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Biomedical subjects

L Schilling

Publications and source records attributed to L Schilling.

At least 19 recordsLinked to original sources
PubMed2006

Cochrane Skin Group systematic reviews are more methodologically rigorous than other systematic reviews in dermatology.

BACKGROUND: The Cochrane collaboration aims to produce high-quality systematic reviews. It is not known whether the methods used in producing Cochrane Skin Group (CSG) reviews result in higher quality reviews than other systematic reviews in dermatology. OBJECTIVES: To determine how the methodological quality of dermatological CSG reviews published in The Cochrane Library and in peer-reviewed journals compare with non-Cochrane systematic reviews. METHODS: Two blinded investigators independently assessed review quality using the 10-item Oxman and Guyatt scale. RESULTS: Thirty-eight systematic reviews (17 Cochrane reviews published in The Cochrane Library, 11 Cochrane reviews published in peer-reviewed journals and 10 non-Cochrane reviews published in peer-reviewed journals) were examined. The Cochrane Library reviews included quality of life (11/17 vs. 1/10, P = 0.014) and adverse outcomes (14/17 vs. 2/10, P = 0.003) more often than non-Cochrane reviews published in peer-reviewed journals. Cochrane reviews published in both peer-reviewed journals and The Cochrane Library were more likely to include comprehensive search strategies (11/11 and 17/17 vs. 6/10, P-values = 0.04 and 0.01), take steps to minimize selection bias (11/11 and 16/17 vs. 3/10, P-values = 0.003 and 0.001) and appropriately assess the validity of all included trials (10/11 and 16/17 vs. 4/10, P-values = 0.04 and 0.007) than non-Cochrane reviews. Overall, Cochrane reviews published both in peer-reviewed journals and in The Cochrane Library were assigned higher quality scores by reviewers than non-Cochrane reviews (median = 6.0 and 6.5 vs. 4.5, P-values = 0.01 and 0.002). CONCLUSIONS: The Cochrane Library systematic review methodology leads to higher quality reviews on dermatological topics.

Dermatology↗
PubMed2005

Statins and fibrates for preventing melanoma.

BACKGROUND: Effective treatment for advanced melanoma is lacking. While no drug therapy currently exists for prevention of melanoma, in vitro, case-control, and animal model evidence suggest that lipid-lowering medications, commonly taken for high cholesterol, might prevent melanoma. OBJECTIVES: To assess the effects of statin or fibrate lipid-lowering medications on melanoma outcomes. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (February 2003), CENTRAL (The Cochrane Library Issue 1, 2005), MEDLINE (to March 2003), EMBASE (to September 2003), CANCERLIT (to October 2002), Web of Science (to May 2003), and reference lists of articles. We approached study investigators and pharmaceutical companies for additional information (published or unpublished studies). SELECTION CRITERIA: Trials involving random allocation of study participants, where experimental groups used statins or fibrates and participants were enrolled for at least four years of therapy. DATA COLLECTION AND ANALYSIS: Three authors screened 109 abstracts of articles with titles of possible relevance. We then thoroughly examined the full text of 72 potentially relevant articles. We requested unpublished melanoma outcomes data from the corresponding author of each qualifying trial. MAIN RESULTS: We identified 16 qualifying randomised controlled trials (RCTs) (seven statin, nine fibrate). Thirteen of these trials (involving 62,197 participants) provided data on incident melanomas (six statin, seven fibrate). A total of 66 melanomas were reported in groups receiving the experimental drug and 86 in groups receiving placebo or other control therapies. For statin trials this translated to an odds ratio of 0.90 (95% confidence interval 0.56 to 1.44) and for fibrate trials an odds ratio of 0.58 (95% confidence interval 0.19 to 1.82). Subgroup analyses failed to show statistically significant differences in melanoma outcomes by gender, melanoma occurrence after two years of participation in trial, stage or histology, or trial funding. Subgroup analysis by type of fibrate or statin also failed to show statistically significant differences, except for the statin subgroup analysis which showed reduced melanoma incidence for lovastatin, based on one trial only (odds ratio 0.52, 95% confidence interval 0.27 to 0.99). AUTHORS' CONCLUSIONS: The melanoma outcomes data collected in this review of RCTs of statins and fibrates does not exclude the possibility that these drugs prevent melanoma. There was a 10% and 42% reduction for participants on statins and fibrates, respectively, however these results were not statistically significant. Until further evidence is established, limiting exposure to ultraviolet radiation remains the most effective way to reduce the risk of melanoma.

