Causes and predictors of death among Finnish patients with systemic sclerosis.

OBJECTIVE: The aim of this study was to assess causes and predictors of death among Finnish patients with systemic sclerosis (SSc). METHOD: Medical records of patients registered with the ICD-10 code M34 from 1996 to 2018 in two university hospitals were reviewed retrospectively. Clinical data were collected until the end of 2020. Death certificates were obtained from Statistics Finland up to August 2021. Using death certificates and patient records, the cause of death for each patient was determined. The mean age at death, median time from SSc diagnosis, and factors predicting death were analysed. RESULTS: Among 313 SSc patients, 91 deaths occurred between April 2000 and September 2020. Overall 5 and 10 year survival rates were 88.4% and 80.2%, respectively. SSc was the most common primary cause of death (n = 35) and interstitial lung disease (ILD) was the most common SSc-related cause of death (n = 13). Moreover, 52% of the patients with diffuse SSc and 33% of those with limited cutaneous SSc died as a result of SSc itself. Patients who died because of SSc were significantly younger [mean ± sd age 65.6 ± 12.7 years, 95% confidence interval (CI) 61.2-70.1] than those who died from other causes (74.2 ± 9.6 years, 95% CI 71.5-76.9) (p = 0.0006). ILD, pulmonary arterial hypertension, gastrointestinal involvement, male gender, and older age at disease onset predicted death. CONCLUSION: The disease itself was the major cause of death among Finnish SSc patients, in both diffuse and limited forms of SSc.

Wrist band photoplethysmography in detection of individual pulses in atrial fibrillation and algorithm-based detection of atrial fibrillation.

AIMS: Atrial fibrillation (AF) is the most common tachyarrhythmia and a significant cause of cardioembolic strokes. Atrial fibrillation is often intermittent and asymptomatic making detection a major clinical challenge. We evaluated a photoplethysmography (PPG) wrist band in individual pulse detection in patients with AF and tested the reliability of two commonly used algorithms for AF detection. METHODS AND RESULTS: A 5-min PPG was recorded from patients with AF or sinus rhythm (SR) with a wrist band and analysed with two AF detection algorithms; AFEvidence and COSEn. Simultaneously registered electrocardiogram served as the golden standard for rhythm analysis and was interpreted by two cardiologists. The study population consisted of 213 (106 AF, 107 SR) patients. The wrist band PPG achieved individual pulse detection with a sensitivity of 91.7 ± 11.2% and a positive predictive value (PPV) of 97.5 ± 4.6% for AF, with a sensitivity of 99.4 ± 1.5% [7.7% (95% confidence interval, 95% CI 5.5% to 9.9%); P < 0.001] and PPV of 98.1 ± 4.1% [0.6% (95% CI -0.6% to 1.7%); P = 0.350] for SR. The pulse detection sensitivity was lower 86.7 ± 13.9% with recent-onset AF (AF duration <48 h, n = 43, 40.6%) as compared to late AF (≥48 h, n = 63, 59.4%) with 95.1 ± 7.2% [-8.3% (95% CI -12.9% to -3.7%); P = 0.001]. For the detection of AF from the wrist band PPG, the sensitivities were 96.2%/95.3% and specificity 98.1% with two algorithms. CONCLUSION: The wrist band PPG enabled accurate algorithm-based detection of AF with two AF detection algorithms and high individual pulse detection. Algorithms allowed accurate detection of AF from the PPG. A PPG wrist band provides an easy solution for AF screening.

Orthostatic Hypotension and Associated Factors among Home Care Clients Aged 75 Years or Older - A Population-Based Study.

OBJECTIVES: The aim of this study was to examine orthostatic hypotension (OH) and associated factors among home care clients aged 75 years or older. DESIGN: Non-randomised controlled study. SETTING AND PARTICIPANTS: The study sample included 244 home care clients aged 75 years or older living in Eastern and Central Finland. MEASUREMENTS: Nurses, nutritionists and pharmacists collected clinical data including orthostatic blood pressure, depressive symptoms (15-item Geriatric Depression Scale GDS-15), nutritional status (Mini Nutritional Assessment MNA), drug use, self-rated health, daily activities (Barthel ADL Index and Lawton and Brody IADL scale) and self-rated ability to walk 400 metres. Comorbidities were based on medical records. RESULTS: The prevalence of OH was 35.7% (n = 87). No association between OH and the number of drugs used or causative drug use and OH was found. In univariate analysis, coronary heart disease, systolic and diastolic blood pressure in a sitting position and lower mean MNA scores were associated with a risk of OH. Multivariate analysis showed that lower mean MNA scores (OR 1.140, 95% CI: 1.014-1.283) appeared to be independently connected to a risk of OH. CONCLUSION: One-third of the home clients had OH and it was associated with lower MNA scores.

