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Biomedical subjects

B Ljunggren

Publications and source records attributed to B Ljunggren.

At least 145 records · Page 8Linked to original sources

Cerebrovascular effects of ammonia in vitro.

The effect of ammonia (ammonium salts) upon human and rabbit cerebral arteries was studied in vitro. Ammonia (NH3/NH4+) caused relaxation of cerebrovascular smooth muscle which was transient and occurred irrespective of how the vessels were preconstricted (potassium-Krebs solution, noradrenaline, serotonin, prostaglandin F2 alpha). The effect was independent of ammonia-induced extracellular changes in pH. It is concluded that ammonia may contribute to the vasodilatation and increase in cerebral blood flow which occurs under certain pathophysiological conditions.

Ammonia↗

Vasoconstrictive effects of human post-hemorrhagic cerebrospinal fluid on cat pial arterioles in situ.

Cat cortical arterioles were exposed in vivo to cerebrospinal fluid (CSF) from four patients with subarachnoid hemorrhage (SAH) due to a ruptured intracranial aneurysm. Pial arteriolar caliber was measured by the television image-splitting technique. There was a consistent vasoconstrictive response to CSF. This effect could be ascribed neither to the pH of the CSF nor to the potassium concentration. The vasoconstriction, which was more pronounced with decreasing arteriolar caliber, could be resolved by the perivascular application of nifedipine.

Adult↗

Results of early operations for ruptured aneurysms.

In a consecutive series of 219 patients with a ruptured aneurysm of the anterior part of the circle of Willis, 119 patients (54%) made a good recovery and 67 (31%) died. Of 53 patients who did not have surgery, six (11%) made a good recovery and 37 (70%) died. Urgent surgery with evacuation of an associated significant intracerebral hematoma was performed in 30 patients; nine (30%) made a good recovery and 15 (50%) died. Delayed surgery was performed in 55 patients of whom 42 (76%) made a good recovery and two (4%) died. Early intracranial operation (within 48 to 60 hours after subarachnoid hemorrhage (SAH)) was performed in 81 patients who were in Grades I to III prior to surgery. Sixty patients (74%) made a good recovery, and eight died within a month. Five patients were severely disabled and died 2 to 8 months after SAH and surgery. In 17 patients, although the immediate postoperative course was uneventful, evidence of cerebral ischemia developed 4 to 13 days after the bleed and resulted in death in eight patients. A poor outcome was correlated with a history of elevated blood pressure before SAH. Seven patients, of whom six were women of child-bearing age, demonstrated pronounced vasospasm on postoperative angiography; nevertheless, they remained well and free from ischemic symptoms after surgery. Early operation combined with removal of subarachnoid clots and rinsing the basal cisterns does not eliminate the risk of delayed ischemic dysfunction. Such early surgery, however, improves overall outcome by preventing recurrent bleeding, and may also reduce the frequency of hydrocephalus.

Adolescent↗

Vasoconstrictor activity in cerebrospinal fluid from patients subjected to early surgery for ruptured intracranial aneurysms.

Vasoconstrictor activity was examined in serial samples of cerebrospinal fluid (CSF) obtained from 10 patients undergoing aneurysm clipping within 48 hours after subarachnoid hemorrhage (SAH). There was no close relationship between vasoconstrictor activity in postoperative CSF samples and the patient's clinical condition or angiographic vasospasm. The identity of the vasoconstrictor substance(s) in CSF was not established, but serotonin, histamine, norepinephrine, epinephrine, acetylcholine, or angiotensin II were eliminated as prime vasoconstrictor agents inducing cerebral vasospasm. Differences in the temporal profile of the responses of isolated tissues to CSF from patients with early and late surgery suggested that differing substances were involved in the production of spasm. A correlation between CSF potassium concentrations and vasoactive substances was found, but potassium could not account for vasoconstrictor activity of CSF. A log:linear correlation between total vasoconstrictor activity and total CSF collected could not be explained. Also, because of possible differences in the identity of vasoactive substances in CSF in this study compared to earlier studies, clinical comparisons based on apparent differences in pharmacological potency of CSF were not warranted. Nevertheless, removal of subarachnoid blood by cisternal rinsing seemed to be a useful surgical adjunct.

