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Biomedical subjects

L Hansson

Publications and source records attributed to L Hansson.

At least 163 records · Page 9Linked to original sources
PubMed1997

The Hypertension Optimal Treatment (HOT) Study: 24-month data on blood pressure and tolerability.

The Hypertension Optimal Treatment (HOT) Study is an ongoing prospective randomized, multicentre trial conducted in 26 countries. There are two main aims of the study. The first is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and the incidence of cardiovascular morbidity and mortality in hypertensive patients. The second is to determine the effect on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) compared with placebo. Altogether 18,790 patients have been recruited and randomized, and two-year data are now available for all patients. This is a report on the blood pressures achieved, the tolerability, and other available data after 24 months of follow-up of all patients. Special emphasis is given to the subgroup of elderly patients (> or = 65 years, n = 5988) compared with young patients (< 65 years, n = 12 802). On average, patients in the < or = 90 mmHg diastolic blood pressure target group have reached 85 mmHg, in the < or = 85 mmHg target group patients have reached 83 mmHg and in the < or = 80 mmHg target group patients have reached 81 mmHg. The percentage of those achieving target blood pressure in each target group at 24 months of follow-up is 85% in the < or = 90 mmHg target group, 75% in the < or = 85 mmHg target group and 57% in the < or = 80 mmHg target group. In the elderly subgroup (> or = 65 years of age), the percentage of patients achieving target at 24 months is higher for all target groups, namely 89% in the < or = 90 mmHg group, 80% in the 85 mmHg group and 62% in the 80 mmHg group. Antihypertensive treatment was initiated with a calcium antagonist, felodipine, at a dose of 5 mg once daily. If target blood pressure was not reached, additional antihypertensive therapy, with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent, was given. Further dose adjustments were made in accordance with a set protocol. As a fifth, and final, step, a diuretic could be added. There have been relatively few side effects in this large, multinational study of hypertensive patients. Only ankle oedema and coughing exceed a frequency of 0.5% (ankle oedema 1.3% in young and 1.7% in elderly; coughing 0.5% in young and elderly). After two years, 84% of all patients are still taking their baseline therapy, felodipine. The 24-month data presented here indicate that it should be possible to fulfil the primary aims of the HOT Study.

Aged↗
PubMed1997

The Captopril Prevention Project (CAPPP) in hypertension--baseline data and current status.

The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality. The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension. The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase. The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.

Adult↗
PubMed1997

Success in the treatment of hypertension: a status report.

BACKGROUND: Pharmacological intervention studies aimed at lowering elevated blood pressure have shown that stroke, and to a lesser degree coronary heart disease, morbidity and mortality are positively affected. These beneficial effects appear to have been obtained mainly with diuretics and beta-adrenoceptor blocking agents, as shown in a meta-analysis of 13 large prospective intervention trials in hypertension. PREVIOUS STUDIES: Benefits of pharmacological antihypertensive treatment were observed in the treatment of patients with malignant hypertension in the late 1950s and early 1960s. Many of these studies were conducted before diuretics became clinically available and long before the first reports of the antihypertensive effect of beta-blockers were published. PROSPECTIVE STUDIES: Prospective intervention trials with newer antihypertensive agents such as calcium antagonists and angiotensin converting enzyme inhibitors are currently in progress. Three recently, open, retrospective case-control studies dealing with comparisons of various antihypertensive drug classes with regard to their effect on cardiovascular mortality have attracted interest. FUTURE BENEFITS: Another question of considerable clinical importance is how far blood pressure should be lowered in order to extract the maximum benefit of treatment. This issue is currently being investigated.

Antihypertensive Agents↗
PubMed1997

Medical and cost-economy aspects of modern antihypertensive therapy--with special reference to 2 years of clinical experience with losartan.