Ultrasonography as a Guiding Method in Breast Micro-Calcification Vacuum-Assisted Biopsies.

Purpose: To assess the visibility of breast micro-calcifications using ultrasonography (US) and the accuracy and clinical usefulness of vacuum-assisted biopsy (VAB) using US guidance (USVAB) as compared to stereotactic guidance (SVAB). Materials and Methods: The study material comprised 158 retrospectively reviewed micro-calcification cases examined with US before VAB. The pre-biopsy US positivity frequency distributions were calculated, and the sensitivity, specificity and accuracy of VAB determined by comparing VAB histology with the surgical pathology or a 12-month follow-up. Results: 158 US examinations yielded 80 positive and 78 negative results. US positivity correlated to a large size and a suspicious BI-RADS category of the calcifications. USVAB was performed in 49 cases with 61 % malignant, 12 % high-risk and 27 % benign results. The percentages for the 109 SVAB cases were 40 %, 28 % and 32 %, respectively. Specimen radiography demonstrated calcifications in 48 of the 49 (98 %) USVAB cases and in 107 of the 109 (98 %) SVAB cases. The overall accuracy of VAB was 94 % (USVAB 98 %, SVAB 94 %), the sensitivity was 88 % (USVAB 97 %, SVAB 83 %), and the specificity was 100 %. The higher sensitivity of USVAB was due to an accumulation of atypical hyperplasia diagnoses in the SVAB group. The final diagnosis was invasive ductal carcinoma in 21 US-positive and in 4 US-negative cases. Conclusion: Approximately 50 % of mammographically detected micro-calcifications could be detected with ultrasonography. US was found to be a valuable alternative guidance method for vacuum-assisted biopsy of micro-calcifications with a technical success rate and diagnostic accuracy well comparable to the stereotactic method.

Ultrasound Screening of Men with Coronary Artery Disease for Abdominal Aortic Aneurysms: A Prospective Dual Center Study.

BACKGROUND AND AIMS: According to the heterogeneous results of previous studies, the prevalence of abdominal aortic aneurysm seems high among men with coronary artery disease. The associating risk factors for abdominal aortic aneurysm in this population require clarification. Our objective was to assess the prevalence of non-diagnosed abdominal aortic aneurysms in men with angiographically verified coronary artery disease and to document the associated co-morbidities and risk factors. MATERIAL AND METHODS: Altogether, 407 men with coronary artery disease were screened after invasive coronary angiography in two series at independent centers. Risk factor data were recorded and analyzed. RESULTS AND CONCLUSION: The mean age of the study cohort was 70.0 years (standard deviation: 11.0). The prevalence of previously undiagnosed abdominal aortic aneurysms in the whole screened population of 407 men was 6.1% (n = 25/407). In a multivariate analysis of the whole study population, the only significant risk factors for abdominal aortic aneurysm were age (odds ratio: 1.04, 95% confidence interval: 1.00-1.09) and history of smoking (odds ratio: 3.13, 95% confidence interval: 1.26-7.80). Non-smokers with abdominal aortic aneurysm were significantly older than smokers (mean age: 80.7 (standard deviation: 8.0) vs 68.0 (standard deviation: 11.1), p = 0.003), and age was a significant risk factor only among non-smokers (p = 0.011; p = 0.018 for interaction). Among smokers, the prevalence of abdominal aortic aneurysm was 8.8%, and 72% (n = 18/25) of all diagnosed abdominal aortic aneurysm patients were smokers. Prevalence of undiagnosed abdominal aortic aneurysms among patients with coronary artery disease is high, and history of smoking is the most significant risk factor for abdominal aortic aneurysm. Effectiveness of selective screening of abdominal aortic aneurysm in male patients with coronary artery disease warrants further studies.

Ultrasonography as a Guiding Method in Breast Micro-Calcification Vacuum-Assisted Biopsies.

