Introducing a new component of the metabolic syndrome: low cholesterol absorption

BACKGROUND: Weight reduction is the recommended treatment of obese type 2 diabetes, but the effects of weight reduction on cholesterol metabolism are poorly understood. OBJECTIVE: We investigated glucose, cholesterol, and lipoprotein metabolism at baseline and 2 y after weight reduction in obese patients with type 2 diabetes consuming an isoenergetic diet. DESIGN: Sixteen subjects were randomly chosen to consume a very-low-energy or low-energy diet for 3 mo, after which they consumed a weight-maintenance diet for up to 2 y. Cholesterol absorption and metabolism, LDL and HDL kinetics, and variables of glucose metabolism were studied at baseline and 2 y. RESULTS: Baseline serum sex hormone binding globulin (SHBG) was significantly related to cholesterol absorption efficiency, and serum glucose and insulin concentrations were associated with cholesterol synthesis. After 2 y, body weight was reduced by 6 +/- 1 kg (P < 0.01), body mass index by 6% (P < 0.05), and blood glucose by 14% (P < 0.01); the ratio of serum SHBG to insulin increased by 66% (P < 0.05). Serum and VLDL, LDL, and HDL triacylglycerol were significantly reduced by 13-24%. Despite unchanged serum concentrations of cholesterol, cholesterol absorption efficiency and the ratio of serum plant sterols to cholesterol-indicators of cholesterol absorption-increased by 28% (P < 0.01) and 20-31% (P < 0. 05 for both), respectively; the fractional removal of LDL apolipoprotein B decreased. Fecal excretion of cholesterol as neutral sterols decreased significantly by 11%. Changes in body weight were significantly negatively correlated with changes in ratios of cholesterol to serum plant sterols and cholestanol. CONCLUSIONS: Baseline cholesterol absorption and synthesis were related to respective serum SHBG, glucose, and insulin values. Weight reduction increased cholesterol absorption and improved variables of glucose metabolism. These results suggest that low cholesterol absorption and high synthesis may be part of the insulin resistance syndrome.     

Preschool behavior disorders: their prevalence in relation to determinants

The occurrence of behavior disorders was investigated in a prospectively followed 3-year-old birth cohort. Of 1116 eligible children, the parents of 918 were successfully contacted. All agreed to complete a telephone interview and were mailed a Childhood Behavior Checklist (CBCL) standardized for 2- to 3-year-old children; 756 (82%) returned the CBCL. The prevalence of one or more of the deviant behavior syndromes identified by the CBCL was 11.1%. From a number of subject characteristics recorded throughout infancy, age-specific determinants for the occurrence of these deviant behaviors were identified. Characteristics most consistently associated with preschool psychopathology included the mother's ill health and lack of social support, the presence of chronic illness in the child, and the frequent use of hospital emergency services. These and other determinant (risk) indicators were entered into logistic regression (LR) models to derived adjusted relative risk estimates for the occurrence of a behavior disorder. The derived LR equations emphasize the important role of both the mother as well and the father and the health of the child.     

美国教学医院教师专业发展的全国性调查

在当前医学教育持续变革的背景中,医学教师的专业发展成为广泛关注的焦点.为了解目前美国以提高教师的教学技能为目标的教师专业发展(faculty development,FD)活动的参与率、课程设计、教学方法和评估策略等情况,美国约翰·霍普金斯大学预防、流行病学和临床研究中心采取邮件调查的方式,对美国277家教学医院进行了调查.     

Epidemiology and prevention: Association of Chlamydia pneumoniae and acute coronary heart disease events in non-insulin dependent diabetic and non-diabetic subjects in Finland

OBJECTIVE: It has been suggested that Chlamydia pneumoniae, a Gram-negativeintracellular bacterium, is a risk factor for both myocardialinfarction and chronic coronary heart disease. Previous studieshave been done predominantly in non-diabetic subjects and thusthe effect of diabetes on the association between C. pneumontaeantibodies and coronary heart disease has not been analysed.The aim of our study was to investigate the association betweenprior chlamydial infection and the risk of serious coronaryheart disease events (myocardial infarction or coronary death)in a 7-year prospective study of cohorts of diabetic and non-diabeticsubjects in two areas of Finland. RESULTS: It was found that the prevalence of elevated chlamydial antibodiesat baseline was higher in non-diabetic subjects who had seriouscoronary heart disease events during the follow-up than in subjectswithout coronary heart disease events (32 vs 15%, relative risk2·56, P=0·013) in East Finland. In non-diabeticsubjects living in West Finland we did not find this association.The association between the C pneumoniae antibodies and coronaryheart disease events did not markedly change after controllingfor other risk factors for coronary heart disease (OR 2·44,P=0·055) in non-diabetic subjects living in eastern Finland.In diabetic patients we did not find any association betweenchlamydial antibodies and coronary heart disease events. CONCLUSION: We found an association between C. pneumoniae antibodies andcoronary heart disease events in non-diabetics living in easternFinland. This association remained strong even after controllingfor the other risk factors for coronary heart disease. In diabeticpatients with high risk for coronary heart disease, C. pneumnoniaewas not a risk factor for coronary heart disease.(Eur HeartJ 1996; 17: 682–688)     

Epidermal growth factor in mice: effects of estradiol, testosterone and dexamethasone

