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Biomedical subjects

A Akesson

Publications and source records attributed to A Akesson.

At least 37 records · Page 2Linked to original sources

Evaluation of kits for measurement of the soluble transferrin receptor.

Three commercially available kits for determination of the soluble serum transferrin receptor (sTfR), R&D Systems, UK, Ramco Laboratories, USA and Orion, Finland were compared with respect to practicability, comparability and ability to discriminate between iron deficient and non-iron deficient subjects. Serum samples representing different concentrations of sTfR were tested. The three kits involved virtually the same laboratory procedures except for a predilution step for Ramco. Both the absolute amounts and the units (mg/L and nmol/L) differed among the kits, emphasizing the need for internationally accepted reference material and comparable units. The correlation coefficients were 0.974 (Ramco and R&D), 0.769 (R&D and Orion) and 0.759 (Ramco and Orion), indicating a lower comparability for Orion compared to the other two kits. The differences between the kits may be attributed to uncertainties in the reference intervals and to variations in kit format. This may have implications for studies of the usefulness of sTfR as a marker of iron deficiency.

Calibration↗

A disease severity scale for systemic sclerosis: development and testing.

OBJECTIVE: To develop and test a severity scale for individual organ involvements in systemic sclerosis (SSc, scleroderma). METHODS: An international study group completed the following tasks: (1) developed a glossary of terms including all pertinent variables for 9 potentially affected organ systems; (2) collected prospective data to determine the feasibility and practicality of each proposed variable; (3) revised the initial list of variables; (4) determined the association of each variable with mortality (a proxy for morbidity) using 579 patients in an existing comprehensive longitudinal scleroderma databank; (5) developed a severity grading scale for each organ system by discussion and consensus; and (6) externally validated the scale using an independent group of 680 patients from the same databank. RESULTS: Nine organ-specific severity scales were developed from 0 (no documented involvement) to 4 (endstage disease). The data required for scale completion are relatively easy and practical for all physicians to obtain. CONCLUSION: This preliminary severity scale will be useful for assessing disease severity status in individual patients both at one point in time and longitudinally. The severity scale will assist in the design and conduct of clinical trials and the comparison of study populations with one another. The scale will serve as a framework for developing a scleroderma disease activity index.

Humans↗

Validation with biological markers for food intake of a dietary assessment method used by Swedish women with three different dietary preferences.

OBJECTIVES: To validate a dietary assessment method, a 4-day food record together with a duplicate portion technique, with biological markers for food intake. DESIGN: Four days of duplicate portions were collected in parallel with food recording. A 24-h urine sample and the faeces corresponding to the food intake (using a coloured marker) were collected. Completeness of urine and faeces collections was assessed using para-aminobenzoic acid (PABA) in urine and cadmium in faeces, respectively. Biomarkers of food intake (energy, protein, fibre, sodium, potassium, calcium) were measured in urine and faeces. SETTING: Swedish west coast. SUBJECTS: Non-smoking Swedish women, 20-50 years of age, consuming a mixed diet (n = 34), a mixed diet rich in shellfish (n = 17) or a vegetarian/high-fibre diet (n = 23). RESULTS: The average ratio (food intake according to the dietary assessment methods/ biological marker) for protein, sodium, potassium and calcium was 0.86. This indicates an underestimation of the food intake by approximately 15%. The ratio of stated fibre intake to biological marker was 1.20 for the mixed diet and the vegetarian diet group, indicating an overestimation by approximately 20%. CONCLUSIONS: The underestimation of the intake of protein, sodium, potassium and calcium by all three groups and the overestimation of the fibre intake by two groups indicate that underreporting is selective to certain nutrients and foods and to various groups of people. The two dependent dietary assessment methods were equally good in measuring protein intake, which indicates that the women recorded what they actually duplicated.

4-Aminobenzoic Acid↗

Serum transferrin receptor: a specific marker of iron deficiency in pregnancy.

