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Biomedical subjects

M Suurküla

Publications and source records attributed to M Suurküla.

At least 19 recordsLinked to original sources

Increased expression of aquaporin 3 in atopic eczema.

BACKGROUND: Dry skin in atopic eczema depends on increased water loss. The mechanisms behind this are poorly understood. The aim of this work was to identify genes that may contribute to water loss in eczema. METHODS: Affymetrix DNA microarrays U133A were used to analyse gene expression in skin biopsies from 10 patients with atopic eczema and 10 healthy controls. RESULTS: DNA microarray analysis showed up-regulation of 262 genes and down-regulation of 129 genes in atopic eczema. The known functions of these genes were analysed using Gene Ontology to identify genes that could contribute to increased water loss. This led to identification of aquaporin 3 (AQP3), which has a key role in hydrating healthy epidermis. Increased expression of AQP3 was found in eczema compared with healthy skin. This was confirmed with real-time polymerase chain reaction (P<0.001). In healthy skin, epidermal AQP3 immunoreactivity was weak and mainly found in the stratum basale. A gradient was formed with decreasing AQP3 staining in the lower layers of the stratum spinosum. By contrast, in acute and chronic atopic eczema strong AQP3 staining was found in both the stratum basale and the stratum spinosum. CONCLUSIONS: Aquaporin 3 is the predominant aquaporin in human skin. Increased expression and altered cellular distribution of AQP3 is found in eczema and this may contribute to water loss.

Adult↗

Radioiodine ablation and therapy in differentiated thyroid cancer under stimulation with recombinant human thyroid-stimulating hormone.

We investigated whether recombinant human TSH (rhTSH) safely and effectively induces uptake of high-dose 131-iodine (131I) to ablate thyroid remnant or treat disease, in patients with well-differentiated thyroid carcinoma. Eleven consecutive patients unable to tolerate thyroid hormone withdrawal received one im injection of 0.9 mg rhTSH on 2 consecutive days before receiving 4000 MBq (approximately 108 mCi) radioiodine orally. Eight patients received one, and 3 patients 2 courses. Our series comprised 7 women and 4 men (mean age, 78 yr, range: 56-87 yr). Ten patients had undergone total or near-total thyroidectomy up to 19 yr earlier. rhTSH-stimulated single course radioiodine with the intention to ablate thyroid remnant was performed in 3 patients, with following estimation of radioiodine uptake and TG measurements. Of another 8 patients given this treatment palliatively, 5 had radiological, clinical and/or laboratory response, including: 80% decreased pathological uptake between treatment courses; pronounced decrease in bone pain; diminished symptoms; improved physical condition and quality of life; lower serum TG concentration; and/or normalization of TG recovery test. Two patients with small lung metastases on computed tomography had no detectable radioiodine uptake or other response; they also lacked uptake after withdrawal-stimulated radioiodine treatment. Despite being elderly and frail, patients generally tolerated treatment well; rhTSH caused nausea in one patient and transiently increased pain in bone and soft tissue lesions in another. We conclude that rhTSH-stimulated high-dose radioiodine for remnant ablation or tumor treatment is safe, feasible and seemingly effective, enhancing quality of life and offering reasonable palliation in patients with advanced disease.

Aged↗

A founder mutation of the BRCA1 gene in Western Sweden associated with a high incidence of breast and ovarian cancer.

The aim of this study was to describe and characterise a founder mutation of the BRCA1 gene in western Sweden. Of 62 families screened for BRCA mutations, 24 had BRCA1 mutations and two had BRCA2 mutations. Tumours that occurred in family members were histologically reviewed and mutational status was analysed using archival paraffin-embedded tissues. The same BRCA1 mutation, 3171ins5, was found in 16 families who were clustered along the western coast of Sweden. Mutation analysis revealed a maternal linkage in 13 families and a paternal linkage in 3. There was complete agreement between mutation analysis results obtained from blood and archival tissues. The penetrance of breast or ovarian cancer by age 70 years was estimated to be between 59 and 93%. There were no differences in survivals between breast or ovarian cancer patients with the mutation and age-matched controls. Thus, a predominant BRCA1 gene founder mutation associated with a high risk of breast and ovarian cancer has been identified and found to occur in a restricted geographical area, thereby allowing timely and cost-effective mutation screening using blood samples or archival histological material.