Anticholesteremic Agents↗
PubMed2005

Circadian periodicity of cerebral blood flow revealed by laser-Doppler flowmetry in awake rats: relation to blood pressure and activity.

Cardiovascular parameters such as arterial blood pressure (ABP) and heart rate display pronounced circadian variation. The present study was performed to detect whether there is a circadian periodicity in the regulation of cerebral perfusion. Normotensive Sprague-Dawley rats (SDR, approximately 15 wk old) and hypertensive (mREN2)27 transgenic rats (TGR, approximately 12 wk old) were instrumented in the abdominal aorta with a blood pressure sensor coupled to a telemetry system for continuous recording of ABP, heart rate, and locomotor activity. After 5-12 days, a laser-Doppler flow (LDF) probe was attached to the skull by means of a guiding device to measure changes in brain cortical blood flow (CBF). After the animals recovered from anesthesia, measurements were taken for 3-4 days. The time series were analyzed with respect to the midline estimating statistic of rhythm (i.e., mean value of a periodic event after fit to a cosine function), amplitude, and acrophase (i.e., phase angle that corresponds to the peak of a given period) of the 24-h period. The LDF signal displayed a significant circadian rhythm, with the peak occurring at around midnight in SDR and TGR, despite inverse periodicity of ABP in TGR. This finding suggests independence of LDF periodicity from ABP regulation. Furthermore, the acrophase of the LDF was consistently found before the acrophase of the activity. From the present data, it is concluded that there is a circadian periodicity in the regulation of cerebral perfusion that is independent of circadian changes in ABP and probably is also independent of locomotor activity. The presence of a circadian periodicity in CBF may have implications for the occurrence of diurnal alterations in cerebrovascular events in humans.

Animals↗
PubMed2004

Experimental approaches to evaluate endothelin-A receptor antagonists.

A large body of evidence suggests a substantial role of the endothelin (ET) system in the pathophysiology of a variety of disease states, mainly of the cardiovascular system. Recently bosentan, an ET receptor antagonist, has received approval by the Food and Drug Administration (FDA) for use in pulmonary artery hypertension. The ET system may also be involved in cerebrovascular disorders such as stroke and, most notably, development of cerebral vasospasm following subarachnoid hemorrhage. The pathophysiological mechanisms contributing to the development of a cerebral vasospasm after subarachnoid hemorrhage may be taken as a paradigm to explore mechanisms leading to secondary ischemic brain damages in a variety of insults such as stroke and trauma. The present review provides the evidence to evaluate ET receptor antagonists for potential prophylactic and therapeutic use in patients suffering from subarachnoid hemorrhage. The rationale to develop selective ETA receptor antagonists is given with respect to basic and applied studies. This may be useful to better define the desired profile of action of a given compound, and it may also help to design appropriate preclinical and clinical trials, most desirably in close cooperation with pharmaceutical companies and neurosurgical departments.

Animals↗
PubMed2003

Growth/differentiation factor-15 (GDF-15), a novel member of the TGF-beta superfamily, promotes survival of lesioned mesencephalic dopaminergic neurons in vitro and in vivo and is induced in neurons following cortical lesioning.

