whenever possible.

Adult↗