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Biomedical subjects

M Karlsson

Publications and source records attributed to M Karlsson.

At least 217 records · Page 12Linked to original sources
PubMed1989

Pharmacokinetics of disodium clodronate after daily intravenous infusions during five consecutive days.

The pharmacokinetics of disodium clodronate was studied in six patients, three females and two males with Paget's disease and one male patient with prostatic cancer. The drug was given at a dose of 300 mg/day as a 3-hour infusion for 5 consecutive days. The concentration of the drug in serum and urine was measured by a gas chromatographic method. The peak concentration of disodium clodronate in serum was 5.7 +/- 1.0 micrograms/ml (means +/- SD) for the males and 10.1 +/- 2.8 micrograms/ml for the females. The elimination half-lives of the drug were 0.76 +/- 0.47 h and 1.79 +/- 0.26 h and the total clearances 18.2 +/- 3.3 l/h and 11.5 +/- 1.9 l/h, respectively. During the fifth day both sexes showed similar mean clearances of 11.9 +/- 1.3 l/h and 11.1 +/- 2.5 l/h and half-lives of about 2 h. The renal clearances was 7.3 +/- 0.5 l/h and 5.9 +/- 0.4 l/h for males and females, respectively. The mean urinary excretion of disodium clodronate during the 5-day period was 59.5% in the male patients and 56.0% in the female patients. We concluded that the slow infusion may increase the accumulation of clodronate in the body causing a higher clearance and a lower urine excretion of the drug than seen in earlier studies with faster infusions.

Aged↗
PubMed1988

Radical formation in the dimeric small subunit of ribonucleotide reductase requires only one tyrosine 122.

The small subunit of ribonucleoside-diphosphate reductase (EC 1.17.4.1) is a homodimer. Its catalytic site contains one tyrosyl radical, which is localized to Tyr-122 in one of its polypeptide chains. The engineered Tyr-122----Phe protein was used to demonstrate that it is possible to form a correct ferric iron center in vitro in the absence of Tyr-122. Heterodimers, consisting of one Tyr-122-containing polypeptide chain and one Phe-122-containing polypeptide chain, were constructed. The heterodimer population contained one-half the amount of tyrosyl radical as compared to a homodimer with Tyr-122, i.e. every second heterodimer contains a tyrosyl radical. Thus, one Tyr-122 is sufficient for radical formation. Radical-containing heterodimers are catalytically competent.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

Prevalence of hemochromatosis in Finland.

Transferrin saturation was determined in 11,431 men and 10,639 women aged 15 or more drawn from different areas in southern and central Finland and attending a multiphasic health screening examination in 1967-1972. All the 163 men and 66 women with transferrin saturation greater than or equal to 70% at the initial examination and still alive at the end of 1983 were invited to a re-examination. Of the invited persons, 76% attended the re-examination. Transferrin saturation and serum ferritin were the initial screening methods in the re-examination. All persons with suspected hemochromatosis were clinically examined and a laparoscopy was performed. Four men and four women were found with unequivocal hemochromatosis. Only one of these cases was diagnosed beforehand. According to these data the prevalence of hemochromatosis in Finland is about 50/100,000.

Adult↗
PubMed1988

CNS-induced natriuresis during dopamine receptor blockade. Further support for the existence of, at least, two separate natriuretic hormonal systems.

Intracerebroventricular (ICV) stimulation with hypertonic sodium chloride solutions has previously shown indications to stimulate the release of a blood-borne natriuretic factor. Sodium excretion in this situation increases in the order of 10-20 times. Acute isotonic volume expansion has shown to be a potent stimulus for endogenous release of the atrial natriuretic factor (ANF). It has also been demonstrated that the natriuretic response to both volume expansion and exogenously applied ANF can be attenuated by the dopamine receptor blocker haloperidol. The present study was performed to investigate if the natriuretic response to ICV stimulation also could be attenuated with haloperidol, thus indicating similar effector mechanisms as for ANF. A first group of anaesthetized animals was, therefore, pre-treated with haloperidol (H) and then ICV stimulated (H-ICV). A second group of animals was subjected to acute isotonic volume expansion (VE, 2% b.w.h.-1) to evoke the documented ANF release. In a third group of animals pre-treatment with haloperidol was followed by volume expansion (H-VE). In the H-ICV group there was a more than 30-fold increase in sodium excretion, due to an increase both in urine flow rate (more than sixfold) and in the urinary concentration of sodium (more than fourfold). Potassium excretion increased more than eightfold, urine osmolality was unchanged, and blood pressure increased by 7%. In the VE group sodium excretion increased more than 18-fold, consequent to large increases in urine flow rate (more than 23-fold), while the urinary concentration of sodium tended to decrease. Potassium excretion increased more than threefold, urine osmolality decreased by 88%, and blood pressure was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Clinical manifestations and diagnosis of neuroborreliosis.

