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Biomedical subjects

J Lanke

Publications and source records attributed to J Lanke.

At least 19 recordsLinked to original sources

Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.

BACKGROUND: Angiotensin-converting-enzyme (ACE) inhibitors have been used for more than a decade to treat high blood pressure, despite the lack of data from randomised intervention trials to show that such treatment affects cardiovascular morbidity and mortality. The Captopril Prevention Project (CAPPP) is a randomised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension. METHODS: CAPPP was a prospective, randomised, open trial with blinded endpoint evaluation. 10,985 patients were enrolled at 536 health centres in Sweden and Finland. Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were randomly assigned captopril or conventional antihypertensive treatment (diuretics, beta-blockers). Analysis was by intention-to-treat. The primary endpoint was a composite of fatal and non-fatal myocardial infarction, stroke, and other cardiovascular deaths. FINDINGS: Of 5492 patients assigned captopril and 5493 assigned conventional therapy, 14 and 13, respectively, were lost to follow-up. Primary endpoint events occurred in 363 patients in the captopril group (11.1 per 1000 patient-years) and 335 in the conventional-treatment group (10.2 per 1000 patient-years; relative risk 1.05 [95% CI 0.90-1.22], p=0-52). Cardiovascular mortality was lower with captopril than with conventional treatment (76 vs 95 events; relative risk 0.77 [0.57-1-04], p=0.092), the rate of fatal and non-fatal myocardial infarction was similar (162 vs 161), but fatal and non-fatal stroke was more common with captopril (189 vs 148; 1.25 [1-01-1-55]. p=0.044). INTERPRETATION: Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality. The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients randomised to conventional therapy.

Adrenergic beta-Antagonists

Improved classifications of myocardial bull's-eye scintigrams with computer-based decision support system.

UNLABELLED: In a recent study, artificial neural networks were trained to detect coronary artery disease using scintigraphic data as input. The performance of the networks was better than that of human experts using coronary angiography as a gold standard. In clinical practice, this type of neural networks will not take over the decision-making process from the physician but will assist by proposing an interpretation of the scintigram. The purpose of this study was to assess the influence of such decision support on the interpretations of the physicians. METHODS: A population of 135 patients who had undergone both myocardial 99mTc-sestamibi rest/stress scintigraphy and coronary angiography within a 3-mo period was studied. An image set consisting of the bull's-eye rest, stress, difference and quote images was constructed for each patient. Three experienced physicians independently classified all image sets regarding the presence and/or absence of coronary artery disease in two vascular territories using a four-grade scale. The physicians classified the image sets twice with and twice without the advice of artificial neural networks. RESULTS: The joint evaluation of the three physicians showed significantly improved performance with decision support, measured as increases in the areas under the receiver operating characteristic curves from 0.65 to 0.70 (P = 0.018) and from 0.79 to 0.82 (P = 0.006) for two vascular territories. Furthermore, the joint evaluation showed significantly less intraobserver and interobserver variability with decision support. CONCLUSION: Physicians classifying myocardial bull's-eye images benefit from the advice of artificial neural networks. These results show the high potential for neural networks as clinical decision support systems.

Adult

The effect of genetic factors for longevity: a comparison of identical and fraternal twins in the Swedish Twin Registry.

BACKGROUND: The relative importance of genetic influences on longevity was studied on data from the population-based Swedish Twin Registry. METHODS: A sample of 3,656 identical and 6,849 like-sexed fraternal twin pairs was studied regarding mortality rates and within-pair similarity for age at death. Genetic and environmental contributions to variation in longevity, expressed by integrated mortality rates, were estimated from a subsample of 1,734 twin pairs reared together and 130 twin pairs reared apart from the cohorts born 1886 to 1900. RESULTS: The intraclass correlation coefficients suggested that the genetic effect was small, and, for males, perhaps absent. Among pairs in which both twins died relatively young and among pairs in which both twins lived until very old age, the variance in age at death seemed to have no genetic component. Model fitting procedures based on twins reared apart and twins reared together indicated that most of the variance in longevity was explained by environmental factors. CONCLUSIONS: Over the total age range examined, a maximum of around one third of the variance in longevity is attributable to genetic factors, and almost all of the remaining variance is due to nonshared, individual specific environmental factors. The evidence that genetic factors play a minor role depending upon age at death merits further examination.

