Measuring the economic value of morning stiffness: consistency over 1 year.

OBJECTIVES: The aims of this study were to determine the within-patient variation in the duration of morning stiffness (MS) over 1 year and the corresponding monetary equivalents assigned to its changes using the willingness-to-pay (WTP) methodology. METHOD: A sample of 100 patients with rheumatoid arthritis (RA) was drawn from the register of the Hospital District of Southwest Finland. Subjects were interviewed by telephone on recruitment and 1 year later, using the same structured questionnaire. The subjects were asked to estimate in minutes the typical duration of their MS during the previous week. Sociodemographic background data and subjects' WTP for a 25, 50, 75, and 100% reduction in MS duration were requested, and years with RA diagnosis and serological data were obtained from hospital records. RESULTS: After 1 year, there was a reduction in average MS duration from 44.7 min to 39.0 min (ns); duration was reduced in 35% of patients, unchanged in 35%, and prolonged in 30%. Changes in MS duration were reflected by within-patient variation in WTP estimates. In linear regression models, change in duration of MS significantly (p < 0.03) explained the variation in change of WTP for symptom reduction. CONCLUSIONS: WTP methodology produces consistent monetary values to assess the relative values patients with RA place on reduction in duration of MS.

Efficacy of a multicomponent support programme for the caregivers of disabled persons: a randomised controlled study.

AIM: The goal of the present work was to measure the efficacy of a multicomponent programme designed to provide tailored support for the caregivers of disabled persons. SUBJECTS: A total of 135 caregivers-care receiver dyads were randomly divided into an intervention group (n = 66) and a control group (n = 69). One-third of the care receivers were demented, and two-thirds had other diseases. SETTING: Health centres (publicly funded primary health care systems) in 8 rural and urban communities in southeast Finland. INTERVENTION: The multicomponent support programme for the caregivers consisted of a 2-week rehabilitation period. The control group received standard care. OUTCOME MEASUREMENTS: Continuation of the caregiver and care receiver relationship, care receiver mortality at the 2-year follow-up as well as the health-related quality of life (15D scale) and Zung's depression scale of the caregiver at the 1-year follow-up were evaluated. RESULTS: At the 2-year follow-up, the caregiver-care receiver relationship was terminated for any reason in 11 cases (17%) in the intervention group, and in 25 cases (36%) in the control group. After adjusting, the primary outcome (i.e., termination of care giving for any reason) indicated statistical significance (p = 0.04) with a hazard rate of 1.83 (95% confidence interval 1.03-3.29). With a similar adjustment, the difference in mortality and placement to institutional care between the two groups demonstrated a trend towards statistical significance. The caregivers' health, as related to quality of life and depressive symptoms, remained unchanged in both groups at the 1-year follow-up. CONCLUSION: These results indicate that a tailored support programme for caregivers may help the caregiver to continue the caregiver-care receiver relationship and delay institutionalization.

Effect of ripening temperature on the chemical composition of lingonberries (Vaccinium vitis-idaea L.) of northern and southern origin.

Lingonberries (Vaccinium vitis-idaea L.) from two locations, northern (69°N, 18°E) and southern (59°N, 10°E) Norway, were grown under controlled conditions in a phytotron at two temperatures (9 and 15 °C) to study the effects of the ripening temperature and origin on the chemical composition of the berries. The concentrations of phenolic compounds, sugars, and organic acids as well as the profile of volatile organic compounds (VOCs) were determined using chromatographic and mass spectrometric methods. Five anthocyanins, eleven flavonols, eight cinnamic acid derivatives, three flavan-3-ols, three sugars, three organic acids, and 77 VOCs were identified, of which 40 VOCs had not previously been reported in lingonberries. Berries from both locations, were found to have higher contents of anthocyanins and cinnamic acid derivatives when ripened at lower temperature (9 °C), compared to the higher temperature (15 °C). Lingonberries of northern origin had a different VOC profile and higher contents of anthocyanins and organic acids than berries originating from the south. Lingonberries from the northern location also had higher proportions of cyanidin-3-O-glucoside and cyanidin-3-O-arabinoside than lingonberries from the southern location. The results show that the composition of lingonberries is influenced by both the environment and the origin of the plants, with phenolic compounds mainly influenced by the growth temperature and VOCs mainly influenced by plant origin.

Consistency of assessments and willingness to pay for a reduction in morning symptoms over time in patients with rheumatoid arthritis.