To clarify the influence of steroids on the metabolism of epidermal growth factor, we studied the effects on its concentrations in adult male and female mice of 1. gonadectomy, 2. postgonadectomy treatments with estradiol and testosterone, and 3. treatment with dexamethasone. We also measured its mRNA levels in submandibular salivary glands and kidneys after ovariectomy. After gonadectomy, the male mice had 1.4-fold higher mean epidermal growth factor concentration in the urine than the female, in contrast to a 1.5-fold reverse difference in intact mice; the female mice had 2.5-fold higher concentration in the submandibular glands than the male animals, in contrast to a 4.5-fold reverse difference in intact mice. The kidney sex difference of intact mice (male greater than female) was abolished. In both gonadectomized sexes, treatment with testosterone increased the concentration of epidermal growth factor in plasma and the submandibular gland; treatment with estradiol increased the concentration in urine and decreased it in the submandibular gland. Treatment with dexamethasone decreased the concentration of epidermal growth factor in plasma of the male mice, and in urine of the female mice, thus decreasing the sex differences. In the submandibular gland and the kidneys, dexamethasone increased the concentration. The mRNA levels were higher in the submandibular gland and lower in the kidneys in the ovariectomized than in the intact female mice. The effects of sex steroids on epidermal growth factor concentrations are mediated through modulation of its gene activity. Testosterone has an increasing and estradiol a decreasing effect in the submandibular gland. Estradiol has also an increasing effect in the kidneys.     

Biliary lathosterol and other cholesterol precursor sterols are increased in patients with ileal exclusion

The human bile contains several noncholesterol sterols, of which the cholesterol precursor sterols are quantitatively the most important. Detailed data on factors that regulate the amount of these sterols in the bile have not been available. In this study the effect of chronic stimulation of cholesterol synthesis on biliary cholesterol precursor sterol content was evaluated by measuring these sterols in the bile and plasma of familial hypercholesterolemia patients with and without ileal exclusion. In the operated patients cholesterol synthesis was fivefold increased, and cholesterol precursor sterols comprised 7% of the biliary sterols, compared with 2% in the control patients. All eight biliary cholesterol precursor sterols measured were significantly increased in the operated patients, and the increase was similar to that of respective sterols in plasma. Hence, the biliary methyl sterols were increased 2 to 4 times, the lathosterols 5 times, but demosterol only 1.5 times. The proportion of lathosterol was higher and that of lanosterol lower in the bile of the operated than in that of the control patients. We conclude that activation of cholesterol synthesis increases the amount of cholesterol precursor sterols in the bile in proportion to the increase of these sterols in plasma and to the overall cholesterol synthesis.     

Autoimmune response in mothers of children with congenital and postnatally diagnosed isolated heart block: a population based study

OBJECTIVE: To study the autoimmune response in mothers of children with isolated congenital heart block (CHB) and heart block (HB) diagnosed postnatally. METHODS: We reviewed the Finnish hospital registries for patients born between 1950 and 2000 and diagnosed with isolated HB before the age of 16 years. Clinical data and sera for the determination of autoantibodies were available from 67 mothers of children with CHB and from 37 mothers of children with postnatally diagnosed HB 9.9 years and 22.6 years (mean) after the index delivery, respectively. Maternal antibodies to 52 kDa and 60 kDa SSA and 48 kDa SSB were determined by time-resolved fluoroimmunoassay (TR-FIA) and by immunoblotting. Other marker antibodies for connective tissue diseases (CTD) were determined by immunoblot and/or by immunofluorescence. The control group comprised 136 mothers with primary Sj?gren's syndrome (SS), systemic lupus erythematosus (SLE), or other CTD with healthy children. RESULTS: Sixty of our 67 mothers (90%) of children with CHB had antibodies to SSA or SSB by the methods initially used in this study. When retests and tests performed previously were taken into account, only 3 (4%) of the 67 mothers did not have any autoantibodies. Two (3%) of the 67 mothers had antibodies to dsDNA and one (1%) each to Jo-1/HRS, RNP-70 kDa, and histone proteins. Of 37 mothers of children with postnatally diagnosed HB, only 3 (8%) had any autoantibodies. Increased risk of having a child with CHB was indicated by maternal primary SS and high levels of anti-SSA and anti-SSB by all assays, whereas low risk was indicated by maternal SLE or other CTD and undetectable or low levels of the antibodies. No single anti-SSA or anti-SSB test was clearly superior to others, but in general, immunoblots were more specific than TR-FIA. CONCLUSION: Maternal autoimmune disorder is almost always associated with CHB but only rarely with postnatally diagnosed HB. Anti-SSA and anti-SSB are marker antibodies for mothers of children with CHB, and an increased risk of having an affected child is indicated by maternal primary SS and high titer antibodies to SSA and SSB.     

Cholesterol metabolism and non-cholesterol sterols in patients with ileal pouch anastomosis

Background: Previous studies suggest only minor changes in bile acid metabolism after panproctocolectomy with ileal pouch construction.Aims/Methods: To investigate these changes further, we studied cholesterol absorption and serum, biliary and fecal non-cholesterol sterols and lipids in 12 ileal pouch patients and 10 controls.Results: In patients, cholesterol absorption was markedly reduced and was associated with low serum total and LDL cholesterol and LDL triglyceride levels, but surprisingly, cholesterol synthesis, as indicated by sterol-balance data or serum cholesterol precursor levels, was within low normal limits. The high proportions of serum plant sterol to cholesterol, particularly that of campesterol, were not related to cholesterol absorption, but were attributable to a markedly reduced biliary cholesterol secretion. Interestingly, in these patients the fractional absorption of campesterol was normal, whereas that of sitosterol, like cholesterol, was reduced and was positively related to the intestinal influx of cholesterol. The patients' serum cholestanol proportion was normal, but the proportion of the cholestanol formed during intestinal passage was significantly reduced (17.9% vs 65.2% in controls).Conclusions: Thus ileal pouch patients are characterized by sterol malabsorption, lowered serum total and LDL-cholesterol levels, but unexpectedly without any increase in cholesterol synthesis. The lack of high serum cholestanol, shown earlier frequently in unoperated patients with ulcerative colitis, may indicate reversible cholestasis, a finding deserving further exploration.