Health economy is often addressed in terms of acquisition cost, i.e. the cost of the pill. For various reasons, mainly the stricter demands from drug regulatory agencies (increased development costs), novel agents must be expected to be more expensive than older drugs. However, if the costs of changing therapy and the costs induced by side effects and extra clinic visits are considered, the economic aspects become less of a consideration. If compliance is enhanced and better blood pressure control is achieved with the newer agents, then the therapeutic gains must be weighed against the economic aspects. Losartan, the first agent of the new class of angiotensin II receptor antagonists of the AT1 type, has been available for clinical use for more than 2 years. Losartan has proven antihypertensive effects and its safety profile in the initial controlled trials (approximately 2900 patients) and in general practice (more than 14,000 patients in Sweden) has been very good. Its effect on long-term morbidity and mortality has not yet been established but a large mortality endpoint trial is underway in hypertensive patients with cardiac hypertrophy (the LIFE trial). In heart failure, losartan has been shown to reduce 3-month mortality (the ELITE trial). Although it is too early to assess the full therapeutic benefit of losartan in relation to the total patient costs, its efficacy and low incidence of side effects has made it a useful new therapy for the treatment of hypertension.

Antihypertensive Agents↗
PubMed1997

Evaluation of endpoints in hypertension.

Cardiovascular mortality is the undisputed "hard endpoint" in hypertension intervention trials. Non-fatal myocardial infarction and stroke are frequently included in this category as well. For obvious reasons, such hard endpoints are not always realistic in relatively short-term (3-5 years) trials comprising patients with a relatively low absolute risk, such as mild hypertension. Nor are they directly applicable in the daily clinical routine care of hypertensive patients. In most situations intermediate endpoints are used as substitutes for the hard endpoints. These intermediate or substitute endpoints are sometimes referred to as surrogate endpoints. The most frequently used intermediate endpoint is blood pressure itself. It is also a most relevant substitute endpoint, being easy to measure and evaluate in routine clinical practice. Blood pressure is obviously a very strong predictor of cardiovascular risks, particularly as regards stroke. An ongoing large intervention trial in hypertension, the Hypertension Optimal Treatment (HOT) Study is specifically designed to evaluate the obtained level of treated blood pressure in relation to hard endpoints such as fatal and non-fatal stroke and myocardial infarction as well as other cardiovascular mortality. In view of the strong link between blood pressure and prognosis in hypertension, as demonstrated in several epidemiologic studies, it is disappointing to note that several recent reports show that only a minority of treated hypertensive patients are well controlled.

Blood Pressure↗
PubMed1996

Structure of the human kappa-casein gene.

The human kappa-casein-encoding gene, Kca, was cloned and sequenced. The structural gene consists of five exons ranging from 33 to 496 nucleotides (nt) separated by introns ranging from 1146 to 2942 nt, and extends over 8821 nt. All intron/exon splice junctions conform to the GT/AG rule. The gene organization is similar to that of the bovine gene. The 5'-flanking region contains an A + T-rich sequence; TTTAATT, close to where the TATA motif is found in most other genes, a CAAT box, and an AP-1 consensus sequence. In addition, one Alu repetitive element was found in the second intron.

Amino Acid Sequence↗
PubMed1996

Characterisation of the complex of plasminogen activator inhibitor type 1 with tissue-type plasminogen activator by mass spectrometry and size-exclusion chromatography.