This review summarizes the evidence that GDF-15, a recently discovered member of the TGF-beta superfamily, is a trophic factor for nigral dopamine neurons, both in vitro and in vivo. Specifically, GDF-15 promotes survival and differentiation of embryonic rat dopaminergic neurons, but not of other neuron populations, with the exception of serotonergic raphe neurons. The neurotrophic effect of GDF-15 seems to be direct and not mediated through glial cells. In the rat 6-hydroxydopamine model of parkinsonism GDF-15 rescues intoxicated dopaminergic neurons and abolishes abnormal turning behavior. The most prominent site of synthesis of GDF-15 within the brain is the choroid plexus, which secretes GDF-15 into the cerebrospinal fluid, from where the molecule can penetrate through the ependymal layer into the parenchyma. Analysis of mouse mutants lacking GDF-15 will reveal whether the endogenous factor also has a role in promoting embryonic and protecting lesioned nigral dopamine neurons.

Adrenergic Agents↗
PubMed2001

Expression of growth differentiation factor-15/ macrophage inhibitory cytokine-1 (GDF-15/MIC-1) in the perinatal, adult, and injured rat brain.

We and others have recently cloned a new member of the transforming growth factor-beta superfamily, growth differentiation factor-15/ macrophage inhibitory cytokine-1 (GDF-15/MIC-1). Using in situ hybridization and immunohistochemistry, we determined the distribution of GDF-15/MIC-1 mRNA and protein in the perinatal and cryolesioned adult rat brain. The choroid plexus epithelium of all ventricles represents the site of strongest and almost exclusive mRNA expression in the normal perinatal and adult brain. The newborn rat brain reveals GDF-15/MIC-1 immunoreactivity (ir) in ependymal cells lining the ventricles, in the striatal subventricular zone, and in populations of nonneural cells of the thalamic/hippocampal lamina affixa, in addition to that in the choroid plexus. Unilateral cryogenic cortical lesioning induced a significant increase of GDF-15/MIC-1 mRNA expression and ir at the lesion site and expression in presumed neurons within the dorsal thalamic area. At the lesion site, GDF-15/MIC-1-producing cells showed immuncytochemical features of neurons, macrophages, and activated microglial cells. Fluorescent microscopy revealed both intra- and extracellular GDF-15/MIC-1 ir. Up-regulation of GDF-15/MIC-1 in activated macrophages (Mstraight phi) is also supported by RT-PCR, ICC, and Western blot experiments showing pronounced induction of GDF-15/MIC-1 expression (mRNA and protein) in retinoic acid/phorbol ester-stimulated human M phi. Our data suggest that 1) GDF-15/MIC-1 is secreted into the cerebrospinal fluid and 2) in the newborn brain may penetrate through the ependymal lining and act on developing neurons and/or glial cells. As a constituent of cells in the lamina affixa, the protein might be involved in the regulation of mesenchyme-epithelial interactions. Finally, GDF-15/MIC-1 may also act within the antiinflammatory cytokine network activated in CNS lesions.

Aging↗
PubMed2001

Specific pattern of growth factor distribution in chronic subdural hematoma (CSH): evidence for an angiogenic disease.

BACKGROUND: The aim of this prospective study was to evaluate the significance of growth factors as determinants of the pathological degree of neovascularisation found in the parietal neomembrane of chronic subdural hematoma (CSH). Thus far the pathogenesis of the vascularisation has not been elucidated. METHOD: The concentrations of growth factors, i.e. vascular endothelial derived growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) were determined using ELISA technique in hematoma fluid and serum of 20 patients with uni- or bilateral CSH. For comparison, growth factor concentrations were determined in cerebrospinal fluid (CSF) of patients undergoing diagnostic myelography. FINDINGS: Concentrations of VEGF and bFGF were significantly (p < 0.001) increased in the hematoma fluid as compared with serum (VEGFh = 8.142 pg/ml, bFGFh = 8.7 pg/ml versus VEGFS = 368 pg/ml, bFGF, = 1.8 pg/ml). In contrast, PDGF concentration was significantly (p < 0.001) lower in the hematoma (PDGFh = 3,456 pg/ml versus PDGF, = 31,937 pg/ml). The serum levels for VEGF, bFGF and PDGF in CSH patients lay within the range of normal volunteers. No growth factors were found in normal CSF. INTERPRETATION: These results reveal a specific distribution pattern of growth factors in CSH patients. This pattern suggests that CSH may be considered a member of the angiogenic disease family.

