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Biomedical subjects

A Freund

Publications and source records attributed to A Freund.

13 recordsLinked to original sources
PubMed1999

All-trans-retinoic acid increases cytosine arabinoside cytotoxicity in HL-60 human leukemia cells in spite of decreased cellular ara-CTP accumulation.

BACKGROUND: Accumulation of the cytosine arabinoside (ara-C) metabolite ara-C-triphosphate (ara-CTP) in leukemic blast cells is considered to be the main determinant of ara-C cytotoxicity in vitro and in vivo. Retinoids such as all-trans-retinoic acid (ATRA) have been shown to increase the sensitivity of acute myelogenous leukemic (AML) blast cells to ara-C. To investigate the mechanism of this sensitisation, the hypothesis was tested that ATRA augments cellular ara-CTP levels in human-derived myelogenous leukemia HL-60 cells. MATERIALS AND METHODS: The effect of ATRA and 13-cis-retinoic acid on ara-CTP accumulation and ara-C-induced apoptosis was studied. Ara-CTP levels were measured by high-performance liquid chromatography (HPLC), cytotoxicity by the tetrazolium (MTT) assay, and apoptosis by occurrence of DNA fragmentation (gel electrophoresis), cell shrinkage and DNA loss (flow cytometry). RESULTS: Pretreatment of HL-60 cells with ATRA (0.01-1 microM) caused a significant decrease in intracellular ara-CTP levels; e.g., incubation for 72 hours with ATRA 1 microM prior to one hour ara-C 10 microM reduced ara-CTP levels to 41% +/- 4% of control. Similar results were obtained after preincubation with 13-cis-retinoic acid. In spite of decreased ara-CTP levels, the cytotoxicity of the combination was supraadditive and ATRA augmented ara-C-induced apoptosis. CONCLUSION: At therapeutically relevant concentrations ATRA increased ara-C cytotoxicity and ara-C induced apoptosis but this augmentation is not the corollary of elevated ara-CTP levels. The feasibility of ara-C treatment optimisation via strategies other than those involving elevation of ara-CTP levels should be investigated further.

Analysis of Variance↗
PubMed1998

Augmentation of 1-beta-D-arabinofuranosylcytosine (Ara-C) cytotoxicity in leukaemia cells by co-administration with antisignalling drugs.

The ribonucleotide reductase inhibitors hydroxyurea (HU), arabinosyl-2-fluoroadenine (F-Ara-A) and 2-chlorodeoxyadenosine (2-CdA) and the antisignalling drugs all-trans retinoic acid (ATRA), staurosporine and quercetin have been reported to enhance the cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C). We tested the hypothesis that the ara-C-sensitising potency of the antisignalling agents is equipotent with that of the ribonucleotide inhibitors. The cytotoxicity, determined by the 3-(4,5 dimethylthiazol-2-yl-)5 diphenyltetrazolium bromide (MTT) assay, of combinations of ara-C with the agents named above was compared in the leukaemia cell lines HL-60, ara-C-resistant HL-60 (HL-60/ara-C) and U937. Furthermore, a range of protein tyrosine kinase inhibitors, genistein, CGP 52411, tyrphostin A48 and nordihydroguaiaretic acid (NDGA), for which ara-C-sensitisation has hitherto not been described, were included in the study. All three cell types acquired increased sensitivity to ara-C when co-incubated with HU or ATRA, but their ara-C sensitivity was not affected by quercetin or genistein. 2-CdA, CGP 52411, tyrphostin A48, staurosporine and NDGA were active as sensitisers against ara-C in HL-60 cells, CGP 52411 and tyrphostin A48 also in HL-60/ara-C cells, and 2-CdA, staurosporine and NDGA also in U937 cells. F-Ara-A increased ara-C toxicity in HL-60/ara-C and U937 cells. To address the mechanism of the observed sensitisation, the influence of agents with ara-C-sensitising properties on ara-C-induced apoptosis was investigated in HL-60 cells as measured by cell shrinkage, DNA loss and DNA fragmentation. HU, ATRA, tyrphostin A48 and NDGA augmented apoptosis induced by ara-C as assessed by all three indicators. CGP 52411 decreased the effect of ara-C on apoptotic indicators after incubation for 4 h, but not after 12 h. The results suggest that ATRA, CGP 52411, tyrphostin A48, staurosporine and NDGA may be suitable alternatives to the clinically applied ribonucleotide reductase inhibitors as modifiers of ara-C cytotoxicity in the treatment of acute myeloid leukaemia.

