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G Karlsson

Publications and source records attributed to G Karlsson.

16 recordsLinked to original sources

Blockade of GABAB receptors accelerates amygdala kindling development.

The aim of this study was to investigate the putative role of GABAB receptors in the development of amygdala kindling in rats. The effects of the GABAB blocker CGP 35348 and the GABAB agonist baclofen on the progressive development of behavioural seizure symptoms (stages 1-5 classified by Racine) and duration of after-discharges (AD) were studied. CGP 35348 at a dose of 300 mg/kg i.p., which blocks central GABAB receptors, moderately but consistently accelerated the development of behavioural seizure symptoms. CGP 35348 had no marked effect on the duration of ADs corresponding to the different seizure stages. L-baclofen (6 mg/kg i.p.) had a dual effect on kindling development. It retarded the development of the behavioural symptoms, but increased the duration of AD. In conclusion, the results suggest that synaptically-released GABA activated GABAB receptors and thereby exerted a depressant effect on kindling development.

Amygdala

Mast cells and eosinophils in the allergic mucosal response to allergen challenge: changes in distribution and signs of activation in relation to symptoms.

An allergen challenge was performed in 10 asymptomatic patients with strictly seasonal allergic rhinitis. For comparison; seven nonallergic subjects were challenged with allergen, and seven allergic patients were challenged with diluent. Cell samples, obtained with use of a brush technique to recover cells from within the epithelium and nasal lavage to collect cells from the epithelial surface, and symptom scores were taken before challenge and at 2-hour intervals during 12 hours. The cell suspensions were cytocentrifuged onto object slides for light microscopy. Histamine was determined in the cell pellets. In brush samples from the allergic patients challenged with allergen, eosinophils, expressed as a percentage of the total granulocytes, increased from 4.3% +/- 2.7% (mean +/- SEM) to 10.3% +/- 3.8% (p < 0.05) 4 hours after challenge. This level was maintained for up to 12 hours. A similar increase was noted in the lavage specimens 2, 6, and 8 hours after the challenge. In the brush samples the proportion of eosinophils containing two or more cytoplasmic vacuoles, taken as a sign of activation, increased from 20% to 72% (p < 0.05) 8 hours after provocation. In brush samples from the allergic patients challenged with allergen, the numbers of metachromatic cells increased to a maximum of eightfold at 10 hours. In the lavage specimens, no metachromatic cells were observed before provocation, but they progressively increased in number 2 to 12 hours after provocation. Cell pellet histamine content decreased temporarily 2 to 4 hours after challenge (p < 0.05) in brush samples from allergen-challenged allergic patients. The local metachromatic cell density before challenge, as reflected in the brush specimens, correlated with nasal congestion, sneezing, and the degree of eosinophilia.

Adult

GABAB receptors in various in vitro and in vivo models of epilepsy: a study with the GABAB receptor blocker CGP 35348.

The effect of the GABAB receptor blocker CGP 35348 on epileptic processes in vitro and in vivo was studied. In hippocampal slices of the rat maintained in vitro, CGP 35348 (100 microM) induced a moderate increase in the frequency of extracellularly recorded spontaneous epileptiform burst discharges induced in CA3 by penicillin (1.2 mM), bicuculline (5 microM) and low Mg(2+) (0.1 mM). This effect was observed in 50-75% of the slices. A similar but less consistent increase was also observed in CA1 in bicuculline and low Mg2+. Data obtained by intracellular recordings from CA1 pyramidal cells in the presence of bicuculline (10 microM) demonstrated that CGP 35348 (100 microM) increased the duration of the paroxysmal depolarization underlying an evoked epileptiform burst and reduced the early component of the after hyperpolarization which followed the burst. In mice pretreated with isoniazid, CGP 35348 (300 mg/kg, i.p.) significantly increased the number of convulsing mice. However, convulsions induced by submaximal doses of pentylenetetrazol, picrotoxin or strychnine were not facilitated by CGP 35348. We conclude that GABAB receptors appear to exert a suppressant effect on various kinds of epileptiform discharges of hippocampal neurons in vitro. In vivo, however, the role of GABAB receptors in regulating convulsions is less prominent since only isoniazid-induced convulsions were facilitated by GABAB receptor blockade.

Animals

The relationship between stressful working conditions and high alcohol consumption and severe alcohol problems in an urban general population.

