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Biomedical subjects

J Carlsson

Publications and source records attributed to J Carlsson.

At least 145 records · Page 8Linked to original sources
PubMed1995

Improvement of global and regional left ventricular function by percutaneous transluminal coronary angioplasty after myocardial infarction.

OBJECTIVES: This study was designed to evaluate how elective percutaneous transluminal coronary angioplasty of the infarct-related vessel after acute myocardial infarction affects global ejection fraction and regional wall function. BACKGROUND: The severity of the residual stenosis of the infarct-related artery after thrombolysis is an important predictor of changes in left ventricular function; however, the optimal time to restore complete perfusion in the infarct area has not been determined. METHODS: We prospectively evaluated patients with a first myocardial infarction, postinfarction ischemia and residual high grade stenosis with reduced flow in the infarct-related artery who underwent successful coronary angioplasty. The group comprised 74 patients (61 men, 13 women with a mean age +/- SD of 55.9 +/- 9.9 years). Global ejection fraction and infarct region function (expressed as area ejection fraction) were angiographically measured before coronary angioplasty (3.9 +/- 2.1 weeks after infarction) and on routine follow-up study 6 +/- 1 months after angioplasty. RESULTS: Restenosis with reduced flow occurred in 15 patients (20%). The global ejection fraction in patients with complete flow at follow-up increased significantly from 56.8% +/- 12% to 62.3% +/- 12.5% (p < 0.001). Regional wall motion of the infarct area increased from 12.1% to 22.5% (p = 0.001) in patients with anterior wall infarction and from 20.4% to 28.5% (p = 0.002) in those with inferior wall infarction. In patients with restenosis there was no difference at follow-up either in global ejection fraction (from 47.7% +/- 7.7% to 47.1% +/- 12.7%, p = 0.57) or in regional wall motion of the infarct area. CONCLUSIONS: Global and regional myocardial dysfunction due to postinfarction ischemia lessens significantly after successful coronary angioplasty of the infarct-related coronary artery with long-term sustained normal, complete flow. In contrast, restenosis with reduced flow prevents long-term improvement of left ventricular function.

Aged↗
PubMed1995

Hemodynamic and antiischemic effects of intravenous elgodipine, a new dihydropyridine calcium channel blocker, in patients with chronic stable angina.

Elgodipine is a new second-generation dihydropyridine calcium antagonist. Its hemodynamic and antiischemic properties were evaluated in a single-blind, placebo-controlled trial in 22 males with chronic stable angina. Coronary artery disease was angiographically confirmed. Measurements were performed with a Swan-Ganz thermodilution catheter during a 30-minute period of rest and before the end of a 4-minute bicycle exercise test at maximum individual workload, both with placebo (IV infusion of 5 ml saline over 30 minutes) and elgodipine (10 micrograms/kg/2 min bolus IV, then IV infusion of 1 micrograms/kg/min for 28 minutes. Elgodipine caused very similar hemodynamic changes at rest and during exercise. Its major hemodynamic modification was the marked decrease in systemic vascular resistance, which was accompanied by an increase in cardiac index and stroke volume. Mean arterial blood pressure was slightly reduced, whereas the opposite small increase in heart rate meant that the double product remained unchanged. Contrary to resting conditions, pulmonary capillary wedge pressure, pulmonary artery pressures, pulmonary vascular resistance, and mean right atrial pressure remained normal or increased to a lesser extent during exercise after elgodipine. After elgodipine ischemic ST depression during exercise was diminished, and 11 of 16 assessable patients remained free from angina pectoris. We conclude that elgodipine is an efficacious antianginal drug. Its major mechanism of action is lowering of systemic vascular resistance. Thus elgodipine improves systolic cardiac function in patients with chronic stable angina and may delay the onset of ischemic diastolic dysfunction during exercise, as indicated by a normal left ventricular end-diastolic pressure (LVEDP). The data also suggest an improvement in coronary blood flow during exercise.

Adult↗
PubMed1995

Irregular variations in radiation sensitivity when the linear energy transfer is increased.

