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Biomedical subjects

L Hansson

Publications and source records attributed to L Hansson.

At least 199 records · Page 11Linked to original sources

Reproductive history and cigarette smoking as risk factors for thyroid cancer in women: a population-based case-control study.

A population-based case-control study was conducted in Northern Norway and Central Sweden to investigate hormonal and reproductive factors and cigarette smoking as determinants of papillary and follicular thyroid carcinoma in women. Information on 191 histologically confirmed cases and 341 age-matched controls was included. No clear association was found with regard to the number of live births, number of pregnancies, a history of incomplete pregnancies, or the use of oral contraceptives or hormonal replacement therapy. However, an early first childbirth (before 20 years of age, or less than 5 years after menarche) was associated with an increased risk of thyroid cancer. There was an increased risk of thyroid cancer among women with a history of artificial menopause compared to those with a spontaneous menopause [odds ratio (OR), 2.52; 95% confidence interval (CI), 0.96-6.62], which was more pronounced for the papillary carcinoma and after adjustment for age at menopause and use of replacement therapy. Cigarette smokers had a decreased risk of borderline statistical significance compared to nonsmokers (OR, 0.69; 95% CI, 0.47-1.01), particularly among premenopausal women (OR, 0.60; 95% CI, 0.38-0.96). This negative association persisted after adjustment for parity, hormonal treatments, and education. Women who started smoking before the age of 15 experienced a marked reduction in risk (OR, 0.38%; 95% CI, 0.18-0.80¿). Moreover, there was a suggestion of a dose-response effect with the amount of cigarettes smoked daily and with duration of the habit. Both the increased risk of artificial menopause and the negative association with smoking are compatible with a relation between levels of estrogens and thyroid cancer among women.

Adenocarcinoma, Follicular↗

How to study the role of hypertension in atherosclerosis. Lessons from MIDAS. Multicentre Isradipine Diuretic Atherosclerosis Study.

The development of atherosclerosis is clearly linked to the level of blood pressure. This is illustrated by the difference of atheroma formation in arteries as compared to veins, the development of atherosclerosis in veins transplanted to the arterial circulation or the finding of atherosclerosis also in the pulmonary circulation as an effect of pulmonary hypertension. Several experimental studies have also illuminated the strong link between high blood pressure and the development of atherosclerosis. From a therapeutic point of view it is worth noting that the lowering of blood pressure per se has a positive effect on the development of atherosclerosis. In particular, calcium antagonists have been shown, in numerous experimental studies, to have an antiatherosclerotic effect. The positive results in animal studies led to studies in man, the first of which was the MIDAS Study. The Multicentre Isradipine Diuretic Atherosclerosis (MIDAS) Study was a comparison between the dihydropyridine-derived calcium antagonist isradipine and hydrochlorothiazide in 883 hypertensive patients. B-mode ultrasonography of the carotid artery was used in order to evaluate changes in wall thickness and the development of atherosclerotic plaques during a 3-year period. The final publication has yet to appear in a medical journal. However, the study and its main findings have been presented at several international scientific meetings. In brief, isradipine was significantly more effective than hydrochlorothiazide in preventing an increase in intima-media thickness at several points of measurement in the carotid artery in spite of the fact that systolic blood pressure was not lowered as effectively by isradipine as by the diuretic therapy. There are numerous lessons to be learnt from MIDAS for future studies of this kind. A good example of this is the European Lacidipine Study of Atherosclerosis (ELSA) which is currently in progress in several European countries. By careful analysis of MIDAS an improved study design has been created, which should result in a definitive and irrefutable answer to the issue of the clinical importance of calcium antagonist treatment in the prevention of atherosclerosis.

Arteriosclerosis↗

Long-term effects of losartan on blood pressure and left ventricular structure in essential hypertension.

In a 12-week, randomized, double-blind study, 24 patients with essential hypertension were given the angiotensin II antagonist losartan, or the beta-adrenoceptor blocker atenolol. Both drugs reduced blood pressure (BP) well, but losartan tended to reduce left ventricular mass (LVM) in contrast to atenolol. Following the double-blind phase 19 patients entered an open treatment period with losartan and additional treatment if BP was uncontrolled. LV structures were measured by echocardiography. The mean follow-up period was 29 +/- 2.6 (range 26-32) months. BP was reduced from 155.6 +/- 15.6/103.4 +/- 5.2 mm Hg to 131.3 +/- 10.5/82.7 +/- 3.3 mm Hg (P < 0.001). LV internal diameter was reduced (50.7 +/- 4.5 to 49.1 +/- 4.0 mm; P = 0.006), while there was an increase in interventricular septal thickness (10.2 +/- 1.1 to 11.2 +/- 1.3 mm; P = 0.001) and posterior wall thickness (10.0 +/- 0.9 to 10.6 +/- 1.1 mm; P = 0.023). Calculated LVM was not significantly altered during the follow-up period. In conclusion, losartan is effective in reducing BP during long-term treatment. No significant effect on LVM was observed, but there was an increase in LV wall thickness.

