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Biomedical subjects

L Lindholm

Publications and source records attributed to L Lindholm.

At least 55 records · Page 3Linked to original sources

Non-obese men with high lipoprotein(a) values--a cardiovascular risk group different from those with the metabolic syndrome?

We have investigated the prevalence of cardiovascular risk factors including insulin and lipoprotein(a) in 40-year old men from the island of Oland (n = 314, 84% of those invited) in order to assess to what extent insulin and lipoprotein(a)--two of the currently discussed risk factors--correlated with each other, as well as with some of the more established risk factors. An inverse correlation was found in bivariate analyses between lipoprotein(a) and some of the risk factors for cardiovascular disease included in the 'metabolic syndrome' (triglycerides; r = -0.15, BMI; r = -0.18, and insulin/glucose ratio; r = -0.18) (p < 0.001). In multivariate analysis only the inverse correlation with triglycerides remained. Since lipoprotein(a) has been shown to be an independent risk factor for myocardial infarction, there may exist two subgroups of cardiovascular risk patients: one more obese, hyperinsulinaemic and with several metabolic derangements; and another comprising non-obese subjects with higher lipoprotein(a) values.

Adult↗

The effects of alpha-trinositol on haemodynamic variables and neuropeptide Y levels in a pilot study of hypertensives and healthy volunteers.

AIMS: The aim of this study was to examine the effects of D-myo-inositol-1,2,6-trisphosphate (alpha-trinositol) on haemodynamic variables and neuropeptide Y (NPY) levels in hypertensives and healthy volunteers. METHODS: Hypertensives (n = 13) and normotensives (n = 11) were recruited after a screening of cardiovascular risk factors of all men aged 40 living in a well defined area. The hypertensives were previously unmedicated. The effect of alpha-trinositol was studied after intravenous infusion at rest, and during and after a maximal exercise test in a double-blind crossover manner with placebo. RESULTS: Haemodynamic variables and NPY levels were recorded. NPY levels did not differ between normotensives and mild hypertensives at the start of the study. However, a significant increase was seen in hypertensives after they had risen to the sitting position. During exercise, the NPY levels increased significantly both in normotensives and hypertensives. After the exercise test, the NPY levels were significantly higher in hypertensives than in normotensives; alpha-trinositol did not modify these responses. In normotensives no significant difference in systolic blood pressure was seen during or after the exercise test whether they were on alpha-trinositol or placebo. In the hypertensives on active drug, however, the blood pressure tended to be approximately 5 mmHg lower during the exercise test as compared with the placebo group. In the hypertensives on active drug, the heart rate increased significantly more during exercise as compared with the placebo groups. In normotensives, the same tendency was seen, but it did not reach statistical significance. CONCLUSIONS: The NPY antagonist, alpha-trinositol, tends to reduce the increase in systolic blood pressure induced by maximal exercise and increases the heart rate in hypertensives but not in normotensives.

Adult↗

Discrimination of MUC1 mucins from other sialyl-Le(a)-carrying glycoproteins produced by colon carcinoma cells using a novel monoclonal antibody.

