A Bayesian hierarchical point process model for epidermal nerve fiber patterns.

We introduce the Thomas process in a Bayesian hierarchical setting as a model for point pattern data with a nested structure. This model is applied to a nerve fiber data set which consists of several point patterns of nerve entry points from 47 subjects divided into 3 groups, where the grouping is based on the diagnosed severity of a certain nerve disorder. The modeling assumption is that each point pattern is a realization of a Thomas process, with parameter values specific to the subject. These parameter values are in turn assumed to come from distributions that depend on which group the subject belongs to. To fit the model, we construct an MCMC algorithm, which is evaluated in a simulation study. The results of the simulation study indicate that the group level mean of each parameter is well estimated, but that the estimation of the between subject variance is more challenging. When fitting the model to the nerve fiber data, we find that the structure within clusters appears to be the same in all groups, but that the number of clusters decreases with the progression of the nerve disorder.

Natural decay process affects the abundance and community structure of Bacteria and Archaea in Picea abies logs.

Prokaryotes colonize decaying wood and contribute to the degradation process, but the dynamics of prokaryotic communities during wood decay is still poorly understood. We studied the abundance and community composition of Bacteria and Archaea inhabiting naturally decaying Picea abies logs and tested the hypothesis that the variations in archaeal and bacterial abundances and community composition are coupled with environmental parameters related to the decay process. The data set comprises >500 logs at different decay stages from five geographical locations in south and central Finland. The results show that Bacteria and Archaea are an integral and dynamic component of decaying wood biota. The abundances of bacterial and archaeal 16S rRNA genes increase as wood decay progresses. Changes in bacterial community composition are clearly linked to the loss of density of wood, while specific fungal-bacterial interactions may also affect the distribution of bacterial taxa in decaying wood. Thaumarchaeota were prominent members of the archaeal populations colonizing decaying wood, providing further evidence of the versatility and cosmopolitan nature of this phylum in the environment. The composition and dynamics of the prokaryotic community suggest that they are an active component of biota that are involved in processing substrates in decaying wood material.

Genetic host-tree effects on the ectomycorrhizal community and root characteristics of Norway spruce.

A greenhouse experiment was used to study the effects of host genotype on short root formation and ectomycorrhizal (ECM) fungal community structure in Norway spruce (Picea abies (L.) Karst.). Rooted cuttings representing 55 clones were inoculated with a mix of vegetative hyphae of five ECM fungal species (Laccaria sp., Amphinema byssoides, Piloderma sp., Cadophora finlandia, Paxillus involutus). After one growing season, the ECM fungal community structure was determined by amplifying the fungal internal transcribed spacer (ITS) of ribosomal DNA directly from ECM root tips. Restriction profiles of obtained amplicons were then compared to those of the inoculated strains. Spruce clones differed in their ECM fungal community composition; we found a statistically significant clone-specific effect on ECM fungal diversity and dominating fungal species. Nevertheless, the broad sense heritabilities of the levels of Laccaria sp., Piloderma sp. and A. byssoides colonisations as well as the ECM fungal community structure were low (H(2) = 0.04-0.11), owing to the high within-clone variation. As nitrogen concentration of needles correlated negatively with ECM fungal richness, our results imply that in the experimental conditions nutrient acquisition of young trees may benefit from colonisation with only one or two ECM fungal species. The heritability of short root density was moderate (H(2) = 0.41) and highest among all the measured shoot and root growth characteristics of Norway spruce cuttings. We suggest that the genetic component determining root growth and short root formation is significant for the performance of young trees in natural environments as these traits drive the formation of the below-ground symbiotic interactions.

Environmental differences in twin pairs discordant for Alzheimer's disease.

The aim of this study was to examine the contribution of environmental factors to the pathogenesis of Alzheimer's disease by comparing environmental differences in twin pairs discordant for Alzheimer's disease. Seventy four twin pairs discordant for Alzheimer's disease were found by linking the Finnish twin cohort and the Hospital Discharge Register from years 1972-91. In 50 pairs (25 monozygotic and 25 dizygotic pairs), both co-twins had responded to a questionnaire survey in 1975. Exposure differences were compared between these pairs. A reduced risk of Alzheimer's disease was significantly associated with a higher level of schooling (relative risk 0.3; 95% confidence interval 0.1-0.9, p=0.029). In addition, a reduced risk was suggestively associated with ambidextrousness or left handedness (p=0.083) and an increased risk with marriage (p=0.052), widowhood (p=0.074), and a history of cholelithiasis (p=0.071). In conclusion, a reduced risk of Alzheimer's disease was associated with a higher level of schooling.

