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Biomedical subjects

J Carlsson

Publications and source records attributed to J Carlsson.

At least 127 records · Page 7Linked to original sources
PubMed1996

Comparison of the Pharmacokinetics and Effects on the Hemostatic System of Saruplase and Urokinase in Patients with Acute Myocardial Infarction.

The aim of the study was to compare in a single trial, using identical methodology, the pharmacokinetic properties and the effect on the hemostatic system of saruplase (unglycosylated scu-PA) and urokinase (glycosylated tcu-PA). Twenty-four patients with an acute myocardial infarction were either treated with saruplase (n = 12; 20 mg IV bolus followed by a 60 mg infusion for 60 minutes) or urokinase (n = 12; 1.5 million IU IV bolus followed by 1.5 million IU infusion for 60 minutes). Blood samples from saruplase-treated patients were analyzed for u-PA antigen and total u-PA and tcu-PA activities; those from urokinase-treated patients for u-PA antigen and tcu-PA activity. The effect of treatment on, including recovery of, plasma alpha2-antiplasmin, fibrinogen, and plasminogen was examined in both groups. The total clearance of urokinase (179 +/- 55 ml/min) is about half that of saruplase (406 +/- 154 ml/min), and the mean residence time of urokinase (59.1 +/- 22.5 minutes) is nearly twice that of saruplase (28.3 +/- 7.8 minutes), which results in a slower elimination of urokinase from plasma. Whether differences in the pharmacokinetic behavior of the unglycosylated saruplase and the glycosylated urokinase observed in this study are due to the difference in glycosylation or to other factors is not resolved. The systemic effect of saruplase on alpha2-antiplasmin, fibrinogen, and plasminogen is similar to that of urokinase, although retarded.

Journal Article↗
PubMed1996

Retention and processing of the monoclonal anti-prostate E4 antibody after binding to prostatic adenocarcinoma DU 145 cells.

Cellular retention and processing of a radiolabelled monoclonal anti-prostate antibody were evaluated after binding to prostatic adenocarcinoma DU 145 cells. An endocytosis assay revealed that the rate of release of radioactivity from the cells had an initially rapid phase within the first hours after antibody incubation, which was presumably due to release of monovalently bound antibodies. This was followed by a slower phase, with the possible release of intact bivalently bound antibodies and excretion of degraded internalized antibodies. The relative amount of released radioactivity of high molecular mass was high, indicating that the major part of the antibodies were released without being internalized and degraded. However, when only the radiolabelled antibody that remained cell-associated after 2 h and longer was considered, a substantial part was found to be internalized and radioactive degradation products were excreted. About 30% of the initially cell-associated radioactivity still remained associated with the cells after 48 h, indicating a rather slow antibody processing, which is favourable if the antibody is to be used for targeted radiotherapy. The retention of cell-associated radioiodine was very similar irrespective of whether the antibodies were radiolabelled with the direct chloramine-T method or the indirect ATE (succinimidyl based reagent) method. Since the ATE method can be used to form stable antibody constructs with the therapeutically relevant alpha-emitting radionuclide, astatine-211, this was an interesting finding that will be further evaluated in the future.

Adenocarcinoma↗
PubMed1996

Dilatation of sinus of Valsalva with displacement and compression of the left coronary artery causing sudden death.

A 69-year-old male patient is described who presented with angina and congestive heart failure 12 years after his aortic valve had been replaced by a bioprosthesis for aortic stenosis. The aortogram showed massive dilatation of the aortic root. Coronary angiography demonstrated a displaced and narrowed left main and circumflex coronary artery. The patient died suddenly before his scheduled elective operation. At autopsy the left main and circumflex coronary artery were patent but severely compressed by extensive dilatation of the aortic root, predominantly of the left sinus of Valsalva. His sudden death was most likely due to external constriction of the left coronary artery with subsequent ischemia and ventricular fibrillation.

Aged↗
PubMed1996

In vitro determination of toxicity, binding, retention, subcellular distribution and biological efficacy of the boron neutron capture agent DAC-1.

