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Biomedical subjects

H B Dinsdale

Publications and source records attributed to H B Dinsdale.

At least 19 recordsLinked to original sources
PubMed1988

Pentoxifylline in acute nonhemorrhagic stroke. A randomized, placebo-controlled double-blind trial.

The efficacy and safety of pentoxifylline were assessed in 297 adult patients with ischemic stroke in a multicenter, double-blind, randomized and placebo-controlled trial. Treatment was started within 12 hours after the stroke onset. Study medication was administered intravenously continuously (16 mg/kg/day, maximum 1,200 mg/day) for 3 days and per os (400 mg t.i.d.) for the remainder of 28 days. Demographic data were comparable, and functional impairment and mortality (pentoxifylline 12%, placebo 10%) were not different between the two groups. Neurologic deficit scores improved from baseline admission scores during the 4-week study in both groups but did not differ between groups at admission or throughout the study except during the first few days when the consciousness level (Days 1 and 2), motor function (Days 1 and 2), cranial nerve function (Days 1-4), and total neurologic deficit scores (Days 1 and 2) were better in the pentoxifylline group than in the placebo group, especially in a subset of patients with severe deficits at admission. Laboratory values and side effects were also comparable between groups. Our study indicates that pentoxifylline can be given safely in patients with acute ischemic stroke. Although pharmacologic effects were present during the first few days, the clinical benefits were small and not sustained.

Acute Disease↗
PubMed1988

Methylmercury and the health of autochthons in northwest Quebec.

We conducted a cross-sectional epidemiologic and clinical study to evaluate the nature, magnitude, and frequency of unfavourable health states among residents of northwest Quebec. Of particular interest were the possible occurrence of Minamata disease and any other neurological abnormalities. We also sought to determine whether industrial or naturally-occurring mercury in the region's environment were causally associated with any disorders that might be detected. A total of 321 subjects were studied in four groups with contrasting exposure to point-source mercury from a chlor-alkali plant in the area. Methylmercury in hair served as the marker of subject's ingestion of any organic mercury (natural or industrial). Ten pre-chosen target variables, seven clinical and three neurophysiological, were assessed in all subjects. Relationships between mercury in hair and each target variable were calculated. We determined whether gradients in target variables corresponded to gradients in potential exposure of the subjects to the aquatic emissions of the chlor-alkali plant. Minamata disease was not found. Diabetes and alcohol-related health problems assessed as important clinically plausible confounders, were common. Differences in frequency or magnitude of clinical, toxicological, and physiological findings among the contrast groups were small and not of clinical or statistical significance. There were definite relationships between mercury in hair and four target variables despite the low values of mercury measured and the mild nature of the health problems observed. This would suggest that verifiable biological threshold levels for clinical effects, if such exist, may be substantially lower among Canadians than those currently adopted as policy for adults elsewhere. A gradient was found only for two of the ten target variables. Clinically meaningful alternate hypotheses for observed health effects emerge in the data and agree with observations in the field made by consulting clinical experts.

Animals↗
PubMed1987

Treatment of migraine with intramuscular chlorpromazine.

We undertook a prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of intramuscular parenteral chlorpromazine (CPZ) in the treatment of the acute migraine attack. Thirty-six patients who presented to the emergency department with migraine headache were given either CPZ (1 mg/kg) or a saline placebo and were observed for one hour. Of those receiving CPZ, nine of 19 (47.4%) had sufficient relief from their headache to carry on with their activities of daily living, compared with four of 17 (23.5%) of the control group. This difference was not statistically significant. However, the drug was more often effective than a placebo in giving some relief from the headache (P less than .005) and in relieving nausea significantly more often than placebo (P less than .001). The only significant side effects were drowsiness (P less than .01), and an asymptomatic drop in blood pressure (10 mm Hg systolic) (P less than .05). This controlled study demonstrates that CPZ is a safe medication that provides some relief from migraine headaches, but it is less efficacious than suggested in earlier reports.

Adult↗
PubMed1986

Pharmacological modification of bradykinin induced breakdown of the blood-brain barrier.

Internal carotid artery infusion of bradykinin caused extensive breakdown of the blood-brain barrier to protein as demonstrated by the extravasation of the marker, horseradish peroxidase, into vessel walls and the adjacent parenchyma. Pretreatment of the animals with indomethacin, trifluoperazine, or imidazole significantly reduced the quantity of abnormally permeable vessels as determined by light microscopy. By electron microscopy, it was determined that bradykinin caused an intense increase in the number of pinocytotic vesicles in the permeable segments, but no change in the interendothelial junctions. After imidazole pretreatment, although the extent of the permeability change was markedly reduced, the intensity of pinocytotic activity in the involved areas was not altered.

Animals↗
PubMed1984

Pharmacological modification of blood-brain barrier permeability following a cold lesion.