Ambulatory 24-hour blood pressure recordings in patients with Parkinson's disease with or without fludrocortisone.

UNLABELLED: Orthostatic hypotension is often associated with patients suffering from Parkinson's disease. Only few studies have been published about the ambulatory blood pressure in patients with Parkinson's disease. Fludrocortisone has been used in management of orthostatic hypotension. This study was made to determine the Circadian rhythm of blood pressure in healthy elderly people, in Parkinson's disease patients without orthostatic hypotension and Parkinson's disease patients with fludrocortisone medication for orthostatic hypotension. Ambulatory 24-hour blood pressure recordings were made in 20 elderly Parkinson's disease patients and 21 healthy elderly persons. Eight of the Parkinson's disease patients were on fludrocortisone (Florinef) therapy because of orthostatic hypotension. The mean daytime systolic blood pressure of Parkinson's disease patients without fludrocortisone was 123 mmHg and the mean nighttime systolic blood pressure was 121 mmHg. There was no significant difference between daytime and nighttime systolic blood pressure (Figure 1). Diastolic blood pressure in this group was significantly higher during the day (68 mmHg) than at night (63 mmHg) (Figure 2). The daytime blood pressure of control patients was 135/74 mmHg and at night 127/69 mmHg (Figures 1, 2). The blood pressure of Parkinson's disease patients with fludrocortisone was higher at night (156/83 mmHg) than during the day (134/77 mmHg) (Figures 1, 2). The daytime and nighttime systolic and diastolic blood pressure was significantly lower by non-fludrocortisone Parkinson patients than the blood pressure of fludrocortisone Parkinson patients (Figures 1, 2). CONCLUSION: The Parkinson's disease patients were non-dippers and with fludrocortisone the blood pressure was higher at night than on day. On day, the blood pressure of the Parkinson's disease patients with fludrocortisone elevated to the level of controls.

Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT)

BACKGROUND: Advantages and disadvantages of postmenopausal oestrogen replacement therapy (ERT) are still not clear. We aimed to analyse the relation between postmenopausal oestrogen replacement therapy (ERT), cardiovascular disease, and cancer. METHODS: We examined 7944 women born between 1923 and 1930, who participated in a mammography screening for breast cancer, and who were followed up from 1987 to 1995. The follow-up consisted of 53,305 person-years. 988 women were current users and 757 were former users of ERT. Information about hormone use and health events was obtained through biennial questionnaires and recording and linking information from the hospital discharge registers of the region, the national cancer register, the social insurance reimbursement register, and the national death register. We used proportional-hazards models to calculate risk ratios and 95% CIs, adjusted for eight confounding variables. FINDINGS: Current ERT was associated with decreased cardiovascular mortality and a decrease in sudden cardiac death. Adjusted risk ratio (RR) for cardiovascular mortality in current users was 0.21 (95% CI 0.08-0.59) and in former users 0.75 (0.41-1.37). Absolute risk per 1000 person-years for deaths from acute myocardial infarction (AMI) was 1.1 in never users, 1.2 in former users, and 0.45 in current users (p=0.197). Corresponding absolute risk for other coronary-artery-disease (CAD) deaths was 1.0, 0.81, and 0 (p=0.009), and for deaths from stroke 1.2, 1.0, and 0.15 (p=0.012). Absolute risk for sudden cardiac death was 1.6 in never users, 1.0 in former users, and 0 in current users (p<0.001). Cardiovascular morbidity was not decreased by ERT: the RR for current use was 1.07 (0.86-1.32) and for former use 1.11 (0.89-1.39). Incidence of cardiovascular disease per 1000 person-years was 24.9 in never users, 23.4 in former users, and 20.9 in current users (p=0.153). Breast-cancer morbidity did not increase with current ERT--the RR was 0.57 (0.27-1.20). Incidence of breast cancer was 1.8, 1.6, and 1.0 in never, former, and current users (p=0.242). Endometrial cancer increased with current ERT--the RR was 5.06 (2.47-10.41). Incidence of endometrial cancer was 0.52 in never users, 0.51 in former users, and 2.1 in current users (p<0.001). INTERPRETATION: Current ERT reduced primarily sudden cardiac death and predicted reduced cardiovascular mortality, but did not reduce morbidity. ERT did not increase the risk of breast cancer, but was associated with increased risk of endometrial cancer.