Adult

Old patients with hypertension. A 25-year observational study of a geographically defined population (Dalby), aged 67 years at entry.

OBJECTIVES: To evaluate the impact of hypertension and other risk factors on mortality, in particular cardiovascular mortality, in a geographically defined population of elderly subjects. DESIGN: An observational 25-year study of a total population. SETTING: The local health centre in the village of Dalby in southern Sweden. SUBJECTS: All men and women born in 1902 or 1903, living in Dalby, were, at the age of 67, invited for medical and psychological examinations. The population comprised 188 subjects (109 men and 79 women); 156 (83%) of them took part in the first medical examination. Blood pressure, heart rate, weight and height were measured and laboratory tests performed at entry. Blood pressures were thereafter recorded six times, and this report is based on a 25-year follow-up period ending in October 1994. MAIN OUTCOME MEASURES: Survival analyses were performed, based on definition of underlying causes of death, divided into all-cause and cardiovascular. RESULTS: At entry, females had higher blood pressure than males, both at baseline and during the first 16 years of the study, regardless of whether they were hypertensives or not. Most men smoked but only a few women. At the end of the follow-up of the present study in 1994, 138 out of 156 (88%) subjects had died and only 18 (12%) remained alive; 78 (57%) had died of a cardiovascular disease. In men, a diagnosis of hypertension as well as increased blood pressure at entry was associated with increased mortality. In women this was the case for blood pressure and risk of cardiovascular mortality. In men, both systolic and diastolic blood pressures during the study were significant risk factors for death, whereas in women this was not the case. CONCLUSIONS: Elderly male hypertensives ran an increased mortality risk even though they were treated according to the then current guidelines; female hypertensives seemed to run the same risk of dying as normotensive females.

Aged

Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum beta 2-microglobulin/cystatin C-ratio.

Recent studies have indicated that serum and plasma cystatin C are better markers for glomerular filtration rate (GFR) than serum creatinine, ubiquitously used for this purpose. To fully exploit the value of serum and plasma cystatin C as GFR markers, reliable age and sex-correlated reference intervals are required. The present study comprised cystatin C determinations in plasma and sera from 259 individuals from a well-defined area in the southernmost part of Sweden. From demographic lists two men and two women were randomly selected from each one-year birth cohort above 20 years of age. No sex differences were found for plasma and serum cystatin C, whereas an increase in the cystatin C levels with age was noted, corresponding to the known age-related decrease in GFR. The following reference intervals are recommended for practical clinical use: S-Cystatin C (both sexes): 20-50 years, 0.70-1.21 mg l-1 and 50+ years, 0.84-1.55 mg l-1. The same samples were also used for determination of beta 2-microglobulin levels in order to calculate reference intervals for the beta 2-microglobulin/cystatin C-ratio, which is a more distinct marker for cell proliferation, particularly lymphoproliferation, than is the serum level of beta 2-microglobulin alone, since the ratio should be virtually uninfluenced by GFR. The beta 2-microglobulin/cystatin C-ratios were uninfluenced by sex and age and 1.45-2.43 is recommended as the serum reference interval for practical clinical use. Serum creatinine was determined in the same samples and the creatinine level was found to be strongly influenced by sex and weakly by age.

Adult

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

Infantile colic--less common than previously estimated?

A two-part population-based study investigating the occurrence of infantile colic was undertaken, in which 92% of mothers with newborn healthy infants were reached. In the prospective part 152 mothers ("diary group") registered crying and fussing in their infants during 12 weeks. In the retrospective part 224 mothers ("interview group") were contacted by telephone at an infant age of 5-7 months. The colic occurrence was determined according to four different definitions; the rate varied from 3.3 to 17.1%. The classical "Wessel-type" colic was present in 9.3%. Colic defined as "crying seen as a problem by parent" was present in 12.1% of the "interview group", but in only 3.3% of the "diary group". Some earlier studies may have overestimated colic occurrence. Another possibility is an actual decline. The contributive part of preventive measures is discussed.

Colic

Decrease in high density lipoprotein cholesterol during prolonged storage. CELL Study Group.

