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Biomedical subjects

E Garde

Publications and source records attributed to E Garde.

At least 19 recordsLinked to original sources
PubMed2006

A pulse-rate dependence of dose per monitor unit and its significant effect on wedged-shaped fields delivered with variable dose rate and a moving jaw.

Wedge-shaped dose distributions are delivered on some modern linear accelerators with a virtual wedge, combining variable dose rate and a moving jaw. Drift in the wedge factor and wedge angle of a 20 X 20 cm field for the 60 degree virtual wedge was found commonplace in several models of linear accelerator from one manufacturer. It was found that errors in dose delivery both on and off axis could exceed 5% if quality assurance checks are limited to 10 X 10 cm or smaller fields or wedge angles of 45 degrees or less. A procedure to easily identify and remedy the problem is presented. In each case the change was due to variation in dose per monitor unit (D/MU) with the electron beam pulse rate. The variation was traced to a pair of circuit boards in the dosimetry system, one for each output measurement channel. Wedge factors and dose profiles measured before and after board replacement on 4 accelerators, and for a set of defective boards placed on one of the accelerators, were compared. The effect was largest for the wedge with the steepest profile (60 degree wedge angle) and the largest field measured: 20 X 20 cm. In this case, a 1% variation in D/MU with a factor of 5 reduction in pulse rate corresponded to an average 0.8% change in wedge factor and 0.8% change in the off axis ratio at 8.5 cm off axis on the high dose side of the wedge field, 0.3% on the low dose side. After board replacement, wedge factors and profiles measured on the 4 machines generally agreed to 2% for the full range of wedge angles and field sizes. Quality assurance of virtual wedges is discussed in light of the new findings.

Equipment Design↗
PubMed2005

Decline in intelligence is associated with progression in white matter hyperintensity volume.

OBJECTIVES: To quantify the time course of white matter hyperintensities (WMH) and assess the association between progression and cognitive decline in non-demented octogenarians. METHODS: From a Danish cohort of 698 people born in 1914, 26 participated in neuropsychological assessment (Wechsler adult intelligence scale) initiated at age 50, including cognitive testing and cerebral magnetic resonance imaging at the 80 and 85 year studies. WMH volumes were quantified and partial correlations were calculated between WMH volume change and decline in WAIS scores from 80 to 85. RESULTS: Progression in WMH volume ranged from 0 ml to 20.7 ml, providing a median increase of 2.6 ml (range 0.1 to 20.7, p<0.001) and, with a mean time interval between scans of 3.8 years, a rate of progression of 0.63 (0 to 6.8) ml/year. WMH volume measures for the two hemispheres were highly correlated (r = 0.95) and did not differ significantly. Increase in WMH volume was correlated with a simultaneous decline in verbal IQ (r = -0.65, p = 0.001), while baseline WMH was associated with subsequent decline in performance subtests (digit symbol, r = -0.57, p = 0.02). CONCLUSIONS: The association between WMH and decline in essential cognitive abilities even in well preserved elderly people suggests that WMH should be regarded as a risk factor for cognitive impairment and dementia.

Aged↗
PubMed2002

Cerebral perfusion and cerebrovascular reactivity are reduced in white matter hyperintensities.

BACKGROUND AND PURPOSE: There is growing evidence that white matter hyperintensities (WMH) should not be considered as benign age-dependent changes on MR images but indicate pathological changes with clinical consequences. Previous studies comparing subjects with WMH to normal controls have reported global reductions in cerebral blood flow (CBF) and cerebral vascular reactivity. In this study, we examined localized hemodynamic status to compare WMH to normal appearing white matter (NAWM). METHODS: A group of 21 normal 85-year-old subjects were studied using dynamic contrast-enhanced MRI together with administration of acetazolamide. From a combination of anatomic images with different signal weighting, regions of interest were generated corresponding to gray and white matter and WMH. Localized measurements of CBF and cerebral blood volume (CBV) and mean transit time were obtained directly within WMH and NAWM. RESULTS: When comparing WMH to NAWM, measurements showed significantly lower CBF (P=0.004) and longer mean transit time (P< 0.001) in WMH but no significant difference in CBV (P=0.846). The increases in CBF and CBV induced by acetazolamide were significantly smaller in WMH than in NAWM (P=0.026, P<0.001). CONCLUSION: These results show that a change in the hemodynamic status is present within the WMH, making these areas more likely to be exposed to transient ischemia inducing myelin rarefaction. In the future, MRI may be used to examine the effect of therapeutic strategies designed to prevent or normalize vascular changes.

Acetazolamide↗
PubMed2001

Cerebral hemodynamic changes measured by gradient-echo or spin-echo bolus tracking and its correlation to changes in ICA blood flow measured by phase-mapping MRI.

