Hot flushes still occur in a population of 85-year-old Swedish women.

OBJECTIVES: Hot flushes and night sweats often cause discomfort and may negatively affect sleep and quality of life. Studies have shown that menopausal symptoms, like hot flushes, may persist for up to 20 years after the menopausal transition, but there are no published studies regarding the occurrence of hot flushes among women older than 80 years. The aim of this study is to determine the prevalence of hot flushes in 85-year-old women. METHODS: All 85-year old women living in Linköping municipality in 2007 (n = 415) received a postal questionnaire. The majority, 74% (n = 307), answered the questionnaire and 47% (n = 194) agreed to visit the Department of Geriatric Medicine; during this visit questions regarding hot flushes and use of hormone therapy were asked. RESULTS: About 16% (n = 29) of the women experienced hot flushes during the day and/or during the night and 6.5% (n = 12) of the women were currently using hormone therapy. Almost 10% (n = 17) of all responding women were very to moderately distressed by their hot flushes. CONCLUSION: Our results confirm and extend previous knowledge based on studies of younger postmenopausal women in showing that menopausal symptoms still occur in elderly women. We found that, while the prevalence of menopausal symptoms decreases with age, these symptoms are still experienced by some 85-year-old women.

In vitro screening for putative psoriasis-specific antigens among wheat proteins and peptides.

BACKGROUND: Patients with psoriasis who had raised IgG and/or IgA antigliadin antibodies showed clinical improvement in a trial with a gluten-free diet. The selection of patients for the diet treatment was based on the presence of specific antibodies, i.e. the result of humoral immunity. OBJECTIVES: As psoriasis is now considered to be a T cell-mediated disease we decided to challenge peripheral blood mononuclear cells (PBMCs) in vitro from randomly selected patients with well-defined wheat proteins/peptides to explore the possibility of identifying a specific antigen with T cell activating properties in a subgroup of patients. METHODS: PBMCs from 37 patients (20 female and 17 male; mean age 49years) and 37 healthy controls (12 female and 25 male; mean age 57years) were included. Not all patients participated in all experiments. The PBMCs were exposed in vitro with the following wheat proteins/peptides in various concentrations: total albumins, 0·28 α-amylase inhibitor and the synthetic peptides, p31-43, p57-68 and p62-75, based on coeliac-active sequences of α-gliadin. The proliferative response was measured as counts per minute after the cells had been pulsed with methyl-(3) H-thymidine. RESULTS: Albumin, α-amylase inhibitor, p31-43 and p57-68 elicited a significant response in both patients and controls but showed no differences between the groups. The response induced by the α-amylase inhibitor was higher than that induced by the albumin fraction and the p31-43 and p57-68 peptides. At a concentration of 25µgmL(-1) , five of 36 patients with psoriasis responded positively to the p62-75 peptide and none of the 33 controls, using a stimulation index of 2·4 as the cut-off level (P<0·05). These five patients did not show clinical features that differed from the remaining patients. Among the responding patients the relative number of CD4+ cells increased in some but not all after in vitro challenge with the albumins, 0·28 α-amylase inhibitor, and p62-75. These antigens could also induce in vitro the expression of the homing antigen cutaneous lymphocyte antigen (CLA) in a few patients and controls. CONCLUSIONS: The wheat protein antigens, especially the p62-75 peptide, might be of interest in a subgroup of patients with psoriasis.

Hearing difficulties, uptake, and outcomes of hearing aids in people 85 years of age.

OBJECTIVE: The aim of this study was to investigate self-reported hearing difficulties, uptake, and hearing-aid outcomes and their relationships to demographic, cognitive, psychosocial, and health variables in 85 year olds. DESIGN AND STUDY SAMPLE: Three hundred and forty-six elderly adults participated in a survey that included questionnaires and home visits. Fifty-five percent of participants admitted to having hearing difficulties, and 59% of these owned hearing aids. The participants' most frequently cited reason for not acquiring hearing aids was that they did not think their hearing problem was perceived as severe enough. Participants with hearing difficulties who did not own hearing aids showed worse general and mental health. Many of the elderly participants were successful in their rehabilitation, and their hearing-aid outcomes were similar to those of a younger group, with the exception of a greater proportion of non-users among the elderly. CONCLUSION: Many older people with self-reported hearing difficulties do not acquire hearing aids, despite this study's findings that older people are likely to have success with hearing rehabilitation. It is important to make greater efforts to try to increase elderly adults' awareness of hearing loss and the benefits of hearing rehabilitation.

