Search PubMed⌕ Search

Biomedical subjects

J Overgaard

Publications and source records attributed to J Overgaard.

At least 37 records · Page 2Linked to original sources
PubMed2000

Histopathological and morphometric analyses of late rectal injury after irradiation.

The aim of the present study was to assess and quantify changes in the structural components of the rectal wall after irradiation with varying single doses of x-rays. A total of 70 CDF1/Bom male mice were irradiated at a selective 1.5 cm of the distal rectum with varying single doses of 0-30 Gy. At 32 weeks postirradiation the mice were sacrificed and the rectum was removed. Sampling of the specimens was based on unbiased stereological principles using systematic random sampling. Vertical tissue sections were used to estimate mucosal surface area density and to measure the thickness and volume fraction of the different intestinal wall layers. The surface area density decreased with increasing dose (p<0.02) due to pronounced injury of the crypts and mucosal morphology. The thickness and the volume fraction of the submucosa were significantly increased in the 20, 25 and 30 Gy treatment groups (p<0.0001 and p<0.0001), whereas the thicknesses of the mucosa, the lamina muscularis propria and the serosa did not change after irradiation. It is concluded that irradiation causes histopathological changes in the rectal mucosa and submucosa, and changes in the thickness of the submucosal intestinal layer. These changes were found to be dose-dependent.

Animals↗
PubMed2000

Time course of radiological lung density changes after postmastectomy radiotherapy.

The purpose of this study was to quantify the time course of radiological lung changes in patients after postmastectomy radiotherapy assessed from routine follow-up chest x-rays. Radiological density changes in the apex of the irradiated lung were quantified by a recent lung densitometry assay. Lung changes were expressed as the so-called Relative change in Equivalent Absorber Thickness (REAT). The clinical series comprised 329 patients treated with postmastectomy radiotherapy between 1978 and 1982. Of these patients 100 were treated with chemotherapy (CTX or CMF) and 41 were given tamoxifen as an additional adjuvant treatment; 290 patients (88.2%) had pretreatment x-rays and at least one x-ray after completion of radiotherapy and these were included in the study. A total of 2,209 chest x-rays was taken during follow-up, and among these 1921 x-rays (86.9%) were judged to be assessable. Late changes were defined as changes occurring more than a year after radiotherapy. A total of 280 patients had at least one chest x-ray taken more than one year after radiotherapy and these were evaluable with respect to late changes. There were 1,390 follow-up x-rays in these patients and 207 patients (73.9%) had three or more follow-up x-rays. Linear regression of REAT vs. observation time was used to identify three patterns of time changes: progressive, regressive, and stable. The results were as follows. Two phases of lung changes were observed. The early phase peaks around 6 months and the density changes may subsequently resolve, completely or in part. In most cases (173 patients or 84%), the lung density changes reached a stable level 12 months after irradiation. Yet, in 16 patients (7.7%) the lung changes progressed for five or more years. Regression of the density changes was seen in 18 patients (8.7%), and in some cases there were signs that this apparent regression was caused by contraction of the fibrotic tissue. We conclude that two phases of lung response can be distinguished and can be graded according to severity using this assay. Early lung changes reach a maximum around 6 months after RT. Late reactions reach a plateau in most patients after one year, but progress in some cases for five or more years.

Adult↗
PubMed2000

Squamous cell carcinoma of the oropharynx--an analysis of treatment results in 289 consecutive patients.

In this retrospective study the results of primary and salvage treatment of oropharyngeal carcinoma were evaluated. A total of 289 consecutive patients (103 females and 186 males) were included in the study. Most tumours originated in the tonsil area (58%) and comprised stages I 8%, II 19%, III 46% and IV 28%. The primary treatment was delivered with curative intent in 276 cases (96%). Of these, 266 received primary radiotherapy. The median radiation dose was 62 Gy, given as laterally opposed fields to the primary tumour and bilateral neck. Eight patients were treated with primary surgery and two with chemotherapy as part of a curatively intended treatment programme including radiotherapy. Six patients received palliative treatment, and seven were not treated at all. Out of 276 tumours treated with curative intent, 173 reappeared; 72% recurred in T position, 38% in N position, and 12% at distant metastatic sites, some in combination. Salvage surgery was possible in 52 patients, and 24 treatments were successful. Salvage radiotherapy or cryotherapy was used in 22 patients and 4 were controlled. For the entire group, the 5-year locoregional tumour control, disease-specific survival and overall survival rates were 38%, 44% and 31%, respectively. For patients treated with curative intent, clinical T- and N-stage, stage, tumour size, gender, age, and pretreatment haemoglobin were significant prognostic parameters in a univariate analysis. The Cox multivariate analysis showed that T-stage, N-stage and gender were independent prognostic factors. It is concluded that T-stage, N-stage and gender are significant independent prognostic factors. The primary control of the carcinoma in the T-position is crucial for overall success, but salvage surgery is found to have a favourable success rate in patients suitable for relapse treatment.