The effect of desipramine, imidazole, thioridazine and trifluoperazine on blood-brain barrier (BBB) permeability after a 24 hour cold lesion was studied in rats. Changes in BBB permeability were determined using a quantitative horseradish peroxidase (HRP) assay. The four drugs tested did not alter the quantity of HRP in the cortex of control animals, or in the contralateral cortex of test animals. However, imidazole, desipramine and trifluoperazine significantly reduced the HRP extravasation in and around the cold lesion. Several mechanisms for this effect are suggested; one possible mechanism common to all these drugs is the reduction of increased vesicular transport in cortical vessels adjacent to the cold lesions.

Animals↗
PubMed1983

Hypertensive encephalopathy.

Hypertensive encephalopathy is examined in the context of an acute cerebral episode precipitated by sudden, severe hypertension. Since it is a medical emergency and responds to prompt and vigorous treatment, the author discusses its clinical manifestations, diagnosis, pathology, pathogenesis, and treatment.

Brain Diseases↗
PubMed1982

Intracerebral arteriolar permeability to lanthanum.

Lanthanum, an electron-dense tracer, has been used extensively in the study of the structure of cell junctions. The present study was undertaken to determine whether the interendothelial junctions of normal intracerebral arterioles allow passage of lanthanum and to document the alterations occurring in these structures in acute hypertension. Perfusion of lanthanum for 12-40 minutes in control animals resulted in passage of tracer into arteriolar walls and into the extracellular compartment of the surrounding brain. The two principal mechanisms associated with tracer extravasation into the brain were diffuse passage through endothelial cytoplasm and through interendothelial spaces bypassing tight junctions. The latter finding has not been previously reported in normal cerebral arterioles and suggests that the tight junctions of these vessels are different from those of capillaries and consist of a meshwork of closely arranged maculae occludentes rather than complete circumferential occluding bands as was previously believed. Hypertensive animals showed accelerated passage of lanthanum, it being demonstrable not only in arteriolar walls but in capillary and venular walls and the surrounding neuropil after only 5 minutes of circulation. Passage of tracer through vessel walls occurred by the same routes as in control. In addition, increased numbers of pinocytotic vesicles were observed in the endothelium, confirming our previous studies that increased vesicular transport occurs in cerebral arteriolar endothelium in acute hypertension.

Animals↗
PubMed1981

Cerebrovascular permeability in mechanically induced hypertension.

Our previous studies of cerebrovascular permeability in angiotensin-induced acute hypertension demonstrated that the principal mechanism resulting in increased permeability is enhanced pinocytosis. In order to exclude the possibility that the enhanced pinocytosis was a direct effect of exogenous angiotensin, cerebrovascular permeability alterations were studied in nonpharmacologically induced acute hypertension. Rats receiving horseradish peroxidase (HRP) intravenously, were sacrificed 2 1/2 minutes after the onset of hypertension induced by placing a clip on the abdominal aorta. These animals showed the same pattern of permeability alterations as had been observed previously in animals with angiotensin-induced acute hypertension. Focal segments of penetrating arterioles in the temporal and parietal cortex showed increased permeability to HRP. Permeable vessels showed increased numbers of pinocytotic vesicles and the interendothelial junctions revealed no alterations. Enhanced pinocytosis appears to be the principal mechanism resulting in increased cerebrovascular permeability in this model as well as suggesting that the alterations of cerebrovascular permeability observed previously in angio-tensin-induced acute hypertension occur due to the hypertensive state and are not a direct drug effect of exogenous angiotensin.

Animals↗
PubMed1980

Morphological changes in spontaneously hypertensive rats.

Our previous studies of angiotension-induced acute hypertension showed increased intracerebral arteriolar permeability associated with markedly enhanced pinocytosis. This study was performed to determine whether similar findings occurred in spontaneous non-pharmacologically induced chronic hypertension. Cerebrovascular permeability to horseradish peroxidase (HRP) was studied over an 82-week period in spontaneously hypertensive rats (SHR) derived from a strain that originated from Japan. In a few animals increased cerebrovascular permeability to HRP was observed, associated with enhanced pinocytosis. Quantitatively, the number of pinocytotic vesicles in permeable arteriolar segments was significantly increased suggesting that enhanced pinocytosis is the principal mechanism of early cerebrovascular changes in SHR. Light microscopy of renal, ocular and cerebral vessels revealed medial hyperplasia affecting renal vessels at 16 weeks and occurring later in ocular and cerebral vessels. Deposition of fibrin in renal vessels was observed from 64 weeks onwards but was not associated with renal failure.

Animals↗
PubMed1979

Quantitative estimate of pinocytosis in experimental acute hypertension.

