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Biomedical subjects

C Lindberg

Publications and source records attributed to C Lindberg.

At least 55 records · Page 3Linked to original sources

Physical training effects in myasthenia gravis.

Eleven patients with mild or moderate myasthenia gravis (MG) were subjected to a strength training program of 27 to 30 sessions during ten weeks. Voluntary maximal muscle force and the degree of fatigue during repetitive maximal isometric muscle contractions were measured in three muscle groups. The subjects did not experience any subjective discomfort or any adverse effect on their MG due to the training. A 23% increase of the maximal voluntary muscle force in knee extension in the trained side was found, compared to 4% in the untrained side (p < 0.05). Only small changes were noted regarding maximal muscle force in elbow flexion and extension or in any of the muscle groups in the fatigue test. Physical training can be carried out safely in mild MG and provides some improvement of muscle force.

Adult↗

Determination of (22R,S)budesonide in human plasma by automated liquid chromatography/thermospray mass spectrometry.

(22R,S)Budesonide was isolated from human plasma by solid-phase extraction. Switching from reversed-phase conditions during sample application and washing to normal-phase conditions during elution afforded a very clean extract. Budesonide was derivatized with acetic anhydride to form the 21-acetyl derivative before analysis by reversed-phase liquid chromatography combined with thermospray mass spectrometry. Deuterium-labelled budesonide was used as internal standard. Standard samples prepared in human albumin solution were used for the calibration curve. An automated liquid chromatography/mass spectrometry system, allowing unattended overnight operation, was used for routine analysis. The recovery of budesonide from plasma was 88.9 +/- 5.9% (mean +/- SD) and the method was linear over the range 0.30-30 pmol (amount analysed), corresponding to plasma concentrations of 0.10-10 nmol l-1. Budesonide could be measured down to 0.10 nmol l-1 with a within-day variation of 10-18% (CV). The error was less than +/- 15% at 0.10 nmol l-1 and less than +/- 7% at concentrations of 0.20 nmol l-1 or higher. The total imprecision between days was 9% (CV) at a concentration of 0.30 nmol l-1.

Administration, Topical↗

Mapping and characterization of 129 cosmids on human chromosome 11p.

We constructed cosmid libraries from human-hamster somatic cell hybrids that possess all or part of the short arm of chromosome 11 as their only human complement and isolated 129 human 11p clones. These cosmids map to 22 of 25 intervals distinguished by a hybrid panel for chromosome 11p. Forty-eight single-copy sequences were subcloned from 25 cosmids. Six of 17 (35%) single-copy sequences tested identify 11 new polymorphisms. Restriction endonuclease analysis identified CpG islands in 16 of 68 cosmids (23.5%). Analysis of the distribution of restriction endonuclease sites recognizing CpG dinucleotides showed that clusters of these sites, including those associated with the 5' region of an 11p13 Wilms' tumor gene, WT1, can span greater distances than generally recognized. The cosmids reported here should contribute to the construction of long-range physical maps and the isolation of additional genes on the short arm of chromosome 11.

Blotting, Southern↗

Thymine photoproduct formation and inactivation of intact spores of Bacillus subtilis irradiated with short wavelength UV (200-300nm) at atmospheric pressure and in vacuo.

Vacuum exposure renders the survival of spores of Bacillus subtilis approximately five times more sensitive to ultraviolet light irradiation than exposure under atmospheric conditions. The photoproduct formation in spores irradiated under ultrahigh vacuum (UHV) conditions is compared to the photoproduct formation in spores irradiated at atmospheric pressure. Compared to irradiation at atmospheric pressure, where only the "spore photoproduct" 5-thyminyl-5,6-dihydrothymine (TDHT) can be detected, two additional photoproducts, known as the c,s and t,s isomers of thymine dimer (T<>T) are produced in vacuo. The spectral efficiencies for photoproduct formation in spores under atmospheric and vacuum conditions are compared. Since there is no increased formation of TDHT after irradiation in vacuum, TDHT cannot be made responsible for the observed vacuum effect. "Vacuum specific" photoproducts may cause a synergistic response of spores to the simultaneous action of ultraviolet light (UV) and UHV. Three different mechanisms are discussed for the enhanced sensitivity of B. subtilis spores to UV radiation in vacuum. The experiments described contribute valuable research information on the chance for survival of microorganisms in outer space.

Bacillus subtilis↗

Remission rate after thymectomy in myasthenia gravis when the bias of immunosuppressive therapy is eliminated.