Lyme borreliosis has in a few years turned out to be a health problem not only in the United States, but also in many European countries. When it affects the nervous system, Lyme borreliosis acts as the great disease imitator. Because of this characteristic it is often difficult to diagnose on clinical grounds. Patients with neuroborreliosis might appear within all medical disciplines. Clinical markers, such as preceding tick bite and/or ECM, are important clues to the diagnosis. Mononuclear pleocytosis and elevated CSF protein are present in most patients with neuroborreliosis. Final evidence for the diagnosis is the demonstration of specific antibodies in serum and/or CSF. Measurement of antibody titers should be carried out in both serum and CSF, since these methods are complementary when trying to obtain a serological diagnosis of neuroborreliosis.

Adolescent↗
PubMed1988

Treatment of Lyme borreliosis with emphasis on neurological disease.

We have studied 113 patients with neurologic Lyme borreliosis and meningitis who were treated with intravenous high-dose antibiotics (penicillin G, 12 g, mostly for 14 days in 47 patients; penicillin G, 9 g, mostly for 10 days in 58 patients; doxycycline, 200 mg, in 5 patients; and cefuroxime, 4.5-9 g, in 3 patients). Seventy percent of the patients had peripheral nerve symptoms and 13% had central nervous symptoms. Almost half of the patients were treated more than 4 weeks after the onset of symptoms and 15% of the patients had persisting or progressive symptoms between 4 and 11 months. There seemed to be clinical benefit as well as a decrease of spinal fluid pleocytosis and spinal proteins. No significant symptoms of Herxheimer reaction were demonstrated.

Anti-Bacterial Agents↗
PubMed1987

Half-site reactivity of the tyrosyl radical of ribonucleotide reductase from Escherichia coli.

A C-terminally truncated form of protein B2, the homodimeric small subunit of ribonucleotide reductase from Escherichia coli, was found as the result of an apparently specific proteolysis. Truncated homodimers contain an intact binuclear iron center and a normal tyrosyl radical but have no binding capacity for the other ribonucleotide reductase subunit, protein B1, and are consequently enzymatically inactive. Heterodimers, consisting of one full-length and one truncated polypeptide, formed spontaneously during a chelation-reconstitution cycle and were easily separated from the two homodimeric variants. The heterodimeric form of B2 shows a weak interaction with the B1 subunit resulting in low enzyme activity. Using heterodimers containing deuterated tyrosine on the full-length side and protonated tyrosine on the truncated side, we could demonstrate that the tyrosyl radical was randomly generated in one or the other of the two polypeptide chains of the heterodimeric B2 subunit. The small subunit of ribonucleotide reductase thus conforms to a half-site reactivity.

Amino Acid Sequence↗
PubMed1987

Fate of haem after parenteral administration of haem arginate to rabbits.

Rabbits were injected either intravenously or intramuscularly with [14C]haem arginate and [59Fe]haem arginate (haem 5 mg kg-1). The main part (80%) of AUCINF of labelled haem was associated with the beta-phase, T1/2 being about 6 h. Only 1% of the haem dose had been taken up by the red blood cells. In contrast, the iron moiety from the haem molecule was effectively utilized. Thirty days post-injection of [59Fe]haem arginate, 40% of the dose after intravenous injection and 60% after intramuscular injection was circulating with the red cells. Radioactivity was shown to concentrate in the liver, where haem is mainly metabolized and eliminated. An accumulation of haem in the adrenals was also evident. Haem itself did not concentrate in the bone marrow, and a negligible amount of radioactivity was recovered from brain, implying a poor penetration of the blood brain barrier.

Adrenal Glands↗
PubMed1987

Antibiotic usage in surgery in a large teaching hospital.

A prevalence study of the antibiotic usage in the surgical departments at the Karolinska Hospital, Stockholm, showed that 126/517 hospitalized patients (24%) received antibiotics and that 100/306 operated patients (33%) received antibiotics. 44 (44%) of the operated patients were given their antibiotics as prophylaxis and 46 (37%) of all patients receiving antibiotics were given them as prophylaxis. Antibiotics were administered intravenously to 35 (28%) patients, orally to 75 (60%), and topically to 16 patients (13%) (eye department only). The most commonly used drugs in prophylaxis were isoxazolylpenicillins and trimethoprim-sulphonamide while cephalosporins accounted for a minor part. In therapy the most commonly used drug was isoxazolylpenicillin, followed by ampicillin derivatives, metronidazole, tetracyclines, trimethoprim-sulphonamide and cephalosporins. The pattern of antibiotic usage differed markedly between departments.

Age Factors↗
PubMed1987

Amantadine for prophylaxis against influenza A.