Antimetabolites, Antineoplastic↗
PubMed1998

Bilateral oedema of the basal ganglia in an echovirus type 21 infection: complete clinical and radiological normalization.

A 4-year-old girl with bilateral striatal oedema in association with an echovirus type 21 infection is reported. In the course of a prolonged upper respiratory-tract infection, the patient developed muscular hypotonia, resting tremor, ataxia, sleepiness, hyperaesthesia, and indistinct speech. T2-weighted cranial MRI revealed bilateral oedema of the basal ganglia and the cerebellar peduncles. At follow-up after 3 months MRI changes and clinical symptoms had fully resolved.

Basal Ganglia↗
PubMed1997

The Y1 antagonist BIBP 3226 inhibits potentiation of methoxamine-induced vasoconstriction by neuropeptide Y.

We investigated the interaction of neuropeptide Y (NPY) with the alpha 1-adrenoceptor agonist, methoxamine, in control of mean arterial pressure, renovascular resistance and mesenteric vascular resistance in anaesthetized rats. Infusion of 3.0 but not 0.3 microgram/kg/min NPY enhanced the elevations of all three haemodynamic parameters caused by bolus injections of methoxamine (10-100 micrograms/kg). These enhancements largely involved a prolongation of the methoxamine effects. While infusion of the Y1 NPY receptor-selective antagonist, BIBP 3226 (10 micrograms/kg/min), alone did not alter methoxamine-induced vasoconstriction, it inhibited the potentiation by NPY. We conclude that NPY can potentiate methoxamine-induced vasoconstriction in vivo. This is mediated predominantly, if not exclusively, via the Y1 receptor. Endogenously released NPY does not appear to reach sufficient concentrations to cause tonic systemic vasoconstriction or potentiation thereof in the anaesthetized rat.

Animals↗
PubMed1997

A hypermedia tutorial for cross-sectional anatomy: HyperMed.

Modern imaging techniques like computer tomography (CT) and nuclear magnetic resonance (MR) imaging have become essential in clinical diagnostics and also in teaching gross anatomy to medical students. As a consequence, special classes in (cross)-sectional anatomy are being added to the curriculum in many anatomical institutions. Since institutional budgets often do not allow extensive supervision beyond the very limited time frame of traditional courses in gross anatomy, a computer-based hypermedia tutorial (HyperMed) was created and integrated into the teaching program of the Institute of Anatomy at Essen University. HyperMed offers two components, one for authors (e.g. teachers who can customize the contents of the program) and a second for users (e.g. students). In the present version, digital cross-sectional human images have been edited. The relevant anatomical structures in these images have been marked, named, and linked to additional information and figures (in particular schematic figures and CT images). Users can obtain information at different levels: (1) index-based retrieval, (2) navigational retrieval (on inspecting cross-sectional images the user is asked to identify structures) and (3) a history list enabling users to go back to any previous point of navigation. HyperMed was first tested in the winter terms 1995/1996 and 1996/1997 during classes on cross-sectional anatomy which are a supplement to the traditional dissection course of the Institute of Anatomy, University Essen. It was well received by the students who found it a helpful adjunct to learning cross-sectional anatomy.

Anatomy, Cross-Sectional↗
PubMed1991

Assessing daily management of childhood diabetes using 24-hour recall interviews: reliability and stability.

Conducted 24-hr recall interviews concerning daily diabetes management with seventy-eight 6- to 19-year-old patients and their parents. Patients and parents were interviewed independently nine times over 3 months. Data obtained were used to construct 13 adherence measures. All measures yielded statistically significant estimates of parent-child concordance. Parent-child agreement was higher for weekday versus weekend behaviors and when based on nine versus three interviews. For the sample as a whole, parent-child concordance remained stable over the course of the study. Compared to the older patients, the 6- to 9-year-olds exhibited poorer parent-child agreement on measures involving time (e.g., injection and exercise-duration measures). This deficit disappeared, however, as the children became more practiced with the interview procedure. The dietary and glucose-testing measures exhibited moderate stability over the 3-month study. Lower stability estimates were obtained for the exercise and injection measures.

Activities of Daily Living↗
PubMed1990

Adherence-health status relationships in childhood diabetes.