Adult↗

Effects of indomethacin and prostacyclin on isolated human pial arteries contracted by CSF from patients with aneurysmal SAH.

In small human cerebral arteries preincubated with indomethacin, contractions induced by cerebrospinal fluid (CSF), from patients with subarachnoid hemorrhage were markedly increased. Also contractions induced by noradrenaline, but not 5-hydroxytryptamine, were augmented. Prostacyclin and its metabolite 6-keto-prostaglandin (PG)E1 reversed the contractions induced by CSF, as well as by noradrenaline, 5-hydroxytryptamine, and PGF2 alpha. The findings suggest that these substances are able to counteract the influence of vasoconstrictor material in hemorrhagic CSF. If the capacity to synthesize these "protective" arachidonic acid metabolites is reduced, the resulting imbalance between contractile and relaxant forces acting on the vessel wall may lead to sustained cerebral vasoconstriction.

Adult↗

Plasma levels of 8-methoxypsoralen determined by high-pressure liquid chromatography in psoriatic patients ingesting drug from two manufacturers.

We have adapted a rapid and sensitive high-pressure liquid chromatographic technique (HPLC) to measure plasma levels of 8-methoxypsoralen (8-MOP) in 22 psoriatic patients receiving photochemotherapy with 8-MOP and long-wave ultraviolet light (PUVA). In this procedure, 1 ml plasma samples containing ammidin as an internal standard are extracted with benzene. After evaporation under nitrogen the residue is redissolved in methylenechloride:acetonitrile, 95:5, and chromatographed using a normal phase HPLC system with a 10 mu silica particle column and a UV detector at 254 nm. The sensitivity of the method is 10 ng/ml plasma. Plasma concentrations of 8-MOP were measured between 2 and 4 hr after ingestion of therapeutic doses of 8-MOP provided by 2 manufacturers. Mean 8-MOP plasma levels were 27 +/- 35 ng/ml plasma 2 hr after ingestion of the only drug presently available on the U.S. market, 8-MOP (Elder). These values were significantly below (p less than 0.001) those obtained with 8-MOP (Roche) which were 104 +/- 79 ng/ml plasma. A number of patients on 8-MOP (Elder) did not have detectable levels of 8-MOP 2 hr after ingestion. The time course patterns also differed, possibly indicating a slower and less complete absorption for 8-MOP (Elder). Repeated time course studies in the same patient were reproducible although the absolute concentrations showed some variation. Preliminary evidence indicates that the plasma levels of 8-MOP have therapeutic relevance.

Adolescent↗

Chlorpromazine phototoxicity: growth inhibition and DNA-interaction in normal human fibroblasts.

Growth was impaired in normal human skin fibroblasts following treatment with chlorpromazine and long-wave ultraviolet light (UV-A). The degree of impairment was dose dependent to chlorpromazine within the concentration range tested, 2.5-20 microgram/ml, in the presence of UV-A, 1 J/cm2. Pre-irradiated chlorpromazine at a concentration of 20 microgram/ml had no effect on fibroblast growth. Chlorprotixene, a thioxanthene compound structurally similar to chlorpromazine at a concentration of 10 microgram/ml, was not phototoxic in this system. The effects of chlorpromazine and UV-A on fibroblast DNA were studied using the technique of zone sedimentation in alkaline sucrose. In the absence of light chlorpromazine did not affect sedimentation of DNA. After UV-A irradiation at 20 degrees or 0 degrees C in the presence of chlorpromazine, labeled DNA sedimented more slowly indicating that it had been reduced to smaller fragments. No evidence for interstrand DNA cross-links was found. Chlorpromazine alone or in combination with UV-A did not alter the size of the DNA. These results with cultured fibroblasts indicate that the phototoxic action of chlorpromazine at 366 nm is at least partially explained by interaction with DNA and is not due to the effects of cytotoxic photoproducts.