PURPOSE: To assess the visibility of breast micro-calcifications using ultrasonography (US) and the accuracy and clinical usefulness of vacuum-assisted biopsy (VAB) using US guidance (USVAB) as compared to stereotactic guidance (SVAB). MATERIALS AND METHODS: The study material comprised 158 retrospectively reviewed micro-calcification cases examined with US before VAB. The pre-biopsy US positivity frequency distributions were calculated, and the sensitivity, specificity and accuracy of VAB determined by comparing VAB histology with the surgical pathology or a 12-month follow-up. RESULTS: 158 US examinations yielded 80 positive and 78 negative results. US positivity correlated to a large size and a suspicious BI-RADS category of the calcifications. USVAB was performed in 49 cases with 61 % malignant, 12 % high-risk and 27 % benign results. The percentages for the 109 SVAB cases were 40 %, 28 % and 32 %, respectively. Specimen radiography demonstrated calcifications in 48 of the 49 (98 %) USVAB cases and in 107 of the 109 (98 %) SVAB cases. The overall accuracy of VAB was 94 % (USVAB 98 %, SVAB 94 %), the sensitivity was 88 % (USVAB 97 %, SVAB 83 %), and the specificity was 100 %. The higher sensitivity of USVAB was due to an accumulation of atypical hyperplasia diagnoses in the SVAB group. The final diagnosis was invasive ductal carcinoma in 21 US-positive and in 4 US-negative cases. CONCLUSION: Approximately 50 % of mammographically detected micro-calcifications could be detected with ultrasonography. US was found to be a valuable alternative guidance method for vacuum-assisted biopsy of micro-calcifications with a technical success rate and diagnostic accuracy well comparable to the stereotactic method.

Effects of individual dietary counseling as part of a comprehensive geriatric assessment (CGA) on nutritional status: a population-based intervention study.

BACKGROUND: Nutritional risk is relatively common in community-dwelling older people. OBJECTIVE: To objective of this study was to evaluate the effects of individual dietary counseling as part of a Comprehensive Geriatric Assessment on nutritional status among community-dwelling people aged 75 years or older. METHODS: Data were obtained from a subpopulation of participants in the population-based Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (GeMS) intervention study in 2004 to 2007. In the present study, the population consist 173 persons at risk of malnutrition in the year 2005 in an intervention (n=84) and control group (n=89). Nutritional status, body weight, body mass index, serum albumin were performed at the beginning of the study and at a two-year follow-up. The nutritional screening was performed using the Mini Nutritional Assessment (MNA) test. RESULTS: A increase in MNA scores (1.8 95% confidence interval [CI]: 0.7 to 2.0) and in serum albumin (0.8 g/L, 95% CI: 0.2 to 0.9 g/L) were a significant difference between the groups. CONCLUSIONS: Nutritional intervention, even dietary counseling without nutritional supplements, may improve nutritional status.

Long-term VEGF-A expression promotes aberrant angiogenesis and fibrosis in skeletal muscle.

Vascular endothelial growth factor A (VEGF-A) induces strong angiogenesis and it has been widely used in proangiogenic gene therapy studies. However, little is known about long-term effects of VEGF-A expression in skeletal muscle. Here the long- term effects of adeno-associated virus (AAV) encoding human VEGF-A(165) (AAV-VEGF-A) gene transfer in normal and ischemic rabbit hindlimb skeletal muscles were studied. AAV-LacZ was used as a control. In one-year follow-up, a remarkable increase in skeletal muscle perfusion compared with AAV-LacZ was observed measured with Doppler and contrast pulse sequence ultrasound. Angiogenesis was also seen in histology as enlarged and sprouting capillaries. In addition to favorable angiogenic effects, aberrant vascular structures with CD31 positive cell layers were seen inside muscle fibers after AAV-VEGF-A gene transfer. Importantly, we found increased amounts of extracellular matrix with a high number of macrophages and fibrosis in AAV-VEGF-A transduced muscles. No changes in skeletal muscle morphology were detected in AAV-LacZ transduced muscles. Our results indicate that local AAV-VEGF-A gene transfer efficiently promotes long-term angiogenesis in large animal model. However, non-regulated expression of VEGF-A causes unfavorable changes in muscle morphology, which suggests the need for regulation of the transgene expression in long-term AAV-mediated VEGF-A gene transfer applications.

Plasma carotenoids are related to intima--media thickness of the carotid artery wall in men from eastern Finland.

