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Biomedical subjects

J Carlsson

Publications and source records attributed to J Carlsson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Low growth hormone secretion in patients with fibromyalgia--a preliminary report on 10 patients and 10 controls.

OBJECTIVE: To evaluate the secretion of growth hormone in patients with fibromyalgia (FM). METHODS: Serum concentrations of growth hormone (24 h profiles), insulin-like growth factor I (IGF), and IGF binding protein-3 were determined in 10 women with FM and in 10 healthy controls. Quality of sleep was assessed by means of a visual analog scale. RESULTS: Sleep was significantly more disturbed in the patients than in controls. A significantly lower secretion of growth hormone was found in the patients in comparison with healthy controls. CONCLUSION: These results suggest that growth hormone secretion is decreased in patients with FM. Substitution therapy with low doses of growth hormone may be worth evaluating in the treatment of FM.

Adult↗
PubMed1998

Uptake of a boronated epidermal growth factor-dextran conjugate in CHO xenografts with and without human EGF-receptor expression.

An epidermal growth factor (EGF)-dextran-boron conjugate for targeting against EGF receptor-rich tumours was investigated regarding uptake and distribution in vivo. EGF served as the tumour-seeking part and dextran was the carrier for the potentially toxic boron. Nude mice carrying subcutaneous tumours on the flanks were injected with conjugate either i.v. or intratumorally. The xenografts were from Chinese hamster ovary cells transfected with the gene for the human EGF-receptor (CHO-EGFR), and these cells expressed the EGFR. Non-transfected cells without EGF-receptors (CHO) were used as controls. No accumulations in tumours could be observed following the i.v. injections but there were, in both tumour types, high accumulations in the liver. Following intratumoral injections the accumulations were higher in the CHO-EGFR tumours than in the CHO tumours. The tumour over blood and liver ratios were also higher for the CHO-EGFR tumours than for the CHO tumours. Thyroid accumulations after the intratumoral injections indicate different degradation patterns of the conjugate in CHO-EGFR animals than in CHO animals. In conclusion, after intratumoral injections the conjugate showed receptor-dependent binding to EGFR-rich tumours, and the tumour-to-blood and tumour-to-liver ratios were promising.

Animals↗
PubMed1998

Risk factors for rebleeding and fatal outcome in elderly patients with acute peptic ulcer bleeding.

OBJECTIVE: Mortality after peptic ulcer bleeding (PUB) is high in elderly patients despite therapeutic advances. Little is known about what actually determines rebleeding and mortality. The objective of this study was to investigate which factors may have an independent influence upon rebleeding and mortality in patients with PUB. DESIGN: Prospective cohort study. PARTICIPANTS: Patients, above 60 years of age, hospitalized due to an endoscopically verified acute PUB were included in the study (n = 508). INTERVENTIONS: The occurrence of rebleeding within 3 days and mortality within 30 days was registered for all patients. A predefined set of variables with a potential to influence rebleeding and mortality was analysed in a multiple logistic regression model. MAIN OUTCOME MEASURES: Odds ratios (with confidence intervals) for all predefined variables with respect to influence upon rebleeding and mortality, respectively. RESULTS: The risk of rebleeding was significantly increased with greater age and if the patient was suffering from shock, while omeprazole infusion, acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drug (NSAID) intake before admission and gastric ulcer localization were associated with a lower risk. Mortality was significantly increased with greater age, heart disease and blood pressure < 100 mmHg at admission. Previous ulcer history and the presence of a Forrest class IIa ulcer significantly reduced this risk. CONCLUSIONS: Elderly patients in shock admitted due to their first peptic ulcer bleeding run the greatest risk of an unfavourable outcome.

Acute Disease↗
PubMed1997

Binding, internalization and degradation of EGF-dextran conjugates in two human bladder-cancer cell lines.

Bladder carcinomas often have an increased number of epidermal growth factor (EGF) receptors. The EGF receptors can, in these cases, be targets for toxic conjugates. In this study, EGF-dextran conjugates were used as targeting agents with therapeutic potential. The binding, internalization and degradation of 125I-EGF-dextran conjugates in J82 and RT4, 2 different bladder cancer cell lines, were investigated. The behaviour of 125I-EGF was studied as a comparison. The 125I-EGF-dextran showed a continuous increase in binding up to 24 hr, while 125I-EGF exhibited maximum binding after about 90 min. Both cell lines showed similar binding patterns. The binding of 125I-EGF-dextran and 125I-EGF was, on both cell lines, receptor-specific since the binding could be displaced with non-radioactive EGF. Analysis of internalized and membrane-bound 125I activity after administration of 125I-EGF-dextran showed that most of the activity was membrane-bound. A large part of both the internalized and the membrane-bound activity remained cell-associated up to 24 hr. The internalized and membrane-bound activity after administration of 125I-EGF decreased rapidly and only a small fraction remained cell-associated after 24 hr. 125I-EGF-dextran remained cell-associated, with only a limited release of low- and high-molecular-weight radioactivity throughout the 24-hr period, while 125I-EGF was extensively degraded and released into the incubation medium as low-molecular-weight radioactivity during this time. Several qualities of the 125I-EGF-dextran conjugates might be favourable for targeted radiotherapy.