OBJECTIVES: To determine the variation in morning symptoms and in the corresponding monetary equivalents assigned to their reduction. METHODS: The sampled (n = 100) rheumatoid arthritis (RA) patients were interviewed twice by a trained interviewer using the same interview, 2 weeks apart. Patients assessed fatigue, pain, and severity of morning stiffness (MS) on waking up and after maximum improvement on a numeric rating scale (NRS). Patients estimated the duration of MS in minutes and reported the number of tender and swollen joints. Patients were also asked to estimate how much they would be willing to pay on a daily basis if pain, duration of MS, and severity of MS when waking up could be reduced by 25, 50, 75, and 100%. Weighted averages of the monetary assessments for symptom reduction were computed. RESULTS: On average, the NRS values at the first and second assessments were close to each other, except for fatigue and pain, which were significantly lower (p < 0.01) in the second assessment. There was limited within-patient variation, with the majority of symptom assessments within a range of ±10%. Weighted average willingness-to-pay (WTP) estimates were consistent across time points for reduction in pain and MS severity and duration. Changes in symptom assessments were reflected in the WTP estimates. CONCLUSIONS: The duration and severity of MS seemed to be more consistent over time than pain and fatigue. WTP estimates and their changes corresponded closely to changes in symptom assessments.

Gas composition in controlled atmosphere stunning affects turkey meat quality traits.

1. Investigations were made into the breast and leg muscle energy metabolism, and the quality of breast meat of turkeys after controlled atmosphere stunning or stun-killing (CAS) with various gas mixtures. In addition, the effect on meat quality of an increase in the chilling rate of turkey breast meat after hypercapnic or anoxic stun-killing was studied. 2. A total of 35 turkey toms within two replicate pens were individually stunned during consecutive weeks using one of 4 CAS methods. The stunning gases tested were high CO(2) concentration (60% CO(2) in air), high N(2) concentration (98% N(2), < 2% O(2)), a mixture of 76% N(2) and 24% CO(2), and a biphasic method (first minute in mixture containing 40% CO(2), 30% N(2), and 30% O(2;) followed by two minutes in a mixture containing 60% CO(2) in air). 3. The birds stunned with N(2) displayed the highest initial reduction in muscle pH, but after 4 h post mortem there were no differences in pH values associated with the various CAS methods. 4. The CAS method alone had no statistically significant effect on the quality of turkey breast muscle when the chilling speed was rapid (0°C for 4 h, followed by storage at 4°C). When the chilling rate was slowed (20°C for 4 h followed by storage at 4°C), a significant decrease in cooking loss and in Warner-Bratzler shear force was recorded for birds stun-killed with CO(2). 5. This study shows that anoxic stun-killing with N(2) had no adverse effects on meat quality despite the rapid post mortem pH decrease. The CAS with N(2) allows rapid cooling of carcases without the risk of cold shortening, whereas with CO(2)-stun-killing of turkeys, the rate of chilling should be slower. Concerning meat quality, all the CAS methods tested were suitable for stunning turkeys.

How much is a reduction in morning stiffness worth to patients with rheumatoid arthritis?

OBJECTIVE: The aim of this study was to determine the monetary equivalent of the emotional and functional impact of morning stiffness (MS) in patients with rheumatoid arthritis (RA), using alternative valuing methods. METHODS: Telephone interviews were conducted among 166 patients with RA to assess utility and clinical symptoms, including MS. Three standard economic methods were used: the human capital approach (HCA), marginal value of time (MVT), and willingness-to-pay (WTP). RESULTS: The monetary equivalent of the impact of MS varied with the method used (from EUR 5.74 to EUR 17.87 per patient per day) and severity of MS (5-8-fold higher in patients with severe MS compared with mild MS). Patients placed considerable value on a reduction in duration and severity of MS. Patients with MS lasting an hour or more were willing to pay EUR 21.74/day to stop the symptom and EUR 10.63/day to halve the duration. Patients with severe MS were willing to pay EUR 47.86/day to stop the symptom and EUR 21.68/day to halve the severity. CONCLUSIONS: The observed variation in the monetary equivalent of the impact of MS obtained with the three estimation methods indicates that the findings of studies using different valuing methods should not be compared directly. The study demonstrates that a reduction in MS is worth a considerable amount to patients with RA, particularly those with severe or prolonged MS. These findings suggest that clinical treatment decisions to improve patients' quality of life should also incorporate therapy that reduces MS.

Phenotype of a homozygous CADASIL patient in comparison to 9 age-matched heterozygous patients with the same R133C Notch3 mutation.