Amantadine, 200 mg daily, for 5 days was used in an attempt to restrict the spread of influenza A in a hospital ward. After index cases of influenza A amantadine was given to 2 patients with clinical symptoms and to 8/10 patients who were not yet ill. No further case of clinical influenza was seen among the patients, but 3 of those receiving amantadine developed subclinical infection. No side effects of amantadine were noted. Amantadine was not given to any of the 23 hospital staff on duty. In this group 8 cases of influenza A appeared, 3 of them during the week after the introduction of amantadine to patients.

Amantadine↗
PubMed1986

Overproduction and purification of the B2 subunit of ribonucleotide reductase from Escherichia coli.

The nrdB gene of Escherichia coli, coding for the B2 protein of ribonucleotide reductase, has been cloned in a runaway-replication vector. The runaway derivative pBEU17 carries the promoter-proximal portion of the E. coli alanyl-tRNA synthetase gene and proved useful for expressing cloned genes lacking their native transcription initiation signals. The alaS promoter is located approximately 500 base pairs upstream of a single BamHI restriction endonuclease cleavage site utilized in the construction of an expression recombinant plasmid, pBS1, for the nrdB product. After 5-h thermal induction of cells carrying the runaway recombinant pBS1, protein B2 constituted 40% of the soluble protein fraction of the cells. The high concentration of protein B2 in crude extracts of induced cells has enabled a simplified purification scheme to be developed for production of homogeneous and concentrated B2 preparations. Protein B2 produced from pBS1 is identical to the chromosomally encoded nrdB product of E. coli as regards molecular mass on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, enzyme activity, tyrosine radical content, and structure of the binuclear iron center. Amino acid sequence analysis showed that the two polypeptide chains of protein B2 are identical. They start with an alanine residue, and the first 30 residues confirmed the amino acid sequence predicted from the nucleotide sequence of the nrdB gene, apart from an NH2-terminal processing removal of the initiator methionine.

Amino Acid Sequence↗
PubMed1986

Analysis of pethidine disposition in the pregnant rat by means of a physiological flow model.

The disposition of pethidine (meperidine) in the pregnant rat is described by means of a physiological flow model. The model includes arterial and venous blood, brain, fat, fetal, hepatic, intestinal, muscular, pulmonar, and renal tissues. The concentration-time profiles of pethidine calculated by the model are consistent with experimental data, except for the brain and renal tissues, where the model predicts initially higher concentrations. Simulations are carried out to further explore the contribution from different organs on the kinetics in blood and tissues. The tissue-to-blood partition coefficients vary over a range from 5 to 316, where fat has the lowest and liver the highest after a correction is made due to hepatic extraction. Rapid uptake occurs into highly perfused organs such as brain, kidneys, liver, and lungs, followed by fetus, intestines, muscle, and fat. Data indicate no marked membrane resistance to pethidine of the investigated organs, except for fetal tissues, but rather a perfusion-limited uptake. Simulations suggest that muscles and adipose tissue play an important role in the rat, becoming the major reservoir of drug during the intermediate and terminal elimination phase, respectively. Volume of distribution and the biological half-life agree with reported findings. Pethidine is subject to a high systemic blood clearance, which exceeds the total hepatic blood flow in the rat. No degradation of pethidine is found in blood, and therefore a pulmonary expression for pethidine clearance is added as a potential source of pethidine elimination. The elimination of pethidine after a single i.v. bolus does is found to be dependent on simulated changes in cardiac output and hepatic blood flow. A simulation is performed with the scaled model to mimic the human concentration-time profiles in maternal blood and brain tissues and fetal tissue during repetitive doses of pethidine.

Animals↗
PubMed1986

Adipogenic activity in human plasma. Effects of feeding state and obesity.

The potential of plasma from obese and non-obese subjects to stimulate the formation of new adipocytes was studied by assays in rat adipose precursor cells in primary culture. Adipogenic activity was followed in terms of rate of lipid filling, analysed by determination of triglyceride contents per unit protein, stimulation of multiplication, measured as rate of incorporation of labelled thymidine into DNA, and stimulation of differentiation, followed as an increase in glycerophosphate dehydrogenase activity. Plasma from obese subjects contained an excess of activity stimulating lipid filling, closely associated to the recent body weight histories with increased activity with a recent increase of body weight and vice versa. There was also a strong association with plasma concentration of triglyceride. The importance of the latter was demonstrated by acute feeding experiments with triglyceride, as well as by addition of isolated very-low-density lipoprotein and chylomicron fractions which caused increases of lipid filling activity closely in parallel to triglyceride contents of the culture medium. Specific stimulatory properties of plasma from weight-increasing obese subjects on adipose precursor cell multiplication and differentiation were not found. It was suggested that human obesity with an increased number of adipocytes is not characterized by elevated circulating specific stimulatory factors of new fat cell formation. Such factors are present in excess in both non-obese and obese subjects. It was hypothesized that the elevated lipid filling capacity in obese subjects might modify local inhibitory factors of adipocyte formation.

Adipose Tissue↗