Changes in cerebral blood flow (CBF) induced by Acetazolamide (ACZ) were measured using dynamic susceptibility contrast MRI (DSC-MRI) with both spin echo (SE) EPI and gradient echo (GE) EPI, and related to changes in internal carotid artery (ICA) flow measured by phase-mapping. Also examined was the effect of repeated bolus injections. CBF, cerebral blood volume (CBV), and mean transit time (MTT) were calculated by singular value decomposition (SVD) and by deconvolution using an exponential function as kernel. The results showed no dependency on calculation method. GE-EPI measured a significant increase in CBF and CBV in response to ACZ, while SE-EPI measured a significant increase in CBV and MTT. CBV and MTT change measured by SE-EPI was sensitive to previous bolus injections. There was a significant linear relation between change in CBF measured by GE-EPI and change in ICA flow. In conclusion, GE-EPI under the present condition was superior to SE-EPI in monitoring cerebral vascular changes.

Acetazolamide↗
PubMed2000

Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: a longitudinal study.

BACKGROUND: White-matter hyperintensities are commonly found on magnetic resonance imaging (MRI) of elderly people with or without dementia. Studies of the relation between severity of white-matter hyperintensities and cognitive impairment have had conflicting results. We undertook a longitudinal study of age-related decline in intellectual function and MRI at age 80 years. METHODS: From a cohort of 698 people born in 1914 and living in seven municipalities in Denmark, 68 healthy non-demented individuals had been tested with the Wechsler adult intelligence scale (WAIS) at ages 50, 60, and 70, and they agreed to further WAIS testing at age 80, and cerebral MRI at age 80-82 (mean age 82.3 years). We scored separately the numbers of periventricular and deep white-matter hyperintensities. FINDINGS: Scores for periventricular hyperintensities in this sample included all possible degrees of severity, but no participant scored more than 75% of maximum for deep white-matter hyperintensities. Neither type was related to the WAIS IQs of the 80-year assessment, but both were significantly associated with decline in performance IQ from age 50 to age 80 years (bivariate correlation coefficients 0.32, p=0.0087, and 0.28, p=0.0227, respectively). An analysis based on two WAIS subtests showed that the association between white-matter hyperintensities and cognitive impairment was significant only for cognitive decline in the decade 70-80 years. INTERPRETATION: Both periventricular and deep white-matter hyperintensities are related to decline in intelligence but, in healthy octogenarians, the cumulative effect of these features alone explains only a small part of the large differences among individuals in age-related decline in intelligence. Interpretation of the presence and severity of white-matter hyperintensities in a diagnostic context must be done cautiously.

Aged↗
PubMed1997

Central nervous system resuscitation.

Traumatic injury to the central nervous system induces delayed neuronal death, which may be mediated by acute and chronic neurochemical changes. Experimental identification of these injury mechanisms and elucidation of the neurochemical cascade following trauma may provide enhanced opportunities for treatment with novel neuroprotective strategies.

Animals↗
PubMed1996

Therapeutic approaches for the prevention of secondary brain injury.

The precise mechanisms underlying secondary brain damage after traumatic injury to the central nervous system (CNS) are not well understood, and delayed neuronal injury may result from pathological changes in neurotransmitter release, synthesis or generation of endogenous autodestructive neurochemicals and/ or inflammatory mediators, or alterations in endogenous protective or trophic factors. Recent identification of such factors and the elucidation of the timing of the neurochemical cascade following CNS injury provides a window of opportunity for therapeutic intervention with pharmacological compounds which modify synthesis, release, receptor binding or physiological activity of neurotoxic factors. A number of recent experimental studies have reported that pharmacological modification of the post-traumatic neurochemical milieu can promote functional recovery in a variety of animal models of CNS trauma. This paper summarizes recent work suggesting that pharmacological manipulation of several key neurotransmitter and neurochemical systems can attenuate neuronal damage and improve functional outcome associated with traumatic brain injury.

Animals↗
PubMed1995

PCA-4248, a PAF receptor antagonist, inhibits PAF-induced phosphoinositide turnover.

The effect of a new PAF (platelet activating factor; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoryl-choline) receptor antagonist, PCA-4248 (2-phenylthio)ethyl-5-metoxycarbonyl-2,4,6-trimethyl-1, 4-dihydropyridine-3-carboxylate), on phosphoinositide turnover evoked by PAF was investigated. PAF treatment resulted in an increased 32P incorporation into phosphoinositides and phosphatidic acid in rabbit platelets. Treatment with PCA-4248 abolished both effects in a dose-dependent manner, 10 microM being the most effective dose. In thrombin stimulated platelets, phosphoinositide turnover was not influenced by PCA-4248. In addition, PAF caused a rapid and significant increase in protein phosphorylation. Thus, PAF treatment resulted in a marked phosphorylation of two proteins of 47 kDa and 20 kDa. Treatment with PCA-4248 resulted in an inhibition of these actions. Serotonin secretion evoked by PAF was also inhibited by PCA-4248. It is concluded that PCA-4248 antagonizes the PAF effects by acting as a competitive antagonist at the PAF receptor level as evidenced from binding studies.

