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Biomedical subjects

L Jacobsson

Publications and source records attributed to L Jacobsson.

At least 163 records · Page 9Linked to original sources

Comparison of seven iodine-labelled monoclonal antibodies in nude mice with human colon carcinoma xenografts.

The biokinetics of seven 131I-labelled monoclonal antibodies (MAbs), directed against human colon carcinoma and one 125I-labelled unspecific MAb have been examined. The study in nude mice, carrying human colon carcinoma, was intended to be a step in the selection of the most suitable antibody for clinical scintigraphy. The biological half-life in blood was found to be between 1.3 and 7.4 days for the different MAbs. Chromatography of plasma samples showed that the radioiodine was mainly bound to IgG-sized molecules. The (normal tissue)/blood ratios were similar for all the MAbs. The tumour/blood ratio was 0.41 for the unspecific MAb and 0.49-1.1 for the specific MAbs, and the tumour/muscle ratio was between 3.2 and 6.8 for the specific MAbs 6 days after injection. For one MAb tumour/blood and tumour/muscle ratios were 3.9 and 9.8 respectively 9 days after injection. Localization indices were at their highest 2.6 6 days after injection. For at least two of the monoclonal antibodies the tumour/blood and tumour/muscle ratios found are high enough to justify clinical trials regarding their usefulness for scintigraphy of colon cancer in man.

Adenocarcinoma↗

External quality assessment of automated blood leukocyte differential counts and other simultaneous measured quantities.

An external quality assessment scheme (EQAS) of automated differential counts of leukocytes has been carried out using selected fresh blood specimens. The measurements were carried out one day after blood drawing because of the delay in the mail. Reference laboratories established target values for differential counts. They counted visually 600-700 cells in each specimen on smears. The consensus value among 12 laboratories for manual count of total leukocytes was used as target value, but was found on average 9% smaller than the average instrumental value. H1 results compared favorable with the target value for the differentials. The less advantageous findings on Coulter S + IV are partly explained by the age of the specimen when measured. The data indicated that better calibration of the instruments could decrease the overall variation of platelets counts and haemoglobin determinations. An EQAS involving measurement on fresh specimens is in progress.

Blood Preservation↗

Correlation of fatty acid composition of adipose tissue lipids and serum phosphatidylcholine and serum concentrations of micronutrients with disease duration in rheumatoid arthritis.

To establish the concentrations of micronutrients in serum, fatty acid composition in serum phosphatidylcholine and in adipose tissue, and their correlation with inflammation and disease duration in rheumatoid arthritis (RA), 21 consecutive patients with recently diagnosed disease (mean duration eight months), 21 patients with longstanding disease (mean duration 15 years), and 57 controls were examined. In the patients with RA low concentrations of the essential fatty acids, linoleic acid (18:2) and linolenic (18:3) acid, and high concentrations of total saturated fatty acids, both in serum phosphatidylcholine and in adipose tissue, were found, abnormalities that increased with disease duration. The proportion of 18:2 in serum phosphatidylcholine correlated inversely with such acute phase proteins as orosomucoid and C reactive protein. It is proposed that the decreases in essential fatty acids are related to increased activity in the desaturase/elongation enzymes, increased production of eicosanoids, or metabolic changes secondary to cytokine mediated inflammatory reaction. When the micronutrients were studied it was found that serum concentrations of selenium were lower in patients than in controls, but not those of ascorbic acid, alpha-tocopherol, retinol, folic acid, or cobalamine. Ascorbic acid concentrations tended to be lower in RA, however, and correlated inversely with those of haptoglobin, orosomucoid, and C reactive protein, indicating a relation between the ascorbic acid concentration and the degree of inflammation.

Acute-Phase Proteins↗

Vascular clearance by the reticuloendothelial system--measurements using two different-sized albumin colloids.