Cell Membrane↗
PubMed1997

[Prehospital thrombolytic therapy in acute myocardial infarction].

The extent of myocardial damage occurring during acute myocardial infarction is time dependent, and there is abundant evidence from most clinical trials that mortality reduction is greatest in patients treated early with thrombolytic agents, although beneficial effects have been shown with treatment initiated up to 12 h after onset of symptoms. All studies on prehospital thrombolysis have conclusively shown the practicability and safety of patient selection and administration of the thrombolytic agent. The accuracy of diagnosis in the prehospital setting was comparable to trials of in-hospital thrombolysis, e.g., in the Myocardial Infarction Triage and Intervention Project (MITI) 98% of the patients enrolled had subsequent evidence of acute myocardial infarction. With regard to time savings, all randomized studies showed positive results. The smallest time gain was observed in the MITI trial: prehospital-treated patients received thrombolytic therapy an average of 33 min earlier than those treated in hospital. In the European Myocardial Infarction Project (EMIP) the difference in time between prehospital and hospital treatment was a median of 55 min. However, none of these trials was able to show a significant short-term mortality difference between the two groups. Only a meta analysis of five randomized studies with a combined median time gain of about 60 min showed a significant 17% reduction in short-term mortality for patients who received thrombolytic therapy in the prehospital phase. In the Grampian Region Early Anistreplase Trial (GREAT), a study performed in a more rural area than other studies, the time gain by prehospital initiation of thrombolysis was a median of 130 min. GREAT was the only study to date reporting a significant mortality benefit for prehospital-treated patients after 3 months and 1 year. In conclusion, prehospital thrombolysis is feasible and safe. Patients with acute myocardial infarction can be correctly identified and treated with thrombolytic agents in the prehospital setting with the same rate of complications as expected for in-hospital thrombolysis, provided basic resuscitation equipment including a defibrillator is available. The results of randomized studies comparing the results of prehospital and in-hospital thrombolysis seem to justify the prehospital institution of thrombolytic therapy, especially in rural areas where transport times to the hospital are long and the expected time gain is largest. The choice of the thrombolytic agent seems to be of minor importance and should follow prehospital practicability (bolus injection) and costs. Aspirin should be given to all prehospital patients with suspected myocardial infarction regardless of thrombolytic therapy.

Acute Disease↗
PubMed1997

Chemistry and biology of some low molecular weight boron compounds for boron neutron capture therapy.

Boronated DNA targeting agents are especially attractive candidates for BNCT because they may deliver boron-10 to the nuclei of tumor cells. Numerous boron-containing analogs have been synthesized and some have shown promising results in initial biological tests. One of the most challenging tasks in this special field of research remains the finding of suitable targeting strategies for the selective delivery of boron rich DNA-intercalator/alkylator to tumor cells. Synthetic and biological studies of boron compounds suitable for DNA-binding are reviewed. The amino acid p-boronophenylalanine (BPA) is presently of considerable clinical interest. Other boronated amino acids might also be candidates for BNCT either per se, as part of part of tumor-seeking peptides or conjugated to targeting macromolecules. A large number of boronated L- and D-amino acids with varying liphophicility and sterical requirements are now available for evaluation. Recent synthetic and biological studies of aromatic boronoamino acids, carboranylamino acids and carboranyl amines are also reviewed.

Amino Acids↗
PubMed1997

Effects of Pb2+, Ni2+, Hg2+ and Se4+ on cultured cells. Analysis of uptake, toxicity and influence on radiosensitivity.