Aged↗
PubMed2001

Day-night variation in the in vitro contractility of aorta and mesenteric and renal arteries in transgenic hypertensive rats.

TGR(mREN2)27 (TGR) rats develop severe hypertension and an inverted circadian blood pressure profile with peak blood pressure in the day-time rest phase. The present study investigated the in vitro responsiveness of different arteries of TGR rats during day and night. Twelve-week-old TGR rats and normotensive Sprague-Dawley (SPRD) controls, synchronized to 12h light, 12h dark (LD 12:12) (light 07:00-19:00), were killed at 09:00 (during rest) and 21:00 (during activity), and endothelium-dependent relaxation by acetylcholine and vascular contraction by angiotensin II were studied by measuring isometric force in ring segments of abdominal aorta and mesenteric and renal arteries. In SPRD rats, consistent day-night variation was found, with greater responses to angiotensin II during the daytime rest span. In TGR rats, biological time-dependent differences were found in the renal vasculature, but not in the aorta and mesenteric artery. Relaxation of SPRD rat aorta and mesenteric artery by acetylcholine was greater at 09:00, whereas in TGR rats, day-night variation was absent (mesenteric artery) or inverted (aorta). In conclusion, based on the study of two time points, day-night variation in vascular contractility of aorta and mesenteric artery is blunted in TGR rats, whereas renal artery segments showed an unchanged day-night pattern compared to SPRD controls.

Acetylcholine↗
PubMed2001

Bedside monitoring of cerebral blood flow by transcranial thermo-dye-dilution technique in patients suffering from severe traumatic brain injury or subarachnoid hemorrhage.

Bedside measurement of cerebral blood flow (CBF) represents an important feature in monitoring of neurointensive care patients which is hard to establish. Therefore, we adopted a recently described thermo-dye-dilution-based approach for monitoring CBF in patients suffering from severe cerebral insults, that is, traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). Combined fiberoptic-thermistor catheters were placed in one jugular venous bulb and in the abdominal aorta of 16 patients. Following central venous injection of a 50-mL bolus of precooled indocyanine green (ICG) solution, CBF was determined as a function of the mean transit times of coldness and dye. In addition, measurements of CBF using stable xenon-enhanced computerized tomography (sXe-CT) were simultaneously performed in 10 patients. A total of 272 thermo-dye-dilution measurements yielded 196 valid results, with CBF ranging from 26.2 to 144.8 mL 100 g(-1) min(-1). Reproducibility was fairly good, with the standard deviation within sets of repeated measurements being 6.3 mL 100 g(-1) min(-1) and 9.4 as the mean coefficient of variation. Simultaneously obtained values with sXe-CT displayed a good correlation (r = 0.843, p < 0.01); however, the thermo-dye-dilution method consistently overestimated CBF. Data analysis using the Bland and Altman methodology revealed a large bias of 45.7 mL 100 g(-1) min(-1) with a +/- 2 SD range of 37 mL 100 g(-1) min(-1), indicating a rather poor agreement. The thermo-dye-dilution method proved a reasonably reproducible technique, enabling repeated long-term bedside measurements of CBF in neurointensive care patients with a minimum of time effort. However, a high failure rate was also noted, and consistent overestimation of perfusion was observed in comparison to sXe-CT measurements. Although the thermo-dye-dilution technique has been successfully validated in patients with normal neurovascular function, its applicability for bedside monitoring of CBF appears uncertain in patients suffering from severe TBI or SAH.

Adolescent↗
PubMed2001

Effect of moderate hypothermia on experimental severe subarachnoid hemorrhage, as evaluated by apparent diffusion coefficient changes.