The relationship between 15 measures of stressful working conditions and high alcohol consumption (35 g 100% ethanol per day or more for men and 25 g or more for women) was studied, using cross-sectional data from a general population survey of 1344 males and 1494 females; the ages 25-64 years in metropolitan Stockholm in 1984. In a longitudinal component of the study, hospitalization and mortality with alcohol-related diagnosis was assessed during 1984-90, and also the association between previous experience of unemployment and high alcohol consumption. Some of the associations, expressed as age-adjusted odds ratios, were positive and some were negative when high alcohol consumption was the endpoint, but there was a clear variation by sex and social class. Generally the positive associations were stronger among male non-manual employees. Among males, there was a clear association between stressful working conditions and subsequent risk of severe medical alcohol-related problems, but the precision of the estimates was low due to low number of cases. The odds ratio was 6.18 (95% confidence interval 1.86, 20.61) for twisted working positions and 6.74 (95% confidence interval 1.67, 27.19). Previous unemployment among males was associated with increased risk for high alcohol consumption, with an odds ratio of 5.71 (95% CI 1.39, 15.97) among those who had been unemployed more than once, and 1.67 (95% CI 0.76, 3.64) among those who had been unemployed once during the previous 5 years. Those and other increased odds ratios were lower when subjects with an alcohol diagnosis at inpatient care during 1980-84 were excluded in the analyses. On the whole, our findings are not conclusive. The strong, but imprecise associations between stressful working conditions and severe alcohol problems, are however challenging, and warrants further studies, preferably with longitudinal design and repeated measurements of both working condition and alcohol habits.

Adult

Peroral chromones. A new way to treat allergic rhinitis?

Disodium chromoglycate (DSCG) is well documented in the topical treatment of allergic rhinitis. Its use does not lead to any major side effects. FPL 57579 is a new chromone compound which is well absorbed after oral administration. In a clinical trial, patients with allergic rhinitis underwent a nasal challenge before and after ingestion of FPL 57579. the effect on nasal airway resistance (NAR) was determined by rhinomanometry. In all cases there was a smaller increase in NAR after the intake of FPL 57579.

Administration, Oral

Individual mercury exposure of chloralkali workers and its relation to blood and urinary mercury levels.

On two occasions, chloralkali workers were investigated with regard to personal air mercury exposure, blood mercury and urinary mercury. The first investigation (13 workers, 2 weeks) was made at an exposure above the threshold limit value (64 microgram/m3, range 36--112), the second (16 workers, 8 weeks) at a lower exposure (23 microgram/m3, range 15--43). At the higher level of exposure, good correlations were found between air exposure and blood or urinary mercury for the group, but not for individuals. At the lower level, the correlations were less pronounced for the group. For individuals, the best correlation was found between mean air exposure during one week and blood mercury about half a week later. Other individuals, mainly the least exposed, showed no such correlation. Corresponding correlations were not found for urinary mercury. The urinary excretion rate was determined only for the last few hours of the workday, but the results agree with earlier investigations of 24-h excretion on a group basis. The threshold limit value for mercury in air (50 microgram/m3) corresponds to 150--175 nmol Hg/1 blood (= 30--35 microgram/1) for the group, with large individual variation.

Adult

New chromogenic peptide substrates for factor X.

The factor Xa-sensitive substrate BZ-Ile-Glu-Gly-Arg-p-nitroanilide has been made more sensitive by making ester and amide derivatives of the gamma-carboxyl group of the glutamyl residue. The morpholinyl and piperidyl amides react 2.5 times more rapidly with factor Xa.

Factor X

Blood transfusion and recurrence of colorectal cancer.

Because perioperative blood transfusions have been shown to have an impaired effect on survival in patients with colorectal cancer, we examined retrospectively the records of 882 patients who had undergone curative operations: 170 patients had distant metastases at the time of operation. Of the 499 patients with colonic cancer 332 (67%) had received perioperative blood transfusions. The corresponding figure for the 213 patients with rectal cancer was 190 (89%). Colonic tumors recurred in 45% of the patients who received blood transfusions and in 39% of those who did not. Corresponding figures for tumors in the rectum were 54% and 55%. When dividing the patients with colonic cancer into different subgroups according to Dukes' grade we found differences in survival rates. The poorer survival for transfused patients was, however, only significant for those with Dukes' A tumors (p less than 0.05). This difference disappeared when the influence of age was eliminated. The estimated risk ratio of recurrence and death was 1.23 with the 95% confidence interval (0.99, 1.53) when taking Dukes' grade, current age and localization into account. Blood transfusion should be avoided if possible until adequate prospective studies have been carried out.

Colorectal Neoplasms