In boron neutron capture therapy (BNCT), 10B is delivered selectively to the tumour cells and the nuclide then forms high-LET radiation (4He2+ and 7Li3+) upon neutron capture. Today much research is focused on development of a variety of boron compounds aimed for BNCT. The compounds must be thoroughly analysed in preclinical tests regarding basic characteristics such as binding and subcellular distribution to enable accurate estimations of dose-modifying factors. DAC-1,2-[2-(3-amino-propyl)-1,2-dicarba-closo-dodecaboran (12)-1-yl-methoxy]- 1,3-propanediol was synthesized at our laboratories and the human colon carcinoma cells LS-174T were used as an in vitro model. The boron compound showed a remarkable intracellular accumulation, 20-100 times higher than the boron content in the culture medium, in cultured cells and was not removed by extensive washes. Approximately half of the boron taken up also remained within the cells for at least 4 days. The DAC-1 compound alone was not toxic at boron concentrations below 2.5 micrograms B/g. The intracellular distribution of the boron compound was investigated by subcellular fractionation experiments and low pH treatments. It is possible that DAC-1 binds to some intracellular molecules or to membranes connected with organelles in the cytoplasm or even to the inside of the outer cell membrane. Another possibility is that the compound, due to the somewhat lipophilic properties, is embedded in the membranes. Thermal neutron irradiations were carried out at the Brookhaven Medical Research Reactor (BMRR). At a survival level of 0.1, DAC-1 + thermal neutrons were about 10.5 times more effective in cell inactivation than the thermal neutrons alone. Monte Carlo calculations gave a mean value of the 10B-dependent specific energy, the dose, of 0.22 Gy. The total physical dose during irradiation of DAC-1-containing cells with a neutron fluence of 0.18 x 10(12) n/cm2 was 0.39 Gy. The dose-modifying factor, at survival level 0.1, when comparing irradiation with thermal neutrons with and without DAC-1 was 3.4, while the dose-modifying factor when comparing neutron irradiations of cells with DAC-1 and irradiation of the cells with 60Co-gamma was 7.3. The results are encouraging and in vivo tests of tissue distributions and tumour uptake should now be carried out.

Biological Availability↗
PubMed1996

Psychosocial functioning in schoolchildren with recurrent headaches.

The psychosocial functioning of 113 schoolchildren (8 to 15 years old) reporting headaches at least once a month was compared to a group of headache-free control subjects matched for sex and age. Thirteen percent of the headache sufferers had migraine headaches, 28% had episodic tension-type headaches, 30% had chronic tension-type headaches, and 29% had migraine coexisting with tension-type headaches. Overall, the headache sufferers experienced more somatic complaints, stress, and psychological symptoms, in addition to being absent from school (due to illness), more often and reported fewer caring persons as compared to headache-free controls. Although few differences between the four headache groups emerged in the children's psychosocial functioning levels, children with migraine coexisting with tension-type headaches had significantly more frequent somatic complaints than those having episodic tension-type headaches. In addition, children with migraine or migraine coexisting with tension-type headaches were more often absent from school than those having tension-type headaches only. A significant but weak relationship between children's headache severity and their somatic complaints was noted.

Adolescent↗
PubMed1996

Rejoining of DNA double-strand breaks induced by accelerated nitrogen ions.

Rejoining of radiation-induced DNA double-strand breaks (dsb) was measured in cultured cells with pulsed-field gel electrophoresis after radiation doses in the range of 5-30 Gy. Human glioma, U-343MG and Chinese hamster, V79, cells were irradiated with either accelerated nitrogen ions of high linear energy transfer, LET approximately 125 keV/ microns, or photons from 60Co. The induction frequencies of dsb were similar for the two radiation qualities with a relative biological effectiveness, RBE, of 0.90 and 0.89 for the human and hamster cell lines respectively. The biphasic rejoining kinetics differed significantly between the two radiation qualities when studied in the human glioma cells. The difference was seen within the first hour after irradiation and after 6 h there were considerable differences in both the total amount of unrejoined dsb and the fraction of dsb rejoined during the slow phase. When rejoining was analysed 20-22 h after irradiation, the nitrogen ions gave 2.5-2.9 times more residual dsb than the gamma photons. The results for the hamster V79 cells were, up to 2h after irradiation, similar, but the difference between the two radiation qualities was less accentuated. In summary, similar initial yields of dsb after exposure of cells to high or low LET resulted in both radiation quality and cell type-dependent differences when the rejoining of these breaks were compared.