BACKGROUND: Current markers of iron deficiency tend to be less reliable in pregnancy. OBJECTIVE: Our aim was to study the usefulness of soluble serum transferrin receptor (sTfR) as a marker for iron deficiency during early and late gestation and to define iron status in 254 pregnant Swedish women. DESIGN: We performed a cross-sectional and longitudinal evaluation of sTfR in comparison with concentrations of serum ferritin and hemoglobin in blood collected around gestational weeks 11 and 36. RESULTS: The specificity of sTfR was 100%. The sensitivity in relation to both anemia and depleted iron stores was approximately 70%, but this figure is less reliable because of few samples. sTfR in early pregnancy was low: 11% of women had a value below the reference interval. sTfR increased significantly from early to late pregnancy even in the group of women with persisting iron stores. In late pregnancy, 14% of women developed tissue iron deficiency and 5% had iron deficiency according to a combination of all 3 markers. CONCLUSIONS: sTfR seems to be a specific and sensitive marker of iron deficiency in pregnancy and may have advantages over serum ferritin and hemoglobin. The low sTfR concentration in early gestation seems to be caused by reduced erythropoiesis, whereas the increase from early to late pregnancy reflects increased erythropoiesis, and in case of iron deficiency, also tissue iron deficiency. Further studies are needed to verify whether decreased erythropoiesis reduces the possibility of detecting iron deficiency during early gestation by sTfR.

Anemia↗

Mortality and causes of death in a Swedish series of systemic sclerosis patients.

OBJECTIVES: To analyse survival rates and the causes of death in a systemic sclerosis (SSc) population, and to evaluate the occurrence of fatal malignant neoplasms and their possible association with oral cyclophosphamide (CYC) treatment. METHODS: Survival was calculated for 249 SSc patients followed up for up to 13 years. Mean (SD) follow up was 5.8 (4.2) years. The 49 decreased patients were subdivided according to causes of death and its relation to SSc. Fatal malignancies in CYC treated patients were compared with those occurring in non-CYC treated patients. RESULTS: The overall 5 and 10 year survival rates were 86% and 69% respectively. There was a 4.6-fold increased risk of death, as compared with the general population. Prognosis was worse in the diffuse cutaneous involvement (dSSc) and male subgroups than in the limited cutaneous involvement (1SSc) and female subgroups. Of the 49 deaths, 24 were attributable to pulmonary complications such as pulmonary fibrosis, pulmonary hypertension, pneumonia or pulmonary malignancy. Treatment with oral CYC did not increase the risk of dying of cancer. CONCLUSIONS: Mortality is increased both in the SSc population as a whole and in its different subsets (dSSc and 1SSc). Prognosis is worst among male patients with dSSc. However, the 5 year survival rate was better than those reported from earlier studies. Most patients die of cardiopulmonary disease. Five of seven fatal lung cancers were adenocarcinomas, possibly caused by chronic inflammatory disease of the lung. In this study, CYC treatment was not associated with an increased incidence of fatal malignant neoplasms.

Adenocarcinoma↗

Assessment of functional ability in patients with scleroderma: a proposed new disability assessment instrument.

OBJECTIVE: To develop a simple assessment of functional ability in patients with scleroderma and to examine its reliability both as a patient self-administered instrument and when administered by a trained observer. METHODS: An 11 item, 4 grade, functional assessment questionnaire was developed after extensive consultation with patients, physiotherapists (PT), and occupational therapists (OT) with the aim of including all functional areas of relevance. The instrument was self-administered by patients after an interval of 7 days. In the interval, the patients were assessed using the same instrument by direct observation from both a PT and an OT. Forty-seven patients with scleroderma, of varying severity, were recruited from 2 centers. Results were similar for both centers and data were pooled for analysis. RESULTS: Agreement between the patients' first and 2nd assessment was good for all questions (estimated kappas 0.69 to 0.94) with no evidence of an order effect. Agreement was also good between therapists (estimated kappas 0.47 to 0.81). There was poor agreement between patients and therapists, with patients rating their disability substantially higher compared to the standardized therapist assessment. CONCLUSION: This assessment schedule has high face and content validity and has excellent reliability both between trained therapists and within patients over a short time period. Its administration either as a self-report or by a therapist depends, in part, on the type of investigation undertaken.