Normal and reticuloendothelial system (RES) stimulated rats were examined with dynamic liver RES scintigraphy using a computerized gamma camera. 99Tcm-labelled albumin colloid, albures (radius 250 nm) or nanocoll (radius 25 nm), or both were used as test substances to study the kinetics of vascular clearance after RES stimulation. Registrations were made of 30 s per frame for 5 min and 300 s per frame for 15 min or 25 min and a region of interest (ROI) was indicated over the liver. Whole body and liver RES clearance rate constants (k) were calculated from the liver uptake vs time curve. Liver parenchyma blood flow was estimated with 133Xe washout technique. The blood clearance rate constant of albures in non-activated rats was twice that for nanocoll (1.08 +/- 0.05 vs 0.49 +/- 0.02 10(-2)s-1). There was no mutual interaction between the two colloids, implying that they may be eliminated from the blood-stream by slightly different processes. In zymosan-stimulated animals, nanocoll given in a single injection showed a significantly increased k-value. Neither the albures clearance rate constant nor the nanocoll/albures k-value ratio revealed RES macrophage activation. By contrast the nanocoll/albures ratio, calculated for the liver, rose significantly. The final colloid uptake in the liver revealed RES macrophage activation. No changes in liver parenchyma blood flow per g tissue could be registered after administration of zymosan. The nanocoll and albures colloid particles did not impair the normal liver parenchyma blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗

Evaluation of blood flow measurements with microspheres and rubidium--an experimental study in rats.

The microsphere method has been widely used for blood flow measurements in normal and tumour tissues. The microsphere method was evaluated for repeated measurements of cardiac output and regional blood flow in anesthetised rats and in anesthetised rats given noradrenalin and thereby having altered haemodynamics with special emphasis on liver blood flow. Comparing the microsphere method with the soluble indicator method (86Rubidium) gave equal cardiac output values. The liver blood flow was lower and the spleen blood flow was higher with the microsphere method. Two microsphere injections at 10 min intervals were performed on anesthetised rats. In one group 817 +/- 10(3) microspheres were injected each time, in a second group 436 +/- 10(3) and in a third noradrenalin was added and then 430 +/- 10(3) microspheres injected twice. There was good reproducibility for cardiac output and for most organ and tissue blood flows between first and second microsphere injection. No influence on arterial liver blood flow was seen. A blood pressure fall and a decreased heart rate was registered after the first injection in the group given 817 x 10(3) spheres. There was also a blood pressure fall in the group given noradrenalin after the first microsphere injection. The microsphere method with two injections of 436 x 10(3) microspheres seems adequate to use in arterial blood flow studies of the liver and simultaneous cardiac output measurements.

Animals↗

Kinetics of radioiodinated monoclonal antibodies in the rat. Influence of tumour growth and reticuloendothelial system host modulation.

This experimental study in rats examines the influence of tumour growth and RES function modulation on the kinetics of iodinated MAb IgG1 C241. The study was designed to investigate unspecific accumulation in liver and blood. C241 is raised against human colon adenocarcinoma COLO 205 and reacts with SiLea tumour-associated antigen, also known as tumour-associated antigen 19-9. In 26 rats, 2 micrograms 125I MAb C241 (lodobead labelling method) was given i.v. Blood, organ and tumour content was measured at 0.5, 24, 72 and 144 h. In 61 rats, 10 micrograms 131I MAb C241 (lodogen labelling method) was given i.v. The rats were divided into a non-tumour and a tumour-bearing group and subjected to RES function modulation with Zymosan stimulation or methyl palmitate depression. A syngeneic nitrosoguanidine-induced colonic carcinoma--mean 11 g--was growing in back subcutaneous tissue and hind leg musculature. Serum content of tumour-associated antigen was not found on IRMA testing and tumour content of SiLea ganglioside antigen was found only on lipid binding phase assay. The half-time in blood of iodinated MAb C241 was three days. In-vivo release of iodine was tested by plasma separation on a gel column. More than 90% of the iodine was in the IgG fraction. The activity distribution was almost in equilibrium after 24 h. A tumour/blood activity concentration ratio of 0.5 and liver/blood ratio of 0.3 remained at 72 h and 144 h. Radionuclide accumulation was equally low in the macrophage-rich liver and the kidneys. Tumour-bearing animals had significantly lower blood content (0.37 versus 0.99% g-1) and liver content (0.09 versus 0.31% g-1) at 144 h than non-tumour-bearing rats. The whole body content at 144 h was also lower (24% versus 35% of administered activity) (p = 0.10). Modulation of RES function had no significant influence on the whole body, blood or liver content of 131I MAb C241 activity in non-tumour-bearing animals. In tumour-bearing animals, RES stimulation with Zymosan increased the whole body, liver and blood content of 131I activity. The two tested methods of iodination gave similar results.

Adenocarcinoma↗

The commonest rheumatic complaints of over six weeks' duration in a twelve-month period in a defined Swedish population. Prevalences and relationships.