Different studies on the stability of high density lipoprotein cholesterol (HDL) in frozen serum or plasma have yielded conflicting results, namely increase, decrease, or no change at all during prolonged storage under freezing conditions. As part of a major trial on lipid-lowering strategies we statistically demonstrated a time-related decrease in HDL cholesterol during storage up to 46 months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been analysed fresh and then stored from 26 to 46 months, using the dextran sulphate 500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on time was performed. The slope was significantly negative (p < 0.0005). The regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e. after 6 months' storage at -20 degrees C there was almost a 1% decrease in the HDL cholesterol concentration per month of storage.

Cholesterol, HDL

Influence of social factors on sugary products behavior in 4-year-old children with regard to dental caries experience and information at child health centers.

The aim was to analyze the steering effects of 15 social factors on sugary products behavior at 4 years of age in 177 children. The parents had in most cases received information on dental health care at child health centers, with due respect to the level of caries among the children, who were classified as 'healthy' (no caries experience) (n = 83) or 'diseased' (caries experience) (n = 84). The parents filled in a mailed diet history form. Only sugary products unsuitable from a cariologic point of view were considered. The products were given scores reflecting the frequency of intake. The social factors were social background, family, information, and conceptual factors. By means of multiple regression analysis, explanatory values of the social variables for sugary products behavior were estimated. For the total material, 13% of the variance was explained by all variables combined. Among the social background factors, 'parents' age' was statistically significant (p < 0.05). Among family factors, 'day-care mainly at home' and 'oldest child' were the most important. All information factors proved to be nonsignificant. Of the conceptual factors, only 'importance of genetic factors' was statistically significant. For the healthy group 26% of the variance was explained by all variables. 'Mother's age', 'importance of genetic factors', and 'oldest child' were statistically significant. For the diseased group all variables were nonsignificant. Explanatory values were negligible. The important conclusions were that very few traditionally conceived social variables seem to influence 4-year-old children's sugar behavior. Parents of children with caries appear to be a heterogeneous group with an irrational behavior.

Attitude to Health

Reference intervals and decision limits for plasma lipids and lipoproteins: a practical evaluation of current recommendations.

As part of a longitudinal study--the Kristianstad Survey--we measured plasma cholesterol, HDL- and LDL-cholesterol, triglycerides and lipoprotein (a) in a reference group consisting of 203 men and women aged 20-80, randomly sampled from a well-defined area in the southernmost part of Sweden. The selection of reference individuals and the collection of specimens for assay of the constituents were performed in accordance with current recommendations. The results were subjected to statistical analyses both with and without application of exclusion criteria. Application of the theoretical exclusion criteria resulted in the exclusion of 22% of the participants; however, this procedure had a remarkably weak impact on the results: the mean values and the standard deviations were almost unaltered. The mean (standard deviation) for cholesterol was 5.9 (1.3) mmol l-1, for HDL-C 1.1 (0.3) mmol l-1, and for LDL-C 4.3 (1.2) mmol l-1. Women had higher values than men. Plasma triglycerides were positively skewed; their median and Q3-Q1-values were 1.0 and 0.5 mmol l-1 respectively, men higher than women. There was an increase with age for cholesterol and LDL-C in both sexes and for triglycerides in women. The steepest increase of cholesterol values with age in women coincided with menopause, which have a more clear-cut separation between high and low cholesterol values than did any age limit.

Adult

Spatial memory and stereotypic behaviour of animals in radial arm mazes.

The symmetric radial arm maze, described by Olton in 1976, has developed into an important tool for the study of spatial memory. In a typical test an animal is placed in the centre of the maze, which contains some small piece of food at the end of each arm. The sampling behaviour of the animal is then recorded. In such studies the score (number of choices of arms which still contain food) of the animal is normally compared with the score of an imaginary animal which changes arms entirely at random. In a new method of analysis the non-random score of the animal is split into two parts, one depending on memory and one on stereotypic choice behaviour. Even mild departures from randomness are shown to alter considerably the expected 'random' score in an eight-armed maze. The part of the score claimed to depend on memory was shown to increase when the animals learn to search the maze, the stereotypic part did not. The general effect from stereotypic choice behaviour is shown to result, in most animals, in an increase in the total score. In an eight-armed maze this increase may amount to more than 20% of the total non-random score, even in a well-trained animal. The effect is less pronounced in mazes with 16 arms. It has been proposed that hippocampal lesions produce a stereotypic behaviour. We propose, based on our analysis, that the stereotypic behaviour is not produced but revealed by hippocampal lesions which destroy almost completely the memory-guided behaviour masking the stereotypic behaviour in the intact animal.

