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Objective: This study analyses the risk of coronary heart disease (CHD) associated with food intake patterns. Design: A cohort study with follow-up in 1996 for first admission to hospital for a CHD diagnosis or death caused by CHD (280 cases). Three food patterns were identified from a food frequency questionnaire: (1) a predefined healthy food index; (2) a prudent diet (reflecting frequent intakes of wholemeal cereals, fruit and vegetables); and (3) a Western food pattern (reflecting frequent intakes of meat products, butter and white bread) derived by factor analysis. Both factor scores had a mean of zero and a standard deviation of 1. Setting: Copenhagen County, Denmark. Subjects: A random sample of 7316 adults participated in health examinations conducted either in 1982–1984, 1987, or 1991–1992. Results: The healthy food index and the Western pattern were not associated with CHD. The prudent pattern was associated with a decreased risk of CHD (Hazard ratio (HR per score unit increase)=0.85; 95% confidence intervals (CI), 0.75, 0.96), but the association vanished (HR=1.06; 95% CI, 0.93, 1.21) after controlling for confounding. Body mass index (BMI) modified the effect of the prudent and the Western patterns on CHD risk, suggesting an inverse association between both patterns and CHD in persons with low BMI, while the risk of CHD seemed to be positively related to the prudent and the Western pattern in those with high BMIs. Conclusions: This study showed no association between dietary patterns and CHD risk, but suggests that BMI modifies the relation between diet and CHD risk.

We used meta-analysis to test hypotheses concerning whether adult celiac disease is reliably linked with anxiety and/or depression.We examined published reports on anxiety and depression in adult celiac disease.Eighteen studies on depression and eleven studies on anxiety in adult celiac disease met selection criteria. They show that depression is reliably more common and/or more severe in adults with celiac disease than in healthy adults (overall meta-analysis effect size: 0.97). The fail-safe margin of unpublished reports that would be required to negate the finding exceeds 8000. Adults with celiac disease do not, however, differ reliably in terms of depression from adults with other physical illnesses, nor do they differ reliably from healthy adults or adults with other physical illnesses in terms of anxiety.Depression is common in adult celiac disease and resembles the condition in other physical illnesses. We view the findings as support for the notion that non-specific mechanisms mediate emotional disorders in adult celiac disease.

The presence of lecithin:cholesterol acyltransferase (LCAT) deficiency in six probands from five families originating from four different countries was confirmed by the absence or near absence of LCAT activity. Also, other invariate symptoms of LCAT deficiency, a significant increase of unesterified cholesterol in plasma lipoproteins and the reduction of plasma HDL-cholesterol to levels below one-tenth of normal, were present in all probands. In the probands from two families, no mass was detectable, while in others reduced amounts of LCAT mass indicated the presence of a functionally inactive protein. Sequence analysis identified homozygous missense or nonsense mutations in four probands. Two probands from one family both were found to be compound heterozygotes for a missense mutation and for a single base insertion causing a reading frame-shift. Subsequent family analyses were carried out using mutagenic primers for carrier identification. LCAT activity and LCAT mass in 23 genotypic heterozygotes were approximately half normal and clearly distinct from those of 20 unaffected family members. In the homozygous patients no obvious relationship between residual LCAT activity and the clinical phenotype was seen. The observation that the molecular defects in LCAT deficiency are dispersed in different regions of the enzyme suggests the existence of several functionally important structural domains in this enzyme.

Growing awareness of risk factors for myocardial infarction (MI), continuous mass campaigns on lifestyle factors, increasing use of heart rehabilitation and improved treatment should imply decreases in the incidence, case-fatality and recurrence rates of MI. The purpose of the study was to assess trends in the incidence, case-fatality and recurrence rate of MI and to analyse whether any changes seen were due to a period or a cohort effect.The Danish MONICA population comprises all men and women aged 25-74 years in the period 1982-1991 living in a suburban area of Copenhagen, Denmark. Fatal and non-fatal attacks classified as definite MI and non-fatal attacks classified as possible MI were included. The incidence rate was analysed by Poisson regression, the case-fatality rate by logistic regression, and the rate of recurrence by Cox regression. Age-period-cohort analyses were carried out according to a method described by Clayton and Schifflers.During the 10-year period a significant decrease in the incidence rate of MI was seen for men and women and for the rate of recurrent MI. The decrease in incidence and recurrence could not unambiguously be ascribed to a period or cohort effect. The rate of case-fatality after a first MI was not changed significantly during the period, whereas men and women had different trends in case-fatality after recurrent MI.In accordance with results from other Western countries we found a decline in the incidence and recurrence rate of MI. Contrary, the lack of a decrease in the case-fatality rate after a first MI was unexpected and difficult to explain.