Earlier studies (Baeckström et al., J. Biol. Chem., 266: 21537-21547, 1991) have revealed that the colon carcinoma cell line COLO 205 produces two different proteins carrying the carcinoma-associated sialyl-Le(a) carbohydrate epitope. One is the MUC1 mucin apoprotein, and the other protein is smaller and has not been characterized in detail. This paper describes a comparison of COLO 205 with three other colon carcinoma cell lines, aided by the use of a novel MUC1-reactive monoclonal antibody, Ma552. Ma552 reacted with H-CanAg, the MUC1 mucin purified from COLO 205, the binding increasing greatly upon partial deglycosylation of H-CanAg with trifluoromethanesulfonic acid. This pattern of reactivity was in contrast with that of the MUC1-reactive monoclonal antibody HMFG-2, which did not recognize H-CanAg without prior deglycosylation. The nature of the epitope of Ma552 was further investigated using a synthetic peptide corresponding to the tandem-repeat sequence of the MUC1 protein. When the peptide was used as an inhibitor of antibody binding to immobilized, partially deglycosylated H-CanAg mucin, Ma552 was inhibited, as was HMFG-2. Using short, immobilized synthetic peptides identical to parts of the MUC1 tandem repeat, the reactivity of Ma552 was mapped to the hexapeptide TRPAPG. Ma552 and C50, a monoclonal antibody reactive with sialyl-Le(a), were used in immunofluorometric assays to analyze gel filtration fractions of extracts and spent media from the colorectal carcinoma cell lines COLO 205, SW1116, LoVo, and LS 174T. Using C50 in a homologous assay, all sialyl-Le(a)-carrying glycoproteins were detected. Among these, mucins based on the MUC1 apoprotein were identified using Ma552 and C50 in a combination assay. The results showed that sialyl-Le(a) was present on more than one glycoprotein not only in COLO 205 but also in SW1116 and LoVo. The Ma552/Eu-C50 assay revealed the presence of sialyl-Le(a)-carrying MUC1 in COLO 205 as expected, as well as in SW1116. The presence of MUC1 in Ma552-reactive fractions was confirmed by deglycosylation followed by assaying with the monoclonal antibody HMFG-2. Furthermore, Northern blots revealed the presence of MUC1 mRNA only in the two Ma552-positive cell lines.

Amino Acid Sequence↗

Cost-effectiveness of a tobacco 'quit and win' contest in Sweden.

Tobacco is one of the major causes of premature deaths in the world, and any effort to improve the cost-effectiveness of smoking cessation is worth while. The costs and effects in years of life saved (YLS) were estimated for a tobacco 'Quit and Win' (Q&W) contest in Sweden. The contest was conducted during the autumn of 1988 and included two strategies: a national mass media strategy and an organizational strategy for Stockholm County. A total of 12,840 people participated in the Q&W contest. The model for analysis included programme effects and programme costs, and the data was presented in (YLS). Both effects and costs were discounted. Data about non-smoking participants after 12 months and the number of spontaneous quitters was based on random samples of participants and of the general population, respectively. The programme costs included intervention as well as evaluation costs, e.g. costs of personnel, campaign materials, distribution, prizes for the contest, rent and administration and overhead costs for the project group and the collaborating organizations. The cost per YLS varied between US$188 and US$1222. The Q&W contest, as a method of helping tobacco users quit, compares favourably with most preventive and treatment programmes, and the method seems to be quite an effective way for society to use scarce resources.

Adolescent↗

Therapy with 125I-labelled internalized and non-internalized monoclonal antibodies in nude mice with human colon carcinoma xenografts.

The therapeutic effects of 125I-labelled (18-97 MBq) monoclonal antibodies (MAb) C-242, C-215 and S-S.1 were studied in nude mice with human colorectal adenocarcinoma tumours. The antibodies were administered 2 or 10-16 days after implantation of the tumour cells. The monoclonal antibody C-242 was internalized into the tumour cells, C-215 was internalized to a lower degree while S-S.1 (unspecific MAb) was not internalized at all. No enhanced therapeutic effect of 125I-C-242 was observed, as a result of Auger electrons, compared with 125I-C-215 and 125I-S-S.1.

Adenocarcinoma↗

To understand and alleviate suffering in a caring culture.

The purpose of this study is to help understand what suffering is, i.e. how patients and nurses describe suffering, and how suffering can be alleviated. The study has a descriptive-explorative design and its approach is phenomenological-hermeneutical. The informant (research group) are 11 nurses (nurses, doctors, hospital theologians) and five patients in a social-psychiatric nursing unit, based on Christian ideology. The results of the study show that the 'what' of suffering is unclear. The nurses tend to describe more the 'why' of suffering, i.e. the reason for suffering. The what of suffering is pain, fear, despair, lack of strength. It is a form of lack of freedom and non-motion. It is a struggle between wanting and knowing, between guilt and responsibility. The form of suffering tends to mould the caring relation. To be touched in some way by another in a meeting can alleviate the deepest suffering. Compassion will always alleviate suffering.

Attitude of Health Personnel↗

The cost of screening for hypercholesterolaemia--results from a clinical trial in Swedish primary health care.