BACKGROUND: Several previous epidemiological studies have suggested that high plasma concentrations of carotenoids may slow the development of early atherosclerosis, but results have been inconclusive. METHODS: We examined the effect of carotenoids on early atherosclerosis in a population-based study. The association between plasma carotenoid concentrations and intima-media thickness of the common carotid artery (CCA-IMT) was investigated in 1212 elderly men (aged 61-80 years) in Eastern Finland. They were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis, and plasma concentrations of carotenoids were measured by high-performance liquid chromatography. RESULTS: Men in the lowest quartile of CCA-IMT had significantly higher concentrations of plasma ß-cryptoxanthin, lycopene and α-carotene than men in the highest quartile (P for the differences: 0.043, 0.045 and 0.046, respectively), after adjustment for age, examination year, body mass index, smoking, alcohol intake, years of education, symptomatic coronary heart disease (CHD) or CHD history, diabetes, low-density lipoprotein cholesterol, medications and season. The concentrations of plasma ß-cryptoxanthin, lycopene and α-carotene decreased linearly with increasing CCA-IMT. CONCLUSIONS: The results of this study suggest that high plasma concentrations of ß-cryptoxanthin, lycopene and α-carotene may be associated with decreased carotid atherosclerosis in elderly men from eastern Finland.

Imaging findings and accuracy of core needle biopsy in mucinous carcinoma of the breast.

BACKGROUND: Diagnosis of mucinous carcinoma can be difficult due to its benign appearance on mammograms and ultrasonographic (US) images. In the light of the rather scarce literature, core needle biopsy (CNB) has proved useful in diagnosing mucinous lesions. PURPOSE: To assess mammographic, US, and CNB findings of mucinous breast tumors and to correlate them with final histology obtained in therapeutic surgery. MATERIAL AND METHODS: From 2000-2006, 25 mucinous carcinomas detected with CNB were surgically removed. The mammography, US, and CNB results were analyzed and correlated with final histology. RESULTS: Ninety-six percent of the mucinous carcinomas (24/25) were visible with US. All except two of the 24 tumors were solid masses. All the mixed-type lesions (group 2) were hypoechoic and had irregular or lobulated margins and heterogeous internal echotexture. The US features were more variable among the 14 pure mucinous carcinomas (group 1) and the six US visible mucinous carcinomas with cancerous cells outside the tumor (group 3). Fifty-seven percent of group 1 and 50% of group 3 tumors had clearly lobulated or irregular margins. Fifty-seven percent of group 1 and 67% of group 3 cancers were hypoechoic. A vast majority of these tumors had heterogenous echotexture. Seventy-one percent (17/24) of the lesions visible with US had posterior acoustic enhancement. Eighty percent (20/25) of the mucinous carcinomas were classified as BI-RADS 4 lesions in US. All the lesions with images available were visible on mammograms, where most of the tumors were seen as a high-density circumscribed lesion and classified as BI-RADS 4 lesions, while none were classified as BI-RADS 1, 2 or 5. The sensitivity and positive predictive value of CNB regarding mucinous carcinoma was 100%. CONCLUSION: CNB was found to be a highly reliable diagnostic tool for diagnosing mucinous carcinoma in this selected material. US findings of pure mucinous carcinoma were variable, however, all reached BI-RADS 4 category. The presence of posterior acoustic enhancement beneath a solid breast lesion should raise suspicion of mucinous carcinoma. Most of the tumors appeared as BI-RADS 4 lesions in US and in mammography thus making both a useful tool for raising a suspicion of malignancy in mucinous cancers.

Glycemic index, glycemic load, and the risk of acute myocardial infarction in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND AND AIM: The role of dietary glycemic index (GI) and glycemic load (GL) in coronary heart disease (CHD) is unclear. Our aim was to study the association between the dietary GI and GL and the risk of acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 1981 Finnish men from the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study, aged 42-60 years and free of CHD at baseline. During an average follow-up time of 16.1 years, 376 new AMI events occurred. In multivariable-adjusted Cox proportional hazards models, the relative risk (RR) for AMI in the highest quartile of GI was 1.25 (95% CI: 0.92-1.69; P for trend=0.08) and for GL 1.11 (95% CI: 0.79-1.57; P for trend=0.21) when compared with the lowest quartile. For overweight (BMI ≥ 27.5 kg/m²) men, the multivariable-adjusted RR for AMI in the highest compared to the lowest tertile of GI and GL were 1.58 (95% CI: 1.03-2.43; P for trend=0.04, P for interaction=0.01) and 2.05 (95% CI: 1.30-3.23; P for trend=0.002, P for interaction=0.002), respectively. For physically less active men; energy expenditure for leisure-time physical activity < 50 kcal/d, the RR for AMI was 1.72 (95% CI: 1.07-2.76; P for trend=0.04, P for interaction 0.80) with higher GL. CONCLUSIONS: Our results suggest that both high dietary GI and GL are associated with increased risk of AMI among overweight and GL possibly among less physically active men.