Adult↗

A new method to quantify postexercise ST-deviation--the ST-deficit. A study in men at high and low-risk for coronary heart disease.

BACKGROUND: Quantitative heart rate adjusted exercise ST criteria like microV/beats per minute (bpm) improve the diagnostic accuracy of the exercise ECG. However, there are few quantitative HR adjusted postexercise variables available. The aim of the present exercise study was to evaluate a new such variable from computerized averaging of the postexercise ECG. METHODS: The presence of possible myocardial ischaemia in a population based sample of 74 elderly male hypertensives at high-risk of coronary heart disease, and in 42 age-matched clinically healthy males (reference group) at low-risk was assessed by exercise ECG. All men had a normal resting ECG without signs of ischaemia. VARIABLES STUDIED: standard ST-criteria, ST/HR slope < or =-2.4 microV. bpm-1, shape of the rate-recovery loop, the latter also with a new quantitative variable, the ST-deficit. RESULTS: In spite of a normal resting ECG many subjects showed an abnormal ST/HR slope during exercise, 43% in the hypertension group and 26% in the reference group. An abnormal rate-recovery loop (ST-deficit) also contributed substantially to identify patients with possible myocardial ischaemia, 30 vs. 10%, respectively (P<0.02); cumulatively for the two HR adjusted criteria 53% vs. 29%, respectively (P<0.02). Mean ST-deficit was significantly lower in the high-risk group. CONCLUSIONS: Effort-related myocardial ischaemia is frequently silent in elderly high-risk hypertensives and necessitates testing, preferably with computerized exercise ECG and heart rate adjusted ST criteria. A new quantitative variable to assess the postexercise rate-recovery loop in the time domain, the ST-deficit is described. This variable seems to effectively discriminate between subjects with low and high-risk for coronary heart disease and thus provides new information. Further studies are warranted to validate this variable against myocardial perfusion scintigraphy and coronary angiography.

Aged↗

The red cell mass, plasma erythropoietin and spleen size in apparent polycythaemia.

It has been shown previously that measurement of the spleen size and plasma erythropoietin (EPO) concentration are valuable adjuncts in the diagnostic work-up of patients with polycythaemia vera. The aim of the present work was to evaluate their value in the assessment of apparent polycythaemia (AP). Therefore, over a 24-month period we routinely performed bone marrow biopsies, measurement of red cell mass (RCM) and plasma volume (PV), spleen size determination by gamma camera scintigraphy and determination of the plasma EPO concentration in consecutive patients referred to us because of elevated values for packed cell volume (>0.48 in females and >0.51 in males). After having excluded patients with clonal and secondary polycythaemias we were left with 38 patients (27 males and 11 females) with AP. In all of them the measured RCM was within normal range, i.e. <36 ml/kg for males and <32 ml/kg for females. The subjects were characterized by moderate increase in RCM and a concomitant moderate decrease in PV. Thus, as an average the measured RCM exceeded the predicted values by 14% in males and by 12% in females; conversely, as compared to the predicted values the average measured value for PV was reduced by 17% in males and by 8% in females. The average RCM for males was 29+/-3 ml/kg; the corresponding figure for females was 23+/-4 ml/kg. It was shown that 86% of the subjects had plasma EPO concentrations within the control range; the remaining had values slightly above or below the control range. The mean posterior spleen scan area was 57+/-16 cm2 and mean left lateral area 57+/-17 cm2; the reference value for spleen scan area (for both projections) is 57+/-12 cm2. Of the patients 35/38 (92%) had a spleen scan area within the mean+2SD for controls and 38 subjects (100%) had values within the mean+3SD. It is concluded that measurement of plasma EPO and a careful assessment of the spleen size should always be considered in the evaluation of patients with elevated values for venous packed cell volume.