Glycosylated human plasminogen activator inhibitor type 1 (PAI-1), produced in Chinese hamster ovary (CHO) cells, showed a variety of compounds with different molecular weights when subjected to electrospray mass spectrometry (ES-MS), owing to the heterogeneity of the carbohydrate chains. However, non-glycosylated human PAI-1, produced in E. coli, gave rise to a prominent species with a molecular weight of 42,774, consistent with the amino-acid sequence. A non-glycosylated mutant of the proteinase domain (B-chain) of tissue-type plasminogen activator (tPA) produced in C 127 cells, had a molecular weight of 28,168. Full-length, glycosylated, tPA showed a large heterogeneity in molecular mass. For a mass study, a tPA-PAI-1 complex was formed, composed of non-glycosylated PAI-1 and non-glycosylated B-chain. This complex was remarkably stable at room temperature in buffer with a neutral pH. The mass spectrum of the complex provided two main species, a peptide with a mass of 3803 and a dominating species of 67,133. These masses are consistent with a complex where PAI-1 is cleaved at the P1-P1' position. A trace of a species with a molecular mass of 70,942 was also found, corresponding to the complete, non-dissociated complex with PAI-1. Separation of the cleaved peptide, corresponding to the hydrophobic C-terminal 33 amino-acid residues of PAI-1, from the complex, was achieved by size-exclusion chromatography in the presence of 30% acetonitrile. Thus, in the complex between tPA and PAI-1, the proteins are held together by a tight covalent bond, but the C-terminal cleaved peptide of PAI-1 is only bound to the complex by hydrophobic forces. To assess whether this is specific to the tPA B-chain alone, experiments with the complex of full-length, glycosylated tPA and glycosylated PAI-1 were also performed, and it was possible to demonstrate the release of the C-terminal PAI-1 peptide by chromatography, mass spectrometry, as well as by SDS-PAGE.

Amino Acid Sequence↗
PubMed1996

The Nordic comparative study on sectorized psychiatry. Utilization of psychiatric hospital care related to amount and allocation of resources to psychiatric services.

As a part of a Nordic comparative study on sectorized psychiatry, utilization of inpatient care was related to resources and dynamic qualities of psychiatric services in seven catchment areas in four Nordic countries. One-year treated incidence cohorts were used. Each patient was followed for 1 year after first contact with the psychiatric service. Data were collected concerning number of beds and staff, number of long-term patients and turnover rate of patients in inpatient care. Findings gave some support to the earlier reports that the utilization of inpatient care is determined by the supply of available beds. Highly staffed community services did not themselves reduce the use of inpatient services, but availability of day care services seemed to reduce utilization of inpatient care among psychotic patients.

Adult↗
PubMed1996

The Nordic Comparative Study on Sectorized Psychiatry. III. Accessibility of psychiatric services, degree of urbanization and treated incidence.

As part of a Nordic Comparative Study on Sectorized Psychiatry, accessibility of psychiatric services and degree of urbanization in seven catchment areas were related to treated incidence. One-year treated incidence cohorts were used. Accessibility was assessed according to referral practice, existence of a round the clock emergency service and geographical location of the services. Accessibility was surprisingly weakly associated with treated incidence. Easy access to the psychiatric services was not related to a high treated incidence of less severe psychiatric problems at the expense of patients suffering from severe illness. Geographical distance to the services did not predict the demand for services. A positive correlation was found between the degree of urbanization and treated incidence of psychoses but not of other diagnostic groups.

Adolescent↗
PubMed1996

Recombinant human bile salt-stimulated lipase: an example of defective O-glycosylation of a protein produced in milk of transgenic mice.

The expression of recombinant human bile salt-stimulated lipase (bssl) was targeted to the lactating mammary gland of transgenic mice. Expression of recombinant genes comprising bsslcDNA, or alternatively genomic bssl DNA, under control of regulatory elements derived from the murine whey acidic protein (wap) gene was achieved and evaluated. Constructs containing genomic bssl sequences mediated high levels (0.5-1 mg ml-1) of recombinant human BSSL in the milk. The recombinant BSSL produced was purified, biochemically characterized and compared to native BSSL and recombinant BSSL produced in mouse C127 and hamster CHO cells. Recombinant BSSL derived from transgenic mice showed a different migration and distribution after SDS-PAGE electrophoresis, lower apparent molecular mass on size-exclusion chromatography and no detectable interactions with a panel of lectins. These results indicate a significantly lower degree of O-glycosylation of recombinant BSSL in milk from transgenic mice than was found for the native enzyme or recombinant CHO- or C127 cell-produced BSSL. Despite these differences, mouse-milk-derived recombinant BSSL exhibited similar lipase activity, the same stability to low pH and similar sensitivity to elevated temperatures as the native enzyme. The observation that mouse-C127-cell-produced recombinant BSSL is heavily O-glycosylated makes species-related restrictions less attractive as an explanation for the reduced O-glycosylation.

Animals↗