Disability Evaluation↗

Cyclophosphamide therapy for scleroderma.

Pulmonary manifestations are the most common cause of death in patients with scleroderma. Consequently, the importance of treatment of both interstital lung disease and pulmonary hypertension has become increasingly evident. Until a placebo-controlled study of any drug has shown its beneficial effect on pulmonary dysfunction, cyclophosphamide may be useful for the treatment of scleroderma lung disease.

Antirheumatic Agents↗

Bioavailability of cadmium from shellfish and mixed diet in women.

Dietary intake and uptake of cadmium (Cd) were studied in nonsmoking women, 20-50 years of age, consuming a mixed diet low in shellfish (N = 34) or with shellfish once a week or more (N = 17). Duplicate diets were collected during 4 consecutive days for the determination of Cd content. The women kept detailed dietary records, and the intake of energy and various nutrients was calculated. The shellfish diets (median 22.3 micrograms Cd/day) contained twice as much Cd as the mixed diets (median 10.5 micrograms Cd/day; p < 0.0001). Cadmium in feces corresponded to 100 and 99% of that in duplicates of shellfish diets and mixed diets, respectively, indicating a low average absorption of the dietary Cd. In spite of the differences in the daily intake of Cd, there was no statistically significant difference in the concentrations of Cd in blood (B-Cd, shellfish group 0.25 micrograms/liter, mixed diet group 0.23 micrograms/liter) or urine (U-Cd, 0.10 micrograms Cd/liter in both groups). This indicates a lower absorption of Cd in the shellfish group than in the mixed diet group or a difference in the kinetics. A higher gastrointestinal absorption of Cd in the mixed diet group could partly be explained by lower body iron stores as measured by the concentrations of serum ferritin (S-fer, median 18 micrograms/liter, compared to 31 micrograms/liter in the shellfish group). In the mixed diet group, S-fer was negatively correlated with B-Cd and the main determining for B-Cd besides U-Cd in the multiple regression analysis, indicating an increased absorption of Cd at low body iron stores. When women with S-fer exceeding 20 micrograms/liter were compared, the higher dietary intake of Cd in the shellfish group compared to the mixed diet group (24 versus 10 micrograms/day) resulted in higher B-Cd (0.26 versus 0.16 micrograms/liter), although not in proportion to the difference in Cd intake. Thus, there seems to be differences in the bioavailability and/or kinetics of dietary Cd related to the type of diet. This is, to our knowledge, the first study where the influence of various types of diets and nutritional factors on the intake and uptake of cadmium in human subjects has been studied.

Adult↗

Computer based quantitative analysis of capillary abnormalities in systemic sclerosis and its relation to plasma concentration of von Willebrand factor.