Animals↗
PubMed1996

A school-based, nurse-administered relaxation training for children with chronic tension-type headache.

Compared the efficacy of a school-based, nurse-administered relaxation training intervention to a no-treatment control condition for children (10-15 years old) with chronic tension-type headache and the outcome at posttreatment and a 6-month follow-up. The study was conducted in a controlled between-group design including 26 schoolchildren who were randomly assigned to the two treatment conditions. Results showed that headache activity in the children treated with relaxation training was significantly more reduced than among those in the no-treatment control group at posttreatment as well as the 6-month follow-up. At these evaluations, 69% and 73% of the pupils, respectively, treated with relaxation had achieved a clinically significant headache improvement (at least a 50% improvement) as compared to 8% and 27% of the pupils, respectively, in the no-treatment control group. Thus, a school-based, nurse-administered relaxation training program seems to be a viable treatment approach for children with chronic tension-type headaches.

Adolescent↗
PubMed1996

Differential toxic effects of lactate and acetate on the metabolism of Streptococcus mutans and Streptococcus sanguis.

Experiments were conducted with Streptococcus mutans NCTC 10449 and Streptococcus sanguis ATCC 10556 to determine whether the acid end-products, lactate and acetate, were involved in the regulation of cellular growth and metabolism. The growth rate and culture biomass of both organisms was inhibited by the addition of lactate and acetate at concentrations as high as 200 mM to the cultures, although the final pH values of the lactate and acetate cultures were similar. In addition, the metabolic conversion of glucose to lactate was decreased by external lactate but stimulated by acetate. In spite of this, calculation of the yield of cell biomass per mole of ATP (YATP) showed that the yield of both organisms actually increased in the presence of added lactate, but decreased with acetate. This indicates that the two acids interacted with the cells of the organisms by different mechanisms. For both organisms, the final external undissociated lactic acid was relatively constant at concentrations between 0 and 200 mM added lactate, 24.9-32.5 mM for S. mutans and 8.0-11.5 mM for S. sanguis. On the other hand, the final concentration of undissociated acetic acid in the S. mutans cultures increased from 2.9 to 83.7 mM as the medium acetate concentration increased, and from 1.0 to 36.0 mM with the S. sanguis cultures. Counterflow experiments provided evidence for a lactate carrier in both S. mutans and S. sanguis, but an acetate carrier in these organisms could not be demonstrated. [14C]-lactate and [14C]-acetate were taken up into de-energized, chemostatgrown cells of S. mutans and S. sanguis in response to an artificially generated pH gradient but not by an imposed electrical gradient. Thus, under these conditions lactate uptake occurred via a symport process with only one proton. Growth of both organisms in the presence of increasing concentrations of acetate resulted in a small reduction (27%) in the transmembrane pH gradient (delta pH) as measured by the permeant acid, [14C]-salicylate. However, the uptake of [14C]-acetate for the estimation of delta pH revealed significant inhibition of the acetate concentration gradient in the presence external acetate, indicating that the cells expelled the acetate anion. The results indicate that, unlike acetate uptake, lactate transport by S. mutans and S. sanguis was strictly regulated via the lactate carrier in order to prevent excessive dissipation of the pH gradient. Clearly, the formation of acetate by oral streptococci is more problematic for cellular homeostasis than the formation of lactate.

Acetic Acid↗
PubMed1996

Prevalence of headache in schoolchildren: relation to family and school factors.

The purpose of the study was to determine the prevalence of recurrent headaches among schoolchildren in Göteborg and the relation of headache to school and family variables. A stratified sample of 1297 pupils was selected to be representative of the Göteborg population. Data were obtained by means of questionnaires. Twenty-six per cent had "headache once a month or more" and 6% had "headache several times a week or daily" (frequent headache). There was a gradual increase of headache with age. In the third grade there was a marked increase of frequent headache. In the highest school level (grades 7-9), girls had significantly more headache than boys. In the lower school level (grades 1-3), a greater number of pupils in the class increases the risk of frequent headache. Pupils in the intermediate school level (grades 4-6) reported more frequent headache in districts with high unemployment. It is concluded that headache among schoolchildren is a health problem which merits increased attention.