OBJECTIVE: The aims of this study were to investigate the early changes in the mean apparent diffusion coefficient (ADC) after severe subarachnoid hemorrhage (SAH), as a marker of ischemic damage, and to examine the effects of moderate hypothermia, induced at various time points, on ADC changes. METHODS: ADC maps were calculated from diffusion-weighted, blipped-epi, spin echo, magnetic resonance imaging sequences (2.35-T BIOSPEC 24/40 scanner; Bruker Medizin Technik GmbH, Karlsruhe, Germany) for 21 anesthetized (0.45-1% halothane, temperature-adjusted/30% oxygen/69% nitrogen) and ventilated Wistar rats. After baseline scanning, bolus injection of 0.5 ml of autologous arterial blood or artificial cerebrospinal fluid (control group), into the cisterna magna, was performed. Serial scanning was performed for 3 hours after injection, using normothermic or hypothermic (32 degrees C) rats. In an additional series of experiments, hypothermia was initiated either immediately or 60 minutes after normothermic SAH. The water contents of the removed brains were calculated using the wet/dry weight method. RESULTS: The ADC values did not change in the control group but decreased to 88.6+/-5.2% (P < 0.05 versus baseline) after SAH and remained significantly decreased throughout the experiment in normothermia. An injection of blood during hypothermia caused an initial decrease in ADC to 96.1+/-5.6% (P < 0.05 versus baseline); values continuously increased and reached normal levels within 60 minutes. Delayed hypothermia also normalized ADC values within the observation period. The brain water content in the control group was 80.3+/-0.1%, that after SAH in normothermia was 81.1+/-0.7%, and that after SAH in hypothermia was 79.3+/-0.5%. CONCLUSION: This model of severe SAH in rats causes significant ADC changes, which are reversible by application of moderate hypothermia even when it is induced after a 60-minute delay. These findings support the concept of moderate hypothermia exerting a neuroprotective effect in severe SAH.

Animals↗
PubMed2001

Xenon-induced flow activation in patients with cerebral insult who undergo xenon-enhanced CT blood flow studies.

BACKGROUND AND PURPOSE: Stable xenon-enhanced CT ((s)Xe/CT) has gained wide acceptance in the assessment of regional cerebral blood flow (rCBF) in patients with intracranial abnormalities. The aim of this study was to test whether the contrast medium (ie, (s)Xe) itself directly induces relevant changes in rCBF, thereby distorting any valid determination of cerebral perfusion by using (s)Xe/CT. METHODS: To characterize the degree and temporal dynamics of (s)Xe-induced flow activation, a thermal diffusion (TD)-based microprobe was placed subcortically into the frontal lobe on either hemisphere to assess rCBF (TD-rCBF) continuously in 23 patients (mean age, 55 +/- 18 years) with severe intracranial insult who were undergoing (s)Xe/CT. RESULTS: In 35, the (s)Xe/CT studies TD-rCBF rose from 25 +/- 17 mL/100 g per minute (range, 5-42 mL/100 g per minute) before (s)Xe administration to 28 +/- 21 mL/100 g per minute (range, 6-46 mL/100 g per minute) after arterial (s)Xe saturation was reached. Analysis of the flow activation curve showed a logarithmic shape with an increase in TD-rCBF between 3% and 7% within the first 76 seconds of (s)Xe wash-in (12% after 190 seconds) and showed no further augmentation until the end of the blood flow study. CONCLUSION: The observed (s)Xe-induced rCBF activation, which showed significant inter- and intraindividual variability, might lead to overestimation of rCBF in patients with severe intracranial insult. The obtained flow activation curve provides essential information that may allow subsequent refinement of the methodology, aiming to further minimize the influence of (s)Xe-induced rCBF activation on rCBF calculations when using (s)Xe/CT technology.

Administration, Inhalation↗
PubMed2000

Targeting angiogenesis inhibits tumor infiltration and expression of the pro-invasive protein SPARC.