Effects of Pb2+, Ni2+, Hg2+ and Se4+ on cultured human glioma U-343MG cells were investigated considering uptake, toxicity and, in combination with radiation, clonogenic cells survival. The cells were exposed to 0-100 microM of the metals for a week before the evaluation. The tests showed a tendency to toxicity with 10 microM nickel although not significant (P > 0.05). Selenium, lead and mercury exerted a significant toxicity (P < 0.05) at 2.5 microM, 10 microM and 1 microM, respectively. To challenge the clonogenic cell survival capacity, the cells were irradiated with 60Co photons after being exposed to the highest nontoxic concentration of the different metals. The clonogenic cell survival tests, after irradiation, showed no significant change if the cells were exposed to 5 microM nickel, 0.5 microM selenium or 5 microM lead compared with those not exposed. Mercury, 0.1 microM, gave a relative reduction in survival compared with only irradiated cells of 58 +/- 17%. Thus, only mercury affected the radiation-induced damage and/or repair. When exposed to the highest nontoxic concentrations of the different metals, the cultures did not display a significant uptake ratio (metal concentration ratio of exposed cells to control cells) of nickel (3.1 +/- 3.3), only a small uptake ratio of selenium (4.0 +/- 0.4), while there was a large uptake ratio of both lead (2.6 +/- 1.7) x 10(2) and mercury (1.5 +/- 0.2) x 10(1). The results indicated that nickel was neither especially toxic nor influenced the clonogenic cell survival after irradiation. Mercury was more toxic and also influenced the radiation sensitivity. Lead was taken up strongly but did not influence the radiation sensitivity. Selenium accumulated but gave no detectable effect on the radiation sensitivity.

Cell Survival↗
PubMed1997

Bacterial metabolism in dental biofilms.

Dental biofilms could have a structure which, in sections, looks like tissue. The internal structure of the dental biofilm could be the result of interbacterial adhesion mechanisms in combination with nutritional conditions characterized by multiple nutrient starvation. The preservation of the structure of the biofilm over time may also involve the ability of the bacteria to withstand environmental stresses such as starvation, reactive oxygen products, and acid. The present review will describe, first, the regulation of the metabolic defense against environmental stresses and then focus mainly on the energy metabolism of dental biofilms.

Adaptation, Physiological↗
PubMed1997

Pharmacokinetics and experimental PET imaging of a bromine-76-labeled monoclonal anti-CEA antibody.

UNLABELLED: Bromine-76 is potentially useful as a radiolabel for monoclonal antibodies (MAbs) in PET imaging. The purpose of the present study was to evaluate the 76Br-labeled anticarcinoembryonic antigen (-CEA) MAb 38S1 as a tumor imaging agent in an experimental tumor model and to study the pharmacokinetics of 76Br-38S1 in comparison with 125I-38S1. METHODS: Nude rats carrying human colon carcinoma xenografts were co-injected with directly labeled 76Br-38S1 and 125I-38S1. Biodistribution of labeled 38S1 was monitored for 4 days after administration, in the case of 76Br activity, including PET imaging. In addition, catabolism of radiolabeled MAbs was analyzed by gel filtration chromatography of blood plasma and homogenized tissues. RESULTS: Tumor sites could be readily identified by PET imaging from 46 hr after administration of 76Br-38S1 and onwards. The concentration of 76Br activity in tumors, blood and most normal tissues was higher than the corresponding 125I concentration at all time points. This was mainly due to catabolism of radiolabeled MAb, resulting in free radiohalides, of which 76Br- was retained in contrast to the rapidly excreted 125I- ion. CONCLUSION: Bromine-76-labeled anti-CEA MAbs may be applied for experimental tumor imaging with PET.

Adenocarcinoma↗
PubMed1997

Comparative PET imaging of experimental tumors with bromine-76-labeled antibodies, fluorine-18-fluorodeoxyglucose and carbon-11-methionine.

UNLABELLED: The potential of a 76Br-labeled anti-carcinoembryonic antigen monoclonal antibody (MAb), 38S1, as tumor-imaging agent for PET was investigated in a comparative experimental study with [18F]fluorodeoxyglucose ([18F]FDG) and L-[methyl-11C]methionine ([11C]Met). METHODS: The three radiotracers were administered to nude rats carrying subcutaneous xenografts or liver metastases from a human colonic carcinoma. Tracer biodistribution was evaluated by PET imaging and radioactivity measurement of dissected tissues and also by whole-body autoradiography for subcutaneous xenografts. RESULTS: For PET imaging of subcutaneous tumors, 76Br-38S1 proved superior to the other radiotracers. Tumor-to-tissue ratios were, except for the tumor-to-blood ratio, generally higher for 76Br-labeled MAb than for [18F]FDG and [11C]Met. Liver metastases were imaged with PET using both 76Br-38S1 and [18F]FDG, and the metastases-to-liver ratios of dissected samples were not significantly different for the two radiotracers. CONCLUSION: The tumor-imaging capacity of 76Br-labeled MAb 38S1 was superior to [18F]FDG and [11C]Met in the subcutaneous tumor model, whereas 76Br-38S1 and [18F]FDG were equally successful for the identification of liver metastases.