Animals

Cold climate is an important factor in explaining regional differences in coronary mortality even if serum cholesterol and other established risk factors are taken into account.

Earlier studies have shown a strong regional association between cold climate and coronary mortality in Sweden and that coronary mortality is more strongly associated with cold climate than with other explanatory factors such as drinking water hardness, socioeconomic factors, tobacco and sales of butter. To examine the joint impact of these factors and to investigate regional differences in serum cholesterol and their relation to cold climate and coronary mortality, regression analyses were performed with 259 municipalities in Sweden as units. Mortality from acute myocardial infarction in men aged 40-64 during 1975-1984 was used as the dependent variable. A cold index was calculated, this index and the above mentioned factors were used as explanatory variables. The main results were: Cold index was the strongest factor when introduced into a multiple regression model. Four other strong factors had to be used to obtain the same explanatory strength as cold index did alone, and even when introduced as the last factor, cold index increased the coefficient of determination substantially. In a subsample of 37 municipalities, serum cholesterol was not significantly associated with coronary mortality. However, there was a significant correlation between cold index and serum cholesterol.

Adult

Calcified cartilage zone and its dimensional relationship to the articular cartilage in the human temporomandibular joint of elderly individuals.

The aim was to describe the appearance of the calcified cartilage zone (CCZ) and to determine its dimensional relationship to the articular cartilage thickness in the normal human temporomandibular joint. An autopsy material comprising 21 joints from 12 elderly individuals was examined microscopically. The appearance of the CCZ was examined, and the thickness of the CCZ and of the total articular cartilage was measured in 18 different positions in each joint. The CCZ was outlined by a flat or gently undulating tidemark and an irregular osteochondral junction. The cellularity of the CCZ varied extensively. The cells were numerous in the CCZ when the overlying articular cartilage displayed high cellularity. Statistical analysis of the measurements demonstrated a relationship (p < 0.001) between the thickness of the CCZ and of the articular cartilage. Our findings, both qualitative and quantitative, indicate a close relationship between the physiology of the CCZ and of the overlying articular cartilage.

Aged

Socioeconomic factors in the community fail to explain the high coronary mortality in cold parts of Sweden.

A regional association between cold climate and coronary mortality in Sweden has already been described. This study aimed to investigate whether this association can be explained by differences in socioeconomic factors and found that there was a regional association between coronary mortality and the following socioeconomic factors: prevalence of manual workers (D = 0.22), unemployment rates (D = 0.19), and proportion of low income earners (D = 0.17). However, these associations were substantially weaker than that between cold climate and coronary mortality (D = 0.39), and when cold climate was introduced into the statistical model the explanatory power of the socioeconomic factors diminished substantially and only the percentage of manual workers enhanced the explanatory power of cold climate. Regional variation in coronary mortality could not be attributed to long distance to emergency hospital. To conclude, the strong association between cold climate and coronary mortality could not be attributed to the influence of socioeconomic factors.

Adult

Usefulness of self-measured blood pressure when diagnosing mild hypertension.

Blood pressure (BP) measured by the patients themselves at home and at their workplaces (self BP) and office blood pressure (office BP) were compared with ambulatory BP (amb BP) in 41 middle-aged borderline hypertensive men when diagnosing hypertension. Ambulatory BP was used as the 'gold standard'. The mean (standard deviation) value for office BP was 142/89 (14/7), self BP 143/92 (14/8), and amb BP 134/88 (12/6) mmHg. There was no difference between diastolic office BP and self BP as instruments for diagnosing hypertension. Furthermore, combining the two added little to the diagnostic value obtained from only one of them.

Blood Pressure Determination

High coronary mortality in cold regions of Sweden.

The hypothesis that cold climate is associated with high coronary mortality in Sweden is tested. Cold exposure was calculated in each of the 284 municipalities of Sweden. There was a significant association between cold exposure and coronary mortality in both sexes in all age groups. The strongest association was found in men aged 40-64 years (coefficient of determination k = 0.39). The decile of men aged 40-64 years who lived in the coldest municipalities had a 40% excess mortality. A significant association was also found between cold exposure and mortality from cerebrovascular diseases. We conclude that there is a strong regional association between cold exposure and high coronary mortality.

Adult