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Biomedical subjects

S Westphal

Publications and source records attributed to S Westphal.

35 records · Page 2Linked to original sources
PubMed2000

Oral trofosfamide and etoposide in pediatric patients with glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme in childhood is rare, and the prognosis for patients with the disease is poor. The Pediatric Oncology Society of the Germanic language group (GPOH) enrolls patients in a series of pilot trials, the first of which is reported here (HIT-GBM-A). METHODS: Twenty-two patients with glioblastoma multiforme, World Health Organization Grade 4, between the ages of 3-15 years (45% male) were enrolled during the period 1995-1997. There were 13 supratentorial tumors, 8 brainstem tumors, and 1 cerebellar tumor. The patients underwent the following procedures: stereotactic biopsy (n = 3 patients), open biopsy (n = 1 patient), partial resection (n = 6 patients), subtotal resection (n = 4 patients), and macroscopic total resection (n = 8 patients). Adjuvant treatment consisted of oral chemotherapy with trofosfamide, 100 mg/m(2), and etoposide, 25 mg/m(2), daily or for 21-day cycles interrupted by 1-week rests. Standard fractionated radiation (54 grays) was started concurrently with the first cycle. RESULTS: The chemotherapy was well tolerated, with no treatment-related deaths and only minor side effects. The responses in 12 evaluable patients after two cycles were as follows: 1 complete response, 1 partial response, 3 patients with stable disease, and 7 patients with progressive disease. The median overall survival was 12 months. The 1-year, 2-year, and 4-year overall survival rates were 52%, 26%, and 22%, respectively, and the event free survival rates were 26%, 22%, and 4%, respectively. None of the four surviving patients (3.2 years, 3.4 years, 4.0 years, and 4.2 years after diagnosis) is event free. Two patients are alive after tumor progression: One patient was diagnosed with a medulloblastoma, and one patient was diagnosed with an osteosarcoma as second malignancies. A control group extracted from the Surveillance, Epidemiology, and End Results data had lower survival rates: the difference between the groups was not statistically significant (P = 0.26). CONCLUSIONS: This chemotherapy will not be used in a randomized trial of patients with glioblastoma; however, it may be evaluated for patients with tumors that have more chemoresponsive histologies.

Administration, Oral↗
PubMed2000

Cardiac troponin T predicts mortality in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T. METHODS AND RESULTS: Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations >0.10 ng/mL (hazard ratio 6.85, 95% CI 3. 04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration). CONCLUSIONS: We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.

Cardiovascular Diseases↗
PubMed2000

Postprandial chylomicrons and VLDLs in severe hypertriacylglycerolemia are lowered more effectively than are chylomicron remnants after treatment with n-3 fatty acids.

BACKGROUND: n-3 Fatty acids lower plasma triacylglycerols not only in the fasting state but also in the postprandial state. However, it is not known whether chylomicrons, chylomicron remnants, and VLDLs are all affected equally or whether some lipoprotein species are lowered preferentially. OBJECTIVE: Lipoproteins, including large and small chylomicron remnants, were determined specifically with the aid of a newly developed method involving a combination of size-exclusion chromatography and fluorometric determination of retinyl palmitate, which served as a marker for exogenous fat. DESIGN: Twelve hypertriacylglycerolemic men were treated for 6 wk with 4 capsules containing 85% fish-oil concentrate/d; each capsule contained 850 mg n-3 fatty acid ethyl esters (49.1% eicosapentaenoic acid by wt and 32.2% docosahexaenoic acid by wt). Oral-fat-tolerance tests were performed before and after the treatment. Blood samples were drawn in the fasting state and until 8 h postprandially. RESULTS: Treatment with n-3 fatty acids reduced the fasting VLDL-triacylglycerol concentration by 44% (P < 0.05) and postprandial chylomicrons and VLDLs at 4, 6, and 8 h (P < 0.05) by 49-64% and 36-43%, respectively. Chylomicron remnants were reduced only in the late postprandial phase: large chylomicron remnants by 19% at 6 h and by 43% at 8 h (P < 0.05) and small chylomicron remnants by 31% at 8 h (P < 0.05). CONCLUSION: n-3 Fatty acids effectively lower chylomicrons and VLDLs, but their effect on chylomicron remnants was observed only in the late postprandial phase.