In 900 randomly selected individuals, 50-70 years old, we examined the prevalence over the preceding 12-month period of rheumatic complaints of more than 6 weeks' duration. We found them to represent a major health problem, with an overall prevalence of 37.8%, the predominant diagnoses being subacromial shoulder pain (6.7%), neck pain (6.5%), low back pain (6.3%), osteo-arthrosis (8.5%), and arthralgia (4.9%). With a prevalence of 1.0%, primary fibromyalgia was as common as rheumatoid arthritis (0.7%) and other chronic arthritides (1.1%). The prevalences of the different diagnoses were higher among participants whose data were obtained from personal investigation by a physician than among non-participants where data were obtained by interview, letter, and scrutiny of case records. The odds ratio from incurring more than one rheumatic disease was higher for subacromial shoulder pain and lowest for arthralgia and osteo-arthrosis.

Aged↗

Comparison of experimental hypercholesterolemia and atherosclerosis in male and female mini-pigs of the Göttingen strain.

The susceptibilities of male and female mini-pigs of the Göttingen strain to experimental hyperlipoproteinemia and atherosclerosis were studied and compared. Hyperlipoproteinemia was induced in groups of pigs of each sex by adding 11.2% egg yolk and 0.5% cholesterol to the diet. The initial increase in the plasma cholesterol concentration was significantly greater in the female animals than in the male ones. In both sexes most of the increase in plasma cholesterol was referable to the low-density lipoprotein fraction. As the experiment proceeded, the difference in the plasma cholesterol level between the sexes became less pronounced. After 18 months on the lipid-rich diet the animals were slaughtered and examined for atherosclerotic lesions. Specimens from the coronary arteries and the thoracic and abdominal aorta were taken for lipid analyses. From colour photographs of the intimal surface of the aorta, the percentage area of visible atherosclerosis in the abdominal part was calculated. Atherosclerotic lesions were present in the coronary arteries and in the abdominal aorta in both sexes. In the abdominal aorta, the results of the lipid analyses, and the calculated percentage area of atherosclerosis, indicated that the degree of atherosclerosis was similar in male and female pigs. In the coronary arteries, the atherosclerosis was more pronounced in the female pigs, as judged from the accumulation of cholesterol.

Animals↗

Glomerular filtration rate estimated from a single plasma sample after contrast-enhanced radiological examinations.

In twenty-six patients examined with radiographic procedures, including a single injection of meglumine metrizoate, blood samples were drawn 180, 200, 220 and 240 min after injection. Plasma was analysed for iodine concentration with X-ray fluorescence analysis and the total plasma clearance of metrizoate was calculated with the single sample method from each sample. The results were compared with the total plasma clearance of 51Cr-EDTA, calculated from multiple samples and determined no more than a few days apart from the X-ray examination. A good correlation, ranging from 0.91 and 0.94, was found. We therefore conclude that kidney function can be estimated from a single plasma sample after contrast-enhanced radiological examinations.

Adult↗

Community attitudes and awareness of mental disorders. A key informant study in two Nicaraguan towns.

Attitudes towards mentally ill people were studied in two Nicaraguan towns through interviews with key informants. They were presented 8 case histories originally developed in a World Health Organization collaborative study. Alcoholism and depressive neurosis were considered the most common disorders, while the schizophrenic case was generally judged as the most severe. The methodology was found useful and valid.

Attitude to Health↗

On the picture of depression and suicide in traditional societies.

The paper deals with three problem areas regarding depression and suicide in traditional society; 1) What is the relation between the depression and suicide? 2) Is there any illness like depression all over the world? 3) What do we know about suicide in traditional societies? The author agrees with Dürkheim's classical conclusion that the incidence of suicide in a society has no clear correlation with the prevalence of mental disorders and no clear correlation with different forms of mental disorders. There are a number of studies showing that depressive syndromes exist in traditional societies. However, there is a clear difference in symtomatology between different cultures which might be the result of differences in the conception of illness. The suicide rate is generally very low in traditional societies. The ultimate solution to an unbearable life situation is apparently known to all human cultures and the suicide rate is an important indication in every society of the existential conditions of life.

Africa↗

Early diagnosis of and surgical strategy for adrenal medullary disease in MEN II gene carriers.