Myocardial infarction incidence rate declined 3-5% per year during 1982-1992 in the Danish study population of the WHO MONICA Project. We examined whether smoking habits, alcohol intake, dietary habits and physical activity levels changed in the population during the same period. Data from 6695 men and women of ages 30, 40, 50 and 60 y, examined in 1982-4, in 1986-7, and in 1991-2, were analysed to estimate trends. A summary healthy eating index and six scores derived by factor analysis were used to analyse food frequency data. The percentage of smokers declined 1.6% per year in men, and 1.0% per year in 30-, 40- and 50-y-old women, but increased 0.9% per year in 60-y-old women. The percentages of heavy cigarette smoking men and women nevertheless remained constant and close to 30%. Total alcohol intake declined among 30-y-olds, but appeared constant in other age groups. However, among 60-y-old men and among women over 30, the percentage of wine-drinkers rose from 6-11% in 1982-4 to 9-18% in 1991-2. Only 60-y-old men became more physically active at work and only 30-y-old women more so in leisure times. The percentage of individuals with a low healthy eating index decreased and the percentage with a high index increased. More importantly, dietary factor scores showed trends suggesting that very profound and potentially beneficial changes in dietary habits occurred. Lifestyle in the DAN-MONICA population changed in several ways that may have contributed to the declining incidence of myocardial infarction during the 1980s.

We developed a method to estimate genotype-specific average relative mortality risk, R, from genotype distributions in cross-sectional studies of people belonging to different age-groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data from a study of 40-year-old Danish men. Twenty-one percent of the centenarians were epsilon 2-carriers (genotypes epsilon 2 epsilon 2 and epsilon 3 epsilon 2) and 15% were epsilon 4-carriers (genotypes epsilon 4 epsilon 4 and epsilon 4 epsilon 3) compared to 13 and 29%, respectively, of the young men. The R-values were 0.95 (95% CI 0.88 to 1.02) for epsilon 2-carriers and 1.13 (95% CI 1.05 to 1.22) for epsilon 4-carriers, using epsilon 3 epsilon 3- and epsilon 4 epsilon 2 genotypes as reference. Corresponding values for epsilon 4-carriers were obtained by using published data from a French and a Finnish study of centenarians, whereas the values for epsilon 2-carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a "frailty gene." On the other hand, if odds ratios are used to summarize data from studies of this kind, they are more impressive and may propagate the misconception that apoE is a "longevity gene".

The objective of the present study was to examine the possible associations between low molecular weight (LMW) apolipoprotein(a) (apo(a)) isoforms (F,B,S1,S2) and coronary heart disease (CHD). We conducted a nested case-control (prospective) study of five cohorts of white men: The 1936 cohort (baseline 1976, n = 548) and four cohorts from MONICA I born in 1923 (n = 463), 1933 (n = 491), 1943 (n = 504) and 1953 (n = 448) studied at baseline in 1983. At follow up in 1991, 52 subjects had developed a first myocardial infarction and 22 had been hospitalized with angina pectoris. Plasma samples obtained at baseline were stored frozen until 1993-94, when case samples (n = 74) were analyzed together with samples from matched (disease free) controls (n = 190). In a statistical model (conditional logistic regression) including all age groups, cholesterol (or apo B) level (P0.01), systolic blood pressure (P = 0.05) and smoking (P = 0.02) predicted CHD. In the statistical model Lp(a) interacted significantly with age (OR = 5.7; 95% CI: 1.4-23.6; P = 0.016), and high Lp(a) (over 45 mg/dl) was associated with significantly increased risk in subjects under 60 years (OR = 3.82; 95% CI: 1.47-9.96), but not in older men (OR = 0.67; 95% CI: 0.235-1.89). Therefore, we studied the impact of Lp(a)/apo(a) and other variables in subjects who had been under 60 years when they became cases. Among the younger subjects the presence of LMW apo(a) isoforms significantly predicted the development of CHD (OR = 3.83; 95% CI: 1.18-12.4). The increased risk pertained to high Lp(a) (above versus below 45 mg/dl: OR = 3.68; 95% CI: 1.03-13.10), and to Lp(a) concentrations when entered into the model as a continuous variable (P = 0.04). Cholesterol or apo B (P0.01), smoking (P = 0.02), systolic blood pressure (P = 0.05) and low alcohol consumption (under nine drinks/week) (P = 0.04) were also significant predictors of CHD. We conclude that LMW apo(a) isoforms are significantly associated with increased risk of CHD in men under 60 years.