Adult↗
PubMed2000

TP53 mutation is an independent prognostic marker for poor outcome in both node-negative and node-positive breast cancer.

TP53 gene-mutation and protein expression of p53 are described as being of prognostic importance for the outcome of breast cancer. The present study was therefore carried out to evaluate whether TP53 mutation would be a feasible prognostic marker in the routine diagnostic evaluation of breast cancer, and, in particular, to analyse the relationship between TP53 mutation and nodal status. Tumour material was obtained from women with sporadic early breast cancer. Gene mutations in exon 2-11 were identified using denaturing gradient gel electrophoresis (DGGE) as the initial scanning procedure and characterized by sequencing. All patients were treated according to the guidelines of the Danish Breast Cancer Cooperative Group for the DBCG 89 protocols. The results were correlated with clinico-pathological parameters and the prognosis evaluated by uni- and multivariate analysis using local control, freedom from distant metastasis, disease-free survival, and overall survival as endpoints. The study included 294 patients. TP53 mutations were found in 23% of cases. Mutations were significantly more frequent in tumours from patients who were node-positive and with tumours characterized as being ductal, large of size, with a high degree of anaplasia, and oestrogen receptor negative. Using univariate analysis, it was found that distant metastasis, disease-free, and overall survival were correlated to tumour size, nodal status, degree of anaplasia, oestrogen receptor status, and TP53 mutation. In addition, overall survival was also correlated to age and menopausal status. When analysed according to nodal status, TP53 mutation was found to have a significantly poor survival probability in each of the subgroups. A Cox proportional hazard analysis, including all 294 patients, demonstrated that positive nodal status and TP53 mutation were the only parameters that had an independent poor influence on the risk of developing distant metastasis and reduced recurrence-free survival. The same factors together with postmenopausal status were found to be significantly associated with increased risk of death. TP53 mutation is a strong marker for the prediction of overall and disease-free survival in breast cancer, irrespective of nodal status. A better understanding of the role of the p53 pathway, including analysis of different types of TP53 mutations, is required in order further to investigate the prognostic potential of this marker.

Adult↗
PubMed2000

Treatment of morbidity associated with the management of the axilla in breast-conserving therapy.

The purpose of this study was to determine the impact of surgery and radiotherapy on late morbidity associated with the management of the axilla in breast cancer patients. Two hundred and sixty-six patients from a randomized breast conservation trial (DBCG-82TM protocol) were called in for a single follow-up interview and clinical examination of several functional outcome measures after a median of 6.6 years (3.5-10.5). All the patients were treated with lumpectomy and axillary dissection, followed by external beam radiotherapy to the residual breast. High-risk patients were given additional radiation to the regional lymph nodes plus adjuvant systemic treatment. Twenty-eight patients (11%) had arm edema (> or = 2 cm), which was associated with the extent of axillary node dissection as well as with age and radiotherapy (relative risk, RR = 4.5 (1.8-11.2, p = 0.001)). Impaired shoulder movement of any degree (7%) was associated with radiotherapy (RR = 4.0 (1.5-13.8, p = 0.007)) and advanced age (p = 0.002), while the extent of axillary dissection as described by the number of nodes retrieved was the only factor that predicted pain on logistic regression analysis (p = 0.02). A moderate to severe change in arm/shoulder strength and working ability was observed in 7% and 5% of patients, respectively, but no independent predisposing factor was discerned for these endpoints. It is concluded that the level of late functional morbidity several years after breast-conserving treatment is relatively low and clearly relates to age, extension of surgery, irradiation of the axilla or a combination of these factors, depending on the specific clinical outcome measure.