The cost of screening for hypercholesterolaemia in a clinical trial was investigated at a primary health care centre. A convenience sample of the population was screened for inclusion in a study of the effectiveness of a lipid lowering programme. Included in the study were adults 30-59 years of age with a S-Cholesterol of 6.50-7.79 mmol l-1 at randomization, plus two previous values > or = 6.50 mmol l-1 at screening and selection, with at least two other cardiovascular risk factors. In total 447 persons were screened and 37 were randomized into the lipid lowering programme. The mean cost per randomized person was estimated at about SEK 7500 (Swedish Crowns). An analysis of different inclusion criteria for treatment was also carried out. The cost of finding a patient to treat in the clinical trial was estimated to be more than three times as high with a total cholesterol cut-off point of 7.80 mmol l-1 compared with a cut-off point of 5.20 mmol l-1.

Adult↗

[Young persons' image of health--a study of high school students' concept of health].

This study is part of the research project "Multidimensional Health". It is empirical and has a descriptive-explorative orientation. Its purpose is to describe high school students' idea of health and it focuses on hopes and possibilities. The theoretical frame of reference consists of a synthesis of theories according to J. J. Rousseau, E. H. Eriksson and K. Eriksson. The results of the study show that the young person's idea of health is relative to his stage of development and to his context. An essential part of the experience of health is the experience of possibility. The young persons' ideals of health consists of faith or confidence, hope and love. Courage is the basis of health for young persons.

Adolescent↗

Treating hypertension in the elderly.

Hypertension is a common problem in the elderly, with a prevalence of about 50%. The risk of cardiovascular disease and death is increased in hypertensive patients aged 60-79 years, whereas this increased risk seems to be diminished or even non-existent in those aged > or = 80 years. Antihypertensive drug treatment has been shown to be beneficial for most elderly patients but whether this is also true for the oldest patients is less clear. Treatment is more difficult in the elderly than in the middle aged or young because of the structural and functional alterations of the cardiovascular system associated with ageing (in particular the impairment of BP homeostasis), which contraindicate some drugs and impose a cautious use of the remaining ones. Isolated systolic hypertension increases the cardiovascular risk but we lack data on the efficacy of treatment in this group.

Age Factors↗

Angio-oedema in relation to treatment with angiotensin converting enzyme inhibitors.

OBJECTIVE: To evaluate and describe the clinical course of angio-oedema reactions induced by angiotensin converting enzyme inhibitors. DESIGN AND METHODS: All reports of angio-oedema reactions associated with angiotensin converting enzyme inhibitors submitted to Swedish Adverse Reactions Advisory Committee were reviewed and the clinical courses summarised. Numbers of cases judged to be induced by angiotensin converting enzyme inhibitors were related to their annual usage, estimated from total sales of defined daily doses, as well as to the estimated number of new patients. All cases of angio-oedema associated with angiotensin converting enzyme inhibitors reported to the World Health Organisation's international drug information system were also summarised. RESULTS: 36 of the 38 reported cases in Sweden between 1981 and 1990 were judged to be related to angiotensin converting enzyme inhibitors. During 1981 through 1990, altogether 1309 cases of angio-oedema associated with angiotensin converting enzyme inhibitors were registered with the international drug information system. The incidence of reported cases of angio-oedema increased largely in parallel with the increased sales (usage) of angiotensin converting enzyme inhibitors. Of the 36 Swedish patients, 77% experienced the reaction within the first three weeks after starting treatment. 10 patients needed hospitalisation, two of whom had life threatening laryngeal obstruction. With one exception all 36 patients were free of symptoms within one week after discontinuing the drug. CONCLUSIONS: Angio-oedema induced by angiotensin converting enzyme inhibitors is a rare but potentially life threatening reaction, which in most instances occurs shortly after the start of treatment. Any patient in whom the reaction is suspected should have the treatment interrupted and, if necessary, be admitted for observation.

Adult↗

Comparison of the biodistribution of 75Se- and 131I-labelled monoclonal antibodies in nude mice.