Adolescent↗
PubMed1996

Effects of permanent eradication or transient clearance of Helicobacter pylori on histology of gastric mucosa using omeprazole with or without antibiotics.

Changes in Helicobacter pylori-associated gastritis of the antrum and corpus were investigated in a large number of patients treated with omeprazole, with or without the addition of amoxycillin. To investigate the role of H. pylori-associated gastritis in ulcerogenesis and its interplay with omeprazole, biopsies were taken and evaluated according to the Sydney system. Successful eradication of H. pylori (assessed histologically 4 weeks after the end of therapy) led to prompt and persistent suppression of gastritis activity, slow, partial regression of mononuclear inflammation and an ulcer recurrence rate of only 14% during the 6 months' follow-up. In patients treated with omeprazole and placebo, or where eradication treatment with omeprazole and amoxycillin had failed, transient clearance of H. pylori from the antral (but not oxyntic) mucosa was seen. In both of these groups of patients transient regression in the antrum, and worsening in the corpus, of gastritis activity and mononuclear inflammation were evident, coupled with ulcer recurrence rates of 72 and 46%, respectively. It was concluded that H. pylori colonization and gastritis activity play a crucial role in ulcerogenesis, that acid inhibition treatment improves antral H. pylori gastritis and worsens the oxyntic mucosal gastritis, and that this can be prevented by eradication of the H. pylori infection.

Amoxicillin↗
PubMed1996

A functional index in myositis.

OBJECTIVE: To evaluate the interrater reliability and the construct validity of a specially constructed functional index and to assess functional status in 23 patients with myositis; and to describe the occurrence, intensity, and distribution of pain in these patients. METHODS: The functional test scored muscle endurance in extremities, neck, and trunk, grip strength, peak expiratory flow, turning in bed, and transferring from lying in bed to sitting. The scores of the different functions were added to create a functional index. The patients' subjective gradings of disability and pain intensity were indicated on a category scale. Blood samples for analyses of muscle enzyme levels were obtained in connection with the functional tests. RESULTS: The interrater reliability of the functional index was high. Grip strength and muscle endurance in shoulder abduction and flexion, hip flexion, and a step test and heel and toe lifting were significantly reduced compared to controls. Peak expiratory flow was lowered in 4 patients. The functional index did not correlate significantly with the laboratory tests, but there was significant correlation between the weakness of the lower extremities and the subjective grading of disability. All patients but one had experienced severe pain during the course of the disease. CONCLUSION: The described functional index has high interrater reliability, but its construct validity and sensitivity as a monitor of response to medication and training need further confirmation.

Adult↗
PubMed1996

Prolonged functional impairments after whiplash injury.

Thirty patients with whiplash injuries were examined 1 to 55 months after the accidents. Pain had appeared on the day of the accident in 24 (80%) of the patients and with different delays in the remainder. The mean pain intensity was 43 mm (SD 26) on a visual analogue scale (VAS). All patients had pain in the neck, 17-33% had headache and 6-17% had pain in various regions of the arms. Thirteen patients (43%) suffered from constant pain, while 17 (57%) had pain-free periods. Muscle tenderness was higher at all tested sites compared with controls. The tolerance level to pressure pain in the index finger as well as grip strength and neck mobility was reduced compared with controls. The whiplash patients showed poorer mental well-being compared with a reference group representing the general population and compared with a group of tension-type headache patients.

Adult↗
PubMed1995

[Cardioversion in atrial fibrillation. Results and complications in 1,152 prospective patients. Study Group of the Working Society of Leading Cardiologic Hospital Physicians].