OBJECTIVES: To evaluate an objective and quantitative method for assessment of capillary abnormalities in systemic sclerosis (SSc). METHODS: Nailfold capillaries were investigated by capillary microscopy and photographed in 17 consecutive SSc patients (five with diffuse cutaneous systemic sclerosis (dSSc) and 12 with limited cutaneous systemic sclerosis (lSSc)) and in 17 healthy controls. Investigators having no access to clinical data made drawings from magnified projections of coded photographs and analysed them using a computer program. Capillary density (capillary loops/mm in the distal row) and median capillary loop area were calculated. Presence of functional or organic arterial changes was evaluated by measurement of finger pressure with finger cooling. Plasma concentration of von Willebrand factor (VWF) was analysed using an enzyme linked immunosorbent assay (ELISA). RESULTS: In 16 of 17 SSc patients and 13 of 17 controls the technical quality of the photographs was sufficient for computer analysis. Capillary density was decreased in dSSc (median 6.9 loops/mm) and in lSSc (median 3.8 loops/mm) compared with healthy controls (8.9 loops/mm) and median capillary loop area was increased in dSSc (7.3 x 10(-3) mm2) and in lSSc (8.5 x 10(-3) mm2) compared with healthy controls (5.0 x 10(-3) mm2). An inverse relation was found between capillary density and median capillary loop area in SSc patients. Plasma VWF was increased in patients (median 401 IE/l in dSSc and 409 IE/l in lSSc) compared with controls matched for age and sex (median 276 IE/l). Computer based analysis showed capillary density below the control range and median capillary loop area above the control range in 14 of 16 SSc patients. Measurement of finger pressure with finger cooling showed organic vascular changes in nine of 13 SSc patients. CONCLUSION: Computer based quantitative analysis has low interobserver variability and is a quantitative and sensitive method of assessing capillary abnormalities in SSc.

Adolescent↗

Occurrence and distribution of peptidergic nerve fibers in skin biopsies from patients with systemic sclerosis.

Systemic sclerosis is characterized by vascular dysfunction. Itch is sometimes present in early stages of the disease. This prompted us to study the innervation of the skin by immunocytochemistry. Antibodies to neuropeptide Y and vasoactive intestinal peptide were used for autonomic nerves. Sensory innervation was studied using antibodies to substance P and calcitonin gene-related peptide. Protein gene product 9.5 was used as a general neuronal marker. Skin biopsies from affected (lower arm) and non-affected (upper back) sites on 10 patients with systemic sclerosis and from corresponding sites on 10 sex- and age-matched healthy controls were studied. Regional variations were found in the occurrence of peptidergic nerve fibers. In the patients the density of nerve fibers (measured semiquantitatively) stained by the panneuronal marker was lower in affected than in unaffected skin (p < 0.05). There were no significant differences in peptidergic innervation between patients and controls. However, there was a tendency to higher density of neuropeptide Y-positive nerve fibers in the forearm skin in 6 to 10 patients, as compared to only 1 of 10 healthy controls.

Adult↗

Altered dermatan sulfate proteoglycan synthesis in fibroblast cultures established from skin of patients with systemic sclerosis.

OBJECTIVE: To study whether changes in the properties of skin from patients with systemic sclerosis (SSc) are the result of altered metabolism of dermatan sulfate proteoglycans. METHODS: Fibroblast cultures were established from skin of healthy controls, and from affected and unaffected skin of patients with SSc. Synthesized proteoglycans were labeled with 3H glucosamine and 35S sulfate. The amount of mRNA of the different dermatan sulfate proteoglycans was determined by hybridization with the corresponding cDNA probes. RESULTS: A 2-fold increase in secretion of total proteoglycans was found in cell cultures from affected and normal appearing skin from patients with SSc. The production of 2 different dermatan sulfate proteoglycans was increased. Aggrecan/versican increased 4-fold and decorin 2-fold in cultures of affected skin from patients with SSc. The mRNA for decorin increased 3-fold, while the mRNA level for versican increased only slightly. Similar but less marked changes were noted in cultures from normal appearing skin. In contrast, the biglycan mRNA level decreased and the product could only be found in very small amounts in SSc cultures. CONCLUSION: This marked alteration of dermatan sulfate proteoglycan metabolism distinguishes not only affected skin but also normal appearing SSc skin from that of controls. The altered proteoglycan production may affect organization of matrix fibers and thereby the fibrotic process observed in patients with SSc.

Adult↗

Esophageal scintigraphy of systemic sclerosis.

