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Biomedical subjects

J Reith

Publications and source records attributed to J Reith.

30 records · Page 2Linked to original sources
PubMed1996

Body temperature in acute stroke: relation to stroke severity, infarct size, mortality, and outcome.

BACKGROUND: In laboratory animals, cerebral ischaemia is worsened by hyperthermia and improved by hypothermia. Whether these observations apply to human beings with stroke is unknown. We therefore examined the relation between body temperature on admission with acute stroke and various indices of stroke severity and outcome. METHODS: In a prospective and consecutive study 390 stroke patients were admitted to hospital within 6 h after stroke (median 2.4 h). We determined body temperature on admission, initial stroke severity, infarct size, mortality, and outcome in survivors. Stroke severity was measured on admission, weekly, and at discharge on the Scandinavian Stroke Scale (SSS). Infarct size was determined by computed tomography. Multiple logistic and linear regression outcome analyses included relevant confounders and potential predictors such as age, gender, stroke severity on admission, body temperature, infections, leucocytosis, diabetes, hypertension, atrial fibrillation, ischaemic heart disease, smoking previous stroke, and comorbidity. FINDINGS: Mortality was lower and outcome better in patients with mild hypothermia on admission; both were worse in patients with hyperthermia. Body temperature was independently related to initial stroke severity (p < 0.009), infarct size (p < 0.0001), mortality (p < 0.02), and outcome in survivors (SSS at discharge) (p < 0.003). For each 1 degrees C increase in body temperature the relative risk of poor outcome (death or SSS score on discharge < 30 points) rose by 2.2 (95% CI 1.4-3.5) (p < 0.002). INTERPRETATION: We have shown that, in acute human stroke, an association exists between body temperature and initial stroke severity, infarct size, mortality, and outcome. Only intervention trials of hypothermic treatment can prove whether this relation is causal.

Acute Disease↗
PubMed1996

Acute stroke with atrial fibrillation. The Copenhagen Stroke Study.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia and a major risk factor for stroke. Many physicians remain reluctant to provide stroke prevention by anticoagulant therapy especially for elderly individuals with AF. Using multivariate regression analyses, we studied the characteristics and the prognosis of stroke in patients with AF. METHODS: The study is part of the Copenhagen Stroke Study, a prospective, community-based study of 1197 patients with acute stroke treated on a stroke unit from the time of acute admission to the end of rehabilitation. Initial stroke severity was measured by the Scandinavian Neurological Stroke Scale (SSS). Neurological and functional outcomes were evaluated by the SSS and the Barthel Index. RESULTS: AF was diagnosed in 18% of the patients. AF increased steeply with age in the stroke population, from 2% in patients < 50 years old, 15% in patients in their 70s, and 28% in patients in their 80s, to 40% in patients > or = 90 years of age. In a multivariate analysis AF was associated with age (odds ratio [OR], 2.0 per 10-year increase; 95% confidence ratio [CI], 1.6 to 2.6), ischemic heart disease (OR, 3.4; 95% CI, 2.4 to 4.8), previous stroke (OR, 1.8; 95% CI, 1.2 to 2.6), and systolic blood pressure (OR, 0.93 per 10-mm Hg increases; 95% CI, 0.88 to 0.99), but not with sex, diabetes, hypertension, previous transient ischemic attack, or silent infarction on computed tomography. Patients with AF had a higher mortality rate (OR, 1.7; 95% CI, 1.2 to 2.5), longer hospital stays (50 days versus 40 days, P < .001), and a lower discharge rate to their own homes (OR, 0.60; 95% CI, 0.44 to 0.85). Neurological and functional outcomes were markedly poorer in patients with AF. Poorer outcome was exclusively explained by initially more-severe strokes. CONCLUSIONS: Stroke in patients with AF is generally more severe and outcome markedly poorer than in patients with sinus rhythm. This accentuates the importance of anticoagulant treatment of individuals with AF. A lower blood pressure in the acute stage of stroke may contribute to the increased stroke severity in patients with AF.

Aged↗
PubMed1996

Factors delaying hospital admission in acute stroke: the Copenhagen Stroke Study.