Ultraviolet B-induced DNA damage in human skin and its modulation by a sunscreen.

The UVB component of solar radiation is a risk factor for skin cancer, the most common cancer in the Western world. Yet little is known about the induction of DNA damage in human skin by UVB and its modulation by sunscreens. Here, we apply a novel postlabeling high-performance liquid chromatography technique to quantify UVB-induced photoproducts in skin biopsies with and without sunscreen. The results showed approximately 30-fold interindividual variations in levels of DNA damage in unprotected skin of the 14 subjects, probably relating to skin cancer susceptibility. On average, sunscreen guards against DNA damage as expected by the erythemal response, but some individuals are poorly protected.

Unaltered Image of Health Maintenance: An Observation of Non-Participants in a Swedish Cohort Study of 85 to 86 Year Olds.

BACKGROUND: Selection bias is often inevitable in epidemiologic studies. It is not surprising that study conclusions based on participants' health status are frequently questioned. OBJECTIVE: This study aimed to assess whether the non-participants affected the characteristics of a general population of the very old people. DESIGN, SETTING AND PARTICIPANTS: Prospective, cross-sectional (N=650, aged 85 years old) analysis and 1-year follow-up (n=273), in Linköping, Sweden. MEASUREMENTS: We analysed data on health-related factors from a postal questionnaire, a home visit and a clinic visit at baseline and at the 1-year follow-up. We calculated the effect size to evaluate the degree of differences between the groups. RESULTS: A greater proportion of non-participants resided in sheltered accommodation or nursing homes (participants vs non-response vs refusal, 11% vs 22% vs 40, P<0.001, φ=0.24). During the home visit or clinic visit, a higher proportion of dropouts reported mid-severe problems in EQ-5D domains (mobility and self-care) and limitations in personal activities of daily living, but the differences between participants and dropouts were very small (φ<0.2). No significant difference was found between the groups with regard to emergency room visits or hospital admissions, despite the fact that more participants than dropouts (φ=0.23) had multimorbidities (≥2 chronic diseases). Living in sheltered accommodation or a nursing home (odds ratio (OR), 2.8; 95% confidence interval (CI), 1.5-5), female gender (OR, 1.8; 95% CI, 1.1-3.1) and receiving more home visits in primary care (OR, 1.03; 95% CI, 1-1.06) contributed positively to drop out in the data collection stages over the study period. CONCLUSION: Non-participants were not considered to be a group with worse health. Mobility problems may influence very old people when considering further participation, which threatens attrition.

Obese very old women have low relative hangrip strength, poor physical function, and difficulties in daily living.

OBJECTIVES: To investigate whether anthropometric and body composition variables and handgrip strength (HS) were associated with physical function and independent daily living in 88-year-old Swedish women. PARTICIPANTS: A cross-sectional analysis of 83 community-dwelling women aged 88 years who were of normal weight (n=30), overweight (n=29), and obese (n=24) was performed. MEASUREMENTS: Body weight (Wt), height, waist circumference (WC), and arm circumference were assessed using an electronic scale and a measuring tape. Tricep skinfold thickness was measured using a skinfold calliper. Fat mass (FM) and fat-free mass (FFM) were measured using bioelectrical impedance analysis, and HS was recorded with an electronic grip force instrument. Linear regression was used to determine the contributions of parameters as a single predictor or as a ratio of HS to physical function (Short Form-36, SF-36PF) and instrumental activities of daily living (IADL). RESULTS: Obese women had greater absolute FM and FFM and lower HS corrected for FFM and HS-based ratios (i.e., HS/Wt, HS/body mass index [BMI]) than their normal weight and overweight counterparts. After adjusting for physical activity levels and the number of chronic diseases, HS-based ratios explained more variance in SF-36PF scoring (R2, 0.52-0.54) than single anthropometric and body composition variables (R2, 0.45-0.51). WC, HS, and HS-based ratios (HS/Wt and HS/FFM) were also associated with independence in IADL. CONCLUSION: Obese very old women have a high WC but their HS is relatively low in relation to their Wt and FFM. These parameters are better than BMI for predicting physical function and independent daily living.

