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Biomedical subjects

L Michaelis

Publications and source records attributed to L Michaelis.

At least 19 recordsLinked to original sources
PubMed2000

Dissociation of osmoregulation from plasma arginine vasopressin levels following thermal injury in childhood.

Although the syndrome of inappropriate anti-diuretic hormone secretion has been recognised as a complication associated with burn and other trauma in adults, relatively little is known about its incidence in children. The objective of this study was to investigate whether it is a complication associated with burn injury in children. Plasma and urine levels of arginine vasopressin (anti-diuretic hormone), sodium and osmolality were measured in samples collected from 16 burn-injured children admitted to the burns unit of the regional children's hospital. No significant correlations were found between plasma vasopressin and plasma sodium or osmolality levels, but there were significant correlations between plasma vasopressin and urine osmolality, 36 (r=0.74, p=0. 009), 60 (r=0.92, p=0.000) and 84 h (r=0.84, p=0.001) after admission, respectively. There were also significant correlations between plasma sodium and plasma osmolality, 24 (r=0.7, p=0.005), 36 (r=0.57, p=0.04) and 84 h (r=0.84, p=0.004) after admission. The data suggest dissociation between the osmolar control of vasopressin secretion and vasopressin levels after burn injury in children, but do not support the incidence of inappropriate secretion of antidiuretic hormone.

Arginine Vasopressin↗
PubMed1999

Role of the carboxyl-terminal region, di-leucine motif and cysteine residues in signalling and internalization of vasopressin V1a receptor.

The structural requirements for internalization and signalling of the vasopressin V1a receptor were investigated in stably transfected HEK-293 cells. Removal of the 51 C-terminal amino acids did not affect vasopressin binding, calcium signalling, heterologous desensitization or internalization of the receptor. Deletion of 14 additional amino acids reduced vasopressin-dependent calcium increase and impaired receptor internalization. Substitution of cysteines 371-372 did not affect intracellular signalling, but decreased endocytosis by 26%. Substitution of the 361-362 leucine by alanine residues reduced by 56% V1a receptor sequestration without affecting calcium signalling. These results indicate that di-cysteine and mostly di-leucine motifs present in the C-terminal region of the V1a receptor are involved in its internalization.

Calcium↗
PubMed1993

[Serum lipids and vitamins in senile macular degeneration].

P6e correlations between serum cholesterol, triglycerides and lipoproteins and serum vitamins A and E were tested in patients with age-related macular degeneration (AMD). Patients diagnosed as having "senile" macular degeneration who were not receiving medical treatment that would interfere with lipid or vitamin metabolism consecutively underwent-fundus photography and fluorescein angiography in a 6-month period. Cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), vitamin A and E were assayed using conventional methods (enzymatic and high-performance liquid chromatography). Sixty-four angiographies from 64 patients were evaluated. The clinical diagnosis was: "hard" drusen (n = 5), geographic atrophy (25), "soft" drusen (10), subretinal neovascularization and disciform scar (24). The percentage of pathological data was calculated: HDL, 89%; cholesterol, 84%; vitamin A, 75%, LDL, 66%; Vitamin E, 33%; triglycerides, 23%. The data differed somewhat between groups. The high prevalence of hypercholesterolemia in older age groups [3, 34] prevents cholesterol from being identified as a risk factor for AMD. Elevated levels of atherogenic LDL and reduced vitamin A are discussed versus "protective" HDL and vitamin E. In many of the AMD cases described, the cardiovascular risks of dyslipoproteinemia demand adequate therapy.

Adult↗
PubMed1992

Carteolol incorporated into FAT-MLV liposomes: prolonged and decreased reduction of IOP.

Liposomes are used as carries providing a prolonged and improved drug action. They are capable of trapping beta-blockers such as Carteolol. In a randomized prospective double-blind clinical trial, Carteolol 2% suspended with frozen and thawed multivesicular large vesicles (FAT-MLV), FAT-MLV, and Carteolol 2% were applied to normal (slightly cataracterous) eyes and immediately after extracapsular cataract extraction or phakoemulsification with implantation of a posterior chamber lens in a standard procedure. Twenty-five patients were included in each group. Intraocular pressure (IOP) was measured for 3 days using applanation tonometry. In the normal eyes, a significant reduction of IOP was found for the patients receiving Carteolol and Carteolol MLV suspension. Moreover, an improved action and a prolongation of drug action was registered in the Carteolol/MLV group as compared to Carteolol treatment alone. After cataract operation, the control groups showed a significant increase in IOP. Carteolol produced a constant level of IOP but the Carteolol/MLV suspension showed a stronger decrease after ECCE and a still stronger decrease after phakoemulsification. Hence, Carteolol is suitable for the reduction of IOP but a Carteolol/MLV suspension is more effective, providing the possibility of a single application of a low-dose beta-blocker after cataract extraction with posterior chamber lens implantation.

Carteolol↗
PubMed1992

[Canthaxanthin retinopathy. Follow-up of over 6 years].