Adult↗
PubMed2000

Late treatment-related morbidity in breast cancer patients randomized to postmastectomy radiotherapy and systemic treatment versus systemic treatment alone.

Late treatment-related morbidity after mastectomy and adjuvant systemic treatment with and without postoperative irradiation was assessed in 84 patients randomized in the Danish Breast Cancer Cooperative Group Trials 82b and c. A structured interview and physical examination, using a standardized assessment sheet, constructed on the basis of the late effects normal tissues (LENT) scoring system, was used. The median length of follow-up from mastectomy was 9 years (range 6-13 years). Lymphedema was measured in 14%, of the irradiated patients versus 3% of the non-irradiated patients (NS). Slightly decreased shoulder morbidity was measured in 45% of the irradiated women versus 15% of the non-irradiated patients, but moderate or more severe impairment was seen in only 5% of the irradiated patients and in none of the non-irradiated patients (p = 0.004). Seventeen percent of the irradiated patients and 2% of the non-irradiated patients found that impairment of shoulder movement caused symptoms (p = 0.001).

Adult↗
PubMed2000

Fibroblast differentiation in subcutaneous fibrosis after postmastectomy radiotherapy.

In order to acquire a better understanding of the mechanism of radiation-induced fibrosis, we studied the differentiation of normal skin fibroblasts cultured from breast cancer radiotherapy patients with different risk of fibrosis. The differentiation state of fibroblasts was characterized in clonal cultures using established cytomorphological criteria. Collagen synthesis was determined by 3H-proline incorporation into pepsin-resistant protein. Radiation-induced inactivation of fibroblasts was paralleled by an increase in terminally differentiated fibrocytes, demonstrating that premature terminal differentiation is an important response to irradiation of fibroblasts from radiotherapy patients. Surviving colony-forming fibroblasts showed a change in differentiation with an increase in the ratio L:E of progenitor fibroblasts in late (L) compared to early (E) differentiation states. Furthermore, increased collagen production was observed after irradiation. The results provide evidence supporting a role of terminal fibroblast differentiation in radiation-induced fibrosis and imply that the progenitor population surviving radiotherapy might be more prone to terminal differentiation than before radiotherapy.

Breast Neoplasms↗
PubMed2000

Risk factors of arm lymphedema in breast cancer patients.

Chronic lymphedema is a life-long, potential complication of axillary treatment for breast cancer patients. In this article we focus on risk factors in the development of arm lymphedema and also discuss definition, type and stage, and incidence of arm edema.

Arm↗
PubMed2000

Feasibility of detecting hypoxia in experimental mouse tumours with 18F-fluorinated tracers and positron emission tomography--a study evaluating [18F]Fluoro-2-deoxy-D-glucose.

The study was designed to investigate the binding of [18F]Fluoromisonidazole ([18F]FMISO) and [18F]Fluoro-2-deoxy-D-glucose ([18F]FDG) in a C3H mouse mammary carcinoma. Non-anaesthetized tumour-bearing animals breathing either normal air or carbogen (to reduce tumour hypoxia) were examined by PET after tracer injection. Tumours were identified by radioactive labelling and methods of defining regions of interest (ROI) in the tumours were investigated. Reference tissue was selected elsewhere in the mice and the ratio between mean radioactivity in tumour and reference tissue was compared. The results showed a correlation between the methods of identifying ROIs and a significantly lower tumour to reference tissue ratio for carbogen-treated mice compared with controls when using [18F]FMISO. Only one of the methods showed a significant difference in the tumour labelling between treatment groups using [18F]FDG. The study supports the contention that [18F]FMISO may be able to identify hypoxia in tumours, whereas a similar role for [18F]FDG is more doubtful.

Animals↗
PubMed2000

Hypopharyngeal squamous cell carcinoma--treatment results in 138 consecutively admitted patients.