UNLABELLED: Esophageal involvement is common in systemic sclerosis, and esophageal scintigraphy can be used to detect and follow esophageal dysfunction. This study assesses the value of visual and quantitative analysis of esophageal scintigraphy performed as a multiple swallow test in normals and patients with systemic sclerosis. METHODS: Forty patients with systemic sclerosis and 40 sex- and age-matched healthy subjects (controls) were studied. A multiple swallow technique was used and both quantitative and qualitative analyses were performed. Visual analysis of condensed images was performed independently by two physicians. Each swallow was assigned a score on a scale from 1 to 4. In the quantitative analysis, time-activity curves based on the mean condensed images were used to calculate the following 3 parameters: residual activity 12 or 25 sec after the beginning of the swallow, measured with or without baseline correction, respectively, and time from onset of swallow to 50% of peak activity. RESULTS: Both visual and quantitative analysis showed a highly significant (p < 0.001) difference between the patient group and the control group. Visual analysis was best reflected by the residual activity 25 sec after the beginning of the swallow without correction for background. Receiver operating characteristic curves were used to study the ability to separate the two groups using visual or quantitative analysis. A high rate of positive tests in the patient group was achieved only at the cost of a relatively high rate of positive tests in the control group. CONCLUSION: Our results indicate high variability in esophageal motility in controls. This variability impairs the possibilities of developing a screening test to identify asymptomatic patients early in the disease course.

Adult↗

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide.

OBJECTIVE: Pulmonary fibrosis is a common feature of systemic sclerosis (SSc) and a major cause of morbidity and mortality. Since alveolitis may be an essential step in the development of pulmonary fibrosis, we investigated the use of immunosuppressive drug therapy to improve pulmonary function in patients with SSc. METHODS: Eighteen patients with progressive pulmonary dysfunction, diminished vital capacity (VC), and/or decreased static lung compliance (Cst) were treated with cyclophosphamide and corticosteroids for 1 year. Eight patients had diffuse cutaneous SSc and 10 had limited cutaneous SSc. The median disease duration was 2.5 years (range 0.5-17 years). RESULTS: VC increased in 14 of 18 patients and the median VC rose from 74% to 80% of predicted. Cst improved in 8 of 12 patients and the median Cst increased from 59% to 66% of predicted. Pulmonary nonfibrotic opacities disappeared in 9 of 12 patients. The erythrocyte sedimentation rate (ESR) and serum concentrations of orosomucoid, C-reactive protein, and aminopropeptide type III collagen all improved. The patients were divided into 2 groups based on the presence or absence of elevations in acute-phase protein levels and ESR before therapy. Among the 12 patients with biochemical signs of inflammation, VC increased in 11, and Cst improved or was unchanged in 7 of the 8 who were tested. The median VC in this subgroup increased from 73% to 80% of predicted and the median Cst increased from 57% to 60% of predicted. In the group of 18 patients overall, the skin score decreased, while esophageal and renal function remained stable. CONCLUSION: Cyclophosphamide may have a beneficial effect on pulmonary fibrosis in patients with SSc and elevated levels of acute-phase proteins. Controlled trials of cyclophosphamide in pulmonary SSc should be performed and should focus on such patients.

Adult↗

Intestinal absorption of dietary cadmium in women depends on body iron stores and fiber intake.

Measurements of intake and uptake of cadmium in relation to diet composition were carried out in 57 nonsmoking women, 20-50 years of age. A vegetarian/high-fiber diet and a mixed-diet group were constructed based on results from a food frequency questionnaire. Duplicate diets and the corresponding feces were collected during 4 consecutive days in parallel with dietary recording of type and amount of food ingested for determination of the dietary intake of cadmium and various nutrients. Blood and 24-hr urine samples were collected for determination of cadmium, hemoglobin, ferritin, and zinc. There were no differences in the intake of nutrients between the mixed-diet and the high-fiber diet groups, except for a significantly higher intake of fiber (p < 0.001) and cadmium (p < 0.002) in the high-fiber group. Fecal cadmium corresponded to 98% in the mixed-diet group and 100% in the high-fiber diet group. No differences in blood cadmium (BCd) or urinary cadmium (UCd) between groups could be detected. There was a tendency toward higher BCd and UCd concentrations with increasing fiber intake; however, the concentrations were not statistically significant at the 5% level, indicating an inhibitory effect of fiber on the gastrointestinal absorption of cadmium. Sixty-seven percent of the women had serum ferritin < 30 micrograms/l, indicating reduced body iron stores, which were highly associated with higher BCd (irrespective of fiber intake). BCd was mainly correlated with UCd, serum ferritin, age, anf fibre intake. UCd and serum ferritin explained almost 60% of the variation in BCd.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Inverse relation between plasma concentration of von Willebrand factor and CrEDTA clearance in systemic sclerosis.