Adult↗
PubMed1998

A collaborative study on media for the enumeration of yeasts in foods.

A collaborative study was made to evaluate the effectivity of a general purpose medium, tryptone glucose yeast extract (TGY) agar on the detection and enumeration of yeasts from food. Nine laboratories participated in the study and compared five media (four kinds of TGY with different concentrations of glucose, one of them without tryptone, and, for comparison, dichloran rose bengal chloramphenicol (DRBC) agar). Six food samples were investigated by each laboratory and 23 additional food samples were investigated individually by different laboratories. No difference was found in the performance of media with either the samples common to all laboratories or the various samples tested in different ones. A medium consisting of tryptone, glucose and yeast extract, at any concentration of glucose tested, appeared reliable for the detection and enumeration of yeasts from foods, and its performance did not differ from that of DRBC. Omission of tryptone as recommended by ISO provided an even simpler medium of equally good performance. TGY without chloramphenicol may result in higher total counts due to the development of bacteria. DRBC incubated in light results in lower counts compared to that incubated in the dark.

Aniline Compounds↗
PubMed1998

Diagnostic relevance of interleukin pattern, acute-phase proteins, and procalcitonin in early phase of post-ERCP pancreatitis.

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has been suggested as a model for acute pancreatitis (AP), which allows evaluation of early alterations in the time course of the disease. The influence of the clinical course on procalcitonin (PCT), serum amyloid A (SAA), and several proinflammatory and inhibitory cytokines was evaluated in patients with AP following ERCP. Blood samples were prospectively collected from patients undergoing ERCP. The incidence of ERCP-induced pancreatic damage, defined as abdominal complaints, a threefold increase of serum lipase, and elevation of CRP from <10 to >20 mg/liter was 12.8% (12/94). Only mild clinical courses of acute pancreatitis were observed. PCT significantly increased in subjects with post-ERCP pancreatitis after 24 hr. However, PCT levels did not exceed 0.5 ng/ml in any patient. Interleukin-1 receptor antagonist (IL-1RA) began to differ from baseline 2 hr after ERCP, followed by interleukin-6 (IL-6, 6 hr), solubilized tumor necrosis factor-alpha receptor II (sTNF-alphaRII, 24 hr) and SAA (24 hr). Interleukin 10 (IL-10) showed marked interindividual variations with no obvious peak. Among all parameters evaluated, only peak values of IL-6 and IL-10 showed significant correlations with the reported pain score (r2 = 0.62/0.78), degree of ampullar irritation (r2 = NS/0.87), and the duration of ERCP (r2 = 0.58/0.76). No correlation was found with the volume of the injected contrast agent. We conclude that IL-10 and IL-6 appear to be useful to monitor patients after ERCP. The absence of any PCT elevation in the present study is in accordance with the clinical course of the patients who suffered from mild pancreatic damage without systemic or infectious complications.

Acute Disease↗
PubMed1998

Compositional and functional changes of low-density lipoprotein during hemodialysis in patients with ESRD.