Seven cell lines were analyzed for clonogenic survival after irradiation with photons (60Co) or accelerated helium or nitrogen ions. The cell lines showed different sensitivity to photon radiation and most of the differences decreased after irradiation with helium ions with a linear energy transfer (LET) of about 40 keV/microns. However, all cell types had individual LET sensitization patterns and the mean relative biological effectiveness (RBE) at 10% survival ranged from 1.46 +/- 0.12 to 2.41 +/- 0.26 for the helium ions. This difference was significant and the differences increased further when higher survival levels were considered. There was only a weak tendency towards a relation between photon and helium ion sensitivity when the linear component of the survival curves, the alpha-values, were compared, and no relation at all for other parameters. It was not possible to predict the response to an increased LET from the photon responses obtained. Three of the cell lines were also irradiated with nitrogen ions with an LET of 125 keV/microns. These cells were, as expected, sensitized further and the average RBE at 10% survival was 3.67 +/- 0.67. However, one cell line was more resistant than the others in this case. Furthermore, the quadratic component of the survival curves, the beta values, were higher after irradiation with nitrogen than with helium ions. Thus, several irregular and unexpected results were seen when the LET was increased.

Animals↗
PubMed1995

76Br-labeled monoclonal anti-CEA antibodies for radioimmuno positron emission tomography.

For the application of anti-tumor monoclonal antibodies (MAbs) in positron emission tomography (PET), labeling radionuclides with half-lives allowing a suitable time frame for imaging are required. The anti-CEA MAb 38S1 was labeled with the positron emitting nuclide 76Br (t1/2 16 h) using bromoperoxidase (BPO), and subsequently affinity purified. A procedure was devised to allow reproducible production of MAb-preparations of high immunoreactivity and with acceptable bromination yield. The biological activity of 76Br-38S1 was retained and comparable to that of chloramine-T labeled 125I-38S1, as tested in vitro.

Antibodies, Monoclonal↗
PubMed1995

Prospective study of autonomic nerve function in type 1 and type 2 diabetic patients: 24 hour heart rate variation and plasma motilin levels disturbed in parasympathetic neuropathy.

To clarify the impact of autonomic neuropathy in diabetic patients, we have conducted a prospective study of 58 Type 1 and 51 Type 2 diabetic patients (investigated at baseline, after 4, and after 7 years). In Type 1 diabetic patients, the sympathetic nerve function (orthostatic acceleration and brake indices) and in Type 2 patients, parasympathetic nerve function (R-R interval variation; E/l ratio) deteriorated during 7 years of prospective observation. Symptoms of autonomic neuropathy were associated with signs of autonomic neuropathy (low brake indices) in Type 1 but not in Type 2 diabetic patients. In the latest assessment 24 h ECG recording was performed and blood samples assayed for neuropeptide Y (NPY) and motilin were obtained. Type 1 diabetic patients with parasympathetic neuropathy (abnormal E/l ratio) showed significantly lower SD value (less variation in the R-R intervals; 29 [17] vs 50 [16], [mean (interquartile range)]; p = 0.001) and higher postprandial plasma motilin values (70 [20] pmol l-1 vs 50 [15] pmol l-1; p < 0.01) than patients with normal parasympathetic nerve function. In Type 2 diabetic patients, sympathetic neuropathy (low brake indices) was associated with an increased frequency of ventricular extra systolic beats during 24 h ECG recording (rs = 0.65; p < 0.01). Postprandial plasma NPY levels were not associated with disturbed autonomic nerve function.

Adolescent↗
PubMed1995

Periodontal and systemic findings in children with marginal bone loss in the primary dentition.