The mortality from ischaemic heart disease (IHD) in 35-64 year old Danish men has declined by 27% from 1981 to 1989. In the same period, a lesser increase in mortality from all other causes was observed. However, this is a heterogenous phenomenon, since the mortality from (in particular) infectious diseases (AIDS), diabetes mellitus, and a number of diseases related to heavy drinking has increased, whereas the suicide rate and mortality from lung cancer (in 1985-89) have decreased. It is not possible to evaluate the contribution of improved treatment of IHD cases and a decreasing incidence of disease, respectively, to the decline in mortality from IHD. A decreasing incidence is very probable, however, since both the percentage of smokers and the plasma cholesterol levels in middle-aged men have declined significantly since mid-1970s and leisure time physical activity has increased. The trend in IHD mortality in the 1980s points to a sustained decline in the 1990s and a levelling off in the increase in mortality from other causes. Thus total mortality is expected to decrease more rapidly in the 1990s, resulting in an increase in life expectancy of Danish men.

Apolipoprotein E (apoE) phenotypes were determined in a random sample of 466 Danish men born in 1948. The frequencies of the common alleles of the apoE gene were (with 95% confidence intervals) epsilon 2 = 0.085 (0.068-0.105), epsilon 3 = 0.741 (0.712-0.769), and epsilon 4 = 0.174 (0.150-0.200). These frequencies were compared to findings in 45 other study populations around the world (n greater than 100). The Danish population was found to cluster with populations from Iceland, Norway, Iceland, Scotland, the Netherlands, Germany, France (Paris), and Caucasian populations in Canada and the USA. The compiled data further show that dissimilarities in apoE allele frequencies among Caucasian populations are comparable to dissimilarities between some Caucasian and Asian populations. Notably, the frequency of epsilon 4 appears to be higher in northern regions of Europe (the Nordic countries, Scotland, Germany, and the Netherlands) than in southern regions (Switzerland, Tyrol, France [Nancy], Italy, and Spain).

Radioimmunoscintigraphy (RIS) was performed in 20 patients with gynecologic tumors, 14 ovarian, 5 cervical, and one endometrial carcinoma. One murine monoclonal antibody (mab) against placental alkaline phosphatase (H7) was used after radiolabeling with 131I. The labeling procedure yielded antibodies with specific activity varying between 60 and 73 MBq/mg mab. Each patient received 57 to 100 MBq of the preparation. RIS was performed 7 to 35 days later. Patients with ovarian adenocarcinoma had an accumulation of activity on RIS at tumor sites (79%, 11/14) verified by ultrasonography, CT, and clinical examination. A low or absent accumulation of activity was seen in patients with cervical tumors. The patient with an endometrial adenocarcinoma was seen to have an activity accumulation at RIS corresponding to tumor sites determined by ultrasound and/or CT. It is concluded that RIS using monoclonal antibodies against placental alkaline phosphatase can provide information which will supplement that gained from other investigations of patients with ovarian adenocarcinomas.