Factors associated with life satisfaction in a 6-year follow-up of depressive out-patients.

BACKGROUND: The major goal of mental health services is to improve mental health and thus also life satisfaction. However, studies assessing factors associated with life satisfaction during recovery from depression are lacking. METHODS: A 6-year natural follow-up of 121 depressive out-patients was carried out with questionnaires at baseline, 1/2, 1, 2 and 6 years completed. A structured diagnostic interview was conducted. Throughout the follow-up, clinical status was assessed with several psychometric scales for life satisfaction (LS), depression (BDI, HDRS), hopelessness (HS), functional ability (GAF, SOFAS) and general psychopathology (SCL). RESULTS: Men and women did not differ in their improvement in life satisfaction. Altogether, 77% of the patients at baseline and 22% at the end were dissatisfied. Life satisfaction on 6-year follow-up was associated with baseline lower interpersonal sensitivity (SCL subscale) and concurrently being loved by someone as well as with baseline and concurrent good self-rated health and wealth. The satisfied were better off in terms of all clinical variables, regardless of the measurement time. Depressive symptoms and hopelessness were the strongest concurrent clinical correlates of LS after 6 years. CONCLUSIONS: Mental health was strongly related to life satisfaction throughout the follow-up, while most of the non-clinical factors were not. Alleviating depression and interpersonal sensitivity and supporting social networks should be focused on in psychiatric treatment in order to improve life satisfaction among depressive patients.

Ultrasonography-guided core needle biopsy in differential diagnosis of papillary breast tumors.

BACKGROUND: Papillary lesions of the breast are considered diagnostically challenging for various reasons. A relatively high malignancy rate in final pathological analysis has in many cases necessitated excision of these lesions, regardless of core needle biopsy (CNB). PURPOSE: To assess mammographic, sonographic, and CNB findings of papillary lesions, and to correlate them with final histology obtained by surgical excision. MATERIAL AND METHODS: From 2000-2006, 29 benign and 19 malignant papillary tumors examined with CNB were surgically removed. Mammographic, sonographic, and CNB results were analyzed and correlated with final histology. RESULTS: On ultrasonography (US), 69% (20/29) of the benign lesions were solid and 31% (9/29) were cystic, and 47% of the malignant lesions (9/19) were solid and 53% (10/19) were cystic. The mammographic findings were nonspecific, although most of the malignant tumors (67%, 12/18) were categorized as BI-RADS 4 lesions. The sensitivity, specificity, and positive predictive value of the core needle biopsy histology was 32% (6/19), 100% (29/29), and 100% (6/6), respectively, for papillary carcinoma. A negative predictive value of 91% (21/23) for malignancy and 48% (11/23) for either atypia or malignancy was shown. Of the lesions with CNB diagnosis of benign papillary lesion with atypia, 58% (11/19) turned out to be malignant and 11% (2/19) were benign on surgery. CONCLUSION: The probability of malignancy is low when the CNB result shows a benign papillary lesion with no atypia. However, the only way to reliably diagnose atypical papillary lesions is to surgically remove all papillary tumors, irrespective of the CNB result. Differentiation between benign and malignant lesions or malignant noninvasive and invasive tumors is not possible based on sonographic or mammographic appearance.

Ultrasonography and core needle biopsy in the differential diagnosis of fibroadenoma and tumor phyllodes.