In a previous population-based study of 3896 7-9-year-old children living in Sweden, it was found that 32 children (0.8%) exhibited radiographic, periodontal bone loss at > or = 2 proximal surfaces of their deciduous teeth. In the present study, 26 of the 32 children were subjected to additional oral and systemic health examination. 20 other children without any radiographic evidence of bone loss in their primary dentition served as referents. None of the cases or the referents were detected to have any systemic disease. The frequency of bleeding and suppuration on probing, radiographic proximal calculus and probing attachment loss was higher among the cases than the referents. Actinobacillus actinomycetemcomitants was found subgingivally in 14 of the cases but in none of the referents. 11 of 22 cases analysed for presence of serum antibodies against A. actinomycetemcomitans leukotoxin were sero-positive compared to none of 7 referents available for analysis. Evaluation of the data from each child revealed wide variations in clinical parameters among the children in the case group. In this group, there were children with deep probing depths, probing attachment loss, suppuration on probing, proximal calculus and presence of subgingival A. actinomycetemcomitans, indicating current periodontitis. However, in the case group there were also children without positive signs of inflammatory disease, similar to the children in the reference group. In fact, the findings suggest that less than half of the number of individuals with > or = 2 proximal sites with bone loss had current periodontitis.

Aggregatibacter actinomycetemcomitans↗
PubMed1995

Competition for peptides and amino acids among periodontal bacteria.

We recently studied the utilization of glutathione (L-gamma-glutamyl-L-cysteinylglycine), L-cysteinylglycine and L-cysteine by anaerobic bacteria. The rate of hydrogen sulfide formation from these compounds was determined and it was concluded that Peptostreptococcus micros and Fusobacterium nucleatum subsp. nucleatum had an active transport of small peptides. In the present study it is shown that methyl mercaptan formation from L-methionine and L-methionyl-containing peptides can also be used to study peptide utilization. There were differences among the periodontal bacteria P. micros, F. nucleatum subsp. nucleatum, and Porphyromonas gingivalis in their capacity to use L-cysteine and L-methionine and peptides containing these amino acids. The peptides were used more efficiently by P. micros and F. nucleatum subsp. nucleatum than by P. gingivalis. All three species used the peptides more efficiently than the free amino acids. The efficiency in utilizing various amino acids and peptides may be among the key determinants of the periodontal microbial ecology.

Amino Acids, Sulfur↗
PubMed1995

Variations with breed, age, season, yield, stage of lactation and herd in the concentration of urea in bulk milk and individual cow's milk.

The concentration of urea in the milk of 510 dairy cows in 10 herds was determined at regular intervals for a year. The herds contained approximately equal numbers of Swedish Red and White, and Swedish Holstein cows. The mean +/- sd concentration in the samples from individual cows was 5.32 +/- 1.13 mmol/l, and the mean concentration in bulk milk was 5.39 +/- 0.96 mmol/l. These values indicated that on average the herds were fed too much protein relative to their intake of energy throughout the year. Herd factors had a strong influence on the milk urea concentration. The concentration was lower during the first month of lactation than later in the lactation, and lower when the cows were housed during the winter than when they were grazing. There was a weak positive relationship between the daily milk yield and urea concentration, particularly during late lactation, but there was no relationship with either breed or age. Bulk milk urea was a reliable guide to the average urea concentration of a herd.

Age Factors↗
PubMed1994

Strategy for boron neutron capture therapy against tumor cells with over-expression of the epidermal growth factor-receptor.

PURPOSE: Gliomas, squamous carcinomas and different adenocarcinomas from breast, colon and prostate might have an increased number of epidermal growth factor (EGF) receptors. The receptors are, in these cases, candidates for binding of receptor specific toxic conjugates that might inactivate cellular proliferation. The purpose of this study was to evaluate whether it is reasonable to try ligand-dextran based conjugates for therapy. METHODS AND MATERIALS: EGF or TGF alpha were conjugated to dextran and binding, internalization, retention and degradation of eight types of such conjugates were analyzed in EGF-receptor amplified glioma cells. The conjugates were labelled with radioactive nuclides to allow detection and two of the conjugates were carrying boron in the form of carboranyl amino acids or aminoalkyl-carboranes. Comparative binding tests, applying 125I-EGF, were made with cultured breast, colon and prostate adenocarcinoma, glioma and squamous carcinoma cells. Some introductory tests to label with 76Br for positron emission tomography and with 131I for radionuclide therapy were also made. RESULTS: The dextran part of the conjugates did not prevent receptor specific binding. The amount of receptor specific binding varied between the different types of conjugates and between the tested cell types. The dextran part improved intracellular retention and radioactive nuclides were retained for at least 20-24 h. The therapeutical effect improved when 131I was attached to EGF-dextran instead of native EGF. CONCLUSION: The improved cellular retention of the ligand-dextran conjugates is an important property since it gives extended exposure time when radionuclides are applied and flexibility in the choice of time for application of neutrons in boron neutron capture therapy (BNCT). It is possible that ligand-dextran mediated BNCT might allow, if the applied neutron fields covers rather wide areas around the primary tumor, locally spread cells that otherwise would escape treatment to be inactivated.