Medical treatment of stroke is dependent on a narrow therapeutic time window. We prospectively analyzed the influence of demographic, medical, and pathophysiologic factors on admission delay in 1,197 unselected, acute stroke patients. Twenty five percent were admitted within 3 1/2 hours, 35% within 6 hours, 50% within 14 hours, and 68% within 24 hours after stroke onset. Living alone (odds ratio [OR] 1.75, 95% CI 1.3 to 2.3) and retired working status (OR 1.61, 95% CI 1.01 to 2.54) delayed admission. A well-working social network thus seems important to early admission. The milder the stroke, the higher was the risk of delayed admission (OR 1.25 per 10 points decrease in stroke severity [Scandinavian Neurological Stroke Scale score on admission], 95% CI 1.14 to 1.36). A history of TIA increased the relative chance of early admission by odds 1.64 (95% CI 1.06 to 2.54). Other factors such as age, sex, diabetes, hypertension, ischemic heart disease, other comorbidity, previous stroke, headache, aphasia, apraxia, anosognosia, neglect, lowered consciousness, mental status (Mini-Mental State Examination) and type of stroke (hemorrhage/infarct) had no independent influence on admission time. Admission was markedly delayed in most patients. This represents a major barrier to medical treatment. Patients with the most severe strokes are admitted early, but patients with milder symptoms should also be encouraged to seek immediate admission. The observation that a history of TIA reduced admission time indicates that an increase in public awareness and knowledge may reduce delay and save precious time.

Acute Disease↗
PubMed1994

Elevated dopa decarboxylase activity in living brain of patients with psychosis.

The hypofrontality theory of the pathogenesis of schizophrenia predicts that cortical lesions cause psychosis. During a search for abnormalities of catecholaminergic neurotransmission in patients with complex partial seizures of the mesial temporal lobe, we discovered an increase of the rate of metabolism of an exogenous dopa tracer (6-[18F]fluoro-L-dopa) in the neostriatum of a subgroup of patients with a history of psychosis. When specifically assayed for this abnormality, patients with schizophrenia revealed the same significant increase of the rate of metabolism in the striatum. The finding is consistent with the theory that a state of psychosis arises when episodic dopamine excess is superimposed on a trait of basic dopamine deficiency in the striatum. The finding is explained by the hypothesis that cortical insufficiency, a proposed pathogenetic mechanism of both disorders, causes an up-regulation of the enzymes responsible for dopa turnover in the neostriatum as well as the receptors mediating dopaminergic neurotransmission.

Adult↗
PubMed1993

[First treatment demands for drug abuse: and indicator of developmental trends].

The county of Geneva, Switzerland, is part of an international multi-city survey under the auspices of the Council of Europe. This survey is designed to use common indicators for assessing and comparing drug misuse and its evolution in participating cities and regions. Its aim is to improve the strategies for controlling drug misuse. The first indicator under study is the "first treatment demand". Its objectives are to evaluate the treatment demand as well as the evolution of drug misuse in terms of patient characteristics, so as to optimise prevention and treatment policies. All treatment demands for drug misuse that meet the study's entry criteria are recorded in a permanent and centralized data bank, through an anonymous encoded form filled in by the treatment centers at the time of the demand. Later demands by the same patient are merged with the precedent ones. In this way, both the totality of treatment demands and the subset of first demands can be analyzed and information about individual trajectories can be collected. The introduction of this indicator is subjected to various problems due first of all to the illicit character of drug misuse. In particular, the necessary measures to guarantee strict confidentiality make it more difficult to obtain reliable data, especially for the merging of different treatment demands by the same patient. This paper reports on the introduction of the indicator in Geneva and its anticipated results.

Confidentiality↗
PubMed1993

Human striatal L-dopa decarboxylase activity estimated in vivo using 6-[18F]fluoro-dopa and positron emission tomography: error analysis and application to normal subjects.

DOPA decarboxylase is the enzyme directly responsible for the synthesis of the neurotransmitters dopamine and serotonin, and indirectly of noradrenaline, in brain. We used the decarboxylation coefficient (k3D) of 6-[18F]fluoro-DOPA (FDOPA) to denote the relative activity of L-DOPA decarboxylase in vivo in the human brain. To determine the relative enzyme activity with positron emission tomography (PET), we evaluated the model that separates the metabolism into compartments of nondiffusible and diffusible (i.e., transient) tracer metabolites. Error analysis indicated that the least-squares optimization alone was not sufficient to yield accurate estimates of k3D in the presence of the inherent error of PET. To improve the accuracy of the k3D estimates by optimizing the number of parameters, we introduced biological constraints which included a tracer partition volume (Ve) common to frontal cortex and striatum, and a fixed ratio (q) between the blood-brain barrier transport coefficients of O-methyl-[18F]fluoro-DOPA and FDOPA, the two sources of radioactivity in plasma. We found that a two-step analysis yielded sufficiently accurate estimates of k3D. The two steps include the initial estimation of the partition volume in frontal cortex and the subsequent use of this value to determine k3D in striatum and other structures. We studied twelve healthy controls (age 45 +/- 15 years). The average k3D value was 0.081 +/- 0.024 min-1 (coefficient of variation (COV) 30%) for caudate nucleus, 0.074 +/- 0.013 min-1 (COV 18%) for putamen, and 0.010 +/- 0.005 min-1 (COV 50%) for cerebral cortex.

