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H Mikkelsen

Publications and source records attributed to H Mikkelsen.

28 records · Page 2Linked to original sources

4,5,6,7-Tetrahydroisothiazolo[5,4-c]pyridin-3-ol and related analogues of THIP. Synthesis and biological activity.

The thio analogues of the GABA (gamma-aminobutyric acid) agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), the GABA uptake inhibitor THPO (4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol), and the glycine antagonist THAZ (5,6,7,8-tetrahydro-4H-isoxazolo[4,5-d]azepin-3-ol) have been synthesized and tested biologically on single neurons in the cat spinal cord and in vitro by using synaptic membrane preparations obtained from rat brains. In contrast to THIP, thio-THIP (4,5,6,7-tetrahydroisothiazolo[5,4-c]pyridin-3-ol, 5) was only a weak GABA agonist. Thio-THPO (4,5,6,7-tetrahydroisothiazolo[4,5-c]pyridin-3-ol, 10) was slightly weaker than THPO as an inhibitor of GABA uptake in vitro, and these two compounds were approximately equipotent in enhancing the inhibition of the firing of cat spinal neurons by GABA. Like THAZ and structurally related bicyclic isoxazole zwitterions, thio-THAZ (5,6,7,8-tetrahydro-4H-isothiazolo[4,5-d]azepin-3-ol, 15) was an antagonist at glycine receptors on cat spinal neurons. The I/U ratios, which reflect the ability of neutral amino acids to penetrate the blood-brain barrier (BBB), were calculated for 5 (I/U = 16), 10 (63), and 15 (200). These low I/U ratios, compared with the findings that THIP (I/U = 500 or 1500) and THPO (I/U = 2500) enter the brain after systemic administration, suggest that the thio analogues may penetrate the BBB very easily.

Animals↗

Local reactions after i.v. injections of diazepam, flunitrazepam and isotonic saline.

Local reactions after i.v. injection of diazepam, flunitrazepam and isotonic saline were studied in patients who received extradural analgesia or general anaesthesia. The frequency of thrombophlebitis on the 1st, 3rd and 5th days after the injection of diazepam was 2.1%, 17.0% and 14.9% respectively, after flunitrazepam 10.0%. 10.0% and 14.0%, and after saline 0%, 6.7% and 4.4%. The differences between the groups were not statistically significant (P > 0.05). One month after the injection 15.6% in the diazepam group, 8.5% in the flunitrazepam group and 9.3% in the saline group had pain or tenderness in the arm used for the injection.

Adult↗

Hypersensitivity reactions to food colours with special reference to the natural colour annatto extract (butter colour).

It is well known that synthetic food colours especially some azo dyes can provoke hypersensitivity reactions such as urticaria, angioneurotic oedema, and astma (Michaëlsson and Juhlin, 1973, Granholt and Thune, 1975). Natural food colours are scarcely investigated with respect to potential allergic properties. Annatto extract, a commonly used food colour in edible fats e.g. butter, has been tested in patients. Among 61 consecutive patients suffereing from chornic urticaria and/or angioneurotic oedema 56 patients were orally provoked by annatto extract during elimination diet. Challenge was performed with a dose equivalent to the amount used in 25 grammes of butter. Twentysix per cent of the patients reacted to this colour 4 hours (SD: 2,6) after intake. Similar challenges with synthetic dyes showed the following results: Tartrazine 11%, Sunset Yellow FCF 17%, Food Red 17 16%, Amaranth 9%, Ponceau 4 R 15%, Erythrosine 12% and Brillant Blue FCF 14%. The present study indicates that natural food colours may induce hypersensitivity reactions as frequent as synthetic dyes.

Angioedema↗

On the effect of vinblastine on ameloblasts of rat incisors in vivo. 2. Protracted effect on secretory ameloblasts. A light microscopical study.