Alzheimer's disease in twins.

Besides familial Alzheimer's disease (AD), the genetic susceptibility has also been found in sporadic cases of AD, mostly related to the apolipoprotein E polymorphism. The penetrance of AD is determined by age and probably by environmental exposure. Gene-environment interaction of a disease can be examined through studies of twins. The relative roles of genetic and environmental influences can be estimated by comparing the concordance rates between monozygotic (MZ) and dizygotic (DZ) twins. Genetic models can be used to specify contributions both from genetic as well as shared and unique environmental effects. The role of environmental factors can be investigated in the co-twin control study, either by comparing environmental exposure in MZ twins discordant for a disease or by comparing MZ twins discordant for an exposure suspected of causing a particular disease. The sampling of twin pairs AD can be carried out using voluntary recruitment, linkage of twin and hospital discharge registries or screening of twin registry population. Potential sources of biases in sampling are discussed. The majority of the published twin studies on AD are case reports or based on selected materials. In MZ pairs, the concordance rates for AD have varied between 31% and 83%. Only one co-twin control study in twins discordant for AD has been published. Published twin studies on AD are briefly reviewed.

Clinical features of leuko-araiosis.

OBJECTIVE: To study the clinical features of leuko-araiosis. METHODS: Age matched groups of patients with a CT finding of pure leukoaraiosis (n = 26) and a control group with a normal CT finding (n = 26) were formed (mean ages 78.6 (SD 3.3) v 76.5 (SD 4.6) years; NS). RESULTS: Dementia, vascular dementia, central brain atrophy on CT, disability in activities of daily living and instrumental activities of daily living, urinary incontinence, gait disorder (assistance needed), personality change, and night time confusion were found to be more commonly present in leuko-araiosis positive patients than in controls, whereas focal neurological symptoms and signs were not associated with leuko-araiosis. The occurrences of heart failure and systolic hypotension-but not hypertension-were higher in the leuko-araiosis positive group than in the controls. Leuko-araiosis was also found to be related to a less sudden onset of symptoms and a lower Hachinski score than true brain infarction(s). CONCLUSIONS: Leuko-araiosis on CT in these elderly patients seems to be a vascular disorder aetiologically different from brain infarction, with clinical manifestations of subtle onset and general disabling nature and no prominent focal neurological signs or symptoms.

Alzheimer's disease in Finnish twins.

BACKGROUND: The genetics of Alzheimer's disease (AD) are obscure. Although most cases are sporadic half the patients with sporadic AD have a positive family history. The mode of genetic transmission and the role of environmental factors are unknown. The purpose of this study was to examine the contribution of genetic factors to the pathogenesis of AD in a twin cohort. METHODS: The Finnish Twin Cohort consists of all Finnish same-sexed twin pairs born before 1958 with both co-twins alive in 1975. The total number of twin pairs is 13 888, of whom 4307 are monozygotic (MZ) and 9581 ar dizygotic (DZ). These data were linked with the Hospital Discharge Register from 1972 to 1991 to identify twins who had dementia or related disease as a discharge diagnosis. The linkage of the registries yielded a total of 285 twin individuals. The medical records of these twins and their co-twins were reviewed to confirm and classify dementia (AD, vascular dementia, mixed dementia, and other dementia). The incidence, concordance, and age at onset of AD were examined. FINDINGS: The incidence of AD was significantly higher in MZ than in DZ twin individuals, with and adjusted MZ/DZ incidence ratio of 1.8 (95% confidence intervals 1.2 to 2.7). In contrast, the incidence of vascular or mixed dementia did not differ between MZ and DZ individuals (MZ/DZ ratio 0.6 [0.3 to 1.2]) for vascular and 1.0 [0.5 to 2.1] for mixed dementia). The pairwise concordance for AD was 18.6% in MZ pairs and 4.7% in DZ pairs and the corresponding probandwise concordance rates were 31.3% and 9.3%. The pairwise concordance for vascular dementia was 18.2% in MZ pairs and 6.7% in DZ pairs with corresponding probandwise rates of 30.8% and 12.5%. The onset age of AD concordant MZ pairs was identical in two pairs and diverged by up to 15 years. INTERPRETATION: The higher incidence of AD in MZ individuals than in DZ individuals may provide a clue to the aetiology of AD. The higher concordance rate of MZ pairs confirms the contribution of the major genetic component while indicating the need to identify environmental triggers.