BACKGROUND: This study focused on the effects of hemodialysis on the atherogenic properties of low density lipoprotein (LDL) in patients with end-stage renal disease (ESRD). The impact of cholesterol ester transfer protein (CETP) activity and lipolysis on LDL composition, particularly the changes during hemodialysis, was investigated. METHODS: Blood was drawn from 15 normotriglyceridemic (NTG) and 15 hypertriglyceridemic patients [HTG; triglycerides (TG) < 2.2 mmol/liter] before hemodialysis, during (1.5 hr after the beginning of anticoagulation) and at the end of treatment. In each sample, lipid values and CETP activity were measured. LDL was prepared and characterized by its components and diameters (2 to 16% PAGGE). To investigate the functional properties of LDL, fractions obtained from NTG and HTG patients were incubated with human skin fibroblasts and a cell line of murine macrophages (P388), and cholesterol ester formation rates were measured. RESULTS: In comparison to LDL from NTG patients at baseline, HTG-LDL were enriched in triglycerides (P < 0.02), depleted in cholesterol proportion (P < 0.01) and small in size (P < 0.001). These LDL induced the cholesterol esterification rates (50 micrograms/mL LDL-protein) in a twofold greater unsaturation in macrophages when compared to LDL from NTG patients (P < 0.04). The rates in fibroblasts were reduced by approximately half (P < 0.05). During hemodialysis, LDL were decreased in size (P < 0.001) and depleted in TG (P < 0.01), particularly in the hypertriglyceridemic state. Although CETP activity increased during hemodialysis (P < 0.001), the cholesterol content remained unchanged. When HTG-LDL obtained during hemodialysis were incubated with cells, esterification rates particularly in macrophages were markedly accelerated in comparison to the unmodified lipoprotein at baseline (P < 0.05). CONCLUSION: LDL from HTG patients with ESRD was TG-enriched, CH-depleted and smaller in size. As the intracellular esterification rates induced by LDL were related to the cellular uptake, these LDL were a superior substrate for murine macrophages with the tendency of intracellular accumulation, and an inferior substrate for fibroblasts suggesting a decreased uptake by the specific receptor pathway. TG-depletion of LDL during hemodialysis, particularly in HTG patients due to a lipase-mediated TG-hydrolysis, increased these effects in macrophages. We suggest that the alterations of LDL that occur during repeated hemodialysis in vivo could contribute to the high prevalence of premature atherosclerosis found in HTG patients with ESRD.

Adult↗
PubMed1997

Chloroquine effects on intrauterine and postnatal dendritic maturation of hippocampal neurons and on lipid composition of the developing rat brain.

The aim of the study was to analyse the intrauterine effects of Chloroquine on the dendritic maturation in the hippocampal region under considering of the lipid composition in brain tissue. 131 brains of rat pups from day 22 of pregnancy and 49 brains from offsprings from day 7 of life were investigated. The findings indicate changes in the geometric dendritic architecture of the CA3 neurons on the 7th day of life. The length of apical shaft, apical dendrites and basilar dendrites of the CA3 neurons showed a significant elongation (p < 0.05) under low doses of Chloroquine. Furthermore a early considerable formation of dendritic spines during the intrauterine period could be observed for CA1 spines at the day 22 p.c. A significant increase of the fatty acids, a reduced amount of sphingomyelines, cephalines and gangliosides was found. These results underline the fact of a mild toxic effect under a low dosis of Chloroquine in our model.

Administration, Oral↗
PubMed1996

Isolation of functionally intact pig retina mitochondria.

Two alternative methods for the isolation of functionally intact mitochondria from pig retina were evaluated by means of differential centrifugation. If ATP and bovine serum albumin were present during the isolation procedures mitochondria exhibited ADP sensitive respiration and membrane potentials, comparable to values from other tissues. The mitochondria fraction of both methods differed in purity, being almost free of synaptosomes when a discontinuous Ficoll gradient centrifugation was used.

Animals↗
PubMed1995

Abnormal dendritic maturation of neurons under the influence of a Tilorone analogue (R 10.874).

