Pirjo Halonen

Apolipoprotein E, Dementia, and Cortical Deposition of β-Amyloid Protein

BACKGROUND The epsilon 4 allele of apolipoprotein E has been associated with an increased risk of late-onset Alzheimers disease. In a cohort of elderly subjects we prospectively investigated the relation between the apolipoprotein E genotype, dementia, and the accumulation of beta-amyloid protein in the cerebral cortex. METHODS Autopsy involving neuropathological analysis and DNA analysis of frozen blood samples were performed in 92 of 271 persons who were at least 85 years of age, who had been living in Vantaa, Finland, on April 1, 1991, and who had died between that time and the end of 1993. All subjects had been tested for dementia. Apolipoprotein E genotyping was done with a solid-phase minisequencing technique. The percentage of the cortex occupied by methenamine silver-stained plaques was used as an estimate of the extent of beta-amyloid protein deposition. RESULTS The frequency of the epsilon 4 allele was significantly higher in the subjects with Alzheimers disease than in the subjects without dementia (30 percent vs. 8 percent, P < 0.001). There was a greater accumulation of beta-amyloid protein in the brain and more neurofibrillary tangles in the subjects with the epsilon 4 allele than in those without it (P < 0.001). The deposition of beta-amyloid protein varied according to the genotype in both the subjects with dementia and those without dementia: it was lowest in those with the epsilon 2/epsilon 3 genotype, intermediate in those with the epsilon 3/epsilon 3 genotype, and highest in those with the epsilon 3/epsilon 4 genotype. A single subject had the epsilon 4/epsilon 4 genotype and had dementia. CONCLUSIONS The epsilon 4 allele of apolipoprotein E is significantly associated with Alzheimers disease. Even in elderly subjects without dementia, the apolipoprotein E genotype is related to the degree of deposition of beta-amyloid protein in the cerebral cortex.

Pain as a reason to visit the doctor: a study in Finnish primary health care

&NA; This study aims to demonstrate the prevalence of pain as a reason for seeing a physician in primary care. We also performed an analysis of the localization, duration and frequency of pains, as well as the diagnoses of patients having pain. A total of 28 physicians at 25 health centers in Finland collected the data, comprising 5646 patient visits. Pain was identified as the reason for 2237 (40%) of the visits. The most common localizations were in the lower back, abdomen and head. One‐fifth of the pain patients had experienced pain for over six months. Analysis of the diagnoses revealed half of the pains to be musculoskeletal. Patients experienced considerable limitations in various activities of life due to pain. A quarter of the pain patients of active working age received sick leave. Our results confirm that pain is a major primary health care problem, which has an enormous impact on public health.

Maternal Preeclampsia Predicts Elevated Blood Pressure in 12-Year-Old Children: Evaluation by Ambulatory Blood Pressure Monitoring

Ambulatory blood pressure (ABP) monitoring offers a reliable method for determining blood pressure (BP) in children. The aim of this cohort study was to examine whether maternal preeclampsia is associated with elevated BP in an offspring. The study population consisted of 57 children born to preeclamptic mothers (PRE) and their 57 age- and sex-matched control subjects born to normotensive mothers (non-PRE). We examined the 24-h ABP at 12 y of age in the PRE and non-PRE children. Within the two groups, the association of anthropometric measures, plasma catecholamine (epinephrine [E], norepinephrine [NE]) concentrations, and ABP was examined. The PRE children had significantly higher mean 24-h systolic and diastolic ABPs than the non-PRE children. The same was true for the mean daytime and nighttime systolic and diastolic ABPs. The PRE boys had higher 24-h systolic ABP than the PRE girls. In the PRE children, high plasma E concentration and being born small for gestational age (SGA) predicted high systolic 24-h ABP in logistic regression analysis. In the non-PRE children, high current body mass index (BMI) and high plasma E concentration was associated with high systolic 24-h ABP. In conclusion, systolic and diastolic ABP values were elevated in the PRE children. High plasma E concentration and being born SGA were associated with high systolic 24-h ABP in the PRE children. Presumably maternal preeclampsia affects offspring via several mechanisms, including genetic ones and metabolic consequences of restricted intrauterine growth.

Serum Lipid Concentrations and Growth Characteristics in 12-year-old Children Born Small for Gestational Age