The solid growth of high-grade glioma appears to be critically dependent on tumor angiogenesis. It remains unknown, however, whether the diffuse infiltration of glioma cells into healthy adjacent tissue is also dependent on the formation of new tumor vessels. Here, we analyze the relationship between tumor angiogenesis and tumor cell infiltration in an experimental glioma model. C6 cells were implanted into the dorsal skinfold chamber of nude mice, and tumor angiogenesis was monitored by intravital fluorescence videomicroscopy. Glioma infiltration was assessed by the extent of tumor cell invasion into the adjacent chamber tissue and by expression of SPARC, a cellular marker of glioma invasiveness. To test the hypothesis that glioma angiogenesis and glioma infiltration are codependent, we assessed tumor infiltration in both the presence and the absence of the angiogenesis inhibitor SU5416. SU5416 is a selective inhibitor of the VEGF/Flk-1 signal-transduction pathway, a critical pathway implicated in angiogenesis. Control tumors demonstrated both high angiogenic activity and tumor cell invasion accompanied by strong expression of SPARC in invading tumor cells at the tumor-host tissue border. SU5416-treated tumors demonstrated reduced vascular density and vascular surface in the tumor periphery accompanied by marked inhibition of glioma invasion and decreased SPARC expression. A direct effect of SU5416 on glioma cell motility and invasiveness was excluded by in vitro migration and invasion assays. These results suggest a crucial role for glioma-induced angiogenesis as a prerequisite for diffuse tumor invasion and a possible therapeutic role for anti-angiogenic compounds as inhibitors of both solid and diffuse infiltrative tumor growth.

Angiogenesis Inhibitors↗
PubMed2000

Time course of apoptotic cell death after experimental neurotrauma.

Traumatic or ischemic brain injury may give rise to the development of secondary brain damage. In the present study the time course of TUNEL staining which is widely used to delineate apoptotic reaction pattern was followed after experimental neurotrauma in order to test the hypothesis that apoptotic cell death may be involved in the development of secondary brain damage. Neurotrauma was induced in male Wistar rats by applying a cold probe to the exposed dura over the temporo-parietal cortex. Animals were sacrificed between 1 and 72 hours after trauma and coronal sections prepared from the lesioned area and adjacent tissue. The TUNEL staining was employed to detect DNA-fragmentation and conventional HE staining of sequential slices to delineate the extent of the lesion. Occurrence of positively stained cells was detected by a computer-based quantification system and stored on hard disk. TUNEL-positive nuclei were observed as early as one hour after lesion and peaked at 3 hours. There after, the number of cells detected decreased steadily. Histological examination revealed two different types of morphology in TUNEL-positive cells. A small proportion termed type I-cells displayed additional signs of apoptotic cell death such as nuclear condensation and fragmentation while type-II were considered to undergo necrotic cell death. Thus, TUNEL staining proved to be an unspecific marker of apoptotic cell death in the present study. Nevertheless, the data suggest that apoptotic cell death does not contribute substantially to the final extent of cold induced brain tissue damage.

Animals↗
PubMed2000

Characterization of the contractile and relaxant action of the endothelin-1 precursor, big endothelin-1, in the isolated rat basilar artery.

The presence of functional endothelin converting enzyme (ECE) activity in basilar artery ring segments was investigated by measuring the contractile and relaxant effects of big endothelin (ET)-1. Under resting tension conditions cumulative application of big ET1-1 elicited a concentration-related contraction with the concentration-effect curve (CEC) shifted to the right against ET-1 by a factor of 31 and 29 in segments with the endothelium intact or mechanically removed, respectively. Preincubation with the ET(A) receptor antagonist, BQ123, induced an apparently parallel rightwards shift without affecting the maximum contraction. This shift was more pronounced for ET-1 than for big ET-1. With the putative ECE inhibitor phosphoramidon (10(-3) M) in the bath a small rightwards shift of the CEC for big ET-1 was observed in control segments and a more marked one in de-endothelialized segments. In segments precontracted with prostaglandin (PG) F(2alpha) big ET-1 induced a significant although transient relaxation whereas ET-1 did not. However, in the presence of BQ123 both ET-1 and big ET-1 elicited concentration-related relaxation with a significantly higher maximum effect obtained with big ET-1. The potency was 13 fold higher for ET-1, which is markedly less than that found for contraction. The results, therefore, suggest 1) the presence of functional ECE-activity in the rat basilar artery wall, and 2) differences in the functional ECE activity located in the endothelium and media.