In a retrospective, consecutive case-control study, the psychosocial work environment of 52 men younger than 55 years, who had survived an acute myocardial infarction, was analysed with respect to workload and work quality using a comprehensive self-administered questionnaire. Patients more frequently reported exhaustion after work, had less responsibility at their job, held less well esteemed positions, and had less possibility of social contact during working hours. These differences bore no simple relationship to social class or conventional risk factor distribution, although higher workloads were associated with a significantly higher frequency of smoking. The study suggests that the ideal cardioprotective job is a well esteemed job at a certain responsibility level with good conditions for social interaction during working hours, in which the experienced job demands are reasonable, and where extra resources are available if needed.

Using Southern blot or in situ hybridization, several studies have recently reported an association between HPV 18 and adenocarcinoma of the uterine cervix. In this study PCR was used to analyse the presence of HPV 16 and 18 in paraffin embedded biopsies of cervical adenocarcinoma in Northern Sweden. HPV DNA was confirmed in 11 (42%) of 26 cases. Seven (27%) were positive for HPV 18 and 4 (15%) for HPV 16. Nine of 13 premenopausal cases were HPV positive compared to only 2 of 13 postmenopausal cases (p less than 0.015). There was also a tendency towards previous negative cytology in HPV 18 positive premenopausal patients. The significance of these findings in relation to epidemiology of cervical adenocarcinoma is discussed.

The results of 969 measurements of total cholesterol in capillary blood from fingerstick, performed with the Reflotron-system in the field, were compared with measurements of total cholesterol in venous serum. The comparison allows an evaluation of the combined effect of differences in sample material, working place, stability of methods and staff training. The mean values for all measurement were nearly identical with the two methods, and approximately 95% of the Reflotron-measurements were within an interval of +/- 0.7 mmol/l around the estimated true value. However, values below approximately 6 mmol/l were systematically underestimated, and values above approximately 7 mmol/l were overestimated with the Reflotron-system. The coefficient of variation of the system is below 5%, but both this precision and the accuracy appear to be unstable. Evaluated as a tool in screening for hypercholesterolemia, measurements with the system resulted in a modest extent of erroneous classification of subjects, but the positive diagnostic predictive value of the statement "cholesterol above 7 mmol/l" is only approximately 76%. Simulations of likely variations in the accuracy and precision of the method show a significant influence on the extent of errors. It is recommended that measurements with the system are routinely controlled by measuring an appropriate control material, at the start of each run and after every 30 samples.

The distribution of serum cholesterol in the population depends on sex and age. By analyzing data for men and women aged 20-69 from the Copenhagen City Heart Study 1981-1983, it is shown that this dependence is of major importance for the sex and age distribution of subjects classified as hypercholesterolaemic, when single threshold values are used to define the condition (7 mmol/l; 6 mmol/l for subjects less than 30 years): 56% are women, and 38% of these are women aged 50-59. Men between 30 and 59 years of age, for whom the association between hypercholesterolemia and ischaemic heart disease is most pronounced, only constitute 28%. As an alternative to single threshold values, one can use sex- and age-specific percentiles for cholesterol. The advantage appears from the explained cumulative percentage distribution curves in Figures 1 and 2. With the 90-percentiles, it is possible to identify the "cholesterol top-10" of the entire population, and although the use may seem more complicated, it has several advantages, notably the possibility of identifying younger hypercholesterolaemic subjects and making more appropriate use of the available resources for treatment.

The prevalence of risk factors for ischaemic heart disease (IHD) was recorded in 1,365 men aged 20-59 years in active employment. The purpose was to evaluate the implications of a high-risk strategy based on the rather conservative Danish guidelines for treatment of hypercholesterolemia. The prevalence of various risk factors depends on age, but in all, 1% had diabetes mellitus, 5% had a family history of premature IHD, 50% were smokers, 21% were obese, 12% had systolic blood pressure greater than or equal to 160 mmHg, 8% had diastolic blood pressure greater than or equal to 100 mmHg and 14% had serum cholesterol greater than 7 mmol/l. Only 24% had none of these risk factors and there was a considerable clustering of risk factors in certain subgroups. Approximately 34%, varying from 17% of the younger to 49% of the older, required medical follow-up as part of the high risk strategy. We have estimated the required number of visits to a general practitioner, if all Danish men aged 20-59 years were screened within three years and approximately 30% required follow-up for five years, with three visits in the first year and one thereafter. The number of visits peaks at 450 visits per year during the third year, and a number of circumstances could reduce this figure considerably. Multifactorial models to estimate risk in connection with screening should be adopted to the Danish guidelines for treatment of hypercholesterolemia and hypertension, and future guidelines for intervention should probably be integrated in such a multifactorial model. To practice preventive medicine, many physicians will need greater knowledge of dietary counselling.