Tilorone analogue (R 10.874) has a close affinity to the lysosomal compartment of cells and forms a non degradable carbohydrate-lipid-drug complex accumulated within digesting organelles. Resembling biochemical and structural changes are seen in hereditary mucopolysaccharidoses accompanied with abnormal dendritogenesis. On the other hand, developmental toxicity (TERRY et al. 1992), antiproliferative effects (ALGARRA et al. 1993) and interactions with DNA (GELLER et al. 1985) are generated by tilorone. Therefore it should be interesting to know whether the amphiphilic cationic compound is able to produce an abnormal dendritogenesis as in storage diseases or an impaired arborisation of dendrites and what could be the reason for the misdevelopment. We demonstrate that there was a fetal retardation in the development of dendritic network, even under influence of low dosis of the analogue R 10.874. The dendritic dismaturation was concomitant with an increased amount of fatty acids and a slightly disarranged metabolic pathway of gangliosides. The dendritic arborisation closed the gap of retarded development between intrauterine treated and untreated rats after 7 days of postnatal drug elimination. We suppose that a fetotoxic effect and not the lysosomopathy is responsible for the reduced dendritic network.

Animals↗
PubMed1989

[Abnormal gangliosides in the plasma of alcoholics].

Gangliosides were isolated from plasma of alcoholics. The pattern of gangliosides was compared with that of healthy humans. Up to seven fractions of gangliosides could be detected. In healthy subjects the following pattern was found: GM3 38.2%, SPG 6.0%, GD3 30.2%, GD1a 10.6%, GD1b 4.8%, GT1b 7.9%, GQ1b 2.2%. In alcoholics, significant differences were observed in the main ganglioside fractions GM3 (52.6%) and GD3 (17.5%).

Adult↗
PubMedDate not supplied

[Lung maturation during artificial placentation and mechanical lung distension].

An new method of lung maturation during artificial placentation was evaluated during a series of 15 animal experiments in premature lambs (gestational age 125-132 days). Perfusion circuit with interposition of a membrane lung was connected with the umbilical vessels. Extracorporeal CO2-removal (ECCO2-R) and apneic oxygenation were provided during lung distension. The ultramicroscopic pattern approved a maturation of the lung during the procedure showing development of lamellar bodies and surfactant secretion into the alveolar space. The biochemical analysis of the tracheal fluid showed a significant increase of both PC and PG concentrations (3.225 +/- 1.112 mg/100g to 24.228 +/- 3.36 mg/100 g respectively 0.249 +/- 0.11 mg/100 g of 0.622 +/- 0.09 mg/100 g. The biophysical function of the lung was also improved as was shown by a significant increase of the statistical compliance. We conclude that artificial placentation and lung distension might be a new mode of prophylaxis for respiratory distress syndrome in critically immature babies.

Animals↗
PubMedDate not supplied

[Endocrine parameters during artificial placentation and postnatal lung maturation].

During a experimental study in premature lamb the adaptation to a artificial placenta was evaluated by means of analysis of endocrine parameters. Performing cesarean section on day 125.-135.13 premature lambs were born and connected to a extracorporeal circuit providing CO2-Removal (ECCO2-R) during apnoic oxygenation over a period of 3 hours and 17 minutes mean duration. The intermittent analysis of 6 endocrine parameters was performed at the beginning of the experiment, after 1 hour and after 3 hours. TSH showed an statistical significant increase from a initial concentration of 0.638 +/- 0.051 microE/ml to 0.992 +/- 0.093 microE/ml after 1 hour (p 0.01). For T3 we found 0.273 +/- 0.074 nmol/l and 0.809 +/- 0.124 nmol/l. For RT3 we detected a decrease as the initial value was 4.304 +/- 0.474 ng/ml whereas after one hour we found 2.040 +/- 0.153 ng/ml. ACTH values increased from 543 +/- 109 pg/ml to 1150 +/- 194 pg/ml after 1 hour. Cortisol values increase from 39.6 +/- 7.5 ng/ml to 55.3 +/- 11.9 ng/ml. No significant change was found during the analysis of beta-endorphin concentrations. We conclude that the adaptation to artificial umbilical circulation is possible. Furthermore detected changes of endocrine parameters, namely cortisol and thyroxin levels, should provide a basis for postnatal organ maturation.

Adaptation, Physiological↗