According to Barkers hypothesis, children born small for gestational age (SGA) are at increased risk for cardiovascular diseases in adulthood. The aim of our study was to determine whether retarded fetal growth is associated with dyslipidemia in childhood and, if so, to find predictive factors in the growth characteristics of SGA children. We studied the serum lipid concentrations of 55 SGA children and their 55 appropriate for gestational age control subjects at the age of 12 y. Growth variables were recorded at birth, 5 y, and 12 y of age. The study group consisted of all full-term SGA children born at our university hospital during a 22-mo period in 1984–1986. Nearly half of the SGA children (47.3%) were in the highest quartile for serum total cholesterol of the appropriate for gestational age children (p = 0.038). In multiple logistic regression analysis, poor catch-up growth in height (odds ratio, 13.8; 95% confidence interval, 2.0–97.5), female sex (odds ratio, 8.1; 95% confidence interval, 1.3–48.9), and early stage of puberty (odds ratio, 7.5; 95% confidence interval, 1.2–46.5) predicted high cholesterol level in the SGA children. By the age of 5 y, 20 (36.4%) SGA children showed catch-up growth of ≥ 2 SD scores in height, and 21 (38.2%) SGA children showed catch-up growth of ≥ 2 SD scores in weight from birth. At the age of 12 y, the SGA children were still significantly shorter (p < 0.001) and lighter (p < 0.05) than the appropriate for gestational age children, even though their pubertal development was similarly advanced. In conclusion, to be born SGA has long-term consequences for later growth and may already influence the level of serum total cholesterol before the teens. SGA children with poor catch-up growth in height may be at the highest risk for hypercholesterolemia.

Efficacy of dietary hempseed oil in patients with atopic dermatitis.

Background: Hempseed oil is a rich and balanced source of omega‐6 and omega‐3 polyunsaturated fatty acids (PUFAs). Anecdotal evidence indicated that dietary hempseed oil might be useful in treating symptoms of atopic dermatitis. Patients and methods: Dietary hempseed oil and olive oil were compared in a 20‐week randomized, single‐blind crossover study with atopic patients. Fatty acid profiles were measured in plasma triglyceride, cholesteryl and phospholipid fractions. A patient questionnaire provided additional information on skin dryness, itchiness and usage of dermal medications. Skin transepidermal water loss (TEWL) was also measured. Results: Levels of both essential fatty acids (EFAs), linoleic acid (18:2n6) and alpha‐linolenic acid (18:3n3), and gamma‐linolenic acid (GLA; 18:3n6) increased in all lipid fractions after hempseed oil, with no significant increases of arachidonic acid (20:4n6) in any lipid fractions after either oil. Intra‐group TEWL values decreased (p = 0.074), qualities of both skin dryness and itchiness improved (p = 0.027) and dermal medication usage decreased (p = 0.024) after hempseed oil intervention. Conclusions: Dietary hempseed oil caused significant changes in plasma fatty acid profiles and improved clinical symptoms of atopic dermatitis. It is suggested that these improvements resulted from the balanced and abundant supply of PUFAs in this hempseed oil.

Delirium in elderly people without severe predisposing disorders : Etiology and 1-year prognosis after discharge

BACKGROUND The etiologic factors of delirium have been frequently studied in hospitalized elderly patients who usually have an underlying disorder, i.e., hip fracture or dementia predisposing to delirium. The etiologic factors of delirium and prognosis in healthy elderly remain unstudied. The aim of our study was to detect the primary and additional etiologic factors contributing to delirium among community-dwelling healthy elderly people without predisposing disorders to delirium and to evaluate 1-year prognosis after discharge to home. METHOD The study subjects consisted of 51 community-dwelling people over 65 years of age, without severe underlying disorders predisposing to delirium, admitted consecutively to the hospital because of a delirious state. The diagnosis of delirium was based on the DSM-III-R criteria. After discharge to home, the subjects were followed up for 1 year. RESULTS The most important primary causes of delirium were infections in 22 cases (43%) and cerebrovascular attacks in 13 cases (25%). After the 1-year follow-up period, 10 patients (20%) had been taken into long-term care and 5 patients (10%) had died. DISCUSSION The plausible etiologic factor of delirium was detected in all cases. Among healthy elderly people, infections and cerebrovascular attacks were the most important etiologic factors for delirium. After discharge to home, 30% of the patients had to be taken into long-term care or had died within 1 year of the delirium.

Total serum cholesterol level, violent criminal offences, suicidal behavior, mortality and the appearance of conduct disorder in Finnish male criminal offenders with antisocial personality disorder.

Associations between low total serum cholesterol (TC) levels and antisocial personality disorder (ASPD), violent and suicidal behavior have been found. We investigated the associations between TC levels, violent and suicidal behavior, age of onset of the conduct disorder (CD) and the age of death among 250 Finnish male criminal offenders with ASPD. The CD had begun before the age of 10 two times more often in non-violent criminal offenders who had lower than median TC levels. The violent criminal offenders having lower than median TC levels were seven times more likely to die before the median age of death in the study material. The violent offenders having lower than median TC levels were eight times more likely to die of unnatural causes. The mean TC level of these male offenders with ASPD was lower than that of the general Finnish male population. Low TC levels are associated with childhood onset type of the CD, and premature and unnatural mortality among male offenders with ASPD. The TC level seems to be a peripheral marker with prognostic value among boys with conduct disorder and antisocial male offenders.