The aim of this study was to evaluate the results of the initial and salvage treatment for hypopharyngeal carcinoma. The study was conducted in 1963 to 1991 and included 138 patients (38 females (28%) and 100 males (73%)). Most of the tumours originated in the piriform sinus (86%). Tumour stage distribution was T1: 20%, T2: 27%, T3: 37% and T4: 17% and nodal stage distribution was N0: 45%, N1: 25%, N2: 10%, and N3: 20%. Primary treatment was delivered with curative intent in 124 out of 138 cases (90%). Treatment failure was noted in 98 patients, with 55% recurrence in T-position, 39% in N-position, and 14% at distant metastases sites. Salvage surgery was successful in 9 out of 32 patients. The overall 5-year locoregional tumour control, cause-specific and overall survival rates were 20%, 25% and 19%, respectively. Univariate actuarial analysis showed that T- and N-stage, clinical stage, tumour size and well-differentiated tumours were significant prognostic parameters. A Cox multivariate analysis showed that only the T- and N-stages were independent prognostic factors. In conclusion, the prognosis for advanced hypopharyngeal carcinoma is extremely poor and the meagre results with conventional radiotherapy alone indicate that other treatment modalities should be introduced in the management of this disease.

Adult↗
PubMed2000

Time-course of the hazard of murine nephropathy induced by total-body irradiation.

PURPOSE: We investigated the form of the hazard function for total-body irradiation (TBI) induced nephropathy in mice during 1.5 years of follow-up. MATERIAL AND METHODS: The material was collected from our previously published data. Following single-dose or fractionated irradiation and bone marrow transplantation (BMT) the mice were tested regularly for kidney damage using the CrEDTA residual activity, percentage haematocrit and blood urea nitrogen endpoints. The hazard rate was studied in the pooled data of 172 mice for all three endpoints, while fractionation sensitivity was estimated from the direct analysis, which was performed using the CrEDTA residual activity endpoint and the actual follow-up data in individual mice. RESULTS: The hazard rate of kidney damage following TBI and BMT showed a biphasic pattern that is most evident with the CrEDTA residual activity endpoint, with a reduced risk of renal failure around week 36 after TBI. Assessment of kidney function in individual animals showed evidence of recovery from radiation damage around week 36 after TBI. An analysis of fractionation sensitivity showed that the first wave was characterized by an alpha/beta ratio of 8.4Gy (95% CI: 4.0-14.3Gy), while the alpha/beta ratio for the second wave was estimated at 6.1 Gy (95% CI: 3.3 9.8 Gy). CONCLUSIONS: The biphasic nature of the hazard function reported here may be a unique feature of TBI-induced renal damage. Differentiation between the two phases in terms of their alpha/beta ratio was not possible. The biological basis of this observation remains to be clarified. The reported high alpha/beta ratio of kidney damage in the TBI situation may have important clinical implications.

Animals↗
PubMed2000

p53 accumulation associated with bcl-2, the proliferation marker MIB-1 and survival in patients with prostate cancer subjected to watchful waiting.

PURPOSE: We describe the association of p53 nuclear protein accumulation with bcl-2 expression, tumor cell proliferation and clinical outcome in a prostate cancer population undergoing watchful waiting. MATERIALS AND METHODS: Immunohistochemical staining for p53 was semiquantitatively scored in archival formalin fixed, paraffin embedded tumor tissue obtained at diagnosis in 221 patients with prostate cancer. At a median of 15 years followup was nearly complete. Eventually 57% of the patients died of prostate cancer. RESULTS: p53 Immunohistochemical staining was heterogeneous but in all cases at least clusters of tumor cells had nuclear staining for p53. The percent of p53 immunoreactive tumor cells was scored as 0 to 4+ in p53 positive hot spots. p53 immunoreactivity correlated with clinical stage and histopathological grade (p = 0.003 and 0.009, respectively). When dichotomized into low (0% to 50%) and high (51% to 100%) immunoreactivity groups of 40 and 181 patients, respectively, p53 accumulation was significantly associated with disease specific survival in the study population overall (p <0. 0001) and in the 125 with clinically localized disease (p = 0.0002). p53 Immunoreactivity was significantly (p <0.001) associated with the proliferation marker MIB-1 (median value 10.3, range 0 to 46.1) but insignificantly (p = 0.8) correlated with bcl-2 expression (52% positive). However, patients with combined favorable MIB-1 and bcl-2 status were stratified into significant (p = 0.02) prognostic groups by p53 immunohistochemical status. Multivariate analysis revealed that p53 immunoreactivity was a significant prognostic factor in patients with clinically localized prostate cancer (p <0.0001). CONCLUSIONS: p53 Nuclear protein accumulation detected by immunohistochemical study was an independent adverse prognostic factor in patients with prostate cancer undergoing watchful waiting.