A simple model for detection of subjects at risk of ischaemic heart disease, based on the addition of scores for different risk factors (Anggaard EE, Land JM, Lenihan J et al. Br Med J 1986; 293: 177-80), is at present widely applied in Denmark. The model could be tested in a prospective study, or a historical follow-up study, but we do not have the possibilities to do so. Instead we have compared the risk score of the model with the estimated five-year coronary mortality risk (ECR) in 742 men aged 40-44 years, calculated on the basis of data from the Seven Countries Study. There is a reasonable consistency in this comparison, in spite of the different principles of calculation, the consideration of different risk factors and/or weighting of risk factors. For example, the model has a sensitivity of 71%, a specificity of 89% and a positive predictive value of 68% in detecting 40-44 year old men in the upper quartile of ECR. The "false positives" are often men, who for other reasons may require preventive medical attention (obese heavy smokers), and the "false negatives" are often men with isolated hypertension.

The concentration of lipids, lipoproteins and apolipoproteins A-I and -B were measured in the plasma of 12 patients with peptic ulcer disease before and after five weeks of treatment with cimetidine. No statistically significant changes were found, but HDL cholesterol and HDL2 cholesterol tended to increase, and VLDL cholesterol and plasma triglycerides tended to decrease. A review of published studies indicates that the data at present are too uncertain to warrant use of cimetidine as a lipoprotein modulating drug.

In an open-label study, 20 patients with peak-dose dyskinesia and/or end-of-dose fluctuations were switched from standard Sinemet to Sinemet CR. Seventeen patients showed good tolerance and therapeutic results for at least 6 months. However, 10 patients showed a slight decrease of this improvement after 6 months; 3 had to be put back on standard Sinemet because of hallucinations (1) or accentuation of dyskinesia and akinesia (2). For optimal results, a higher dosage is needed (mean = 33%), but the number of doses per day can be reduced (mean = 30%).

Plasma concentrations of cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein (apo) B, and lipoprotein(a) (Lp[a]) in 46 persons heterozygous for the apo B-3500 mutation causing familial defective apo B-100 (FDB) were compared with those in 57 non-FDB relatives. FDB patients had 50% to 70% higher mean concentrations of cholesterol, LDL cholesterol, and apo B than non-FDB relatives (P < 10(-4) for all three variables). Triglycerides were higher (P = .016) and HDL cholesterol was lower (P = .021) in FDB patients. The concentration ranges of these variables were broad in each family, and there was no between-family difference in means for cholesterol and LDL cholesterol. There was no phenotype-specific difference in Lp(a) concentrations between FDB patients and non-FDB relatives. Apo E4 is normally associated with higher concentrations of LDL and apo E2 with lower concentrations. This relation was partly reversed in FDB patients: apo E4 was associated with lower apo B concentrations and apo E2 with higher apo B concentrations. Tendon xanthomata were found in members of two of the five families. Six of 12 FDB patients > 50 years old had atherosclerotic disease. In contrast, all 18 non-FDB relatives > 50 years old were apparently healthy. A total of 8 FDB patients with atherosclerotic disease had 36% higher cholesterol concentrations, 28% higher apo B concentrations, 50% higher triglyceride concentrations, and 120% higher Lp(a) concentrations than FDB patients without clinical atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined ectopic and intra-uterine gestations are uncommon, especially if the ectopic pregnancy is located in the ovary. A case of combined ovarian and intra-uterine pregnancy that resulted in a full-term delivery is reported.