Adult↗

Multiple risk intervention in high-risk hypertensive patients. A 3-year ultrasound study of intima-media thickness and plaques in the carotid artery. Risk Intervention Study (RIS) Group.

In spite of optimal blood pressure control, available data indicate that the risk of coronary heart disease remains high in many patients with hypertension. Multifactorial risk intervention programs have therefore been advocated. The aim of the present randomized study was to analyze whether a favorable change in risk factors caused by a comprehensive risk factor modification program (focused mainly on nonpharmacological intervention) might beneficially affect ultrasound-assessed far-wall common carotid intima-media thickness or plaques in the carotid artery in high-risk hypertensive patients (n=81) in comparison with those undergoing usual care (n=83). A further aim was to analyze whether risk factors measured at baseline or follow-up were related to the change recorded in intima-media thickness during follow-up. The results showed in the intervention group a favorable change in LDL cholesterol (-9%), in smoking habits (32% of smokers quit smoking), and in HbA1c (-17% in patients with diabetes mellitus) over the 3.5-year observation period. However, no difference between the two randomization groups could be observed for far-wall common carotid intima-media thickness or plaque status during follow-up. Of all tested potential risk factors, only fasting insulin at baseline (available in nondiabetic patients) was significantly related to the change in mean intima-media thickness during follow-up (r=.25, n=92, P<.01). The relationship (negative) between follow-up serum HDL and change in mean intima-media thickness during the preceding follow-up was of borderline significance. Patients with moderate to large plaques in the carotid artery region at baseline had a significantly larger increase in common carotid artery intima-media thickness during follow-up than patients with no or only small plaques. The results are disappointing and may indicate that either the change in risk factors occurred too late in life or a considerably larger change in concomitant risk factors than we observed is needed to favorably affect intima-media thickness during an observation period of around 3 years in high-risk hypertensive patients.

Aged↗

Atherosclerotic disease in the femoral artery in hypertensive patients at high cardiovascular risk. The value of ultrasonographic assessment of intima-media thickness and plaque occurrence. Risk Intervention Study (RIS) Group.

The aim of the present investigation was to examine the occurrence of ultrasound-assessed morphological changes in the right common femoral artery and relate these findings to the ankle-arm index and to symptoms of lower-extremity arterial disease in hypertensive men at high cardiovascular risk (n = 143). Comparisons were made with a healthy reference group consisting of age-matched men at low risk (n = 46). The results showed that it was possible to obtain high-quality measurements of intima-media thickness in about 80% of all men and that the intraobserver variability was satisfactory (14%). A normal mean intima-media thickness was defined, using data from the low-risk group. Plaque occurrence and mean intima-media thickness in the right common femoral artery were significantly associated with ankle-arm index both in the right and left leg. There were more and larger plaques, as well as thicker mean and maximum intima-media complexes, in the high-risk group than in the low-risk group. In the high-risk group, 11% suffered from symptoms of right lower-extremity artery disease, 20% had an ankle-arm index < or= 0.9, 62% had moderate or large plaques (compared with 28% in the low-risk group, P < .001), and 77% had an enlarged intima-media complex. The cumulative frequency of signs of atherosclerosis in the right leg was 81% among the 110 patients in whom complete results from all examinations were available. Our conclusion is that ultrasound measurement of the intima-media thickness of the common femoral artery is a valuable method to evaluate morphological changes related to atherosclerotic disease in the lower extremity.

Aged↗

Carotid artery wall morphology, haemostatic factors and cardiovascular disease. An ultrasound study in men at high and low risk for atherosclerotic disease.