The clinical course of all 86 myasthenia gravis (MG) patients who were thymectomized at Sahlgrenska Hospital between 1955 and 1980 was evaluated in order to estimate what the rate of complete clinical remission (with or without anticholinesterase medication) would be without immunosuppressive (IS) therapy; 19 of 73 patients without thymoma received IS therapy. A suitable way of dissociating the course after thymectomy from the influence of IS therapy is the Markov method. The calculated probability of remission was 0.18, 0.35, 0.43, 0.53 and 0.56 in the 0-1, 2-3, 4-5, 5-10 and more than 10-year periods after thymectomy. A similar result (53 +/- 7%) was obtained by a life-table method with censoring of IS-treated patients when they received such therapy. Time to remission was significantly shorter for patients with age of MG onset before 35 years. Timing of IS therapy after thymectomy is discussed, considering the post-thymectomy remission rate.

Adult↗

Immunochemical and clinical effects of immunosuppressive treatment in monoclonal IgM neuropathy.

A pathogenic role of the M protein in monoclonal IgM neuropathy has been suggested. This is based among other things on a close relation between immunosuppressive treatment, lowered concentration of M protein, and clinical effect. We studied five patients with monoclonal IgM and antibodies to peripheral nerve myelin. The immunosuppressive treatment was beneficial in three of the patients. In three patients there was a relationship between antibody concentration and clinical effect (in one there was no change in antibody concentrations and correspondingly no change in clinical status, and in two patients clinical improvement corresponded to decreased antibody concentrations). In two patients, however, there was no clear correlation, since one patient improved despite increasing antibody concentrations and one patient did not improve despite a lowered antibody concentration. It is therefore possible that other mechanisms may contribute to the effect of treatment.

Adult↗

Increasing thermospray response for cortisol by derivatization.

The 21-hydroxyl group of cortisol was selectively acetylated under mild conditions without affecting the more sterically hindered 11 beta- and 17 alpha-hydroxyl groups. The reaction was performed with a mixture of acetic anhydride and triethylamine in acetonitrile and was complete in less than 15 min at room temperature. The thermospray mass spectrum of cortisol 21-acetate showed minimal fragmentation with the [M + H]+ ion as the base peak. High sensitivity was achieved for acetylated cortisol during selected ion monitoring, the signal-to-noise ratio being increased by a factor of about 4, compared to underivatized cortisol. The limit of detection of cortisol 21-acetate was estimated at 0.24 pmol injected, making thermospray liquid chromatography-mass spectrometry competitive with gas chromatography-mass spectrometry for the determination of cortisol in biological fluids.

Acetylation↗

Evaluation of an automated thermospray liquid chromatography-mass spectrometry system for quantitative use in bioanalytical chemistry.

An automated thermospray liquid chromatography-mass spectrometry system is described, including an autosampler and a gradient liquid chromatography system controlled from the mass spectrometer data system. The performance and reliability of the equipment during unattended operation were evaluated by repeated injections of standard solutions of some antiasthmatic drugs, using deuterium-labelled analogues as internal standards. High sensitivity and reproducibility were achieved during a 19-hour run, incorporating gradient elution and a total of 54 injections. The relative standard deviation of the peak area measurement of the internal standards was in the range of 6.5-8.2%. The corticosteroid budesonide can be routinely measured in plasma down to 0.1 nmol/l. Direct injection of a small plasma volume into the thermospray liquid chromatography-mass spectrometry system could be used to monitor drug plasma levels during a toxicity study in dogs.

Animals↗

Inclusion body myositis and Welander distal myopathy: a clinical, neurophysiological and morphological comparison.

Five patients with inclusion body myositis (IBM), an acquired inflammatory myopathy, and five patients with Welander hereditary distal myopathy (WDM) were compared clinically and with neurophysiological and morphological techniques. Both diseases have a late insidious onset, but the course of IBM is more severe. IBM mainly affects proximal muscles in the lower extremities, while distal muscle groups are involved in both upper and lower extremities. In WDM there is always a strict distal muscle involvement. The neurophysiological characteristics of the two conditions include both myopathic and neurogenic components. In both diseases there were rimmed vacuoles in muscle fibres and at the ultrastructural level cytoplasmic 15-18 nm filamentous inclusions. Although the histopathology of muscle in IBM and WDM has some common features, inflammatory infiltrates were never found in WDM. Such infiltrates seem to be an important clue to the correct diagnosis of IBM.

Aged↗

Action spectra for survival and spore photoproduct formation of Bacillus subtilis irradiated with short-wavelength (200-300 nm) UV at atmospheric pressure and in vacuo.

Spores of Bacillus subtilis are approximately ten times less likely to survive UV light irradiation in a vacuum than under atmospheric conditions. Photoproduct formation was studied in spores irradiated under ultrahigh vacuum (UHV) conditions and in spores irradiated at atmospheric pressure. In addition to the "spore photoproduct" 5-thyminyl-5,6-dihydrothymine (TDHT), which is produced in response to irradiation at atmospheric pressure, two additional photoproducts, known as the cis-syn and trans-syn isomers of thymine dimer, are produced on irradiation in vacuo. The spectral efficiencies for photoproduct formation in spores are reduced under vacuum conditions compared with atmospheric conditions by a factor of 2-6, depending on the wavelength. Because formation of TDHT does not increase after irradiation in vacuo, TDHT cannot be responsible for the observed vacuum effect. Vacuum specific photoproducts may cause a synergistic response of spores to the simultaneous action of UV light and UHV. An increased quantum efficiency, destruction of repair systems and formation of irreparable lesions are postulated for the enhanced sensitivity of B. subtilis spores to UV radiation in vacuo.