Effect of constitutional pigmentation on ultraviolet B-induced DNA damage in fair-skinned people.

Ultraviolet light has been implicated as a dominant factor in skin cancer development. Skin pigmentation is traditionally regarded as an important protection against skin cancer. Yet, little is known about how skin pigmentation is modulating induction of DNA damage, which is the primary event in carcinogenesis. We applied a recently developed 32P-postlabeling technique to measure the effect of constitutional pigmentation on the formation of major ultraviolet-induced DNA damage in human skin in vivo. The induction of photoproducts showed a statistically significant negative correlation with erythemal response and skin pigmentation. Our results demonstrated that the constitutional pigmentation is efficiently guarding DNA against the formation of photoproducts. The difference in melanin content is likely to be one of the reasons for the observed interindividual variation in levels of DNA damage after the uniform exposure to ultraviolet B.

Diagnosis of dementia at the primary care level.

In Sweden, as in many other industrial countries, the majority of patients with symptoms of dementia are initially evaluated by a general practitioner (GP), and many do not receive a follow-up assessment by a specialist. Accordingly, GPs play a vital role in identifying patients with possible dementia and undertaking additional diagnostic procedures. Currently, however, the ability of most GPs to perform assessments for dementia is limited. It is important that tests to confirm the presence of dementia be performed uniformly, irrespective of the specialty of the examining physician. Once a diagnosis of dementia has been established and appropriate living arrangements for the patient have been made, the GP should continue to monitor the patient's health status. In Sweden, "dementia teams" of health care professionals have been successful in providing a consistently high level of care to patients with dementia, reducing the incidence of hospitalization for acute illness.

Brain 5-HT1A, 5-HT1D, and 5-HT2 receptors in suicide victims.

We report on 5-HT1A, 5-HT1D, and 5-HT2 binding sites in 23 control subjects and 18 suicide victims subdivided according to the method of death and the previous existence of depressive symptoms. No difference in maximum binding (Bmax) or binding affinity (Kd) was found between the control and overall suicide groups for the binding sites studied. The drug overdose subgroup showed, however, a significant decrease in the 5-HT1A binding affinity, probably explained by the higher sensitivity of this binding site to the acute administration of tricyclic antidepressants. A significant decrease in 5-HT1D binding affinity was also found in the depressed suicides, together with a significant decrease in the number of 5-HT1D binding sites in the nondepressed suicides. Further studies should be carried out on the 5-HT1D binding site as it might represent a new tool in the understanding of the depressive illness.

Serotonergic, noradrenergic, and dopaminergic measures in suicide brains.

Concentrations of the three main monoamines (5-HT, NA, and DA), their metabolites (5-HIAA, DOPAC, and HVA), and the serotonin precursor 5-hydroxy-L-tryptophan were simultaneously measured in frontal cortex, gyrus cinguli, and hypothalamus from 23 controls and 18 suicide victims. Overall suicides did not show significant differences with respect to the control group in any of the measured compounds. Significant increases in noradrenaline and dopamine concentrations were noted in the carbon monoxide poisoning suicides, together with a significant increased hypothalamic dopamine in the drug overdose suicides. It is suggested that the suicidal behavior is not related to substantial changes in cortical and hypothalamic monoaminergic function; however, the reported results could be secondary to the rapid effect of hypoxia and of the acute self-administration of certain drugs in specific metabolic pathways.

[3H]paroxetine binding in human platelets in relation to age and sex.

The binding of [3H]paroxetine to serotonin uptake sites in human platelets from 47 individuals between 15 and 95 years of age was investigated. There were no significant age-related changes in maximal binding capacity (Bmax) or apparent binding affinity (Kd). There were no significant differences in binding between males (n = 19) and females (n = 28).

Age-correlated loss of dopamine uptake sites labeled with [3H]GBR-12935 in human putamen.