Adult↗

Differences in the glycosylation of recombinant and native human milk bile salt-stimulated lipase revealed by peptide mapping.

The milk of some mammals contains a bile salt-stimulated lipase (BSSL). Human milk BSSL is heavily glycosylated (30-40% carbohydrate) and present at a concentration of approximately 100-200 mg/l, thereby being one of the most abundant human whey proteins. BSSL has been shown to have an important role in the uptake of energy from human milk. The risk of HIV contamination has restricted the use of banked human milk for nutritional purposes. This has evoked an interest in the production of a recombinant form of the protein for supplementation of formula. We have produced BSSL in mouse C127 and hamster CHO cells, and used chromatographic methods for the characterization of the products. This study was focused on study of the glycosylation of the protein by using peptide mapping and isolation of glycosylated fragments. The results show how human BSSLs from different sources differ both in extent of glycosylation, in glycan heterogeneity, and in lectin binding.

Animals↗

Carbohydrate specificity of the Escherichia coli P-pilus papG protein is mediated by its N-terminal part.

The adherence of pyelonephritic Escherichia coli isolates to mammalian host cells is mediated by the P-pili structures on the bacterial surface. The protein constituting the distal part of the pili structure, papG, interacts with glycan receptors on the host cell. Variation in specificity for different glycoconjugates between the isolates, that may reflect variation in host tropism, has been correlated to three different classes of papG. Truncated variants of the class I, II and III papG adhesins were produced as fusion protein in E. coli and analysed for carbohydrate binding. The results showed that both carbohydrate binding and specificity of the papG adhesin resided in a linear part of the N-terminus of the protein.

Adhesins, Escherichia coli↗

Recombinant human-milk bile-salt-stimulated lipase. Functional properties are retained in the absence of glycosylation and the unique proline-rich repeats.

Human milk bile-salt-stimulated lipase ensures efficient utilization of milk lipid in breast-fed infants. The N-terminal two-thirds of the peptide chain is highly conserved and shows striking similarities to typical esterases. In contrast, the remaining C-terminal part consists of a unique sequence of 16 proline-rich O-glycosylated repeats of 11 residues each. Recently we could show, using recombinant lipase variants, that neither these repeats nor the single N-linked sugar chain are essential for catalytic efficiency. In the present study, we report on the lack of importance of glycosylation and the unique repeats for other important functional properties, i.e. bile-salt activation, heparin binding, heat stability, stability at low pH and resistance to proteolytic inactivation. Compared to native enzyme, recombinant full-length lipase produced in two mammalian cell lines differed slightly in glycosylation pattern with no effects on the functional properties. Moreover, a variant lacking all repeats and the C-terminal tail following the last repeat exhibited the same functional characteristics as purified native milk enzyme. Thus, the structural basis for all the typical and functionally important properties reside in the N-terminal conserved part, in spite of the fact that none of these properties are shared by typical esterases. We could however, demonstrate that the C-terminal repeats are responsible for the unusual behaviour of the enzyme in size-exclusion chromatography, resulting in a considerably higher than expected apparent molecular mass.

Animals↗

Expression of truncated and full-length forms of the Lyme disease Borrelia outer surface protein A in Escherichia coli.