Bacillus subtilis↗

Epidemiological investigation of the association between infectious mononucleosis and multiple sclerosis.

By matching a cohort of 494 infectious mononucleosis (IM) cases with a multiple sclerosis (MS) register, 3 MS cases were retrieved. The interval between IM and MS was 12 years. This corresponds to a relative risk of 3.7 for MS to occur subsequent to IM (p = 0.05). This relationship between a manifestation of a relatively late Epstein-Barr virus infection and MS may indicate that a microbiologically shielded environment is important in the pathogenesis of MS.

Adolescent↗

Determination of bambuterol, a prodrug of terbutaline, in plasma and urine by gas chromatography/mass spectrometry.

(R,S)-Bambuterol was isolated from plasma and urine by solid-phase extraction and analysed as its trimethylsilyl derivative by gas chromatography/chemical ionization mass spectrometry with ammonia as the reagent gas. Deuterium-labelled bambuterol was used as internal standard. An esterase inhibitor was added to plasma to prevent hydrolysis of bambuterol in the plasma sample. Bambuterol could be measured in plasma down to 1 nmol l-1 with a within-day variation of less than 5% (coefficient of variation). The lower limit of measurement in urine was judged to be 8 nmol l-1, a concentration at which the within-day variation was 5.4% (coefficient of variation).

Bronchodilator Agents↗

Inclusion body myositis: peripheral nerve involvement. Combined morphological and electrophysiological studies on peripheral nerves.

The occurrence of neuropathy in 5 cases of inclusion body myositis (IBM) was studied. The intramuscular nerve branches showed variable ultrastructural changes in all cases. The observed changes were loss of axons, wallerian degeneration and axon terminal atrophy. EMG with concentric needles showed myopathic motor unit potentials in all cases. A reduced interference pattern due to loss of motor units was found in all cases. All but one patient showed fibrillation potentials in several muscle groups. Motor nerve conduction velocities and F-wave latencies were pathological in two of the cases, in which there were motor unit potentials with increased amplitude and duration as evidence of reinnervation. Sural nerve biopsy in one of these cases revealed slight neuropathy of the axonal type. These findings support the concept of peripheral nerve involvement in many cases of IBM.

Action Potentials↗

Pharmacokinetic evaluation in man of terbutaline given as separate enantiomers and as the racemate.

1. The pharmacokinetics of the two enantiomers of terbutaline, (+)T and (-)T, and the racemate (+/-)T, have been evaluated after single intravenous and oral dosage to six healthy volunteers. 2. The mean systemic clearance, CL, was 0.19 and 0.13 l h-1 kg-1 for (+)T and (-)T, respectively. This difference was statistically significant. The mean clearance of (+/-)T was 0.20 l h-1 kg-1. Volumes of distribution were similar (1.9 l kg-1) after the three intravenous administrations. The differences in CL were reflected in values of the elimination half-life and MRT. 3. The difference in CL of the isomers could be explained by a corresponding difference in their renal clearance, CLR. Competition for stereoselective active reabsorption in the tubule might explain why (+)T seemed to enhance the CLR of (-)T when the drug was given as the racemate. 4. Oral bioavailability, calculated from plasma data, of (+)T was 7.5% and that of (-)T was 14.8%. This difference was statistically significant and was mainly due to a difference in absorption of (+)T and (-)T, but also to a difference in their subsequent first-pass metabolism. The bioavailability of (+/-)T was similar to that of (-)T. 5. (-)T appears to govern the absorption properties of the racemate, while (+)T determines its elimination behaviour. Systemic metabolism of the two enantiomers was similar and, therefore, a greater first-pass metabolism of (+)T would reflect a higher capacity of the gut wall to metabolise this isomer.

Absorption↗

Pharmacokinetics of intravenous terbutaline in asthmatic children.

Seven asthmatic children were given terbutaline intravenously. The intact drug was measured in plasma and urine, and its conjugates were measured in urine. The decreasing plasma concentrations of terbutaline did not attain a terminal slope until 8-12 h after dosing. This was most likely due to different kinetics of the enantiomers. The terminal half-life was 8.8-15.8 h. Body clearance was 2.73-5.44 ml/min/kg, two-thirds of which were of renal origin. The volume of distribution (Vss) was 1.28-1.83 l/kg. The disposition pharmacokinetics of terbutaline do not rationalize a higher dose per kg body weight in children than in adults.

Asthma↗