Aged↗
PubMed2000

Heterogeneity in the clinical phenotype of TP53 mutations in breast cancer patients.

TP53 mutation is a strong independent marker for survival in breast cancer with some heterogeneity in the clinical phenotype of various types of mutations. Based on 315 patients with breast carcinoma, we suggest a new model for the differentiation of TP53 mutations. Although TP53 mutation in general was associated with aggressive tumor/patient characteristics, missense mutations outside any conserved or structural domain did not affect the clinical outcome (risk of disseminated disease and death). In contrast, patients with missense mutations affecting amino acids directly involved in DNA or zinc binding displayed a very aggressive clinical phenotype. Null mutations (including missense mutations disrupting the tetramerization domain) and the remaining missense mutations displayed an intermediate aggressive clinical phenotype. When patients with primary early breast cancer were divided into three groups (wild-type together with missense mutations outside structural/conserved domains, null mutations and missense mutations with intermediate clinical phenotype, and very aggressive missense mutations), disease-specific survival rates were 89%, 58%, and 35% (5-year actuarial values, P < 0.0001), respectively. In a Cox proportional hazards analysis, separation of TP53 mutations according to these criteria eliminated the prognostic importance of all investigated classical factors except nodal status.

Alleles↗
PubMed2000

Effects of feeding on arterial blood gases in the American alligator Alligator mississippiensis.

Reptiles habitually ingest large meals at infrequent intervals, leading to changes in acid-base status as the net secretion of acid to the stomach causes a metabolic alkalosis (the alkaline tide). In chronically cannulated and undisturbed amphibians and reptiles, the pH changes in arterial blood are, nevertheless, reduced by a concomitant respiratory acidosis (increased P(CO2) caused by a relative hypoventilation). Alligators (Alligator mississippiensis) have been reported to exhibit exceptionally large increases in plasma [HCO3(-)] following feeding, but these studies were based on blood samples obtained by cardiac puncture, so stress and disturbance may have affected the blood gas levels. Furthermore, crocodilian haemoglobin is characterised by a unique binding of HCO3(-) that act to reduce blood oxygen-affinity, and it has been proposed that this feature safeguards oxygen offloading by counteracting pH effects on blood oxygen-affinity. Therefore, to study acid-base regulation and the interaction between the alkaline tide and oxygen transport in more detail, we describe the arterial blood gas composition of chronically cannulated and undisturbed alligators before and after voluntary feeding (meal size 7.5+/-1% of body mass). Digestion was associated with an approximately fourfold increase in metabolic rate (from 0.63+/-0.04 to 2.32+/-0.24 ml O(2) min(-1)kg(-1)) and was accompanied by a small increase in the respiratory gas exchange ratio. The arterial P(O2) of fasting alligators was 60.3+/-6.8 mmHg (1 mmHg = 0.133 kPa) and reached a maximum of 81.3+/-2.7 mmHg at 96 h following feeding; there was only a small increase in lactate levels, so the increased metabolic rate seems to be entirely aerobic. Plasma [HCO3(-)] increased from 24.4+/-1.1 to 36.9+/-1.7 mmol l(-1) (at 24 h), but since arterial P(CO2) increased from 29.0+/-1.1 to 36.8+/-1.3 mmHg, arterial pH remained virtually unaffected (changing from 7.51+/-0.01 to 7.58+/-0.01 at 24 h). The changes in plasma [HCO3(-)] were mirrored by equimolar reductions in plasma [Cl(-)]. The in vitro blood oxygen-affinity was reduced during the post-prandial period, whereas the estimated in vivo blood oxygen-affinity remained virtually constant. This supports the view that the specific HCO3(-) effect prevents an increased blood oxygen-affinity during digestion in alligators.

Alligators and Crocodiles↗
PubMed2000

Association between immunohistochemical expression of vascular endothelial growth factor (VEGF), VEGF-expressing neuroendocrine-differentiated tumor cells, and outcome in prostate cancer patients subjected to watchful waiting.