A monoclonal antibody, C-215, against colon cancer, was internally labelled with [75Se]methionine. The biodistribution was studied in tumour-bearing nude mice and compared with the biodistribution of [131I]C-215. The tissue uptake was divided into three parts: antibody bound to the antigen, antibody in the extracellular space and uptake of the released radionuclide. [75Se]C-215 showed a greater amount of antigen-bound antibody in the tumour, but also a greater unspecific uptake both in tumour and normal tissue.

Animals↗

Sensitivity and specificity of CA242 in gastro-intestinal cancer. A comparison with CEA, CA50 and CA 19-9.

A serological assay for the quantitative determination of the novel tumour-associated epitope CA242 was developed and used for determination of sensitivity and specificity of CA242 in gastrointestinal cancer. The CA242 assay showed a better tumour specificity than CA50 (and CA 19-9). This was most noticeable in benign hepatobiliary disease. The sensitivity at 90% specificity cut-off level was approximately three times higher for CA242 compared to CA50 in colo-rectal cancer Dukes A, B and C, while in pancreatic cancer the sensitivity of CA242 and CA50 was similar. CA242 was expressed independently of CEA, and the combination of CEA and CA242 gave in colo-rectal cancer considerably higher sensitivity than the use of only one of the markers. This was most pronounced in Dukes A and Dukes B patients. CA242 is a novel tumour marker of potential clinical use, particularly in colo-rectal cancer.

Animals↗

Coexpression of ganglioside antigen Fuc-GM1, neural-cell adhesion molecule, carcinoembryonic antigen, and carbohydrate tumor-associated antigen CA 50 in lung cancer.

With the aid of specific monoclonal antibodies, tumor tissues from 68 patients with lung cancer were examined for their expression of two small cell lung carcinoma (SCLC) antigens, Fuc-GM1 (fucosyl GM1; IV2FucII3NeuAc GgOse4) and neural-cell adhesion molecule (NCAM), and two broader tumor antigens, carcinoembryonic antigen (CEA) and carbohydrate cancer-associated antigen CA 50. Expression of Fuc-GM1 was seen in 75% and NCAM in 78% of the SCLC specimens, but also in 12 and 20% of non-SCLC. Either or both of these antigens were expressed in more than 90% of SCLC and in 25% of non-SCLC. CEA was found in more than 80% of SCLC and non-SCLC. Expression of CA 50 was seen in 65-68% of non-SCLC and SCLC, showing preference for SCLC and lung adenocarcinoma. In SCLC, cellular expression of Fuc-GM1 was generally seen together with NCAM and CA 50, but rarely with CEA. There was considerable inter- and intratumor heterogeneity in the expression of all four antigens. The results suggest that CEA is the antigen of choice for the detection of lung cancer regardless of histotype. In combined analysis of CEA, CA 50, Fuc-GM1 and NCAM, two patterns of antigen expression were recognized that appear to discriminate between SCLC and non-SCLC tumors, respectively. A considerable fraction of SCLC and non-SCLC tumors, however, exhibited similar patterns of antigen expression. The biological and clinical significance of these observations remains to be investigated.

Antibodies, Monoclonal↗

Monoclonal antibody C242-Pseudomonas exotoxin A. A specific and potent immunotoxin with antitumor activity on a human colon cancer xenograft in nude mice.

Two immunotoxins were constructed by chemically coupling the monoclonal antibody C242 to Pseudomonas exotoxin A (PE) or a modified form, NlysPE40, that lacks the cell binding domain of PE. Monoclonal antibody C242 recognizes a specific sialylated carbohydrate epitope on a high molecular weight membrane glycoprotein present on cells of human colon, pancreatic, and cervical cancers. C242-PE and C242-NlysPE40 were very cytotoxic for cells expressing this antigen with 50% inhibition of protein synthesis occurring on Colo205 cells at 0.2 ng/ml (0.9 pM) for C242-PE and 6.0 ng/ml (31 pM) for C242-NlysPE40. The two immunotoxins also exhibited a strong antitumor effect on a human colon cancer xenograft grown in nude mice. The specificity and potency of these two C242 immunotoxins warrant their further development for the treatment of cancer.

ADP Ribose Transferases↗