Haemodynamic response to head-up tilt in elderly hypertensives and diabetics.

To examine the haemodynamic mechanism associated with postural hypotension (PH) in elderly people, haemodynamic response to head-up tilt was studied in 14 elderly hypertensives and 13 elderly diabetics. Hypertensives and diabetics were divided into those with or without PH, defined as > or = 10 mmHg decline in mean blood pressure in response to head-up tilt. There was no significant change in cardiac output in hypertensives or diabetics with PH, whereas there was a significant increase during tilt in hypertensives without PH (p < 0.0001) and diabetics without PH (p = 0.0054). Hypertensives without PH showed a significant decrease in total peripheral resistance in response to head-up tilt (p = 0.0043). In hypertensives with PH and in both diabetic groups, there was no change in total peripheral resistance in response to head-up tilt. There was no difference in ejection fractions or heart rate responses between subjects with and without PH in either disease group. The difference in cardiac output change was not explained by myocardial changes observed at echocardiography nor by heart rate response nor by differences in total peripheral resistance. The results suggest that an increase in cardiac output in response to changing posture may be more important than vasoconstriction in protecting elderly subjects from PH.

Clinical characteristics of rapidly progressive leuko-araiosis.

INTRODUCTION: 38 patients found to have either pure leuko-araiosis (LA) or LA combined with infarction(s) on computer tomography (CT) in 1989 were re-examined in 1992 in order to evaluate the progression of LA. The follow-up period averaged 3.2 years. MATERIAL AND METHODS: The clinical and radiological data on patients in 1989 were collected from hospital records and re-evaluated. The patients were re-examined clinically (including 24 hour ambulatory blood pressure measurement), and neuroradiologically (CT) in 1992 for this study. RESULTS: 11 (29%) patients were found to have significant (rapid) progression of the extent of LA on CT during the follow-up. At baseline, there was no significant difference in the mean number of brain infarctions between the groups with progressing (prLA) and non-progressing LA (nprLA) or between the number of cortical and central infarctions within these groups. At follow-up, the total number of infarctions had increased significantly in both groups, but it was mostly because of the increase in cortical infarctions in the prLA group (p = 0.043) and, conversely, the central ones in the nprLA group (p = 0.011). prLA was found to be related to heart failure (82% vs 37%, p = 0.029) and atrial fibrillation (55% vs 19%, p = 0.047), whereas nprLA was strongly associated with a sudden onset of symptoms (78% vs prLA 18%, p = 0.001) like a true brain infarction. Other clinical factors, including mean blood pressure and heart rate, did not clearly differentiate between the groups. CONCLUSION: The results suggest that there are different subgroups of patients with LA associated with various vascular factors. The occurrence of LA is not related to the distribution of infarctions. The progression of LA is not related to the number of brain infarctions or to the simultaneous increase of infarctions on CT.

The role of potassium in postural hypotension: electrolytes and neurohumoral factors in elderly hypertensive patients using diuretics.

