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Biomedical subjects

T G Bolwig

Publications and source records attributed to T G Bolwig.

At least 127 records · Page 7Linked to original sources

The Bech-Rafaelsen Mania Scale and the Hamilton Depression Scale.

In a study of 18 patients with manic symptomatology and 31 patients with melancholic symptomatology the Bech-Rafaelsen Mania Scale (BRMS) and the Hamilton Depression Scale (HDS) have been compared. The results showed that the inter-observer reliability of the BRMS was adequate compared with the HDS. Both scales are constructed for assessing the severity of manic or melancholic states, and no difference was found in the total BRMS or HDS score between the various diagnostic groups, when the patients were classified by an index of the course and symptomatology otive disorder, using the Multi-axial Classificetion System for Affective Disorders (MULTI-CLAD). The homogeneity of the BRMS seemed more adequate than that of the HDS, when each item was correlated to the corresponding total score. Although the homogeneity of the BRMS needs to be evaluated by other statistical models than correlation analysis, our results seem to indicate that the improvement in assessing manic-melancholic states quantitatively is a matter of redefining items or incorporating new items in the melancholic rather than the manic part of these rating scales.

Adult↗

Increased permeability to horseradish peroxidase across cerebral vessels, evoked by electrically induced seizures in the rat.

Under normal conditions a slight vesicular transfer of intravenously injected horseradish peroxidase (HRP) occurs across the endothelium of cerebral vessels, especially short segments of arterioles. The vesicular transport can be notably increased by chemically induced acute hypertension. In the present investigation 4 groups of animals received HRP, and the permeability of the cerebral endothelium was studied semimacroscopically, light microscopically and electron microscopically. The rats in group 1 were given 10 electroshocks. This caused a significant rise in the blood pressure (BP). Furthermore, a noticeable extravasation of HRP was observed, especially across the endothelium in cerebral arterioles. From the basement membranes of the vessels reaction product could be followed into the extracellular spaces of the neighbouring neuropil. Group 2 comprises rats that were given 10 electroshocks preceded by transection of the cervical part of the spinal cord. The BP remained at normal level and the permeability was unaltered. The animals in group 3 received only 1 electroshock. Usually, the BP was markedly increased and this was accompanied by enhanced permeability across the vessels of the brain. Group 4 consists of control animals, injected with HRP and treated as groups 1 and 3 with the difference that electrical stimulation was not performed. A general feature was that no endothelial damage was observed and that reaction product was not found between neighbouring endothelial cells from the first luminal to the first abluminal tight junction. Based on the observations it seems reasonable to assume that the increased permeability of tracer that occurs after 10 electroshocks or only one is caused by the acute hypertension evoked by the electrical stimulation; furthermore, the transfer is concluded to be vesicular transport.

Animals↗

The permeability of the blood-brain barrier during electrically induced seizures in man.

The blood-brain barrier (BBB) in man was studied during various conditions using the indicator dilution method of Crone [8]. Using 113m In-DTPA as reference substance the extraction, E, of the small test substances 24Na+, 36Cl-, 14C-urea and 14C-thiourea was estimated from the areas under the venous outflow curves following intracarotid slug injection of tracers. Interlaminar diffusion and red cell carriage were taken into consideration when calculating E. Cerebral blood flow (CBF) was measured using the intra-arterial 133Xe-injection method. Twenty-two patients receiving electroconvulsive therapy (ECT) were studied before and during seizures and during hypercapnia. Before seizures the extraction values in % were as follows: ENa+ 1.6, ECl- 1.9, Eurea 3.9 and Ethiourea 7.8; the corresponding values for the permeability-surface area products (PS) in ml/100 g x min were 0.5, 0.3, 0.7, 4.1, respectively. During seizure a decrease of Ethiourea and an increase of PSurea were significant. During hypercapnia PSNa and PSthiourea rose significantly. Due to the similarity of the findings in those two high flow situations it is suggested that the changes of CBF and not the epileptic activity are responsible for the changes in permeability. The mechanism of action may be a stretching of endothelial cells in the cerebral vessels or an opening up of new capillaries, or a combination of both.

Adult↗

Blood-brain barrier during electroshock seizures in the rat.

The effect of electrically induced seizures on the permeability of the rat blood-brain barrier was investigated. The small radioactive tracers sodium (24Na+), chloride (36Cl-) carbon labelled thiourea (14C-thiourea) and glucose (14C-D-glucose) were studied in indicator dilution experiments with indium labelled diethylenetriaminepenta-acetic acid (113mIn-DTPA) as reference substance. This method allows a quantitative estimate of the transcapillary loss of solutes, the extraction (E), during a single passage through the brain. Passage of macromolecules was studied using as marker substance Evans Blue which binds to plasma albumin. In the resting state ENa, ECl, Ethiourea and Eglucose were 2.9, 4.8, 9.3 and 12.5%, respectively. During seizures and during shortlasting hypercapnia E glucose decreased while E for the other tracers was unchanged. As cerebral blood flow increased, there must be an increased transfer of test substances into the brain. This finding is in agreement with recent human studies [15]. When Evans Blue was injected intravenously prior to electroshock, there was no staining of brain tissue after one electroshock but following repeated electroshocks some staining was observed. In an attempt quantify this transcapillary loss of albumin by means of indicator dilution, 51Cr-labelled erythrocytes were used as intravascular reference substance against 113mIn-DTPA (a plasma tracer). However, the albumin loss (by pinocytosis or otherwise) occurring after ten electroshocks could not be detected during a single passage through the brain.