The aim of this study was to examine whether there was a relationship between haemostatic factors and ultrasound-assessed morphology of the common carotid artery and cardiovascular disease in 57- to 77-year-old men at high risk for atherosclerotic disease (hypertension and at least one of the following risk factors: hypercholesterolaemia, smoking, diabetes mellitus). They were divided into one group with (n = 59) and one group without (n = 70) manifest cardiovascular disease. An age-matched reference group with no cardiovascular risk factors was used as a comparison (n = 51). Significant associations, independent of smoking, were found between plasma fibrinogen and both the maximal intima-media thickness and the occurrence of plaque in the high-risk group. High-risk patients with clinical signs of cardiovascular disease had higher levels of plasma fibrinogen and prothrombin 1 + 2 fragment compared with both high-risk patients without concomitant cardiovascular disease and low-risk subjects. Plasminogen activator inhibitor, von Willebrand factor and thrombin/antithrombin complex were increased in the high-risk group with signs of cardiovascular disease in comparison with the low-risk group. In conclusion the results indicate that plasma fibrinogen may be operative in the development of atherosclerosis. Clinical signs of cardiovascular disease were associated with increased plasma levels of fibrinogen, von Willebrand factor, plasminogen activator inhibitor, thrombin/antithrombin complex and prothrombin 1 + 2 fragment.

Aged↗

Ultrasound evaluation of atherosclerotic manifestations in the carotid artery in high-risk hypertensive patients. Risk Intervention Study (RIS) Group.

The aim of this study was to evaluate whether high-risk hypertensive patients (n = 137) had larger far-wall common carotid artery intima-media thickness than a control group (n = 37) and to study whether intima-media thickness was related to other signs of atherosclerotic disease. The results showed that intima-media thickness was significantly larger in the hypertension group than in the control group. Lumen diameter and mean cross-sectional area of the intima-media complex were larger both for hypertensive patients with a positive history of manifest clinical cardiovascular disease and for hypertensive patients with no such history than in the control group. There was a significant relationship between far-wall common carotid artery intima-media thickness and plaque status (visual scoring, no, small, moderate/large) in the carotid artery region. In univariate analyses, low diastolic blood pressure and high pulse pressure were both significantly related to plaque status. In multivariate analyses, pulse pressure was significantly and independently related both to common carotid artery intima-media thickness and to plaque status in the carotid artery region. In multivariate analyses, there was also an independent relationship between age and common carotid artery intima-media thickness, between smoking status and plaque status, and between a positive history of manifest clinical cardiovascular disease and plaque status. In conclusion, common carotid artery intima-media thickness and lumen diameter were increased in elderly high-risk hypertensive patients, in whom more than one third of the patients also had a moderate to large plaque in the carotid artery region.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗

Regional distribution of melanocytic naevi in relation to sun exposure, and site-specific counts predicting total number of naevi.

The role of exposure to ultraviolet light in the formation of melanocytic naevi was analysed by investigating the regional naevus distribution in 310 subjects (30-50 years) from a Swedish census file. The lateral aspect of the arms and the back had the largest concentration of naevi. The mean naevus count per unit surface area was higher in intermittently exposed than in rarely exposed skin (p less than 0.001), while the lowest mean count was found in chronically exposed skin. These results support the idea that intermittent exposure to ultraviolet light has a "naevogenic" effect while chronic exposure might be protective. Dysplastic naevi had a distribution pattern quite different from common naevi. Considering the distribution pattern solely, dysplastic naevi seem to develop independently of exposure to ultraviolet light. The numbers of naevi in different skin areas were tested for their power in predicting the total body naevus count. The strongest correlations were found between total counts and counts on the anterior surface of the thighs and the lateral aspect of the arms. Counts from any of these areas will provide a practical and satisfactory estimate of the total number of naevi.

Adult↗

Prevalence of common and dysplastic naevi in a Swedish population.

The naevus profile was examined in a Swedish population that was randomly selected from a census file. The participation rate was considered high at 82%. The number of common naevi (CN) and the prevalence of dysplastic naevi (DN) were investigated in 379 subjects (aged 30-50 years). The mean total body count of CN greater than or equal to 2 mm was 67 (range 1-300). As many as 22% of the population had 100 naevi or more and only 18% had less than 25. The counts were not influenced by age or sex. DN were diagnosed clinically in 18% (CI 14-22%) of the subjects and histologically in 8% (CI 5-11%). Subjects with dysplastic naevi had a significantly larger number of common naevi and a more sun-sensitive skin type than subjects without DN, P less than 0.001.

Adult↗

Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of a computerized analysing system.