OBJECTIVE: To study the association between postural hypotension and (i) electrolyte levels and (ii) neurohumoral factors in elderly hypertensive patients using diuretics. DESIGN: Cross-sectional study of patients and controls. SETTING: The subjects were gathered from senior citizen clubs or they were referred to the study by general practitioners. The subjects were examined on a geriatric ward in Turku City Hospital. SUBJECTS: Seven subjects with postural hypotension and 13 controls. MEASUREMENTS: Plasma electrolyte levels and neurohumoral response to head-up tilt. RESULTS: There were significantly more hypokalaemic subjects in the postural hypotension group (5/7) than in the control group (1/13) (P < 0.01). The plasma potassium level was negatively correlated to plasma aldosterone (r = -0.57; P < 0.01) and renin activity (r = -0.69; P < 0.001). Subjects with postural hypotension had higher levels of noradrenaline, both supine (P < 0.05) and during tilt (P < 0.05). There were no significant differences in supine or tilt levels of plasma adrenaline, vasopressin, atrial natriuretic peptide, aldosterone and renin activity between the groups. CONCLUSION: The results suggest that potassium depletion is associated with postural hypotension in elderly hypertensive patients using diuretics. However, it is unclear whether there is a causative link between potassium depletion and postural hypotension or whether they are both caused by some other factor, e.g. volume contraction.

Spectral analysis of heart rate variability in evaluation of sympathetic function in elderly subjects.

Plasma concentration of noradrenaline is often used as a measure of sympathetic nervous activity. Recently, the method of spectral analysis of heart rate variability has been introduced to detect autonomic dysfunction. To examine whether spectral analysis of heart rate variability is useful in evaluating sympathetic function, changes in the heart rate variability in the low-frequency spectral band were compared with the change of plasma noradrenaline in response to head-up tilt in elderly hypertensives (n = 13) and diabetics (n = 13). In hypertensive subjects, there was an increase in relative low-frequency power (p = 0.015) and an increase in plasma noradrenaline level (p = 0.040) in response to head-up tilt. Diabetics did not show corresponding changes. There was no change in absolute low-frequency power in either group. It is concluded that spectral analysis of heart rate variability can be useful in evaluating sympathetic function in elderly subjects.

Delay in diagnosis of colorectal cancer in elderly patients.

The medical histories of 178 colorectal cancer patients were studied retrospectively from hospital records. The average age at the time of diagnosis was 71 years. Visible loss of blood or anaemia were the commonest features. The mean time from first symptom to first medical consultation was 82.8 days. Men under 65 years and women over 80 years waited the longest time before consulting a physician. The mean time from the first medical consultation to diagnosis was 44.7 days. The delay was longer for men than for women but longest for women aged over 80 years. Information about digital rectal examination was lacking in over half of all patients and in two-thirds of patients over 80 years. In patients in whom rectal examination had been made, as many as 60% of rectal cancers were digitally palpable. Barium enema missed the cancer diagnosis in 11.2% of patients at the first examination; the missed cancers were located in the sigmoid area and in the right colon. Colonoscopy can be recommended as the primary investigation method when colorectal cancer is suspected. Re-examination is necessary in elderly patients with sideropenic anaemia if the first examination is negative.

Subjective evaluation of sleep and the use of hypnotics in nursing homes.

The purpose of the study was to evaluate the sleep habits and the use of hypnotics in the elderly living in nursing homes. The study population consisted of 60 subjects aged 61-99 years who were interviewed by a geriatrician. The use of hypnotics was frequent (53%), but not associated with gender, memory impairment, moving disability, depression, quality of sleep or sleep behaviour. Users of hypnotics had shorter total sleep time (TST) and got up earlier from bed in the morning than the non-users. Most of the subjects perceived their sleep as interrupted but satisfactory. The elderly with impaired memory slept longer, stayed in bed longer, and took their hypnotics significantly earlier than those with normal memory. As we found no explaining factors for the use of hypnotics, we suggest regular evaluation of their administration in nursing homes. The subjective need for hypnotics, not the nursing home practices, should decide the necessity of these drugs and the medication times in nursing home residents.

Midazolam and flunitrazepam: pharmacokinetics and effects on night time respiration and body movements in the elderly.

