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Biomedical subjects

K E Andersen

Publications and source records attributed to K E Andersen.

At least 127 records · Page 7Linked to original sources

Abnormalities of lymphocyte function and phenotypic pattern in a case of toxic epidermal necrolysis.

We examined the blood lymphocyte function and phenotypic pattern in a patient with toxic epidermal necrolysis after taking salazopyrin. We studied cell surface markers, natural killer cell activity and mitogen-induced lymphocyte transformation. Our results point to temporary immunosuppression as evidenced by lymphopenia with a large "null cell" population, reduced natural killer cell activity, and impaired lymphocyte response to mitogens.

Acute Disease↗

Nickel contact sensitivity in the guinea pig. An efficient open application test method.

Nickel contact sensitivity was successfully induced in guinea pigs using an open epicutaneous application method. Immediately after pretreatment with 1% aqueous sodium lauryl sulfate, upper back skin was treated daily for 4 weeks with 0.3%-3% nickel sulfate in either a 1% lanolin cream (Vaseline, pH 5 SAD crème) or hydroxypropyl cellulose. Weekly intradermal injections with aluminium potassium sulfate were used as adjuvant. The animals were challenged twice with a one week interval, with nickel sulfate 2% in water and 1% in petrolatum, respectively. The response rates in the test groups treated with nickel sulfate 1% or 3% in the lanolin cream or 1% in hydroxypropyl cellulose were significantly different from the response rate in the control group. Considering both readings at both challenges, the frequency of sensitization was 57-93% (8 of 14 to 13 of 14 animals) in the group treated with 1% in the lanolin cream, 60-100% (9/15 to 15/15 animals) in the group treated with 3% in the lanolin cream, and 67-75% (8/12 to 9/12 animals) in the group treated with 1% in hydroxypropyl cellulose. Rechallenge of initially sensitized animals 10 weeks later confirmed that a lasting contact allergy had been obtained.

Animals↗

Characterization of tiagabine (NO-328), a new potent and selective GABA uptake inhibitor.

Tiagabine (NO-328) (R(-)-N-[4,4-bis(3-methylthien-2-yl)but-3-enyl]nipecotic acid, hydrochloride) is a new centrally acting GABA uptake inhibitor. The anticonvulsant activity of tiagabine was evaluated against seizures induced by methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), pentylenetetrazol, bicuculline, maximal electrostimulation (MES), or high intensity sound. The sedative actions of tiagabine were evaluated in tests for traction, rotarod performance and exploratory behavior. Finally, interoceptive properties of tiagabine were assessed using diazepam-, CGS 9896-, pentylenetetrazol-, or amphetamine-discriminating rats. Tiagabine was an effective anticonvulsant in doses which did not produce sedation or motor debilitation, although it was not potent against MES. In a manner similar to other anti-epileptic drugs, tiagabine potentiated dopaminergic function (methylphenidate-induced gnawing in mice) although it did not substitute for amphetamine in amphetamine-trained animals. Furthermore, although tiagabine antagonized DMCM-induced convulsions, it exhibited neither CGS 9896 or diazepam-like interoceptive effects, nor did it block (or potentiate) pentylenetetrazol-discrimination. Thus, GABA uptake inhibition represents a novel rationale for a valproate-like anticonvulsant drug therapy.

Animals↗

[Prevention of athletic injuries by changing the regulations. Experiences with a military obstacle track].

During a period of 12 months of military conscription, all of the injuries occurring on the obstacle track at the Antvorskov Barracks in Slagelse were registered. During the period of investigation, the regulations for employing the track were altered so that the heights of jumping down from obstacles were considerably reduced. The object of this investigation was to demonstrate any possible effect on the pattern of injuries. During the period, a total of 26 injuries were registered (3.78 injuries/conscript/1,000 hours activity). As compared with previous investigations, the frequency of injuries was reduced and practically all of the serious injuries were prevented. The proposed alterations in the techniques are recommended in future when conscripts employ the military obstacle track.

Adult↗

Reduced frequency of nickel allergy upon oral nickel contact at an early age.

From animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such 'oral tolerance' is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could be an effective way to prevent undesired T cell-mediated immune functions, such as playing a role in allograft reaction, autoimmune and allergic diseases. In the present study allergic contact hypersensitivity (ACH) to nickel, currently presenting the most frequent contact allergy in man, was chosen to establish the feasibility of oral prevention of undesired T cell-mediated immunity in man. Potentially tolerizing (oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed by means of a confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel-releasing appliances (dental braces) at an early age, but only if prior to ear piercing, showed a reduced frequency of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man.

Adolescent↗

Nickel-sulphate-induced contact dermatitis in the guinea pig maximization test: a dose-response study.

