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A myeloproliferative condition in blastic phase is described in an 18-year-old male who was also found to have a mediastinal malignant teratoma. Myeloid metaplasia was found in the lymph nodes and spleen, and an infiltration of granulocytic blast cells was observed in the bone marrow and the lymph nodes. Aneuploidy with an extra chromosome (trisomy 8) was present in bone marrow cells. To our knowledge the combination of a myeloproliferative disorder and a malignant teratoma has not been earlier described.

Frequency of anaemia and anaemia subtypes in east-west European inception cohort : an ECCO-EpiCom cohort study

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.

Background The common polymorphism of the apolipoprotein E (APOE) gene is associated with differential risk of atherosclerosis; the gene could be a candidate gene in abdominal aortic aneurysms (AAA). Methods APOE genotypes were determined in 57 men aged 65–73 years with a small AAA (30–50 mm). The patients were included in a population ultrasonographic screening programme and were followed with at least two examinations during an interval of 2–4·5 years. The AAA expansion rates in patients with four different APOE genotypes were studied, with adjustment for initial AAA size and smoking. Results APOE genotype was a significant determinant of AAA expansion rate (P = 0·001). The adjusted mean (95 per cent confidence interval) rate was 2·1 (1·7–2·6) mm/year in 31 men with genotype E3E3, 1·3 (0·7–1·9) mm/year in 17 men with E3E4, 3·1 (2·0–4·1) mm/year in six men with E2E3 and 4·2 (2·7–5·6) mm/year in three men with E2E4. The mean expansion rate was 2·2 (1·5–2·8) mm/year in non-smokers and 3·0 (2·5–3·6) mm/year in smokers (P = 0·014). Conclusion APOE genotype seems to influence AAA expansion rate, but the effects of the individual genotypes, in particular E3E3 and E3E4, are contradictory when compared with the effects of the genotypes on risk of atherosclerosis.

The negative correlation between coronary heart disease and plasma levels of HDL has been attributed to the ability of HDL to take up cellular cholesterol. The HDL3-induced removal of cellular cholesterol was reported to be impaired in fibroblasts from patients with familial HDL deficiency (Tangier disease, TD). In addition, we have recently shown that HDL3 stimulates the hydrolysis of phosphatidylcholine (PC) in cholesterol-loaded fibroblasts. To investigate whether this cell signaling pathway is involved in cholesterol efflux mechanisms, we compared the HDL3-induced PC hydrolysis in normal fibroblasts and in fibroblasts from a TD kindred, in whom the HDL3- and apolipoprotein A-I (apo A-I)-induced mobilization of cellular cholesterol was found to be reduced by 50%. The HDL3-induced formation of phosphatidic acid (PA) via PC-specific phospholipase D (PC-PLD) was markedly reduced by 60-80% in these cells, whereas the formation of diacylglycerol (DG) via PC-specific phospholipase C (PC-PLC) was two- to threefold enhanced. Defective regulation of PC-PLC and PC-PLD was similarly observed in response to apo A-I and endothelin, but not in response to the receptor-independent stimulation of PC hydrolysis by PMA. A Tangier-like PA and DG formation pattern could be induced in normal cells after preincubation with pertussis toxin, suggesting the involvement of a G-protein. The impaired mobilization of radiolabeled cellular cholesterol in TD cells could completely be overcome by increasing the PA levels in the presence of the PA phosphohydrolase inhibitor propranolol. Conversely, the inhibition of PA formation in the presence of 0.3% butanol as well as the inhibition of DG formation in the presence of the PC-PLC inhibitor D 609 reduced the mobilization of cellular cholesterol both in normal and in TD cells. Our data indicate that the coordinate formation of PA and DG via PC-PLD and PC-PLC is essential for efficient cholesterol efflux. The molecular defect in this TD kindred appears to affect an upstream effector of protein kinase C responsible for the G-protein-dependent regulation of PC-specific phospholipases.

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.