BACKGROUND: The diagnosis of phyllodes tumors of the breast is challenging due to many similarities with common fibroadenomas. PURPOSE: To determine the diagnostic accuracy of core needle biopsy in diagnosing phyllodes tumors and to analyze the ultrasonographic (US) features of phyllodes tumors and fibroadenomas. MATERIAL AND METHODS: From 1999 to 2003, 1010 breast lesions underwent imaging-guided core needle biopsy. Of these, 57 fibroadenomas and 12 phyllodes tumors were removed surgically. The US and needle biopsy results of a total of 64 lesions (52 fibroadenomas and 12 phyllodes tumors) were further analyzed, compared, and correlated with surgical histological results. RESULTS: The median sonographic sizes of the phyllodes tumors and the fibroadenomas were 3.2 cm and 1.6 cm, respectively. At US, 58% of the phyllodes tumors (7/12) were classified as equivocal or suspicious of malignancy and 42% (5/12) as probably benign, while 54% of the fibroadenomas (28/52) were classified as probably benign and 46% (24/52) as equivocal. The sensitivity, specificity, and positive and negative predictive values of core needle biopsy histology regarding tumor phyllodes were 83%, 92%, 71%, and 96%, respectively. CONCLUSION: Imaging-guided core needle biopsy was accurate in differentiating between fibroadenomas and phyllodes tumors. US classification was unreliable due to considerable overlap in the findings. Combined use of US feature analysis and needle biopsy may help to avoid the misinterpretation of phyllodes as fibroadenoma.

Overexpression of VEGF-A induces neovascularization and increased vascular leakage in rabbit eye after intravitreal adenoviral gene transfer.

AIM: The aim of this study was to determine dose-response effects of vascular endothelial growth factor A as delivered using an adenoviral vector on vascular growth and pathological changes in the rabbit eye. Moreover, we wanted to develop a large animal model for angioproliferative diseases in the eye. METHODS: Seventeen New Zealand White rabbits were injected with adenoviral vascular endothelial growth factor-A (AdVEGF-A) intravitreally with different doses (10(9)-10(11) vp). Controls were injected with an empty virus (AdCMV). Some animals had a combination of AdVEGF-A and AdsKDR (a soluble form of the VEGF receptor-2). Animals were killed 6 days after the gene transfer. On the basis of these results, 14 rabbits were injected intravitreally with AdVEGF-A or adenoviral LacZ (AdLacZ) with 10(10) vp in a volume of 0.1 mL. Animals were killed 3, 6, 14 and 28 days after the gene transfer, eyes were removed and analysed histologically. RESULTS: In enzyme-linked immunosorbent assay (ELISA) analysis, human VEGF-A was present in vitreous humour in all VEGF-A transduced eyes. The amount of VEGF-A showed a dose-dependent increase with the AdVEGF-A dose and was the highest 6 days after the gene transfer. Histologic analyses revealed an increased capillary area and density in the AdVEGF-A eyes when compared with the AdLacZ eyes (P < 0.05). In the AdVEGF-A/AdsKDR eyes the average capillary area was not increased compared with AdLacZ eyes. CONCLUSION: This model could be useful for large animal studies regarding the pathogenesis of neoangiogenesis and for the development of new therapeutic strategies for angioproliferative diseases of the eye. Our results establish the key role of VEGF-A in the induction of neovascularization and pathological changes in the rabbit eye.

Gene transfer using the mature form of VEGF-D reduces neointimal thickening through nitric oxide-dependent mechanism.

Gene transfer to the vessel wall using vascular endothelial growth factors (VEGFs) has shown therapeutic potential for the treatment of restenosis. In this study, we evaluated the effect of catheter-mediated adenoviral (Ad) gene transfer of the mature form of VEGF-D (VEGF-D(DeltaNDeltaC)) in balloon-denuded cholesterol-fed rabbit aorta. AdLacZ was used as a control. Transduced VEGF-D(DeltaNDeltaC) mRNA was detectable in the arterial wall with RT-PCR at 6, 14 and 28 days. Gene transfer efficiency as detected with X-gal staining 6 days after the AdLacZ transduction was 1.91 +/- 1.32% in intima. AdVEGF-D(DeltaNDeltaC) gene transfer led to 52% reduction in intima/media ratio (I/M) as compared to the AdLacZ controls at 14 days time point. At 6 days there were no differences in I/M, but the number of macrophages in the vessel wall was 85% lower in the AdVEGF-D(DeltaNDeltaC) group as compared to the controls. The therapeutic effect was no longer detectable 28 days after the gene transfer. The therapeutic effect of VEGF-D(DeltaNDeltaC) was nitric oxide (NO)-dependent as the feeding of NO synthase inhibitor, L-NAME, blocked the reduction in intimal thickening. It is concluded that AdVEGF-D(DeltaNDeltaC) gene transfer reduces intimal thickening and macrophage influx into the vessel wall in balloon-denuded rabbit aortas.

Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.

OBJECTIVE: Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event. RESULTS: The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. CONCLUSION: We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.

Dynamics of contrast enhancement in MR imaging and power Doppler ultrasonography of solid breast lesions.

PURPOSE: To evaluate the dynamics of contrast enhancement in solid breast lesions at contrast-enhanced MR imaging and power Doppler ultrasonography (US) and to compare the methods to histology and to each other. MATERIAL AND METHODS: Forty breast lesions were prospectively examined with dynamic MR and power Doppler US. Time-signal intensity curves of enhancement were obtained for both methods. The shape of the curve was analyzed to be benign, indeterminate or malignant. The curves were also analyzed quantitatively by calculating the slope of the curve and the area under the curve (both methods), relative enhancement (MR), and time to peak (US). The lesions were divided into malignant lesions, fibroadenomas, and other benign lesions. The results were compared to histology. RESULTS: In the subjective analysis of the MR curve in differentiating between benign and malignant lesions the accuracy was 90%. The MR curve also enabled differentiation between fibroadenomas and malignancies. The accuracy of the US curve was 38%. Quantitatively, statistically significant differences were found using all the MR variables, except between malignancies and fibroadenomas. Using the US variables, no significant difference was found between the groups. CONCLUSION: The dynamics of contrast-enhanced MR were reliable in the differential diagnosis of solid breast lesions, but contrast-enhanced power Doppler US was of limited value.

Phloem fortification in rye bread elevates serum enterolactone level.

OBJECTIVE: To analyse the lignan content of phloem powder enriched rye bread and to study the dose-response relationship of the effect of dietary plant lignans derived from phloem on intestinal production of enterolactone by measuring enterolactone concentration in serum. DESIGN: A randomized double-blind supplementation trial. SUBJECTS: Seventy-five non-smoking men recruited by newspaper advertisements. INTERVENTION: Subjects were randomized to three study groups receiving either rye bread high in phloem (HP, 14% of rye flour substituted with phloem powder), rye bread low in phloem (LP, 7% of rye flour substituted with phloem powder) or placebo rye bread. Participants consumed 70 g of study bread daily for 4 weeks and provided serum samples for enterolactone analysis at baseline and at the end of the intervention. RESULTS: There was a significant increase in serum enterolactone concentration in the LP and HP groups compared with the placebo group (P=0.009 and P=0.003, respectively). Considerable interindividual differences were observed in the response to dietary lignans within the study groups. CONCLUSIONS: Our results indicate that plant lignans attached to insoluble fibre layer in phloem can be further metabolized and converted to enterolactone presumably by the bacteria present in the colon. Phloem powder is useful source of lignans for functional foods aimed to elevate serum enterolactone levels. SPONSORSHIP: Phloem powder and the study breads were provided by Finnpettu Oy and Linkosuo Oy, respectively. The clinical study work was sponsored in part by Oy Jurilab Ltd.

Serum fatty acid composition predicts development of impaired fasting glycaemia and diabetes in middle-aged men.

AIMS: Dietary fatty acid intake is reflected in serum fatty acid composition. Studies prospectively investigating serum fatty acids and development of impaired fasting glycaemia (IFG) or diabetes mellitus (DM) are largely lacking. We assessed the association of serum fatty acid composition with development of IFG or DM. METHODS: Middle-aged normoglycaemic men (n = 895) participating in a prospective cohort study were followed up after 4 years. RESULTS: At baseline proportions of serum esterified and non-esterified saturated fatty acids were increased and polyunsaturated fatty acids decreased in men who after 4 years had developed IFG (n = 56) or DM (n = 34). No differences in dietary fatty acid composition as recorded in 4-day dietary records were noted. In logistic regression analyses adjusting for age; obesity; and fasting lipid, glucose and insulin concentrations, men with proportions of non-esterified and esterified linoleate in the upper third had nearly half the risk for IFG or DM compared with the lower third. In covariate analyses, baseline non-esterified linoleate proportions were associated with changes in fasting insulin and glucose concentrations over the 4-year follow-up. Baseline esterified fatty acid composition was also associated with changes in insulin. CONCLUSIONS: High serum linoleate proportions decreased the risk of developing IFG or DM in middle-aged men over a 4-year follow-up, possibly mediated in part by insulin resistance. These findings support recommendations to substitute vegetable fat for animal and dairy fat in the prevention of disturbances of glucose and lipid metabolism.