After long-term treatment with high dosages, canthaxanthin causes a characteristic retinopathy with circular, macula surrounding crystals. As changes in retinal functionning disappear relatively easily after withdrawal of the drug, the crystals dissolve rather slowly--over about several years. Five patients showing a profound crystalline retinopathy were re-examined with an average of 69.7 months after withdrawal of the canthaxanthin-containing drug. Three of the patients were treated for erythropoetic protoporphyria (EPP) with Phenoro (2/5 beta-carotene, 3/5 canthaxanthin), two sisters took a canthaxanthin-containing formulation (1/8 beta-carotene, 7/8 canthaxanthin) for cosmetic reasons. Two female patients complained about an increased glare sensitivity, which was explainable for one of them with a subcapsular cataract. The retinal crystals decreased quite differently. Minor deffects of the retinal pigment epithelium remained unchanged in two patients. They increased slightly in the female patient with the smallest crystal formation but highest plasma cholesterol. Shortly after withdrawal of the drugs usually an increase of a-wave amplituded of the electroretinograms was found. The a-waves returned to normal and the b-wave amplitudes showed an increase up to the final control paralleling the reduction of the retinal crystals. A- and b-wave peak latencies which were prolonged under treatment returned to normal.

Adult↗
PubMed1992

[The effect of carteolol. Prolonged and increased effect by liposome suspension].

Liposomes are small lipid vesicles capable of trapping beta-blockers such as carteolol within their bilayer structure, the advantage being improved drug action, prolonged action time, and a reduction in drug concentration. In a prospective, randomized double-blind trial, carteolol 2%, liposomes (frozen and thawed multilamellar vesicles, FAT-MLVs), or carteolol 2% suspended with FAT-MLVs was applied to 25 eyes of 25 patients per group in a single 20 microliters dose. Intraocular pressure was measured for 3 days. A significant reduction in the IOP was observed in the patient groups receiving carteolol and carteolol suspended with liposomes. Moreover, improved action and prolongation of drug action was noted in the carteolol/MLV group as compared to carteolol treatment alone. Hence, carteolol 2% is suitable for reduction of IOP, but a reduction of drug concentration can be achieved by suspension with liposomes, thus reducing the side effects.

Animals↗
PubMed1989

[Liposomes--drug carriers for retinally active drugs?].

Small lipid droplets, the so-called liposomes, can serve as drug carriers and can in theory be targeted directly at diseased tissue. Thus, comparatively smaller quantities of drugs than usual are necessary. However, liposomes are recognized by the immune system and are absorbed by the reticuloendothelial system and therefore also by the Kupffer cells in the liver. These cells are storage compartments for esterified vitamin A. As about 80% of the liposomes are metabolized in the liver, retinoids form a pool for substances transported with retinoid-binding proteins. Whether retinoids reach the retina via direct liposome contact or through the endocytotic process is still not clear. In rabbits, however, retinoids applied in small unilamellar liposomes (SUV) produce photoreceptor malfunctioning (isotretinoin and etretinate) and photoreceptor outer segment damage with an increase in phagocytotic activity of the retinal pigment epithelium (etretinate).

Drug Carriers↗
PubMed1988

[Disorders of retinal function in long-term therapy with retinoid etretinate].

Four patients receiving etretinate as long-term therapy were examined. The accumulated dosage was 135 g for Patient 1, about 80 g for Patients 2 and 3, and 31 g etretinate and 4.8 g etretine (Ro 10-1670; main metabolite of etretinate) for Patient 4. Clinical examinations, visual fields (Haitz, Amsler, Goldmann), and EOGs (two patients) were normal. Patient 1 (135 g) showed a decreased level of rod sensitivity at dark adaptation (Goldmann-Weekers), whereas the cone responses were regular in all cases. Furthermore, Patient 1 showed reduced scotopic ERG amplitudes. Aside from this, photopic and scotopic ERGs were normal as far as a- and b-wave amplitudes and peak latencies were concerned. The flicker fusion frequencies were found to be regular. The peak latencies of the R2-component of the early receptor potentials seemed rather short. In all four patients alterations of color sense were analyzed in the Farnsworth Munsell 100 Hue test. The color sense defect seems to originate in the blue-yellow spectrum and--at higher dosages--extends to the red-green spectrum. Examinations with the anomaloscope revealed deuteranomalous settings. Ophthalmological checks for patients receiving long-term aromatic retinoid therapy are recommended, especially with regard to dark adaptation and color sense.

Adult↗
PubMed1987

Experimental carotenoid retinopathy. II. Functional and morphological alterations of the rabbit retina after acute canthaxanthin application with small unilamellar phospholipid liposomes.