The lipidated major outer surface protein, OspA, of the Lyme disease spirochaete may be important in the pathogenesis during Lyme borreliosis. To produce sufficient amounts of purified OspA variants to perform pathogenesis studies in vivo and in vitro, different recombinant OspA expression systems in Escherichia coli were constructed. Recombinant OspA variants were produced as a full-length molecule, as a truncated variant lacking the N-terminal lipidated cysteine, or as a fusion protein with the synthetic dimer of Staphylococcus aureus protein A IgG binding domain (ZZ). In order to produce the full-length protein, four different promoters were evaluated. These were combined with either the OspA original signal sequence or the E. coli Brauns lipoprotein signal sequence, lpp. The most efficient production of the full-length lipidated OspA was mediated by the constitutive beta-lactamase promoter in combination with lipoprotein signal sequences. For production of truncated nonlipidated OspA the S. aureus protein A signal sequence was ligated to the OspA open reading frame. Alternatively, truncated OspA was produced intracellularly using expression vectors that lack signal sequences. Production of nonlipidated protein with a heterologous signal peptide resulted in a soluble protein located mainly in the periplasm and in the culture medium. The full-length lipidated OspA, on the other hand, was associated mainly with the membrane fraction. The production level of the lipidated recombinant OspA was much lower than the level obtained with the truncated ZZ-OspA fusion protein.

Antigens, Surface↗

Cardioprotective potential of antihypertensives.

The main reason for treating arterial hypertension is obviously to reduce hypertension-induced cardiovascular morbidity and mortality. Numerous studies have demonstrated a preventive effect against stroke when elevated blood pressure has been lowered by pharmacological intervention. A preventive effect of such therapy has also been shown with regard to coronary heart disease (CHD). However, the issue here is much less clear, perhaps because diuretics have been the main therapy in the majority of the large intervention trials. There are reasons to believe that newer therapy, e.g., the angiotensin converting enzyme inhibitors, would be more effective in preventing CHD in hypertensive patients. Some of this evidence will be reviewed in this paper.

Adrenergic beta-Antagonists↗

What is important in psychiatric outpatient care? Quality of care from the patient's perspective.

The development of quality assurance programmes for psychiatric care has increased the interest in quality of care and accountability from the patient's perspective. The aims of this study were threefold. First, to map descriptive characteristics of ideal outpatient psychiatric care through open-ended patient interviews, using a sample of 94 psychiatric outpatients, second, to have another sample of 84 outpatients rank the importance of 57 treatment characteristics extracted from the qualitative analysis of the interviews, and third to make comparisons with a previously performed investigation on quality of care of psychiatric inpatients. Results of the content analysis showed that characteristics of ideal outpatient treatment could be classified in eight content categories: accessibility of care, treatment content, staff-patient relationship, continuity of care, staff's professionalism, patient information/co-influence, treatment environment and cost of care. Results from the patients' rating of the importance of treatment characteristics showed that patients put the highest emphasis on staff's empathetic qualities in being interested, understanding, listening and respecting patients. Comparisons with the previously studied inpatient sample, showed great similarities in what was considered important to reach a satisfactory care situation. It is concluded that in order to secure content validity of investigations of the quality of psychiatric care from the patient's perspective, effort should be put into including the areas of staff-patient relationship and patient information and co-influence.

Adult↗

Choosing the optimal antihypertensive dose regimen.

THE OPTIMAL DOSE-RESPONSE CURVE: From a pharmacological point of view the optimal dose regimen of an antihypertensive agent is relatively easy to define. By constructing dose-response curves the most effective dose can usually be identified. From a clinical point of view the problem is more complicated. FACTORS THAT INFLUENCE THE IDEAL CLINICAL DOSE: The most important consideration is the relationship between efficacy and adverse effects. Ideally, dose-response curves for both antihypertensive efficacy and adverse effects should be produced. From these curves the optimal dose may be established. Drugs such as lacidipine that demonstrate a good overlap between efficacy and tolerability provide a wide therapeutic window. PRACTICAL CONSIDERATIONS: It may be less effective to increase the dose of a single drug until the desired effect is obtained; the addition of another therapeutic agent is often preferable. Cost is also a factor. If the dose-response curve flattens, it may not be cost-effective to recommend a higher dose, even if the higher dose is slightly more effective. Furthermore, if an unnecessarily high dose has been recommended, doctors will soon learn to prescribe half the dose or less, which may have budgetary implications for the manufacturer. The choice of the optimal dose regimen is a complicated, multifactorial problem. The aim is to find a reasonable balance between efficacy and adverse effects, at a competitive cost.

Antihypertensive Agents↗

Human milk kappa-casein and inhibition of Helicobacter pylori adhesion to human gastric mucosa.