Animals↗

Acute hypertension causing blood-brain barrier breakdown during epileptic seizures.

The influence of shortlasting (less than 1 min) epileptic seizures on the permeability to protein of the blood-brain barrier (BBB) was studied in rats. The protein tracer, horseradish peroxidase (HRP) was used as marker substance. Monitoring arterial blood pressure (BP) and electroencephalogramme (EEG) seizures were induced electrically after HRP was given intravenously. Following a single electroshock seizure slight staining of brain tissue was seen, while after 10 electroshock stimuli followed by sustained seizure activity, this phenomenon was more pronounced. If 10 electroshock stimuli were preceded by transsection of the spinal cord, blood pressure increase was abolished and no tissue staining was seen in spite of epileptic seizure activity recorded on EEG. This means that the acute hypertension and not the seizure activity per se is the mechanism behind the breakdown of the BBB during epileptic seizures. Electron microscopy revealed an increased vesicular transport (pinocytosis) across the endothelial cells, while the vascular structure remained intact.

Acute Disease↗

EEG and extracelluar K+ in rat brain during pentylenetetrazol seizures and during respiratory arrest.

The relationship between changes in EEG and the extracellular potassium concentration (K+e) in brain cortex was studied in rats during petylenetetrazol seizures and during respiratory arrest. During seizures an increase of K+e occurred subsequent to the electrical discharges, while during postictal depression of EEG normal levels of K+e were measured. During respiratory arrest K+e rose considerably one minute after flattering of EEG. These findings are against a concept of K+e determining the changes of the EEG pattern. It is hypothetized that during seizures the increased K+e may play an important role in the coupling of neuronal activity to cerebral blood flow and metabolism.

Animals↗

Blood-brain barrier studies in the rat: an indicator dilution technique with tracer sodium as an internal standard for estimation of extracerebral contamination.

(1)The single injection-indicator dilution method of Crone was adapted for use in the rat. A bolus containing a non-diffusible reference tracer and the test tracer was injected into the internal carotid artery. Simultaneously venous blood was sampled from the confluence of sinuses. It proved necessary to take special steps to avoid extracerebral contamination of the samples. Therefore the extracerebral branches of the carotid tree on both sides were ligated, and the venous sampling was done without suction. Results obtained in animals prepared surgically in different ways were compared. (2) 24Na+ was used to assess the degree of extracerebral contamination, the transcapillary loss of 24Na+ being a sensitive measure since the permeability of cerebral capillaries for sodium is about 4-5% that of muscle. (3) The transcapillary fractional loss, extraction E, was determined in this preparation with minimal extracerebral contamination. ENA+ was 2.9%, Eglucose was 12.5% at normal blood glucose levels whilst the net glucose extraction (calculated from arterio-venous difference) was about 10%. (4) It is concluded that extracerebral contamination is an important pitfall in indicator dilution studies on the brain. Use of 24Na+ as an indicator of extracerebral contamination is therefore recommendable.

Animals↗

Quantitative rating of depressive states.

A step-by-step analysis of Beck's and Hamilton's rating scales showed that both scales failed to differentiate adequately between moderate and severe depression measured by a global clinical assessment. Each item of the scales was tested for calibration, ascending monotonicity, and dispersion parallel to the clinical assessment. Twelve items of Beck's scale and six items of Hamilton's scale were found valid with respect to these criteria. Those items should be taken into account in future research for baseline ratings and for change ratings of depressive states quantitatively.

Adult↗

Quantitative rating of manic states. Correlation between clinical assessment and Biegel's Objective Rating Scale.

We have investigated Biegel's manic-state rating scale and found the interrater reliability high when the scale was administered both by nurses and psychiatrists. In our study of validation, we tested each item of the scale for calibration, ascending monotonicity and dispersion parallel to a global clinical assessment of the manic state. Six of the scale items were then found valid and those items differed from the valid items in studies of Biegel by including increased social contact. Like Biegel, we found a positive correlation between items concerned with depressed mood, indicating a fluctuation in the mood of manic patients during 8 hours of observation.

Adult↗

The diffusion permeability to water of the rat blood-brain barrier.

The diffusion permeability to water of the rat blood-brain-barrier (BBB) was studied. Preliminary data obtained with the Oldendorf tissue uptake method (Oldendorf 1970) in seizure experiments suggested that the transfer from blood to brain of labelled water is diffusion-limited. More definite evidence of such a limitation was obtained using the single injection technique of Crone (1963). 14-C-labelled sucrose was used as intravascular reference substance and tritium-labelled water as test substance. The non-exchanging (transmitted) fraction, I-E equals T, of labelled water during a single passage increased from 0.26 to 0.67 when the arterial carbon dioxide tension was changed from 15 to 85 mm Hg, a change increasing the cerebral blood flow about sixfold. This finding suggests that water does not pass the blood-brain barrier as freely as lipophilic gases.

Animals↗