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial the patients were treated with 25 to 50 mg captopril, 50 to 100 mg metoprolol, 12.5 to 25 mg hydrochlorothiazide, and placebo, each given twice daily for 8 weeks. Antidiabetic treatment remained unchanged during the study. After receiving placebo for a 4 week run-in period, arterial blood pressure was 168/101 +/- 93/10 (mean +/- SEM) mm Hg. Diastolic blood pressure was lowered significantly during all active treatment periods compared to the placebo value of 97 +/- 2 mm Hg: captopril, 92 +/- 1 mm Hg; metoprolol, 90 +/- 1 mm Hg; hydrochlorothiazide, 91 +/- 1 mm Hg. Metabolic variables were not significantly altered by captopril and metoprolol, while hydrochlorothiazide treatment increased hemoglobin A1c from 7.5 +/- 0.3 to 8.2 +/- 0.4% (P less than .001), decreased high-density lipoprotein-cholesterol from 1.19 +/- 0.08 to 1.10 +/- 0.06 mmol/L (P less than .05). Glomerular filtration rate, urinary albumin excretion, orthostatic blood pressure response, and digital systolic blood pressure in the lower limb remained unchanged during the active treatment periods. The frequency of subjective adverse effects was acceptable during active treatment and not significantly different compared to placebo. We conclude that antihypertensive treatment for 8 weeks with captopril or metoprolol in NIDDM patients is well-tolerated and causes no deterioration in metabolic control and kidney function, while hydrochlorothiazide causes a slight deterioration in glycemic control and lipid profile.

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.

Composting of poultry carcasses represents an alternative method for disposal in case of an outbreak of an epizootic disease. Two composting experiments, each with a different construction of the compost pile, were carried out in a stable. In the first experiment two layers of turkey carcasses were formed. This compost pile covered with straw was directly built on the ground. In the second experiment no layers of carcasses were formed, and it was assembled on straw bales covered with plastic foil. One part of this compost pile was covered with straw, the other one was additionally covered with plastic foil. In the first experiment in the upper layers of the compost pile temperatures of up to 54.9 degrees C were reached and the decomposition of carcasses was very advanced with no soft tissues remaining after 30 days. In contrast temperatures of only 45.2 degrees C were reached in the lower layers and decomposition was far less advanced. This difference in decomposition was most likely caused by the temperature difference observed. In the second experiment the near complete decomposition seen in the upper layers of the compost pile at the first trial, was not achieved. Decomposition was more advanced in the straw covered part of this compost pile than in the part covered with straw and plastic foil. On the other hand, higher temperatures of up to 48.4 degrees C were measured in the lower layers of this compost pile most likely as a result of the increased heat insulation in particular to the ground.

In this paper first the general cascade of animal disease eradication from the voluntary control programme up to culling of infected animals is described. Afterwards the development of the eradication of Bovine Herpes Virus in Lower Saxony is illustrated. Obvious the number of farms which are not eradicating decreases since the testing on BHV1 is obligate in Germany. In 2004 60% of the cattle holdings were free from BHV1. At least the measures which will be taken in Lower Saxony to increase the success of eradication are explained.

In this article firstly the standards of the killing methods of poultry because of animal diseases and the parameter for the choice of a method are described. The following part deals with the effects of the different killing methods. Finally the most important control points during the killing of poultry are discussed.

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.

Tangier disease (also known as familial HDL-deficiency) is characterized by very low high density lipoprotein (HDL) plasma levels, splenomegaly, and massive cholesteryl ester accumulation in the cytoplasm of various cell types. Since this phenotype may in part be caused by a defect in the pathway mediating cholesterol efflux from peripheral cells, we investigated the HDL3-mediated mobilization of cholesterol synthesized de novo from [14C]-mevalonolactone in cultivated fibroblasts from two patients with Tangier disease. Our results indicate that the HDL3-induced translocation of [14C]-cholesterol from intracellular pools to the plasma membrane and its subsequent secretion into the extracellular medium was approximately 50 % less in the cells from the patients than in controls. The same result was also obtained with artificial apolipoprotein A-I-containing phospholipid vesicles. By contrast, no significant difference in HDL3-induced cholesterol efflux was observed when plasma membrane was labeled with exogenous [14C]-cholesterol. We conclude that inefficient cholesterol efflux in Tangier disease is primarily caused by impaired HDL3-induced activation of cholesterol translocation from intracellular pools to the plasma membrane.