Tumor growth is dependent on angiogenesis, which is thought to be controlled by angiogenic factors. Therefore, the immunoreactivity of the angiogenic cytokine vascular endothelial growth factor (VEGF) was semiquantitatively scored in archival prostate tumors obtained at diagnosis in 221 patients followed expectantly. At diagnosis, 125 patients suffered from clinically localized disease. Median length of follow-up was 15 years, and 57% of the patients eventually died of prostate cancer. All of the tumors exhibited cytoplasmic staining for VEGF. The staining intensity was weak in 47 tumors and moderate and strong in 107 and 67, respectively. VEGF expression was significantly correlated with microvessel density (MVD; median, 43; range, 16-151; P = 0.014), increasing T-classification (P = 0.001), dedifferentiation (P < 0.001), and disease-specific survival (P = 0.013). Strongly VEGF-immunoreactive, neuroendocrine-differentiated (NE) tumor cells were observed in 125 tumors. NE expression was significantly correlated with increasing MVD, increasing T-classification, dedifferentiation, and survival (all, P < 0.001). MVD and NE tumor cell expressions were significant variables in a multivariate analysis that included patients with clinically localized prostate cancer only. VEGF and NE expression were significantly correlated with MVD, clinical characteristics, and disease-specific survival. NE expression was a significant prognostic marker in localized prostate cancer patients, whereas the applied semiquantitatively scoring of VEGF expression was inadequate to make this growth factor provide any additional prognostic information. Moreover, the significant VEGF expression of NE tumor cells suggests an additional important character of these cells in the involvement in disease progression.

Aged↗
PubMed2000

Combretastatins novel vascular targeting drugs for improving anti-cancer therapy. Combretastatins and conventional therapy.

Combretastatins are a new class of compounds that appear to have anti-tumour activity as a result of specifically targeting the vasculature of tumours. The aim of this study was to investigate the potential of combretastatin A-4 disodium phosphate (CA4DP) to induce vascular effects in a C3H mouse mammary carcinoma, and to see if the anti-tumour response could be improved by combining the drug with conventional anti-cancer therapies. It was found that CA4DP (250 mg/kg) significantly decreased tumour perfusion within 30 minutes after injection and maintained this decrease for several hours, although there was a return to normal by 24 hours. Similar changes were seen in the tumours bioenergetic and oxygenation status. The drug also significantly increased tumour necrosis and had a small inhibitory effect on tumour growth. It was also able to enhance the tumour response to radiation and hyperthermia, when given at the same time or 30 minutes after the radiation and hyperthermia, respectively. Giving the drug 1 hour after cisplatin injection only resulted in a tumour response that was no greater than additive. These results confirm the anti-vascular effects of CA4DP and demonstrate its potential to enhance the anti-tumour activity of conventional therapy.

Animals↗
PubMed1999

Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group.

BACKGROUND: Radiotherapy in addition to systemic treatment after mastectomy prolongs survival in high-risk breast-cancer patients. However, adjuvant radiotherapy has a potential association with ischaemic heart disease. We assessed morbidity and mortality from ischaemic heart disease in patients treated with postmastectomy radiotherapy. METHODS: Between 1982 and 1990, we randomly assigned 3083 women at high risk of breast cancer, after mastectomy, adjuvant systemic treatment with (n=1538) or without (n=1545) radiotherapy. An anterior photon field was used against the periclavicular region and the axilla. The chest wall was treated through two anterior shaped electron fields, one including the internal mammary nodes. The intended dose was 48-50 Gy in 22-25 fractions, at four to five fractions per week. We obtained information on morbidity and mortality of ischaemic heart disease over a median of 10 years. Analysis was by intention to treat. FINDINGS: More women in the no-radiotherapy group than in the radiotherapy group died of breast cancer (799 [52.5%] vs 674 [44.2%]), whereas similar proportions of each group died from ischaemic heart disease (13 [0.9%] vs 12 [0.8%]). The relative hazard of morbidity from ischaemic heart disease among patients in the radiotherapy compared with the no-radiotherapy group was 0.86 (95% CI 0.6-1.3), and that for death from ischaemic heart disease was 0.84 (0.4-1.8). The hazard rate of morbidity from ischaemic heart disease in the radiotherapy group compared with the no-radiotherapy group did not increase with time from treatment. INTERPRETATION: Postmastectomy radiotherapy with this regimen does not increase the actuarial risk of ischaemic heart disease after 12 years.

Adult↗