OBJECTIVE: Microvascular abnormalities involving endothelial cell dysfunction occur as an early event in systemic sclerosis. We studied plasma concentrations of von Willebrand factor (vWf), a substance released from injured endothelial cells, and its relation to pulmonary and renal dysfunction. METHODS: vWf was determined by immunoelectrophoresis. Renal function was assessed by CrEDTA clearance, an accurate measure of glomerular filtration rate and pulmonary function by spirometry and carbon monoxide diffusing capacity. Pulmonary pressure was measured by Doppler cardiography. RESULTS: In 22 patients with scleroderma, vWf concentrations related inversely to CrEDTA clearance. In contrast, no relationship between plasma vWf and pulmonary function was found; 9/10 patients with pulmonary hypertension and 9/12 patients with normal pulmonary pressure showed elevated levels of vWf. However in 5 patients with pulmonary hypertension without radiographic evidence of pulmonary fibrosis there was a strong correlation between plasma vWf and pulmonary pressure (rho = 0.90) which fell short of statistical significance due most likely to small population size. CONCLUSION: Renal but not pulmonary dysfunction was associated with elevated plasma levels of vWf.

Adult↗

Gastrointestinal regulatory peptides in systemic sclerosis.

OBJECTIVE: Gastrointestinal involvement commonly occurs in systemic sclerosis (SSc), but its pathogenesis is not well understood. Since there is evidence of a defect in neurotransmitter release, we were interested in examining the relationship between gastrointestinal dysfunction and plasma concentrations of gastrointestinal regulatory peptides in patients with SSc. We studied 43 consecutive patients, 18 with diffuse and 25 with limited cutaneous disease. METHODS: Levels of corticotropin-releasing hormone (CRH), gastrin, motilin, neuropeptide Y (NPY), and peptide YY (PYY) were determined by radioimmunoassay and high-performance liquid chromatography (HPLC). RESULTS: Plasma concentrations of CRH, motilin, NPY, and PYY were significantly increased among SSc patients compared with healthy control subjects, and HPLC-characterization of motilin, NPY, and PYY showed a different pattern of fragments. No correlation was found between esophageal hypomotility and the concentration of peptide. Acid output did not correlate with gastrin levels, but was more often increased in patients with increased CRH and NPY values. Fat malabsorption, assessed by the triolein breath test, was more common among patients with increased motilin and PYY. CONCLUSION: This study shows that elevated peptide concentrations commonly occur in patients with SSc. Since regulatory peptides are involved in gastrointestinal motility, secretion, and absorption, further characterization of this neuroendocrine system may help in understanding the complex regulation of gastrointestinal dysfunction in SSc.

Adult↗

A survey of Q-fever in Sweden.

Coxiella burnetii, the etiological agent of Q-fever has recently been isolated from sheep in southern Sweden. In this region 24-30% of sheep farmers have been exposed to the organism as shown by serological measurements. In veterinarians, another group with high risk of exposure to C. burnetii, about 12% have antibodies to the bacteria. The seropositive veterinarians are scattered all over the country. In two non-risk groups, draftees and hospital employees, 5-7% were found to be positive. This survey showed that Q-fever is a domestic disease which is spread throughout Sweden.

Adolescent↗