Animals↗
PubMed1995

[Apoplexy with rapidly deteriorating symptoms--"stroke in progression". Hemodynamic and clinical aspects].

Stroke-in-progression, SIP, occurs in about 30% of patients with acute stroke and negatively affects the prognosis and mortality. The underlying caused are thought to be clot propagation, cerebral haemorrhage or oedema. In some cases these rather obvious mechanisms cannot be demonstrated, and other variables such as a decrease in blood pressure must be considered as major factors. In this paper the basic haemodynamic mechanisms of cerebral blood flow and the relevant pathophysiology of focal cerebral infarcts are described with emphasis on the penumbra. In addition, available clinical studies are reviewed and current treatment discussed. Our main conclusion is that to assure sufficient collateral flow a high perfusion pressure must be maintained, and we advocate withholding antihypertensive therapy during the acute phase of focal cerebral ischaemia.

Cerebrovascular Disorders↗
PubMed1995

[Treatment of high blood pressure in patients with acute apoplexy].

The study was performed to investigate how often reduction of high blood pressure (> or = 220 mmHg systolic and or > or = 120 mmHg diastolic) was attempted in patients with acute stroke or transient ischemic attacks (TIA). Of 1351 consecutive patients with acute stroke or TIA 119 had high blood pressure on admission. In 15 patients the stroke was so severe that treatment was not considered. In the remaining 104 patients reduction of the blood pressure was attempted in 28 (27%); in 23 patients immediately following admission. None of the patients had symptoms or signs of hypertensive encephalopathy. It is concluded that reduction of high blood pressure in patients with stroke or TIA is attempted too often. As autoregulation is commonly impaired in acute stroke, reduction of systemic blood pressure may enhance ischaemic tissue damage. Reduction of blood pressure in acute stroke should be considered only in case of hypertensive encephalopathy.

Acute Disease↗
PubMed1995

[Reducing hypertension may worsen symptoms of acute apoplexy].

Patients with acute stroke often present with high blood pressure (BP) on hospital admission. Because hypertension is a risk factor for stroke, and because severe BP elevation may increase oedema and the risk of haemorrhage, acute antihypertensive therapy might seem reasonable. On the other hand, the increase in BP in the acute stage might be considered a beneficial pathophysiological response maintaining the perfusion pressure to the ischaemic area and, in particular, the surrounding penumbra. As illustrated in the case presented here, lowering the BP in the early stage may be associated with progression of neurological deficits, very likely due to a reduction of perfusion to the penumbra thus enlarging the infarct.

Acute Disease↗
PubMed1994

Dissociation between secretion and protein phosphorylation in agonist-stimulated platelets; action of PCA-4230, a new antithrombotic drug.

We have studied the effects of PCA-4230, a new dihydropyridine derivative with antithrombotic activity, on the secretion of dense and alpha-granules from platelets and on the protein phosphorylation in platelets after stimulation by agonists. The drug prevented both dense and alpha-granule secretion evoked by thrombin, platelet-activating factor (PAF) and ionophore A23187, the former secretion being more sensitive than the latter one to the PCA-4230 action. These inhibitory effects on secretion processes did not correlate with the differential action of PCA-4230 on protein phosphorylation. Thus, the 40 kDa protein phosphorylation evoked by thrombin was potentiated whereas that elicited by ionophore A23187 was partially inhibited. The 20 kDa protein phosphorylation was practically insensitive to the drug action. These data, together with previous evidence reported by us on PCA-4230, lead us to suggest the existence of a common and critical step for platelet secretion evoked by agonists with different signal transduction pathways.

Animals↗
PubMed1994

8-methoxypsoralen increases daytime plasma melatonin levels in humans through inhibition of metabolism.