Nickel sulphate is a sensitizer in guinea pigs, but the frequency of sensitization varies from study to study. The dose-response relationship for NiSO4.6H2O was evaluated in the guinea pig maximization test in this study. 6 intradermal (0.01%-3.0% aq.) and 6 topical (0.25%-10.0% pet.) concentrations were chosen for induction and NiSO4.6H2O 1% pet. was used for challenge, based on the absence of skin irritation in a pilot study. Blind reading was performed. A logistic dose-response model was applied to the challenge results. At 48 h, a linear relationship was obtained between the intradermal induction dose (but not topical dose) and the response, resulting in a maximum sensitization rate of 40% after 3% i.d. The reactivity disappeared at re-challenge 1 week later. Following a booster closed patch on day 35, using NiSO4 10% pet., the animals were challenged with NiSO4 2% pet. and statistical analyses of 72-h readings revealed a non-linear dose-response relationship, giving a maximum response frequency of 40% after initial induction with NiSO4 3% i.d. and 2% topical.

Administration, Cutaneous↗

Contact sensitization to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (MCI/MI). A European multicentre study.

The frequency of positive reactions to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (MCI/MI) were studied at 22 European contact dermatitis clinics over a period of 1 year. A total of 4713 patients participated. All the patients were patch tested with nickel sulphate, formaldehyde, paraben-mix, and MCI/MI. 19.4% of the patients had positive patch tests to nickel, making this the most common allergen. 3% of the patients reacted to 100 ppm MCI/MI, while 2.6% reacted to formaldehyde and 1.1% to parabens. There was great variation in the frequency of MCI/MI sensitivity among the 22 centres. MCI/MI contact allergy was most common among women and in patients with facial dermatitis, while it was rarely seen in patients with dermatitis on the lower legs. There were no fluctuations in the number of positive patch tests to MCI/MI on a monthly basis when the results from all centres were combined. 117 of the 141 MCI/MI sensitized patients included in the study were retested. 88% had positive patch tests when retested. 101 of the MCI/MI-sensitive patients participated in a double-blind, placebo-controlled product use test. This test showed that 31% of the MCI/MI-sensitive patients had a positive reaction to a MCI/MI-preserved product. Only a few patients reacted to a control product. It is concluded that the preservative MCI/MI is an important new contact allergen.

Adolescent↗

(R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain gamma-aminobutyric acid uptake carrier.

(R)-N-[4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid (NO 328) has previously been shown to be a potent anticonvulsant in both mice and rats. Here, we report that NO 328 is a potent inhibitor of gamma-[3H]aminobutyric acid [( 3H]GABA) uptake in a rat forebrain synaptosomal preparation (IC50 = 67 nM) and in primary cultures of neurons and astrocytes. Inhibition of [3H]GABA uptake by NO 328 is apparently of a mixed type when NO 328 is preincubated before [3H]GABA uptake; the inhibition is apparently competitive without preincubation. NO 328 itself is not a substrate for the GABA uptake carrier, but NO 328 is a selective inhibitor of [3H]GABA uptake. Binding to benzodiazepine receptors, histamine H1 receptors, and 5-hydroxytryptamine1A receptors was inhibited by NO 328 at 5-30 microM, whereas several other receptors and uptake sites were unaffected. [3H]NO 328 showed saturable and reversible binding to rat brain membranes in the presence of NaCl. The specific binding of [3H]NO 328 was inhibited by known inhibitors of [3H]GABA uptake; GABA and the cyclic amino acid GABA uptake inhibitors were, however, less potent than expected. This indicates that the binding site is not identical to, but rather overlapping with, the GABA recognition site of the uptake carrier. The affinity constant for binding of [3H]NO 328 is 18 nM, and the Bmax is 669 pmol/g of original rat forebrain tissue. The regional distribution of NaCl-dependent [3H]NO 328 binding followed that of synaptosomal [3H]GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Patch testing with the "sesquiterpene lactone mix": a marker for contact allergy to Compositae and other sesquiterpene-lactone-containing plants. A multicentre study of the EECDRG.

6278 patients were patch tested with a sesquiterpene lactone mix (SL-mix) in 10 European clinics. 4011 patients were tested only with 0.1% SL-mix, 63 (approximately 1.5%) of whom were positive, with 26 (41%) of these cases being considered clinically relevant. There were no cases of active sensitization, though 5 cases of irritation were reported. 22 irritant reactions and 22 cases of active sensitization occurred when testing also with 1% and 0.33% concentrations of SL-mix. SL-mix 0.1% pet. is shown to be an important patch test and many relevant sensitizations will be missed without routine screening with such a mix. Most patients with SL-mix sensitivity presented with hand and/or face dermatitis, apparent photodermatitis or more generalised eczema.

Dermatitis, Contact↗

Clinical patch test data evaluated by multivariate analysis. Danish Contact Dermatitis Group.

The aim of the present study was to evaluate the influence of individual explanatory factors, such as sex, age, atopy, test time and presence of diseased skin, on clinical patch test results, by application of multivariate statistical analysis. The study population was 2166 consecutive patients patch tested with the standard series of the International Contact Dermatitis Research Group (ICDRG) by members of the Danish Contact Dermatitis Group (DCDG) over a period of 6 months. For the 8 test allergens most often found positive (nickel, fragrance-mix, cobalt, chromate, balsam of Peru, carba-mix, colophony, and formaldehyde), one or more individual factors were of significance for the risk of being sensitized, except for chromate and formaldehyde. It is concluded that patch test results can be compared only after stratification of the material or by multivariate analysis.

Adolescent↗