A B-mode [two-dimensional (2D)] image from the carotid artery may be described as containing seven echo zones. The aim of the present work is to discuss how lumen diameter and wall thickness can be measured from these zones, and to review some of the basic principles of ultrasound physics and imaging. Simple experiments were performed to identify the echoes defining intima-lumen interfaces. The results showed that: (1) The intima-media thickness of the near wall cannot be measured in a valid way. (2) The lumen diameter of a blood vessel is defined by the distance from the leading edge of the intima-lumen interface of the near wall (echo zone 3) to the leading edge of the lumen-intima interface of the fall wall (echo zone 5). (3) Previously published studies have validated the intima-media complex of the far wall as the distance from the leading edge of the lumen-intima interface of the far wall to the leading edge of the media-adventitia interface of the far wall (echo zone 7). We suggest that if measurements on the near wall are performed, measurements from the far wall should also be presented separately, and if lumen diameter is measured, that this measurement is carried out according to the leading edge principle. We describe a computerized analysing system for the measurement of wall thickness and plaque area on the carotid and femoral arteries. The system is based on a low-cost PC and a frame grabber board and calculates minimum, maximum and mean values of lumen diameter and wall thickness from a section of the artery.

Carotid Arteries↗

Melanocytic naevi in sun-exposed and protected skin in melanoma patients and controls.

The possible link between exposure to ultraviolet light and naevus development was studied in 121 melanoma patients and 310 controls by comparing the number of naevi in a sun-exposed area on the back with that in a sun-protected area on the buttocks. Both patients and controls had a four-fold increase in the number of naevi in the exposed compared with the protected area, p less than 0.001. The difference in naevus count between the exposed and the protected area was larger in patients than in controls, p less than 0.001. Subjects with dysplastic naevi, melanoma patients as well as controls, had a larger difference in the number of naevi between the two areas than subjects without dysplastic naevi, p less than 0.001. These results support the idea that sunlight plays an important role in naevus development and may explain why a high naevus count is a risk marker for malignant melanoma.

Adult↗

Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population.

Common naevi, dysplastic naevi (DN) and other phenotypic features were evaluated as melanoma risk factors in a Swedish case-control study. One-hundred and twenty-one prevalent melanoma cases and 378 randomly selected controls participated. The mean total body naevus count was 115 in the cases and 67 in the controls. Fifty-six per cent of the cases and 18% of the controls had clinical DN. The corresponding figures for histologically diagnosed DN were 40% and 8% respectively. Clinical DN was as good as histologically diagnosed DN in identifying individuals at risk for melanoma. Subjects with sun-sensitive skin, greater than or equal to 150 naevi and presence of DN have 50 times higher melanoma risk than those without these characteristics.

Adult↗

UVB-induced melanocyte proliferation and 5-S-cysteinyldopa excretion in dysplastic nevus syndrome.

This is the first in vivo study of the effects of UV on the epidermal melanocytes in dysplastic nevus syndrome (DNS). Eleven DNS patients and 22 healthy subjects were given total body UVB irradiation 8 times during 17 days and the melanocyte population was estimated in biopsies from shielded and irradiated skin. There was a doubling of the melanocyte counts in irradiated skin and a less pronounced but significant increase in the shielded skin area. The urinary excretion of 5-S-cysteinyldopa (5-S-CD) was measured before, during and after the irradiation period. The 5-S-CD excretion reached a maximum after 2 weeks of irradiation and returned towards the basal value after the irradiation period. We were not able to document any abnormal melanocytic UV response in DNS patients before, during or after the irradiation.

Adult↗

Biochemical characterization and tissue distribution of the scleredema in a case of Buschke's disease.

Biopsies from a patient with a longstanding form of scleredema adultorum Buschke were analysed for morphological and biochemical changes in the dermal connective tissue. By light microscopy the tissue changes were located to the deep part of the reticular dermis. Therefore dermal tissue was separated into a superficial and a deep part and analysed biochemically. By this procedure it was possible to show that the concentration of hyaluronan in the deep part of the dermis was increased. The urinary excretion of methylimidazole acetic acid, an indicator of the mast cell mass in the body, was also elevated.

Diabetes Mellitus, Type 2↗