It is well established that in healthy humans oral intake of 5- or 8-methoxypsoralen (5- and 8-MOP) is followed by a significant increase in plasma melatonin concentrations. The effect of psoralen on rat melatonin has been studied in vitro and in vivo and a stimulation of release or secretion from the pineal gland has been suggested. In this study we examined the time-related changes in plasma concentrations of 8-MOP, melatonin and 6-sulfatoxymelatonin in 15 patients admitted for routine psoralen plus UVA therapy. On the first day of treatment blood samples were collected before, and 30, 60, 66 and 90 min after intake of 8-MOP (0.6 mg/kg). Although the rate of 8-MOP absorption varied greatly, a significant increase (P = 0.0002) in melatonin levels was found 60 min after 8-MOP intake. During UVA exposure a strongly correlated decrease in mean melatonin and mean 8-MOP concentrations was found, indicating an effect of UVA radiation, either direct or 8-MOP mediated, on circulating melatonin levels. Plasma 6-sulfatoxymelatonin concentrations decreased significantly between all time points, suggesting inhibition of melatonin metabolism.

Adult↗
PubMed1993

Platelet-activating factor stimulates protein kinase C translocation in cerebral microvessels.

The effects of platelet-activating factor (PAF) on distribution of protein kinase C activity in brain microvessels have been examined. Our results indicate that PAF caused an increase of protein kinase C activity in membrane, accompanied by a loss of activity in the cytosol. This effect resulted to be dose-dependent and the translocation was evident after 30 min of PAF treatment. These results suggest that PAF could play a role in transport processes in the blood-brain barrier, involving protein phosphorylation by activation of protein kinase C.

Animals↗
PubMed1993

[Physiopathologic mechanisms behind eye symptoms in primary tumors of the pineal body].

Primary tumors of the pineal body can produce dyscoordinative movements of the eye, pupillary dilatation, paralysis of adduction during convergence and nystagmus. Obstruction of the aqueduct can cause hydrocephalus, increased intracranial pressure and papilledema. Diabetes insipidus may be a presenting symptom. Pinealocytes and the photoreceptors of the eye contain several autoantigens. In man, the best known is the S-antigen. This antigen can be detected in the cerebrospinal fluid of patients with primary tumors of the pineal body. The S-antigen, and possibly other related autoantigens, can elicit an autoimmune mediated reaction causing inflammatory eye symptoms. This recently described paraneoplastic neurologic syndrome shares properties in common with other known cancer-associated ophthalmologic syndromes characterised by rapid development of eye symptoms, rapid loss of sight and by eye manifestations prior to evident appearance of symptoms related to primary tumor growth. A primary tumor of the pineal body should be considered in patients where a monosymptomatic uveoretinitis presents without associated provoking factors. Furthermore, analyses of S-antigen in the spinal fluid can be useful in the clinical diagnosis of the same primary tumors.

Autoimmunity↗
PubMed1993

PAF and thrombin actions in platelets are selectively affected by a new 1,4-dihydropyridine derivative.

In the present study we described the effects of a new 1,4-dihydropyridine derivative with antithrombotic activity on phosphoinositide turnover in washed platelets stimulated by either platelet-activating factor or thrombin. In 32P-labeled rabbit platelets, both PAF and thrombin evoked a transient loss of [32P]phosphatidylinositol 4,5-bisphosphate (PIP2) and, thereafter, labeling increased over the control value. Concomitantly, a progressive formation of phosphatidic acid was observed. In [3H]arachidonate labeled platelets, both agonists elicited an increase in diacylglycerol (DAG) levels and arachidonate release. Pretreatment of platelets with the new dihydropyridine derivative (PCA-4230) prevents, in a dose-dependent fashion, the PAF-evoked variations in phosphoinositide turnover and DAG production. However, thrombin-induced variations were rather enhanced by PCA-4230. With respect to arachidonate release and platelet aggregation, the drug was again selective against PAF and thrombin. Although PCA-4230 shows some PAF antagonistic activity, its effects on PAF-evoked responses did not seem only due to an antagonism at receptor level. In view of the present results, the drug is not only able to discern the pathways of platelet activation by which PAF and thrombin exert their action, but it also affects selectively the enhanced phosphoinositide turnover and arachidonate release evoked by thrombin. Thereafter, PCA-4230 is a suitable tool to explore the mechanisms of action of the natural agonists.

Animals↗
PubMed1993

Sudden natural death in childhood. A review of forensic autopsy protocols in cases of sudden death between the ages of one and five years, 1982-1991, with a special view to sudden unexplained death.

All cases of sudden death of individuals between the ages of one and five years examined at the Forensic Institute, Copenhagen, in a 10-year period were identified to assess the impact of sudden unexplained death in this age group. Of a total of 68 cases, 27 cases were due to accidents, there were 13 cases of homicide, 27 cases were sudden natural deaths and in 1 case the manner of death was uncertain. The autopsy records and histological sections in the 27 cases of natural death were reviewed; the cause of death was not explained in 11 of these cases (40%). Seven cases were previously considered to be caused by infectious disease or aspiration. Criteria for classification are discussed.

Accidents↗