The effects of age (19-100 years) upon dopamine uptake sites labeled with [3H]GBR-12935 in human postmortem putamen from 20 individuals were studied. There was a 70% decrease in binding density (Bmax) over the adult age range. No significant changes in binding affinity (Kd) were detected, the mean Kd being 1.0 +/- 0.2 nM (mean +/- S.E.M.). Nor were there any changes in binding related to the postmortem delay. Based on the findings that [3H]GBR-12935 labels the uptake site for dopamine, it is suggested that the age-related loss of [3H]GBR-12935 binding in human putamen reflects a degeneration of dopamine neurites.

Platelet [3H]paroxetine binding to 5-HT uptake sites in Alzheimer's disease.

Platelet serotonin (5-hydroxytryptamine, 5-HT) uptake sites were studied in a control group (n = 30) and an Alzheimer group (n = 40) using [3H]paroxetine as radioligand. The maximum number of binding sites (Bmax) for control (1250 +/- 60 fmol/mg protein) was not different from the Alzheimer group (1280 +/- 40 fmol/mg protein). There were no differences in apparent binding affinity (Kd): 0.046 (0.024-0.062) nM for control and 0.040 (0.027-0.061) nM for Alzheimer. Thus even though several previous studies have demonstrated marked atrophy of 5-HT containing neurites and 5-HT uptake sites in Alzheimer's disease, these findings are not found in the periphery on platelets. The platelet 5-HT uptake site cannot be used as a peripheral marker of Alzheimer's disease.

Serotonin concentrations in normal aging human brains: relation to serotonin receptors.

Concentrations of serotonin (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in 7 regions of normal human brains and, in some of the regions, were compared to the number of serotonin receptors (S1 and S2). Neither 5-HT nor 5-HIAA concentrations correlated significantly with increasing age (from 17-100 years) in any of the regions investigated. Positive correlations between 5-HT and 5-HIAA were found in all regions studied, significantly (p less than 0.05) so in 5 of the areas. When comparing 5-HT transmitter and metabolite concentrations to the number of S1 and S2 receptors, no significant correlations were found either within any brain area of between different brain regions. These data confirm that 5-HT transmitter concentrations are not altered by increasing age, support the ideas that S1 and S2 receptors are not presynaptic and also that 5-HT transmitter concentrations and receptor densities are separately controlled.

Divergent changes in D-1 and D-2 dopamine binding sites in human brain during aging.

The density of D-1 and D-2 dopamine receptors in human caudate nucleus and putamen, obtained postmortem, were studied throughout the adult lifespan using [3H]fluphenazine as the dopamine receptor ligand. The D-1 subtype increased progressively with age in both regions, while the D-2 subtype declined in caudate nucleus. The ratio of D-1/D-2 Bmax in both regions increased from approximately 1 at age 20 to 2 by age 75. The dopamine content in putamen declined with age and was inversely correlated with D-1 receptor density. We suggest that D-1 receptor density is up-regulated by loss of dopamine during aging. The D-2 receptor density in caudate nucleus was positively correlated with choline acetyltransferase activity, suggesting that loss of intrastriatal neurons with age may contribute to the decrease in D-2 sites. These divergent changes in dopamine receptor subtypes with age result in an altered complement of dopamine receptors in older humans and may provide a basis for selective pharmacotherapy in disorders of the basal ganglia.

Chronic amitriptyline treatment induces hippocampal NGFI-A, glucocorticoid receptor and mineralocorticoid receptor mRNA expression in rats.

Adult male rats were treated with the antidepressant drug amitriptyline for 21 days and the expression of specific transcription factors was examined. NGFI-A mRNA expression was increased in the hippocampus and in the cerebral cortex. MR mRNA was increased in the hippocampus while GR mRNA was increased in selective hippocampal regions. There was no change in the NGFI-B mRNA expression. Thus, NGFI-A may be a mediator of plasticity-related phenomena induced by antidepressant drugs.

Langerhans cells in prurigo nodularis investigated by HLA-DR and S-100 immunofluorescence double staining.