BACKGROUND AND PURPOSE: CADASIL is an autosomal dominant arteriopathy, characterized by multiple brain infarcts, cognitive decline, and finally dementia, which is caused by mutations in Notch3 gene encoding a Notch3 receptor protein. We describe the clinical, neuropsychological, imaging, genetic, and skin biopsy findings in a CADASIL patient homozygous for the C475T mutation resulting in R133C amino acid substitution, in comparison to 9 age-matched heterozygous patients with the same mutation. METHODS: The patients were examined clinically and neuropsychologically and with MRI and positron emission tomography for assessment of cerebral blood flow. The gene defect was analyzed by sequencing the products of polymerase chain reaction of exons 3 and 4 of the Notch3 gene. Dermal arteries were analyzed electron microscopically. RESULTS: The homozygous patient had his first-ever stroke at age 28 years. This is markedly earlier than the average, but the patient's heterozygous son had his first transient ischemic attack-like episode at the same age and another heterozygous patient had his first-ever stroke when only 2 years older. He was neuropsychologically more severely deteriorated than all but 1 of the heterozygous patients. These 2 patients had the most severe (confluent grade D) white matter MRI changes. Positron emission tomography showed markedly reduced cerebral blood flow. Skin biopsy revealed profuse deposits of granular osmiophilic material. The progression of disease in the homozygous case was, however, slower than in the most severely affected heterozygous patient. CONCLUSIONS: Our homozygous patient's phenotype is within the clinical spectrum of CADASIL, although at its severe end. Thus, CADASIL may follow the classic definition of a dominant disease, according to which the heterozygous and homozygous patients are clinically indistinguishable.

Oral parameters for the diagnosis of Sjögren's syndrome.

Agreement is probably world wide in the medical profession that patient history is the most relevant part of the patient examination, but at the same time the most demanding part because there is no substitute to lack of knowledge and experience. These form the basis for an often subconscious process of selecting the most important pieces of information to help in decision making. We describe a stepwise forward discriminant analysis with a jackknife-validation in analysis of questionnaires as to diagnosis of Sjögren's syndrome. The second topic of current interest, also due to the need of generally acceptable criteria for diagnosis and classification, is the place of labial salivary gland (LSG) biopsy in such sets of criteria. In the histopathological part of our work we describe findings of a postmortem LSG study from the coroner's office.

Anti-oxidant supplementation decreases TBA reactants in serum of elderly.

An "anti-oxidant cocktail" consisting of betacarotene, vitamins B6, C, E, zinc, and selenium or corresponding placebos were given for one y as daily dietary supplements to 45 elderly residents of a nursing home. Initially, the serum TBA reactant levels were higher (2.7 +/- 0.7 mumol/L) than those of an ad hoc control group of healthy younger adults (2.3 +/- 0.6 mumol/L), p less than 0.01. After three mo supplementation, the levels among the verum elderly had decreased to 2.2 +/- 0.6 mumol/L, and they remained at this lower level until the end of the study period, whereas the placebo group showed no change. A significant inverse correlation (r = -0.428, p less than 0.01) existed between the concentrations of serum TBA reactants and whole blood selenium (B-Se), but only B-Se levels above 200 micrograms/L were associated with a decrease in serum lipid peroxides. Serum alpha-tocopherol concentration also correlated inversely with serum TBA reactants but this correlation (r = -0.273, p less than 0.76) was not as strong as that of B-Se. Deficient vitamin B6 status, in biochemical terms, was observed in 25% of the elderly; a daily supplement of 2 mg B6 fully cured all cases of deficiency. The verum group improved slightly in several psychological tests, whereas subjects on placebo remained unchanged or deteriorated during the follow-up period. Clinical amelioration among the verum subjects was reported by the nurses; no toxic side effects were reported. In conclusion, the elderly benefited biochemically and clinically of dietary antioxidant supplements.

Vitamin B6 status of Finnish elderly. Comparison with Dutch younger adults and elderly. The effect of supplementation.

About 25% of Finnish and Dutch elderly appeared to be more or less deficient in vitamin B6 as compared to younger adults. Deficiency was observed at the cellular (PLP, EGOT and alpha-EGOT) as well as at the plasma level (PLP). The benefit of a one-year daily supplementation with 2 mg of pyridoxine-HCl was investigated at the biochemical and psychological level as compared to a placebo group. After one year, none of the supplemented elderly was deficient in biochemical terms. At the psychological level and at the level of general well-being, the elderly supplemented with vitamin B6 showed slight improvements. However, for the psychological variables significant correlations with the vitamin B6 parameters were not observed. Plasma fatty acids (e.g. gamma-linolenic acid) showed no correlation with the vitamin B6 status.