Factors related to non-compliance with antihypertensive drug therapy

The objectives were to study the associations of perceived health care-related and patient-related factors with self-reported noncompliance with antihypertensive treatment. General practitioners identified all of their hypertensive patients in 26 health centres during 1 week in 1996 (n = 2219). A total of 1782 (80%) patients participated in the study, of whom 1561 were on antihypertensive medication. Based on 82 opinion statements in two questionnaires, 14 problem indices were formed by using factor analysis. Out of these, summary variables concerning problems related to the health care system and the patients were formed. Logistic regression models, including interaction analyses, were used to study the associations with non-compliance. The results were that the majority of patients had at least one perceived health care system-related (88%) and patient-related problem (92%). A high number of both perceived health care system-related problems (adjusted OR 4.77; 95% CI 2.76, 8.26) and patient-related problems (adjusted OR 3.23; 95% CI 1.79, 5.81) were associated with self-reported non-compliance. The experience of adverse drug effects was also associated with non-compliance (adjusted OR 1.41; 95% CI 1.03, 1.94). In conclusion self-reported non-compliance was associated with multiple risks of both perceived health care system-related and patient-related problems.

Systematic intervention for supporting community care of elderly people after a delirium episode.

OBJECTIVE To investigate the effects of a systematic intervention with a case manager concept and rehabilitation periods compared to standard aftercare in elderly community-dwelling patients discharged from the hospital after a delirium episode. DESIGN Before/after intervention cohort study with 3-year follow-up. SETTINGS Acute geriatric wards of a city hospital and a private rehabilitation center. SUBJECTS AND METHODS The intervention group consisted of 51 community-dwelling people over 65 years of age without severe underlying disorders, who were consequently admitted as emergency cases to the hospital because of a delirious state or who were delirious immediately after admission. The intervention included continuous support and counseling by a nurse specialist and rehabilitation periods at a rehabilitation center. The control group consisted of 51 age- and gender-matched patients admitted to the same hospital for delirium fulfilling the same inclusion and exclusion criteria during preceding years. The main outcome measures were duration of community care, the use of long-term institutional care, the use of short-term hospitalizations during the follow-up, and the death of the patients. RESULTS Delirium even in the healthy community-dwelling subjects indicated a poor prognosis. After 3 years, 18 patients (35%) from the intervention group and 9 patients (18%) from the controls were in community care. The mean duration of community care was 671 days in the intervention group and 503 days in the control group, p = .025. A reduction of 19 years was achieved in the cumulative time spent in long-term institutionalized care. The use of short-duration hospitalization was similar in both groups. CONCLUSION The institutionalization of elderly patients after a delirious state could be delayed using rehabilitation periods and systematic intervention with the case manager concept.

Metoprolol Versus Amiodarone in the Prevention of Atrial Fibrillation After Cardiac Surgery: A Randomized Trial

BACKGROUND Current guidelines recommend β-blockers as the first-line preventive treatment of atrial fibrillation (AF) after cardiac surgery. Despite this, 19% of physicians report using amiodarone as first-line prophylaxis of postoperative AF. Data directly comparing the efficacy of these agents in preventing postoperative AF are lacking. OBJECTIVE To determine whether intravenous metoprolol and amiodarone are equally effective in preventing postoperative AF after cardiac surgery. DESIGN Randomized, prospective, equivalence, open-label, multicenter study. (ClinicalTrials.gov registration number: NCT00784316) SETTING 3 cardiac care referral centers in Finland. PATIENTS 316 consecutive patients who were hemodynamically stable and free of mechanical ventilation and AF within 24 hours after cardiac surgery. INTERVENTION Patients were randomly assigned to receive 48-hour infusion of metoprolol, 1 to 3 mg/h, according to heart rate, or amiodarone, 15 mg/kg of body weight daily, with a maximum daily dose of 1000 mg, starting 15 to 21 hours after cardiac surgery. MEASUREMENTS The primary end point was the occurrence of the first AF episode or completion of the 48-hour infusion. RESULTS Atrial fibrillation occurred in 38 of 159 (23.9%) patients in the metoprolol group and 39 of 157 (24.8%) patients in the amiodarone group (P = 0.85). However, the difference (-0.9 percentage point [90% CI, -8.9 to 7.0 percentage points]) does not meet the prespecified equivalence margin of 5 percentage points. The adjusted hazard ratio of the metoprolol group compared with the amiodarone group was 1.09 (95% CI, 0.67 to 1.76). LIMITATIONS Caregivers were not blinded to treatment allocation, and the trial evaluated only stable patients who were not at particularly elevated risk for AF. The withdrawal of preoperative β-blocker therapy may have increased the risk for AF in the amiodarone group. CONCLUSION The occurrence of AF was similar in the metoprolol and amiodarone groups. However, because of the wide range of the CIs, the authors cannot conclude that the 2 treatments were equally effective. PRIMARY FUNDING SOURCE The Finnish Foundation for Cardiovascular Research and the Kuopio University EVO Foundation.