Animals↗
PubMed1997

Cytotoxicity and subcellular localization of boronated phenanthridinium analogues.

Binding and toxicity of boronated phenanthridinium analogues were studied in vitro using cultured human malignant glioma cells. The compounds, 5-ortho- (5-o-CP), 5-para- (5-p-CP), 5-nido- (5-n-CP) and 6-nido-carboranyl phenanthridinium (6-n-CP) showed varying toxic effects. The cells were exposed to the compounds for 2 or 24 h. The span between non-toxic and toxic concentrations seemed to be very narrow. 5-p-CP was the most toxic compound, causing total cell death at a concentration of 5 micrograms/ml cell culture medium. None of the compounds showed toxic effects at a concentration of 1 microgram/ml. Viable cells incubated with the compounds at this concentration showed a > 100-fold accumulation of boron. Only approximately 1/4 of this accumulation was found in cells permeabilized and inactivated with acetone. Fluorescent images of acetone-treated cells showed clear uptake of the compounds in the cell nucleus, as for ethidium bromide, while for viable cells binding to structures other than DNA was also observed. These results were confirmed by subcellular boron determination. All tested compounds intercalate into DNA, as was demonstrated in cell-free systems with calf thymus DNA. The hypothesis is that the compounds are trapped in the cellular membranes of viable cells because of their lipophilicity, before reaching nuclear DNA.

Boron↗
PubMed1996

Cardioversion of atrial fibrillation in the elderly. ALKK-Study Group. Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausaerzte.

The purpose of this investigation was to define cardioversion success rates, frequency of complications of cardioversion, and current treatment practices in elderly patients (aged > or = 65 years) with atrial fibrillation (AF). The results were compared with those in younger patients (aged < 65 years). The investigation was a prospective multicenter observational study with 61 participating cardiology clinics. Consecutive patients in whom cardioversion of AF was planned had to be prospectively registered. Of 1,152 patients registered, 570 (49.5%) were < 65 years old (group 1) and 582 (50.5%) were > or = 65 years (group 2). The overall success rate of cardioversion on an intention-to-treat basis was 76.1% in group 1 and 72.7% in group 2 (p = 0.18). In multivariate analysis, left atrial size and New York Heart Association functional class before cardioversion were identified as predictors of success (p < 0.001, respectively; p = 0.025). These clinical factors were not equally distributed between the age groups: Left atrial size was larger in the elderly than in younger patients (44.0 +/- 6.4 mm vs 42.8 +/- 6.4 mm; p = 0.006) and a New York Heart Association functional class > or = II was more prevalent in group 2 than in group 1 (48.6% vs 29.6%; p < 0.001). The overall complication rates were not significantly different between the 2 groups (4.2% in group 1 vs 5.3% in group 2; p = 0.37). The frequency of patients who were adequately anticoagulated for cardioversion was 56.9% in age group 1 and 39.6% in age group 2 (p < 0.001). In chronic AF the same trend for age-dependent underuse of anticoagulation was observed. Age itself was not a predictor of cardioversion success and did not predispose to higher complication rates. Therefore, cardioversion should be considered in older patients with the same criteria and emphasis as in younger patients. Anticoagulation and antithrombotic medication is underused for cardioversion and in treating chronic AF, especially in elderly patients.

Adult↗
PubMed1996

Relative role of chloramines, hypochlorous acid, and proteases in the activation of human polymorphonuclear leukocyte collagenase.

The activation of collagenase released by polymorphonuclear leukocytes (PMNs) has been extensively studied in vitro, but the activation of the enzyme in vivo is not fully understood. For further evaluation of the relative role of oxidative and proteolytic mechanisms in the activation of collagenase, PMNs were stimulated by serum-opsonized zymosan under both aerobic and anaerobic conditions. The results showed that similar amounts of collagenase were released by the PMNs under aerobic and anaerobic conditions, but the activity of the released collagenase was twice as high under aerobic conditions as under anaerobic conditions. Under aerobic conditions the enzyme was rapidly activated by hypochlorous acid and chloramines, which are products of the myeloperoxidase-H2O2-chloride system of the PMNs. There was also a slow proteolytic activation of the enzyme, which could be ascribed to cathepsin G and possibly to some other serine proteases of PMNs. When extrapolating these findings to in vivo conditions, it seems probable that the oxidative activation of collagenase will proceed mainly by chloramines, which are more long-lived in the tissue than hypochlorous acid. In poorly oxygenated tissues, collagenase may be mainly activated by proteolytic mechanisms.

Adult↗