Adult rhabdomyoma is an exceedingly uncommon tumor in the head and neck. We present a case localized to the left parapharyngeal area in a 57-year-old woman. The various diagnostic measures used are discussed. Surgical removal is the treatment of choice.

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.

Colloidal carbon was injected i.v. in mature virgin rabbits at different times after induction of ovulation by human chorionic gonadotrophin (hCG, 100 iu) or mating. Before induction of ovulation, slight carbon leakage was observed in the inner vascular ring of the theca interna of antral follicles, but blood vessels in the other ovarian compartments were unstained. Between 4 and 10.5 h after hCG-treatment or mating, vascular leakage was most marked in the blood vessels of the interstitial gland and in the theca interna of antral follicles. Just before ovulation, carbon particles were observed between granulosa cells and some carbon was seeping into the follicular fluid of preruptured follicles. Vascular leakage was also observed over the follicle dome before rupture as well as at the dorsomedial junction between the mesovarium and the ovary. The blood vessels stained with carbon were 7-70 microns diameter, representing capillaries and postcapillary venules. About 6 h after hCG injection, an increased number of polymorphonuclear leucocytes migrated from the vessels of these ovarian compartments into the surrounding interstitial tissue. The number of leucocytes seen in the follicular wall and ovarian medulla increased markedly towards ovulation. During early corpus luteum formation, the number of leucocytes decreased markedly. The localized vascular changes seen after mating and hCG stimulation were similar to an inflammatory reaction and could form the basis for the formation of peritoneal exudate after ovulation in rabbits and periovulatory ascitic accumulation seen in the peritoneal cavity of women during the menstrual cycle.

In a prospective study comprising 447 women with endometrial carcinoma stages I-II, the prognostic significance of clinical and flow cytometric variables was evaluated in univariate and multivariate analyses. The parameters studied included age, uterine cavity depth, clinical stage, histopathologic grade, myometrial invasion, weight, body mass index (BMI), parity, diabetes, oestrogen treatment, DNA - content and S-phase fraction. Patient selection for surgery influenced prognosis with a better survival in operated patients. In the univariate analysis the following parameters correlated with survival: age, grade, myometrial invasion, DNA - content and S- phase fraction. In the multivariate analyses which included clinical variables only, age, grade and myometrial invasion remained significant, but when flow cytometric variables were added, only S-phase fraction and myometrial invasion contained prognostic information. S-phase fraction also generally correlated with time of recurrence.

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).

Background Carriers of the E4 allele for the gene encoding apolipoprotein E (apoE) have an increased risk of atherosclerosis. The distribution of apoE genotypes among men with a small abdominal aortic aneurysm (AAA) was compared with that among healthy men, and any differences between the genotypes in aneurysm expansion measured over 2–4·5 years were examined. Methods The patients originate from a population ultrasonographic screening programme with about 4800 participating 65–73-year-old men in a defined geographical region. Of 191 patients diagnosed, 57 of 77 who have been followed for 2 years or more were genotyped. Aneurysm expansion rates were determined from linear regression of diameter versus time of examination. The influence of apoE genotype on expansion rate was analysed using analysis of variance, with initial aneurysm size and smoking status as covariates. Results The E4E4 genotype was not seen among patients with an AAA, whereas three patients had the rare E2E4 genotype. These patients had higher expansion rates than patients with the common genotype E3E3 (P = 0·009), whereas patients with the genotype E3E4 had lower rates (P = 0·034) (see Table over). Conclusion The findings suggest that the common polymorphism of the apoE gene influences the prognosis in patients with a small AAA. As regards the E3E4 genotype, the findings are unexpected, when compared with the known influence of E4 on the risk of atherosclerosis. This may partly explain the familial tendency of AAA, and inconsistent finding of coexisting atherosclerosis in patients with AAA. However, an impact of selection bias, due to differential survival or referral to surgery of patients with AAA, cannot be excluded.