Adenocarcinoma↗
PubMed1994

[Paradoxical cerebral embolism during fibrinolysis therapy in deep vein thrombosis and pulmonary embolism].

A 37-year-old woman with increasing dyspnoea over several months suddenly developed severe ortho- and tachypnoea as well as cyanosis of the lips and acrocyanosis. Pulmonary angiography revealed massive bilateral pulmonary emboli with a systolic pulmonary artery pressure of 75 mm Hg. Phlebography demonstrated a thrombotic occlusion of the deep veins of the left leg extending to the distal femoral vein. Thrombolysis treatment was started via an indwelling pulmonary artery catheter (500,000 IU urokinase and 10,000 IU heparin as bolus, then 1 mill. IU urokinase and 1,000 IU heparin per hour). After two hours an incomplete left-sided paresis occurred (involving ocular and facial muscles, dysarthria, left arm and left leg) and the thrombolytic infusion was stopped. But cerebral computed tomography (CT) did not demonstrate any intracerebral haemorrhage. The heparin infusion was restarted (partial thromboplastin time between 70 and 90 s). CT examinations during the next few days showed the development of an ischaemic infarction in the distribution of the right medial cerebral artery. Angiography demonstrated occlusion of the right internal carotid artery. The diagnosis of a paradoxical embolus was supported by easy cardiac catheter passage through a patent foramen ovale. Subsequent pulmonary angiography demonstrated a thrombus-free pulmonary arterial circulation with a normal pulmonary arterial pressure. There was gradual and extensive regression of the incomplete hemiparesis.

Adult↗
PubMed1994

Internalization and excretion of epidermal growth factor-dextran-associated radioactivity in cultured human squamous-carcinoma cells.

Certain tumor cells, such as squamous carcinomas and gliomas, can have an increased number of epidermal-growth-factor (EGF) receptors. The EGF receptors can in these cases be targets for toxic conjugates with specific binding. EGF-based toxic conjugates are potential targeting agents. We have analyzed the internalization and excretion of 125I administered in the form of 125I-EGF-dextran in squamous-carcinoma A431 cells. 125I-EGF without dextran was used for comparison. A431 cells have large numbers of EGF receptors and are capable both of recycling and of degradation of internalized receptor-ligand complexes. The binding of 125I-EGF-dextran and 125I-EGF was receptor-specific, since both ligands competed with non-radioactive EGF for binding. The amount of internalized 125I as a function of time increased continuously within 24 hr following administration of radioactivity as 125I-EGF-dextran. The time pattern was quite different when 125I-EGF without dextran was applied. In the latter case, the amount of internalized radioactivity decreased already after a few hours, probably depending on degradation of EGF. Pre-incubation of the cells with 125I-EGF-dextran or 125I-EGF and analysis of retained and released 125I activity at different times after washing showed that the 125I activity was retained for longer periods of time when EGF-dextran was used instead of EGF. About 30% of the internalized 125I activity was retained after 24 hr when EGF-dextran was used, compared with excretion of nearly all the radioactivity within 5 hr when EGF was used. In some experiments a high concentration of non-radioactive EGF, 5 micrograms/ml, was given to the cells after pre-incubation with 125I-EGF-dextran. This changed the retention and excretion patterns, so that a larger amount of 125I was excreted in the macromolecular fraction and a smaller amount of 125I activity was retained in the cells. Gel chromatography of the 125I activity released into the culture medium showed that the variations in molecular weight were larger after administration of a high concentration of non-radioactive EGF, most likely due to partial degradation of EGF-dextran. The results regarding excretion are in conformity with a model of competition between recycling of EGF-dextran-EGF-receptor complexes and "trapping" of EGF-dextran in the lysosomes followed by slow degradation. For targeting purposes, it is worth noting that the radioactivity administered in the form of 125I-EGF-dextran had a longer retention time than when 125I-EGF without dextran was used, and that the retention and excretion rates could be modified by post-treatment with the receptor ligand itself.