Sixteen multiple endocrine neoplasia type II (MEN II) gene carriers--12 who had undergone thyroidectomy because of medullary carcinoma of the thyroid and 4 whose thyroid glands had been removed because of C cell hyperplasia--were examined for the presence of pheochromocytomas. No patient had sought medical advice for pheochromocytoma symptoms. Fourteen patients had MEN IIa syndromes, one patient had a MEN IIb and another patient had a mixed syndrome of von Recklinghausen's neurofibromatosis and MEN II. Eight patients had undergone unilateral adrenalectomy for pheochromocytoma 11 +/- 4 years before. The patients underwent clinical examination, determination of the urinary excretion of catecholamines and metabolites, and 131I-metaiodobenzylguanidine (131I-MIBG) and CAT scans. 131I-MIBG scanning was performed with images 1, 4, and 7 days after the radionuclide injection. In seven of eight patients who had undergone unilateral adrenalectomies, the 131I-MIBG scans showed accumulation of the radionuclide in the remaining adrenal gland. Bilateral adrenal accumulation of the radionuclide was demonstrated in seven of eight MEN IIa gene carriers who had not undergone adrenalectomy. Five patients, two of whom had undergone adrenalectomy, were found to have unilateral pheochromocytomas less than 2 cm in diameter. Only one of these five patients had an elevated excretion of urinary catecholamines. Between day 4 and day 7 after 131I-MIBG injection, adrenal glands with pheochromocytomas increased their relative accumulation of the radionuclide significantly more (p less than 0.02) than did adrenal glands without any demonstrable pheochromocytomas. All the pheochromocytomas were viewed by means of CAT scans. Only one MEN IIa patient had bilateral pheochromocytomas, but our findings indicate that there is a tendency to bilateral adrenal medullary hyperfunction in most MEN II gene carriers. As 131I-MIBG and CAT scans can facilitate the early diagnosis of pheochromocytomas, unilateral adrenalectomy can safely be performed in most MEN IIa patients. Bilateral pheochromocytomas develop in a majority of patients with MEN IIb syndromes. Bilateral adrenalectomy should therefore be performed in these patients.

3-Iodobenzylguanidine↗

Methodology and dosimetry in adrenal medullary imaging with iodine-131 MIBG.

Iodine-131 MIBG scans were performed in 59 patients in order to localize intra- or extra-adrenal pheochromocytomas (pheos), or to visualize hyperplastic adrenal medulla. Images were obtained from the pelvis to the base of the skull on Days 1, 4, and 7 after tracer injection. The 15 patients with histopathologic confirmation of adrenal medullary disease had positive scans. In three of these, the pheos were visible only on images obtained on Day 7. One scan was false negative. After excluding patients with a predisposition to adrenal medullary disease, nine subjects (28%) without verification of pheo displayed adrenal uptake of the radionuclide. Late images produce a low rate of false-negative scans; the background activity diminishes and even small pheos can be detected. In order to increase the quality of late images, 40 MBq [131I]MIBG was used instead of 20 MBq. The dosimetric considerations are discussed.

3-Iodobenzylguanidine↗

Influence of clofibrate on the plasma lipoprotein pattern and on the lipid content and protein and collagen synthesis in atherosclerotic coronary arteries and abdominal aorta from hypercholesterolemic mini-pigs.

The influence of clofibrate on the plasma lipoprotein pattern in hyperlipidemic mini-pigs was studied and an attempt was made to characterize the type of atherosclerosis produced in this animal model. Thirty-two female mini-pigs of the Göttingen strain were used. Experimental hypercholesterolemia and atherosclerosis were produced in 16 of the animals by adding 11.2% egg yolk and 0.5% cholesterol to the diet for 14 months. In groups of 8 normolipidemic and 8 hyperlipidemic animals clofibrate was added in a dose of 2 g per animal and day. The remaining 8 animals of each category served as controls. Two months of clofibrate treatment normalized the plasma cholesterol in the hyperlipidemic group mainly by reducing the elevated LDL-cholesterol fraction. In normolipidemic animals clofibrate significantly reduced the HDL-cholesterol. At the end of the treatment period the animals were slaughtered and autopsied. The right coronary artery and normal and atherosclerotic pieces of the abdominal aorta were taken for biochemical analysis. There was a marked accumulation of free and esterified cholesterol in the right coronary artery from hyperlipidemic animals. Clofibrate treatment significantly reduced the content of esterified cholesterol in this vessel. Atherosclerotic pieces from the abdominal aorta were also rich in free and esterified cholesterol and showed a higher rate of proline and hydroxyproline incorporation than the adjacent normal tissue. The contents of proline and hydroxyproline were relatively unchanged, however, suggesting that there may be an increased turnover of protein and collagen synthesis rather than an increased total protein and collagen production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