Used 24-hr recall interviews to assess adherence in a sample of seventy-eight 6- to 19-year-olds with insulin-dependent diabetes mellitus over a 3-month period. Thirteen adherence measures were quantified and grouped into six adherence factors (Injection, Exercise, Diet Type, Testing/Eating Frequency, Calories Consumed, and Concentrated Sweets). Prevailing glucose levels over a 2- to 3-month interval were indexed by glycosylated hemoglobin A1c (HA1c) and glycosylated serum protein (GSP) assays. Fasting triglycerides (TRIG) and total cholesterol (CHOL) assays were used to estimate lipid metabolism. Adolescents were generally less adherent than their young counterparts. Using hierarchical multiple-regression techniques, HA1c and GSP were not reliably predicted by most of the adherence factors; only Calories Consumed showed any predictive power. No significant regression equations emerged for CHOL. In contrast, TRIG was significantly associated with five of the six adherence factors; in all cases, adherence interacted with the patients' metabolic status (as defined by HA1c) at study entry, suggesting that adherence had different effects for youngsters in good versus poor diabetes control.

Adolescent↗
PubMedDate not supplied

[Pediatric characteristics of adult respiratory distress syndrome: a meta-analysis].

A meta-analysis of the literature is carried out in order to present the current knowledge of ARDS in childhood (0-15 years). This might be helpful for planning controlled studies on new therapeutic measures (e.g. surfactant replacement, antioxidants, extracorporeal gas exchange). By means of Medline all available publications were taken into account referring to minimal criteria defined before. There were 4 studies (50 patients) and 48 individual case-reports (48 patients). Most often ARDS was caused by infection (21 resp. 30%), aspiration (12 resp. 23%) and trauma (10 resp. 23%). Therapeutically high respiration pressures and toxic oxygen tensions were applied generally (average maximum PEEP: 14.7 resp. 15.8 cm H2O; average maximum PIP: 59.6 resp. 61.9 cm H2O; FiO2 > 0.5 for an average of 10.1 resp. 10.4 days). The most frequent complications were barotrauma (43.8 resp. 78%), infection (60.4%) and multiorgan failure (66.7%). Mortality rate was 31.3 resp. 52%. So also in childhood almost every second case is fatal. Especially multiorgan failure as well as high levels of FiO2 and PEEP indicate bad prognosis at an early stage. Therefore it is necessary and justified to perform clinical trials on therapeutic agents successfully tested in animal studies before.

Adolescent↗
PubMedDate not supplied

[Tuberculous meningitis in a 13-month-old boy: a case report].

We present the case of a 13-month old Turkish boy of Kurdish origin with tuberculous meningitis. Fever of unknown origin and neurologic symptoms (loss of ability of walking and free sitting, cerebral seizures, central paresis of the VII. cranial nerve, coma) led to the diagnosis. Cranial CT demonstrated hydrocephalus and enhancement of the basal meninges after contrast injection; the chest x-ray showed an infiltrate in the right upper lobe of the lung and the cerebrospinal fluid (CSF) mild pleocytosis with elevated protein and reduced glucose concentrations. Diagnosis was confirmed by detection of Mycobacterium tuberculosis in the CSF by polymerase chain reaction (PCR). Immediately, surgical and level-controlled tuberculostatic treatment was initiated. The patient recovered completely.

Antitubercular Agents↗
PubMedDate not supplied

Subjective symptoms, blood glucose estimation, and blood glucose concentrations in adolescents with diabetes.

Twenty-five adolescent campers with insulin-dependent diabetes mellitus (IDDM) completed a Symptom Rating Checklist and estimated their blood glucose (BG) immediately before having their BG assessed four times daily for 11 days. Consistent relationships between BG and symptoms were not identified when the data were analyzed for the group as a whole. However, when each camper's data were analyzed separately, 23 of the 25 adolescents had at least one significant glycemia-symptom (G-S) correlation. Each camper seemed to have a unique G-S pattern; only one symptom (hungry) was significantly related to BG for more than half of the youngsters studied. Almost all of the significant G-S correlations were indicative of low rather than high BG. However, when asked, few campers were able to accurately identify which symptoms were reliably associated with low or high BG. In this study, different measures of BG estimation error led to different results. The percent of estimates +/- 20% of the actual BG value (55% in this study) was strongly influenced by the actual BG reading because higher BG values have larger accuracy ranges than lower BG concentrations. When estimated BG was simply subtracted from actual BG, under- and overestimates canceled each other out, resulting in an unusually small estimated error (5 mg/dl in this investigation). The absolute difference score ignores the direction of estimation error, but may more accurately reflect patients' average estimation error (68 mg/dl in this study). When actual and estimated BG values were correlated for the group as a whole, the patients appeared to be highly accurate at estimating BG (r = .93, P less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