Binding, Competitive↗
PubMed1994

Radiation dose heterogeneity in receptor and antigen mediated boron neutron capture therapy.

Boron neutron capture therapy, BNCT, might be a valuable tumour therapeutical modality for the treatment of cells that are difficult to handle with conventional methods such as surgery or external radiotherapy. The principle is that tumour associated 10B atoms capture thermal neutrons and thereby forms high-LET helium and lithium ions as reaction products. An interesting development is to conjugate 10B atoms to macromolecules that bind to tumour cells with over-expressed receptors or specific antigens. The targeting macromolecules might be receptor-ligands, antibodies or antibody-fragments containing 10B. The present study deals with the limitations of such an approach. One problem is the background dose from capture of neutrons in physiologically occurring elements, especially nitrogen. We showed, with computer simulations, that the background specific energy (the stochastic analogy of dose) in the cell nuclei, due to captures in nitrogen, had a wide spread and could be rather high, up to 3 Gy in some cells, when relevant neutron fluencies were applied. The maximal amount of 10B that can be delivered to single tumour cells due to receptor-ligand, receptor-antibody or antigen-antibody mediated binding is probably in the range 10(8)-10(10) atoms/cell. Our calculations showed that the tumour cells had to contain about 10(9) 10B/cell to give a therapeutically interesting dose to the nuclei of the targeted cells. The doses were highest when the boron was in the cell nucleus. There was also a wide spread of specific energy absorbed by the nuclei after neutron capture in 10B. When, for example, 10(8) 10(10)B/nucleus were applied the specific energy to the analysed nuclei varied from 0 Gy up to about 7 Gy. These variations were due to the stochastic nature of the capture processes. Some helium or lithium ion tracks passed through the centre of the cell nuclei delivering a lot of energy, some passed through only a smaller part delivering small amounts of energy and sometimes the nuclei escaped without any hits at all. The results were obtained when relevant neutron fluencies (2-5 x 10(12) n/cm2) were applied. Increased neutron fluencies gave higher doses both due to capture in boron and in nitrogen but in order to improve the ratio between the dose to targeted tumour cells and the dose to normal cells, the number of 10B atoms in the targeted cells had to be increased and/or the boron placed in the cell nuclei.

Boron↗
PubMed1994

Clonogenic cell survival and rejoining of DNA double-strand breaks: comparisons between three cell lines after photon or He ion irradiation.

Three cell lines, human glioma U-343MG, Chinese hamster V79-379A and human colon carcinoma LS-174T, were analysed for clonogenic survival and with pulsed-field gel electrophoresis regarding induction and rejoining of double-strand breaks (dsb) in DNA. The cells were irradiated with either intermediate linear energy transfer (LET approximately 55 keV/microns) He ions or with 60Co photons and showed cell type-specific variations in their survival curves. The induction of dsb, per DNA unit, increased linearly with dose for both radiation qualities, and there were no cell type-dependent differences. However, the dsb induction frequency increased for all three cell lines with an RBE of 1.31 +/- 0.08 (SD) after He ion irradiation. All three cell lines showed biphasic dsb rejoining patterns with cell type-specific differences. The differences between the cell lines were somewhat smaller after irradiation with He ions, although the patterns were very similar to those seen after photon irradiation. The shoulders in the survival curves disappeared after He ion irradiations, however the cells retained the capacity to rejoin dsb. After 8-h rejoining the increase of LET to intermediate values did not give a higher fraction of residual dsb.

Animals↗