Cell Count↗

Effects of nifedipine of pial arteriolar calibre: an in vivo study.

In cats the response of individual pial arterioles to perivascular microapplication of the Ca++-antagonistic drug nifedipine was studied using the image-splitting technique developed by Baez. It has previously been shown that the coefficient of variation for repeated measurements of pial vessel diameter using this system is 1%, under conditions of steady arterial pressure and blood gas tensions. All investigated pial arterioles invariably responded with a dilatation at an injected nifedipine concentration of 10 microM. The dilatatory response was inversely proportional to the resting vessel calibre, i.e., arterioles less tham 70 microns responded with a significantly stronger dilatation as compared with arterioles greater than 100 microns in diameter. In experiments where a minor subarachnoid hemorrhage was made by the injection micropipette injuring capillaries just before the perivascular microapplication of nifedipine, a dilatatory response invariably ensued in spite of the perivascular blood which in itself constricted the arterioles under examination.

Animals↗

Antinuclear antibodies during Puva therapy.

During PUVA therapy 7 patients out of 34 with severe psoriasis developed circulating antinuclear antibodies (ANA) (21%). Before treatment only 3 patients of 50 (6%) considered for PUVA had detectable ANA. The ANA titres were usually low. Antibodies against native DNA as studied with the Crithidia luciliae test, were not found, and blood and urinary screening for collagenosis was negative. All 7 patients responded well to the PUVA treatment. The significance of these findings remains to be determined.

Adult↗

Liver injury following administration of 8-methoxypsoralen during PUVA therapy.

A case of liver injury caused by 8-methoxypsoralen given orally during PUVA therapy is presented. The reaction, manifested by elevated serum alanine-aminotransferase and serum aspartate-aminotransferase, was provoked on three consecutive occasions, on the last one with 8-MOP only. The liver injury seems to be of the hepatocellular and nonpredictable type.

Alanine Transaminase↗

Dynamics of ultraviolet dermatitis as studied with the mouse tail technique.

Time course and dose-response relationships have been studied for medium-wave ultraviolet radiation (UVB) in the mouse by measuring the inflammatory oedema of tail tissue. The time course was shown to be dose dependent, larger doses peaking earlier than smaller ones. For intermediate doses the reaction culminated after 48 h. Dose-response curves were sigmoid-shaped with good linear correlation in the region of maximal slope. The dose-response curve was studied at varying intervals after irradiation and the relationship could be shown to be time dependent. UVB differs in some of these respects from phototoxic reactions to chlorpromazine and 8-methoxypsoralen.

Animals↗

Fibromuscular dysplasia of the cervico-cephalic arteries.

Six cases of fibromuscular dysplasia of the cervical and cephalic portions of the internal carotid arteries, including their intracranial branches are reported. It should perhaps be pointed out that one of the cases was from the Sudan. As far as we know, the condition has never before been reported in a male African. The condition was associated with an intracranial aneurysm in four of our cases. To our knowledge only three autopsied cases of fibromuscular dysplasia involving intracranial arteries are on record. In our six cases the diagnosis was based on angiographic evidence, and three of the cases, two with intracranial involvement, were verified post mortem.

Adult↗

Drug phototoxicity in mice.

A series of agents with alleged photosensitizing properties has been studied in mice by a quantitative in vivo method for acute drug phototoxicity. The method, originally developed for phenothiazine studies, was found suitable for several drug groups with varying mechanism of action, such as tetracyclines, protoporphyrin and psoralens. In the sulfa group only sulfanilamide was active, although weakly. Phototoxicity in vivo, hitherto not demonstrated, was observed with griseofulvin, nalidixic acid, imperatorin, kynurenic acid and amiodarone.

Animals↗