BACKGROUND: Pharmacological and direct-current cardioversion of atrial fibrillation are often performed interventions. Little is known about results and complications of cardioversion in daily practise. PATIENTS AND METHODS: Demographic, procedural and outcome data from patients with cardioversion of atrial fibrillation were collected in a prospective, multicenter registry of 61 hospitals. RESULTS: Between July 1994 and December 1994 1152 patients with a mean age of 64 +/- 11 years were registered on an intention-to-treat basis. 62% were male. The most prevalent underlying disorders were coronary artery disease (34.7%), valvular heart disease (18.1%), and cardiomyopathy (6.9%). 16.4% of patients had lone atrial fibrillation. New onset atrial fibrillation was reported in 21%, paroxysmal in 32% and chronic in 47% of patients. The mean duration of atrial fibrillation was 7 +/- 26 weeks (range 1 day to 7 years, median 5 days). In 3.8% of patients no cardioversion attempt was made and follow-up was not possible in another 5.5%. 19.2% of patients cardioverted spontaneously. Direct current cardioversion was attempted in 39.7% and pharmacological cardioversion in 31.8% of patients. Cardioversion was successful (sinus rhythm at discharge) in 96.4% of spontaneous cardioversion, in 73.1% of direct current cardioversion and in 84.4% of pharmacological cardioversion. Success of cardioversion was significantly related to duration of atrial fibrillation, NYHA functional class and left atrial diameter (p < 0.001). In 55 (4.8%) cases complications were reported of which 14 were fatal. Five cases of sudden death occurred, all of which were related to quinidine therapy for pharmacological cardioversion. Five cases of embolism were reported. Two were not associated with cardioversion attempts and 3 occurred within 24 hours after successful direct current cardioversion. Two of these patients were effectively anticoagulated at the time of cardioversion. A total of only 62% of patients with atrial fibrillation of more than 48 hours duration were anticoagulated for cardioversion with coumadine or i.v. heparin. CONCLUSIONS: The main risks of cardioversion are fatal proarrhythmic events in pharmacological attempts to restore sinus rhythm. The risk of embolism is despite low rates of effective anticoagulation low.

Aged↗
PubMed1995

Radioimmunotherapy of prostatic adenocarcinomas: effects of 131I-labelled E4 antibodies on cells at different depth in DU 145 spheroids.

Spheroids of the human prostatic adenocarcinoma cell line DU 145 were used to study experimental radioimmunotherapy. Spheroids were incubated with the 131I-labelled monoclonal E4 antibody until the radionuclide immunoconjugate had bound the 5 to 6 outermost cell layers of the spheroids. A set of 50 spheroids were exposed, either immediately or 48 hr after antibody incubation and washings, to a dilute trypsin solution with the aim of stripping off cells from the spheroid surface. Stripped cells were collected in fractions corresponding to defined spherical shells. Cells were subsequently plated for clonogenic growth. The technique of automated sequential trypsinization of spheroids followed by a clonogenic survival assay permits studies on therapeutic efficacy for radionuclide immunoconjugates on cells from different layers of spheroids. In addition, the absorbed doses throughout a spheroid were calculated. The binding and retention kinetics of the radionuclide immunoconjugate and the excess of 131I-E4 in the culture medium during incubation are factors that were all accounted for in the calculations. If the calculated absorbed doses were inserted into the linear-quadratic survival model and the low dose rate was taken into account, survival values were well in accordance with the experimentally obtained values. The results demonstrate that the 131I-labelled E4 antibody is capable of sterilizing cultured tumour cells that have bound the radionuclide immunoconjugate and, by means of radiation "cross-fire", those cells located in close proximity.

Adenocarcinoma↗
PubMed1995

[ACE inhibitor-associated interstitial lung infiltrates].

HISTORY AND CLINICAL FINDINGS: A 60-year-old woman was prescribed Captopril, 37.5 mg daily, for severe left-ventricular dysfunction with associated mitral regurgitation. Left ventricular function improved markedly in the subsequent 6 months and the mean pulmonary capillary wedge pressure became normal. However, exertional dyspnoea unexpectedly did not improve but rather increased and she also developed severe dry cough. TESTS: The chest radiogram and computed tomography revealed multiple small interstitial infiltrates in both lungs without signs of congestion. Body plethysmography did not demonstrate any obstructive or restrictive ventilatory abnormalities. TREATMENT AND COURSE: When captopril was discontinued, the cough improved and the exertional dyspnoea quickly disappeared without any further treatment. All immunological tests, including those for antibodies against bird antigens and for antinuclear antibodies, were negative. The interstitial infiltrates had already markedly regressed 9 days after captopril had been discontinued and they had disappeared after 2 months. CONCLUSION: This case indicates that angiotensin-converting enzyme inhibitors should be considered as a cause of interstitial pulmonary infiltrates associated with dyspnoea.

Angiotensin-Converting Enzyme Inhibitors↗