Adult↗
PubMed1991

Dopa decarboxylase activity of the living human brain.

Monoaminergic neurons use dopa decarboxylase (DDC; aromatic-L-amino-acid carboxy-lyase, EC 4.1.1.28) to form dopamine from L-3,4-dihydroxyphenylalanine (L-dopa). We measured regional dopa decarboxylase activity in brains of six healthy volunteers with 6-[18F]fluoro-L-dopa and positron emission tomography. We calculated the enzyme activity, relative to its Km, with a kinetic model that yielded the relative rate of conversion of 6-[18F]fluoro-L-dopa to [18F]fluorodopamine. Regional values of relative dopa decarboxylase activity ranged from nil in occipital cortex to 1.9 h-1 in caudate nucleus and putamen, in agreement with values obtained in vitro.

Brain↗
PubMed1990

Blood-brain transfer and metabolism of 6-[18F]fluoro-L-dopa in rat.

In a study designed to reveal the rates of blood-brain transfer and decarboxylation of fluoro-L-3,4-dihydroxyphenylalanine (FDOPA), we discovered a major discrepancy between the DOPA decarboxylase activity reported in the literature and the rate of FDOPA decarboxylation measured in the study. "Donor" rats received intravenous injections of 6 mCi fluorine-18-labeled FDOPA. The donor rats synthesized methyl-FDOPA. Arterial plasma, containing both FDOPA and methyl-FDOPA, was sampled from the donor rats at different times and reinjected into "recipient" rats in which it circulated for 20 s. The blood-brain clearance of the mixture of labeled tracers in the plasma was determined by an integral method. The individual permeabilities were determined by linear regression analysis, according to which the average methyl-FDOPA permeability in the blood-brain barrier was twice that of FDOPA, which averaged 0.037 ml g-1 min-1. The permeability ratio was used to determine the fractional clearance from the brain of FDOPA (and hence of methyl-FDOPA), which averaged 0.081 min-1. In the striatum, the measured average FDOPA decarboxylation rate constant (kD3) was 0.010 min-1, or no more than 1% of the rate of striatal decarboxylation of DOPA measured in vitro and in vivo. We interpreted this finding as further evidence in favor of the hypothesis that striatum has two dopamine (DA) pools, of which only DA in the large pool is protected from metabolism. Hence, no more than 1% of the quantity of fluoro-DA theoretically synthesized was actually retained in striatum.

Animals↗
PubMed1990

Regional glucose phosphorylation rate in rat brain during acute ethanol intoxication.

The effect of ethanol on regional cerebral metabolic rate for glucose (rCMRglc) was studied in rats using [6-14C]glucose. After intravenous injection, radioactivity was determined in 14 brain regions, corrected for loss of label, and divided by the integral of the arterial plasma glucose concentration measured during tracer circulation. When blood ethanol concentration was maintained at 6 g/l by intravenous infusion of ethanol for approximately 1 h, rCMRglc was found to be reduced significantly in 7 forebrain regions, compared to values of conscious control animals. In 7 further regions including brain stem regions, rCMRglc was not significantly reduced. We conclude that the effects of severe acute alcohol intoxication resemble those of global anesthesia.

Animals↗
PubMed1987

Saturable retention of vasopressin by hippocampus vessels in vivo, associated with inhibition of blood-brain transfer of large neutral amino acids.

Vasopressin receptors have been reported in the endothelium of brain capillaries. The function of these receptors is not known. To test the prediction that vasopressin receptors in brain capillary endothelium affect amino acid transport across the blood-brain barrier and to assess the role of vasopressin transport across the cerebral vascular endothelium, we measured (a) the endothelial permeability to the large neutral amino acid leucine in the absence and presence of arginine vasopressin (AVP) and (b) the permeability of the blood-brain barrier to AVP relative to manitol. In brain regions protected by the blood-brain barrier, after circulation for 20 s, coinjection of leucine and AVP intravenously led to a decrease of leucine transport unrelated to changes of blood flow. The decrease was most pronounced in hippocampus (42%) and least pronounced in olfactory bulb and colliculi (17 and 19%, respectively). In the latter regions, the endothelial permeability to AVP did not significantly exceed that of mannitol. In hippocampus and in regions with no blood-brain barrier (pituitary and pineal glands), AVP retention in excess of mannitol retention was blocked by unlabeled AVP. The findings do not contradict the hypothesis of a role for AVP in the regulation of large neutral amino acid transfer into brain tissue.

Amino Acids↗