Animals↗
PubMed2000

Endothelin b receptor deficiency is associated with an increased rate of neuronal apoptosis in the dentate gyrus.

The dentate gyrus retains neuronal proliferative potential throughout life. Using immature endothelin B receptor-deficient (sl/sl) rats, a rabbit model of pneumococcal meningitis and autopsy brains from humans who died from pneumococcal meningitis, we explored the role of endothelin B receptors in physiological and pathological neuronal apoptosis in the dentate gyrus. At postnatal days 3-4, the rate of apoptosis in the dentate gyrus was high in all rats, declining to low levels in wild-type rats (+/+) on days 14 and 22, but remaining high in both homozygous (sl/sl) and heterozygous (sl/+) endothelin B receptor-deficient rats. Increased apoptosis was not significantly compensated for by neuronal proliferation. Hippocampal neuronal cultures also exhibited genotype-dependent apoptosis with the highest rate in neurons from homozygous endothelin B receptor-deficient (sl/sl) rats. In rabbit and human pneumococcal meningitis, increased apoptosis in the dentate gyrus was associated with loss of neuronal endothelin B receptor immunoreactivity. In conclusion, endothelin B receptors appear to act as neuronal survival factors in the dentate gyrus in rodents and man, both during postnatal development and under pathological conditions.

Aging↗
PubMed2000

Differential glial and vascular expression of endothelins and their receptors in rat brain after neurotrauma.

We characterized the time-course, intensity of expression and cellular origin of components of the endothelin (ET) system in the rat brain after a standardized neurotrauma (cryogenic lesion of the parietal cortex). ET mRNAs were expressed at sham level after neurotrauma, whereas immunoreactivity for ET-1 was enhanced in glia and endothelium of the lesioned hemisphere and both hippocampi. The number of ET-3 positive mononuclear cells in the lesion perimeter increased starting at 24h after injury. At 48h after neurotrauma, ET-receptor immunoreactivity was increased in astrocytes. In basilar artery endothelium, ETB-immunoreactivity was reduced at 48h to 72h recovering at 7 days whereas ETA-receptor and ET-peptide immunoreactivities were not altered. In summary, neurotrauma leads to a multicellular stimulation of endothelins in the brain along with a delayed selective loss of vascular ETB-receptors. These changes seem to be posttranscriptional and cell type specific. They favor vasoconstriction increasing the risk of late vasospasm and ischemia.

Animals↗
PubMed2000

Alternative/complementary medicine: wider usage than generally appreciated.

OBJECTIVE: To test the hypothesis that there is substantial use of a practitioner of alternative/complementary medicine by patients traditionally considered to be underserved. DESIGN: Cross-sectional, self-administered survey study. SETTINGS: Three university hospital-affiliated general ambulatory clinics serving patients of different socioeconomic status and racial origin. SUBJECTS: Five hundred and thirty-six (93% of those attending) consecutive clinic attendees. OUTCOME MEASURES: Past use and desired future use of one or more practitioners of five modalities of alternative/complementary medicine and willingness to pay for these modalities out-of-pocket. RESULTS: Past usage and desired future usage of one or more practitioners of alternative/complementary medicine was comparable at the three clinic sites despite wide differences in socioeconomic status and willingness/ability to pay out-of-pocket for these services. Multivariable analyses revealed lower self-rated health status and female gender (both p < 0.006) but not income, race, age or education as independent, significant predictors of use of a practitioner of alternative/complementary medicine. CONCLUSION: Usage of alternative/complementary medicine is not confined to any well-circumscribed socioeconomic group and is common in patients often considered to be underserved. Self-assessed lower health status is significantly and independently associated with use of a practitioner of alternative/complementary care.

Adolescent↗