Cerebral cortical arterioles in focal neocortical areas develop increased permeability to plasma proteins and protein tracers in experimental hypertensive encephalopathy. The mechanism underlying this increased permeability has been the subject of several studies. In our previous studies of angiotensin-induced acute hypertension, pinocytosis appeared to be the principal mechanism for the increased blood-brain barrier (BBB) permeability observed. In the present study pinocytotic activity was assessed quantitatively to determine whether enhanced pinocytosis was confined to the permeable arteriolar segments of hypertensive animals. In addition, the effect of horseradish peroxidase (HRP) itself on the pinocytotic activity of normal cerebral cortical arteriolar endothelium was determined. In 12 rats following administration of HRP, hypertension was induced by an infusion of angiotensin. The animals were perfusion-fixed 90 s after the onset of the infusion. Control animals received saline only or HRP only. The area of arteriolar endothelium in cross section was determined by a planimeter from overlapping electron micrographs taken at a constant magnification around the circumference of the vessel wall. Results indicate a significant (P less than 0.001) increase in the number of pinocytotic vesicles in the permeable arteriolar segments of hypertensive animals as compared with nonpermeable arteriolar segments of the same animals and comparable segments of normotensive rats. In addition, eight times as many vesicles appear to be transporting tracer in the permeable arteriolar segments of hypertensive animals as compared to the nonpermeable segments of the same animals and normotensive animals. HRP alone did not affect the pinocytotic index, there being no difference (P greater than 0.05) in the number of vesicles in normotensive animals receiving saline only and those receiving HRP only. Our previous observation that disruption of endothelial cells or their tight junctions did not occur was confirmed.

Animals↗
PubMed1978

Cytoplasmic filaments in intracerebral cortical vessels.

Actin filaments measuring 5 nm in diameter are present in the endothelium of systemic vessels and presumably have a contractile function that may be related to vascular permeability. Little attention has been directed to the presence of similar cytoplasmic filaments in the endothelium of cerebral vessels. This study was undertaken to determine whether filaments are present in the endothelial cells of intracerebral cortical vessels of rats and humans. Ultrastructural studies revealed two populations of endothelial cytoplasmic filaments 5 nm and 10 nm in diameter, respectively. The 5-nm filaments were abundant in the endothelium of penetrating cortical arterioles, being grouped near the cytoplasmic margins in proximity to cell junctions and along the abluminal side of the endothelial cells. The filaments were scant in capillaries and venules.

Animals↗
PubMed1978

Hypertension and the blood-brain barrier.

Acute hypertension leads to alternating regions of dilation and vasoconstriction of surface cerebral vessels. It remains to be determined conclusively if either or both of those calibre changes are essential in the production of degenerative vascular changes of malignant hypertension. There is no evidence of ischemic or other morphologic change to components of the blood-brain barrier including the interendothelial tight junctions which remain intact. An early phase of evolving cerebral edema is swelling of astrocytic foot processes that occurs only in regions of abnormal protein permeability. The cortical location of these acute hypertensive lesions stands in contrast to the ganglionic location of the microaneurysms found as complication of chronic hypertension in man. The location of permeability changes to protein do not necessarily reflect changes in brain water permeability susceptible to sympathetic regulation.

Acute Disease↗
PubMed1977

Cerebral cortical changes in acute experimental hypertension: An ultrastructural study.

Multiple focal cortical areas of increased vascular permeability to tracer substances occur in experimental hypertensive encephalopathy. In this study, rats with angiotensin-induced acute hypertension were used to determine whether increased permeability was associated with focal cerebral edema and if so, the tissue component involved. In addition, the mechanism of increased permeability and the types of vessels involved were investigated using horseradish peroxidase as a tracer. Quantitative morphometric studies 8 minutes after the onset of hypertension demonstrated significant perivascular glial swelling around arterioles, venules, and capillaries; the swelling was confirmed to the permeable areas and absent in the nonpermeable areas of the same animals. Ninety seconds after the onset of hypertension, horseradish peroxidase reaction product was present in focal superficial segments of the walls of penetrating arterioles but rarely in venular and capillary walls. At this time period endothelial cells showed prominent pinocytotic uptake of tracer. Eight minutes after the onset of hypertension, reaction product was again found in arteriolar walls and had extravasated into the surrounding extracellular space of the neuropil as well. Extravasation also occurred through capillary and venular walls but was less frequent. At this time interval endothelial pinocytotic activity was still prominent. There was no mechanical damage of vessel walls in the form of endothelial discontinuities or disruption of interendothelial spaces. Tracer was not found in interendothelial jundtions in continuity from lumen to base. The principle mechanism of increased permeability was enhanced pinocytosis, which occurred rapidly, being demonstrable 90 seconds after the onset of hypertension; it was observed principally in permeable arteriolar segments.

Acute Disease↗