Readily digested caseins, which account for almost half of the protein content in human milk, are important as nutritional protein for breast-fed infants. It has also been advocated that part of the antimicrobial activity of human milk resides in the caseins, most likely the glycosyated K-casein. Top explore this possibility, we purified K-casein from human milk to homogeneity by a two-step size-exclusion chromatography procedure. Purified human K-casein, in contrast to K-casein purified from bovine milk, effectively inhibited the cell lineage-specific adhesion of fluoroisothiocyanate-labeled Helicobacter pylori to human gastric surface mucous cells. The inhibitory activity was abolished by metaperiodate oxidation and considerably reduced by preincubation with alpha-L-fucosidase but not with alpha-N-acetylneuraminidase or endo-beta-galactosidase. These results strongly support the view that fucose containing carbohydrate moieties of human K-casein are important for inhibition of H. pylori adhesion and, thus, infection. They also suggest that breastfeeding may protect from infection by H. pylori during early life and that species-specific glycosylation patterns, as illustrated by human bovine K-casein, partly determine both the narrow host spectrum of this human gastric pathogen and the capacity to resist infection.

Animals↗

The Nordic comparative study on sectorized psychiatry. II. Resources of the psychiatric services and treated incidence.

As a part of a Nordic comparative study on sectorized psychiatry, treated incidence was related to the resources and dynamic qualities of psychiatric services in 7 catchment areas. One-year treated incidence cohorts were used. Data was collected concerning number of beds and staff, number of long-term patients and turnover rate of patients in the services and availability of specialized services. A positive correlation was found between rates of outpatient staff and treated incidence. No statistically significant correlation was found between the dynamic qualities of the services and treated incidence. Treated incidence of dependence was the highest in a center that had a special service unit for abusers. Special services for young and old people were not clearly reflected in treated incidence in respective patient groups.

Adolescent↗

The assessment of needs in psychiatric patients. Interrater reliability of the Swedish version of the Camberwell Assessment of Needs instrument and results from a cross-sectional study.

The assessment of needs has been put forth as an important dimension in both the planning, development and evaluation of psychiatric services. A needs assessment tool for routine use should ideally be brief, not require additional staff, be valid and reliable with respect to setting, gender and culture, and also be sensitive to changes in needs and differences in needs between subgroups of patients. In this study, the interrater reliability of the Swedish version of the Camberwell Assessment of Needs instruments (CAN), measuring needs in 22 areas, was investigated in a cross-sectional sample consisting of 119 psychiatric inpatients and outpatients. The prevalence and severity of needs, prevalence of unmet needs, as well as current help received was also investigated. The interrater reliability of the instrument was found to be good both measured as total percentages of agreement in ratings, where an agreement of 80% or above was found in 90% of the comparisons, and as measured by Cohen's kappa. Predominant needs in the sample were in addition to clinical needs concerning psychological distress and psychotic symptoms, social needs such as the need for company, daytime activities and information concerning condition and treatment. The CAN seems to be a instrument with a high interrater reliability also when used under routine conditions as in this study. It also seems to have a high degree of feasibility with regard to different types of patients and settings and a sensitivity concerning differences in needs in subgroups of patients.

Adolescent↗

Psychiatric morbidity in primary public health care: a Nordic multicentre investigation. Part I: method and prevalence of psychiatric morbidity.

The prevalence of mental illness in five different Scandinavian primary care populations was investigated in this study. Patients consecutively consulting their general practitioner a particular week-day were included in the study. Initially the SCL-25 was applied and next the high scores and a sample of the low scores were interviewed by the PSE. In the analysis the screening procedure was first validated. The internal validity of the SCL was tested by means of Rasch latent structure analysis and the external validity tested by ROC/QROC analysis. Based on this, a short 8-item version of the SCL was developed. The prevalence of mental illness in all centres was 0.26 with a minimum of 0.14 in Nacka and a maximum of 0.34 in Turku.

Adolescent↗

The Nordic comparative study on sectorized psychiatry. I. Treated point prevalence and characteristics of the psychiatric services.

Comparative studies relating characteristics of psychiatric services to rates of treated prevalence are scarce. As part of a Nordic comparative study on sectorized psychiatry, a point-prevalence study was performed in 5 sectorized psychiatric services with comprehensive service facilities for a defined population under responsibility. The rates of treated prevalence on a census day were related to a number of characteristics of the respective services and to accessibility of care. The results showed a great variation in one-day point prevalence in the 5 services, with almost fourfold differences. There were also marked differences in the diagnostic distribution of the cohorts. A positive correlation was found between number of beds and point prevalence, measured both as total point prevalence and impatient prevalence. The rates of beds and psychiatrists were most strongly related to the prevalence of patients with organic disorders and functional psychoses. A closed referral system was associated with a lower level of treated prevalence.

Adolescent↗