The Langerhans cell is one of the antigen-presenting cells in the immune system. To study the presence of cutaneous Langerhans cells in prurigo nodularis, age- and sex-matched prurigo nodularis patients and healthy volunteer skin biopsies were investigated by an HLA-DR and S-100 immunohistochemical double staining method. The results showed that the HLA-DR- and S-100-immunoreactive (IR) Langerhans cells were altered in prurigo nodularis epidermis and dermis. The number of epidermal Langerhans cells in the prurigo nodularis patients was decreased in five and increased in two cases. In the dermis, the HLA-DR- and S-100-IR cells were apparently more numerous than in the controls. In the involved skin there were also more S-100-IR coarse nerve fibres in the dermis as compared to controls. The results indicate that dermal Langerhans cells (HLA-DR and S-100 double-labeled) as well as other dermal HLA-DR- and S-100-IR dendritic cells, but most likely not epidermal Langerhans cells, may be critically involved in the development or persistence of prurigo nodularis.

Rearrangement of S-100 immunoreactive Langerhans' cells in human psoriatic skin treated with peptide T.

Dendritic cells marked by protein S-100 (S-100) antiserum in the suprabasal layers of the epidermis have previously been identified to be Langerhans' cells. In this study, S-100 immunoreactive cells have been investigated in psoriatic lesioned skin during and after peptide T treatment. Peptide T is an octapeptide with affinity for the CD4 receptor. Nine patients were intravenously infused with peptide T, 2 mg in 500 ml saline per day for 28 days. Sections from involved skin before, every week during, and after the treatment were processed by indirect immunofluorescence using S-100 antiserum. Before the treatment the epidermal Langerhans' cells were numerically decreased or even completely gone in the involved skin of psoriasis as compared to skin from normal healthy controls, while the dermal dendritic cells instead were increased and gathered in cell clusters around vascular structures. Four of the nine patients had histopathological improvements after the peptide T treatment, and, in those cases, the dendritic cells in the dermis were reduced in number, and the Langerhans' cells in the epidermis were numerically increased as well as even reversed to normal position and morphology. These changes in the distribution and density of Langerhans' cells represent their rearrangement during the course of psoriasis and/or the remission after peptide T treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding of some antidepressants to the 5-hydroxytryptamine transporter in brain and platelets.

Antidepressant agents with properties to inhibit 5-hydroxytryptamine (5-HT, serotonin) uptake in brain tissue and platelets bind with high affinities to neuronal and platelet membranes. [3H]Imipramine, [3H]paroxetine and [3H]citalopram label specific binding sites related to the 5-HT transporter. [3H]Paroxetine and [3H]citalopram appear to be better ligands than [3H]imipramine. The former label a homogenous population of binding sites, whereas the displaceable binding of [3H]imipramine is heterogenous. Recent observations in several laboratories, which have taken the heterogeneity of [3H]imipramine binding into account, indicate that the binding of antidepressants to the 5-HT transporter probably occurs to the same site that binds 5-HT for transport and not to a separate site as previously suggested. Additional bonds to subsites in close vicinity to the 5-HT recognition site may contribute to the binding. No convincing evidence has been presented of the existence of an endogenous ligand other than 5-HT itself that binds to the [3H]imipramine binding site. Recent studies also suggest that repeated treatment of rats with antidepressant agents does not produce any alterations of the binding of [3H]imipramine or [3H]paroxetine to membranes of cerebral cortex. It is also doubtful whether the density of the 5-HT uptake site in platelets measured with these ligands is decreased in affective disorders as first reported.

Unaltered 5-HT- and desipramine-sensitive [3H]imipramine binding and [3H]5-HT uptake in rat brain after chronic imipramine and norzimeldine treatment.

Several reports have shown heterogeneity of [3H]imipramine binding to brain membranes. Recently, a high affinity and 5-HT sensitive [3H]imipramine binding site of protein nature, that was suggested to be identical to the substrate recognition site for 5-HT uptake, was demonstrated. Since most studies on the regulation of the [3H]imipramine binding sites by antidepressants have used desipramine displaceable binding, which is heterogenous in nature and contains binding not related to 5-HT uptake sites, the present report studies the possible effects of chronic (3 weeks) administration of imipramine or norzimeldine (10 mg/kg intraperitoneally twice daily) on 5-HT sensitive [3H]imipramine binding sites. For comparison, desipramine sensitive binding was also studied, as well as the physiological correlate 5-HT uptake. There were no changes in either [3H]imipramine binding or 5-HT uptake after the antidepressant treatment.