Serum concentrations of progesterone (P), androstenedione (A) and testosterone (T) were measured in 128 postmenopausal women with endometrial adenocarcinoma. The correlations between these hormones were studied and related to such clinical parameters as: stage, histopathology, age, gynaecological history, body mass index and related diseases. In previous studies we have shown the relations between oestron (E1) and oestradiol (E2) serum concentration and clinical parameters. A clear correlation was seen between E1 and E2. Both E1 and E2 also strongly correlated with BMI. In this study androstenedione is found to correlate with E1 and E2, p less than 0.03 and p less than 0.02 resp. Progesterone and E1 were correlated, p less than 0.01, but not P and E2. Testosterone correlated with E1, p less than 0.002, E2, p less than 0.003 and A, p less than 0.02. None of the hormones P, A or T correlate with BMI. Androstenedione and age, and A and menopausal years showed a negative correlation, p less than 0.01 for both. Testosterone correlated with menopausal years, p less than 0.03; and correlated negatively with years of menstruation, p less than 0.03. These results do not support the hypothesis that A is the exclusive precursor for conversion to E1 in fat tissue. The correlation between P and E1 could indicate a relation to steroids higher up in the synthesis chain. The influence of P, A and T on the investigated clinical factors can not be strong, since correlations are virtually missing.

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.

The influence of endogenously produced oestrogen on the growth of endometrial carcinoma was studied in postmenopausal 128 patients with endometrial adenocarcinoma. Plasma concentration of oestrone (E1) and oestradiol (E2) showed wide variations. Hormone levels were analysed in relation to growth rate, expressed as S-phase rate measured by flow cytometry, and to ploidy level. When the whole unclassified group was studied, no statistical relationship between E1 and E2 levels and S-phase rates were found. However, when peridiploid tumors (1.8-2.2 c) were divided according to histopathological grades, well differentiated tumors with low oestradiol concentrations (less than 60 pmol/I) had significantly lower S-phase rates than those with higher oestradiol levels (p less than 0.01). Aneuploid tumors showed high S-phase rates regardless of plasma oestradiol concentrations.

Serum concentrations of endogenously produced oestrogens were studied in 128 postmenopausal women with endometrial carcinoma. Radioimmunoassays of serum oestrone (E1) and oestradiol (E2) were performed on admission to hospital. Results showed a wide variation in serum concentrations of E1 and E2 in patients with endometrial carcinoma. Some patients had high E1 values and low E2, while none of the patients had low E1 and high E2 values. Hormonal levels were correlated with increasing BMI (E1; p less than 0.000001; E2; p less than 0.000001). Uterine cavity depth was also related to both E1 and E2 (E1; p less than 0.00001; E2; p less than 0.0003). Concentrations of E1 and E2 were higher in diabetic women than in the non-diabetic. (E1; p less than 0.002; E2; p less than 0.01). E2 concentration was higher in hypertensive patients than in the non-hypertensive patients (p less than 0.04). Parameters such as age, menstrual history, clinical stage and histopathology showed no significant correlation with hormone concentrations.

Interaction of various substituted phenolsulphonphthalein dyes to rabbit plasma and rabbit serum albumin has been studied by ultrafiltration, equilibrium dialysis and spectrophotometry. The results obtained by ultrafiltration and equilibrium dialysis showed that the degree of binding of these dyes to protein increases in the following order: Phenol red less than bromophenol blue less than bromocresol green less than bromothymol blue. Analysis of binding results revealed that five molecules of bromothymol blue bound very strongly to a molecule of rabbit albumin, whereas only two and three molecules of bromophenol blue and bromocresol green strongly interact with the protein, respectively. It is suggested that strong binding of these substances to protein may be related to the hydrophobicity of these compounds. Finally, an attempt has been made to evaluate the possibility, whether the spectral changes occurred during interaction of dyes to albumin can be utilized for the determination of binding of these ligands to proteins.