Eight "chinchilla bastard" pigmented rabbits were treated intravenously with sonicated phospholipid liposomes (SUV) consisting predominantly of egg yolk phosphatidylcholine (PC). Four rabbits were treated with canthaxanthin incorporated into PC liposomes in a single injection and fractionated over a period of 19 days. The total amount of PC used was a single dose of 260 mg administered as a 50-ml suspension and 13.7 mg/fraction given as a 5-ml suspension. The total amount of canthaxanthin used was a single 40 mg as a 50-ml suspension and 2.1 mg/fraction as 5-ml suspension. Electroretinography showed that canthaxanthin produced a depression of the a-waves and prolongation of the scotopic a- and b-wave peak latencies. A single high-dose injection of PC and PC plus canthaxanthin resulted in a transitory reduction in ERG amplitudes. A single injection of PC and canthaxanthin also produced hypernormal a-waves within the recovery time. Electron microscopy demonstrated that in contrast to the controls (PC), the canthaxanthin-treated rabbits showed alterations in the RPE/photoreceptor complex, indicating that these layers are the primary site of canthaxanthin effects on the retina.

Animals↗
PubMed1985

Location of ubiquinone-10 (CoQ-10) in phospholipid vesicles.

Egg yolk phosphatidylcholine (PC) liposomes were prepared by ultrasonic irradiation. At least 25 mol% of coenzyme Q-10 (CoQ-10) can be incorporated nonstoichiometrically into PC liposomes. Electron microscopy showed no visible influence of CoQ-10 on the membrane structure. Nuclear magnetic resonance spectra of sonicated PC liposomes containing CoQ-10 showed two peaks (3.82 and 3.98 ppm) due to CoQ-10 methoxyl protons and a 'high-field component' (1.52 and 1.58 ppm). The areas of these peaks were inversely related and influenced by the time of ultrasonic irradiation. After short sonication the low-field positions (3.98/1.58 ppm) are favoured, after long sonication the high-field positions (3.82/1.52 ppm). No gradual shift of the two peaks is observed. The 'critical' liposome diameter was found to be between 500 to 700 A. Lanthanide induced pseudocontact shift on CoQ-10 resonances ('high-field component' and methoxyl) does not lead to a split of the peaks and the difference between them remains constant. It is concluded that CoQ-10 is incorporated into the membrane core, beyond C-2 of the PC acyl chains, with two bilayer curvature-dependent resonance positions.

Animals↗
PubMed1985

Prophylaxis of supraventricular tachyarrhythmia after coronary bypass surgery with oral verapamil: a randomized, double-blind trial.

This study investigated the efficacy of oral administration of verapamil, started 24 hours after coronary artery bypass grafting (CABG), in reducing the incidence of postoperative supraventricular tachyarrhythmia (SVT). Two hundred patients were randomly assigned in a double-blind fashion to receive a one-week course of either a placebo or 80 mg of verapamil every 6 hours. Overall, SVT developed in 23 control and 14 verapamil-treated patients, a 39% reduction in incidence (p less than 0.10). Of the patients who received at least four doses and continued to receive the study drug, 17 in the control and 7 in the verapamil group experienced SVT, a 53% decrease in incidence (p less than 0.06). Atrial fibrillation constituted 34 of the 37 SVT episodes and was associated with a slower ventricular response in the group given verapamil (115 +/- 8 versus 156 +/- 4 beats per minute; p less than 0.001). No evidence was found linking postoperative SVT with the withdrawal of beta-blocking drugs. Adverse effects required that 20 patients in the verapamil and 6 in the placebo group be removed from the study. Hypotension or pulmonary edema or both developed in 13 of the patients receiving verapamil, but in only 1 of the control patients (p less than 0.001). We conclude that although verapamil has potential merit for the prophylaxis of SVT after CABG, its use in this setting is associated with a high incidence of unacceptable hemodynamic side effects.

Administration, Oral↗
PubMed1983

[Detection of aprindine and its metabolites in plasma and urine].

In 36 patients with cardiac arrhythmias (predominantly ventricular premature beats), who were on oral aprindine long-term therapy with 50 to 400 mg daily, plasma levels were measured by gas chromatography after 3.5 hours of the last administration. There was a general dependency of plasma levels on the given dose, however, with considerable overlapping in individual values. In 24 patients the arrhythmias ceased, in six patients there was a clear, in two a moderate improvement. There was no clear therapeutic effect in four patients who were treated with a daily dose of 50 and 100 mg, respectively. Among the 36 patients, three who had plasma levels exceeding 2 micrograms/ml developed tremor and dizziness. After dose-reduction these side effects disappeared. The present results suggest that therapeutic plasma levels of aprindine are in the range of 1.0 to 1.75 micrograms/ml. A plasma level of 2 micrograms/ml should not be exceeded because of the possibility of side-effects. In six healthy males time-concentration curves of aprindine and its metabolites in plasma and urine were measured by gas chromatography. From the results a two-compartment model may be applied, the half-life of elimination was calculated to be 37 hours (plasma) and 31 hours (urine). With respect to the metabolites, in plasma only des-ethyl-aprindine (DEAP), in urine DEAP, hydroxy-, des-phenyl- and des-indanyl-aprindine could be found. Unlike aprindine, the DEAP-concentration curve in plasma showed a very slight decrease until the end of the 96-hour period of determination.

Aprindine↗