The effects of vinblastine sulphate at a dosage of 0.2 mg per 100 g body weight on the secretory ameloblasts of rat incisors were studied 3, 6 and 24 hours and 3 and 7 days after administration of the drug. The vinblastine affected the secretion profoundly, caused a reduction in size of the cells and death of many ameloblasts. Most of the surviving ameloblasts restored initially-induced loss of polarity. Many also resumed secretion and deposition of enamel matrix. The Tomes' processess were extremely sensitive to vinblastine and all matrix deposited after administration of the drug appeared abnormal in structure. Ameloblasts not resuming secretory activity were less than half the size (height) of normal cells. In some areas all the ameloblasts were destroyed with the exception of a varying number of surviving ameloblasts parts consisting only of a nucleus and a small amount of cytoplasm. The ameloblasts which had re-established secretory activity, and most of the ameloblasts which had not, retained their ability to transform into transporting ameloblasts. Large amounts of ameloblast debris present 3 and 6 hours after administration of the vinblastine were effectively engulfed and digested by the cells of the striatum intermedium within 24 hours.

Ameloblasts↗

Light microscopical and ultrastructural observations on the effect of vinblastine on ameloblasts of rat incisors in vivo. I. Short-term effect on secretory ameloblasts.

The highly polarized secretory ameloblasts in the incisors of rats fixed by perfusion with glutaraldehyde two or three hours after intravenous administration of vinblastine sulfate at a dosage of 5 mg per 100 g body weight were studied in the light microscope and the electron microscope. The following effects were observed: 1. All cytoplasmic microtubules in the ameloblasts had vanished. This was not accompanied by the appearance of paracrystals of microtubular protein or macrotubules. 2. The ameloblasts preserved their external features of polarized cells but lost their ability to maintain normal orderly segregation of the cell constituents; i.e. their normal internal compartmentalization and polarity had vanished. 3. The ameloblasts lost their capability of directional translocation of the secretory granules towards the cell apex. 4. Secretory granules already translocated to the cell apex regurgitated in the cell and a probably delayed discharge of secretory material had started in abnormal site at the surface. 5. The normal arrangement of ribosomes into polyribosomes on the membranes of the rough endoplasmic reticulum was no longer present; the ribosomes were apparently distributed at random. 6. New secretion was inhibited or brought to a standstill but secretory material already present in the Golgi complex appeared to be transported normally. 7. The centriole had started to develop into a cilium in many of the cells. 8. The number of autophagic vacuoles had increased.

Ameloblasts↗

Acute epiglottitis in a rural area: experiences with an anesthesiologist-staffed ambulance helicopter.

The majority of fatalities due to acute epiglottitis (AE) result from prehospital airway problems. We reviewed the courses of 14 patients with AE treated by an aeromedical team consisting of an anesthesiologist and a paramedic. Eight patients were transported from a physician's office or from the patient's own home. One patient was intubated at the scene, and two received ventilatory support with mask and bag en route to the hospital. Two patients suffered cardiopulmonary arrest before arrival of the aeromedical team, both resulting in severe hypoxic encephalopathy. All six patients transported from hospitals were intubated prior to the helicopter transport. Based on our own experience and a review of the literature, we discuss prehospital airway management in this group of patients.

Acute Disease↗

Moclobemide versus fluoxetine for double depression: a randomized double-blind study.

The efficacy and tolerability of the selective reversible monoamine oxidase A inhibitor, moclobemide (300 mg/day) and the selective serotonin uptake inhibitor, fluoxetine (200 mg/day), were compared in a six-week single-centre double-blind fixed-dose study in patients (n = 42) with double depression (DSM-III-R: dysthymia with superimposed major depressive episode) using weekly assessment on the Hamilton depression rating scale (HDRS-17 items) and clinical global impression (CGI) scale. The primary efficacy outcome measure was a decrease > or = 50% in end of treatment HDRS score, secondary measures were the mean total endpoint HDRS scores and percentages of CGI very good and good responses. Tolerability was measured by the frequency and severity of volunteered adverse events. There were no significant differences in secondary efficacy outcome measures, but more patients achieved a > or = 50% decrease in HDRS score on moclobemide (71% vs 38%, p < 0.05). The only adverse event was mild transient anxiety (n = 1) with moclobemide. The results suggest that moclobemide and fluoxetine are equally well tolerated and at least similar in efficacy in double depression. Evidence that moclobemide may be more effective requires confirmation in a larger comparative study incorporating a placebo control group.

Adult↗