Mast cells and their mediators.

Mast cells (MC) are the most important cells in hypersensitivity reactions. Their functions in other pathological conditions are, however, not completely understood. At least two different MC subtypes have been isolated and it seems that due to environmental changes further differences in the morphology and functions of MC:s exist. The activation of MC:s can be both due to immunological and non-immunological factors and results in a release of different mediators and production of so called newly generated MC mediators. The functions following mediator release are complicated and several other inflammatory cells are involved in these reactions. Due to the more slowly effect of the newly generated mediators and the interaction of different cell types the effects of these reactions are often spread over a long time. It seems that MC:s may play an important part not only in hypersensitivity reactions but also in other pathological conditions as in inflammatory disorders.

Solitary fibrous tumour of the oral cavity: clinicopathological and immunohistochemical characterization of three cases.

Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm rarely located in the oral cavity. To characterize further oral SFT, we describe three new cases. Each tumour originated in the buccal mucosa of a middle-aged/elderly patient. Histological examination showed well-circumscribed tumours with densely cellular areas alternating with hypocellular areas in a variedly collagenous, vascular stroma. Mast cells were abundant. The spindle-shaped, neoplastic cells immunostained strongly for CD34 antigen and vimentin and weakly for bcl-2, but not for epithelial cell markers, alpha-smooth muscle actin, or neurofilament or S-100 proteins. Compatible with the virtual absence of mitoses and of marked nuclear atypia, the overall frequency of proliferating cells expressing Ki-67 was low. The expression of CD34 was useful in the differential diagnosis. The consistent location in the cheek and expansion of one tumour after local trauma does not preclude a traumatic element in the development of oral SFT.

Mast cells in the labial salivary glands of patients with Sjögren's syndrome: a histochemical, immunohistochemical, and electron microscopical study.

Mast cells in labial salivary glands obtained from patients with xerostomia with or without focal sialadenitis/Sjögren's syndrome were studied. There was no significant correlation between the intensity of local lymphocyte infiltration and the morphometrically analysed number of mast cells staining positive with toluidine blue. Histamine staining with heterologous 11C antiserum showed significantly fewer positive cells than staining with toluidine blue (mean (SD) 62 (10) v 138 (30)). This suggests heterogeneity of the mast cell population. Furthermore, there was a correlation between the focus score and the number of mast cells containing histamine. This suggests that the proliferation of mast cells containing histamine may be locally regulated by the immune inflammation, possibly through mediators from macrophages and fibroblasts. In contrast, the number of mast cells staining positive with toluidine blue could not be used as a marker of the degree of local inflammation. Although transmission electron microscopic analysis did not disclose signs of 'en masse' mast cell degranulation, mast cells may have a role in the local disease process.

Role of nitric oxide in Sjögren's syndrome.

OBJECTIVE: To measure levels of salivary nitrite (NO2-) and to localize nitric oxide synthases (NOS) in the labial salivary glands (LSGs) of patients with Sjögren's syndrome (SS). METHODS: NO2- was measured by the Griess reaction. LSGs were analyzed using NADPH-diaphorase histochemical and immunohistochemical studies to determine the constitutive NOS (neuronal [ncNOS] and endothelial [ecNOS]) and inducible NOS (iNOS) isoforms. RESULTS: The NO2- concentration (mean +/- SEM 307 +/- 51 microM versus 97 +/- 16 microM; P < 0.05) and output (166 +/- 46 nmoles/minute versus 37 +/- 7 nmoles/minute) were increased in SS patients compared with healthy control subjects. NADPH-diaphorase was found in some nerve fibers and endothelial cells, and, in SS, was found in myoepithelial, acinar, and ductal epithelial cells, but in only a few inflammatory cells. In SS, ncNOS-immunoreactive nerve fibers were sparse and ecNOS was found in a minority of the CD31-positive vascular endothelial cells and acinar cells, whereas iNOS was localized in myoepithelial, acinar, and ductal epithelial cells, often together with tumor necrosis factor alpha. CONCLUSION: Nitrite was found in normal human saliva. NO produced by ncNOS probably acts as a nonadrenergic, noncholinergic neurotransmitter, whereas that produced by ecNOS exerts a vasodilatory effect. SS patients had increased NO2- concentrations, with most of the superfluous salivary NO being produced not by the immigrant inflammatory cells, but rather, by the resident salivary gland cells. NO may contribute to inflammatory damage and acinar cell atrophy in SS.