In a double-blind crossover study, the pharmacokinetics and effects on night-time respiration and body movements of midazolam 7.5 mg, flunitrazepam 1 mg, and placebo were studied in 5 elderly insomniac patients with the static charge sensitive bed-method (SCSB). In a supine position, the gastrointestinal absorption rate of flunitrazepam (tmax 0.6 h) was faster than that of midazolam (tmax 0.95 h). The elimination phase half-life of midazolam was about twice as long as reported earlier in healthy adult volunteers, but ageing did not affect the elimination of flunitrazepam. The shape of the serum concentration-time curve of both benzodiazepine derivatives was quite similar. The sleep of these five insomniacs became more peaceful and the respiration more regular during midazolam and flunitrazepam, compared with placebo. Both benzodiazepines significantly decreased body movements and the cumulative movement time remained shorter throughout the night, compared with placebo. Total variability (VI) was clearly decreased with flurazepam, and a similar but not statistically significant tendency was seen with midazolam, compared with placebo. Accordingly, the proportion of quiet sleep (QS) increased (p = 0.014) and the proportion of active sleep (AS) decreased (p = 0.019) with both benzodiazepines, compared with placebo. This reflects the changed control of respiration by higher brain structures. No signs of increased respiratory resistance (i.e. ballistocardiographic respiratory amplitude variation BRV < 60%) were seen with either of the drugs or placebo. There were no differences in the subjects' own estimation of their sleep during medication with these drugs. Only the sleep onset latency was shorter with flunitrazepam compared with midazolam and placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between vascular factors and white matter low attenuation of the brain.

To study the relationship between vascular factors and white matter low attenuation of the brain (WMLA), computer tomography findings of 251 patients were re-interpreted. Clinical data on patients were collected from the hospital records. It was possible to obtain sufficient clinical data on 204 patients who were included in the study. WMLA changes, on computer tomography, were found in 51.5% of patients. WMLA was most commonly present in patients with vascular (69.8%) and combined (69.2%) dementia. The occurrence of WMLA did not differ between patients with Alzheimer's disease (26.7%) and those without dementia (35.9%). Arterial hypertension, coronary heart disease, or diabetes were not associated with WMLA. Heart failure and orthostatic hypotension, were found to be more commonly present in patients with than in those without WMLA (34.0% vs 14.3%, p = 0.0012; 10.0% vs 2.0%, p = 0.036). Both systolic and diastolic low blood pressure values were associated with WMLA unlike hypertensive blood pressure values. Atrial fibrillation in electrocardiography was associated with WMLA, while neither left ventricular hypertrophy nor myocardial infarction was. When several explanatory variables were adjusted by logistic regression analysis, age, heart failure, and systolic blood pressure below 130 predicted WMLA. In conclusion, the association between WMLA and vascular factors with hemodynamic significance suggests that cerebral hypoperfusion may contribute to the genesis of WMLA.

Characteristics of colorectal cancer in elderly patients.

The aim of the study was to examine the characteristics of colorectal cancer in elderly patients. The medical histories of 178 consecutive patients (79 men and 99 women) with colorectal cancer were studied from hospital records. The studied parameters were compared between three age groups: under 65 years old, 65-80 years old and over 80 years old. In the two older age groups, cancer was situated more commonly in the proximal colon than in the youngest age group (p = 0.029). Especially in elderly subjects, rectosigmoidoscopy is not sufficient since up to 40% of cancers are located in the right colon. Colonoscopy is recommended as the method of choice in old patients if colorectal cancer is suspected. Cancers in the oldest age group more often fell into to Dukes' stages C1, C2 and D (metastatic growth) (p = 0.072) and they were greater in size than those of patients under 80 years old (p = 0.029). Small cancers (under 5 cm) had obvious blood in the stools as the main symptom and represented nonmetastatic Dukes' stages. If these cancers could be detected earlier by testing for occult blood, the prognosis of colorectal cancer would improve. The resectability of cancer was lower in patients over 80 years than in other age groups (p = 0.016). However, in logistic regression analysis, the large size, poor or moderate cell differentiation, and distal location of the cancer, but not age, were associated with poor resectability.

Pituitary gonadotrophins and prolactin in patients with endometrial cancer, fibroids or ovarian tumours.

The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and, prolactin (PRL) were measured before and after gonadotrophin releasing hormone (GnRH) and thyrotrophin releasing hormone (TRH) stimulation in 17 patients with endometrial cancer, in 15 patients with uterine fibroids, in 11 patients with ovarian cystadenomas or cancer and in 14 age-matched controls. The women with fibroids had a low FSH level and a diminished FSH response to GnRH but an excessive PRL response to TRH while the other patient groups did not differ from the controls. The results indicate no relation between pituitary function and endometrial or ovarian tumor.