Ca2+ efflux from sarcoplasmic reticulum vesicles was studied by measurements of net Ca2+ uptake, 45Ca2+ flux and hydrolysis of energy-rich phosphate. The maximal Ca2+ uptake capacity (150-200 nmol/mg protein at pH 6.7, 10 mM MgCl2 and mu = 0.26) was independent of the nature and concentration of the energy-donating substrate (ATP or carbamyl phosphate) and of temperature (15-35 degrees C), suggesting coupling between influx and efflux of Ca2+. In the presence of high concentrations of ATP, this efflux of Ca2+ was much higher than the passive Ca2+ permeation, measured after ATP or Ca2+ depletion of the reaction medium. Ca2+ efflux was imperceptible at vesicle filling levels below 35-40 nmol Ca2+/mg protein, and uncorrelated to the inhibition of the Ca2+-ATPase by high intravesicular Ca2+ concentrations. Analysis of the data indicated that Ca2+ efflux under our conditions probably is associated with one of the Ca2+-ATPase partial reactions, occurring after dephosphorylation, rather than with a reversal of the Ca2+ translocation step in the phosphorylated state of the enzyme. Furthermore, passive Ca2+ permeation may be concurrently reduced during the enzymatically active state. It is proposed that both Ca2+ efflux and passive Ca2+ permeation (Ca2+ outflow) proceed via the same channels which are closed (occluded) during part of the Ca2+-ATPase reaction cycle.

All attempts to reconstruct the topography of the brain in the living from studies of animal material are handicapped by technical difficulties. The best method is to compare exact X-ray pictures, which have been taken under stereotactic conditions. From a large collection of such X-rays the authors have composed contours of the internal table of the skull and of the ventricles, which best match the brains, selected for the Schaltenbrand-Bailey sterotactic atlas. For practical purposes these contours were combined with the transparent overlays for the nomenclature and the border lines of the different parts of the basal ganglia, which have been used in the myelin sections part of the atlas. A comparison of our sagittal series with the new X-ray findings shows, that the sagittal schemata of the atlas represent an extreme variation in the position of the Meynert axis and of the contours of the 4th ventricle. We have chosen a new axis system for the hindbrain, which corresponds to the average of our brains in constructing a new set of typical overlays for the atlas. The contour of the posterior fossa had to be completed. An independent axis system dor the structures of the 4th ventricle was developed, consisting of the base of the 4th ventricle, and a tangent, to the upper contour of the pons. In sterotactic procedures the axis systems for the forebrain and the hindbrain should be used independently. The results obtained are the basis for a new series of lantern slides which can be projected against the X-ray pictures with the Würzburg stereotactic equipment. In the course of this investigation we discovered a source of error. When air enters the puncture hole of the dura, the brain may sink back, so with the patient lying on his back, all structures may shift a few millimeters towards the occipital region. When the patient is lying on his side, as during an approach to the amygdala through the planum temporale, the ventricular system may collapse, so that almost no air is visible in the ventricles and the 3rd ventricle may appear to be in the lower hemisphere, the dislocation being more than 5-8 mm. But filling the ventricle with air through the ventricular catheter is sufficient to blow up the brain and to restore the normal topography.

Myelolipoma is a benign oligosymptomatic tumour of the adrenal gland. Clinical diagnosis and surgical removal are extremely rare. We report an operated case found incidentally by urography in a 52-year-old woman with a toxic hepatitis. The previously reported and operated cases are briefly reviewed.

1. The renal excretion of phenol red and other phenolsulphophthalein dyes (bromophenol blue and bromothymol blue) was studied in clearance experiments on anaesthetized rabbits. 2. Net tubular excretion of phenol red reached a maximal value of 8 mumole/min at a plasma concentration of ultrafiltrable dye of about 0.1 mM and was decreased at higher plasma concentrations. Decreases in net tubular excretion at high plasma concentrations were also obtained for bromophenol blue and bromothymol blue suggesting tubular reabsorption in addition to tubular secretion of the dye. Conclusive evidence for reabsorption was provided by administration of probenecid which caused a fall in the excretion of the dyes below that filtered by the glomeruli. 3. Tubular reabsorption of phenol red during probenecid administration appeared to be proportional to the glomerular load and was increased under experimental conditions leading to a decrease of urinary pH. Experiments involving efflux of phenol red from liposomes gave no evidence of a significant role of transmembrane passage by non-ionic diffusion. It is suggested that the pH dependence of the reabsorptive process is the result of preferential reabsorption of the acid as compared to the basic form of the indicator dye across a hydrophilic pathway in the transporting membranes. 4. Clearance ratio of phenol red to that of p-aminohippurate at low plasma concentrations was about 0.3. They low degree of extraction of phenol red from renal plasma is attributed both to tubular reabsorption and binding of the dye by plasma proteins.

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%).