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Biomedical subjects

A Lindgren

Publications and source records attributed to A Lindgren.

At least 19 recordsLinked to original sources

Risk factors for local recurrence after breast-conserving surgery.

BACKGROUND: It is not clear whether risk factors for local recurrence after breast-conserving surgery differ in women having surgery for in situ or invasive cancer. Furthermore, the Nottingham Prognostic Index (NPI) and Nottingham Histological Grade (NHG) have been little studied as determinants of local recurrence risk. METHOD: In a case-control study (491 cases and 1098 controls) nested within a cohort of 7502 women who had surgery for in situ or invasive cancer of the breast, patient characteristics, tumour characteristics and treatment-related variables were evaluated as risk factors for local recurrence. RESULTS: Multivariate conditional logistic regression analyses showed that age below 40 years, tumour multicentricity and an unclear or unknown surgical margin were significant risk factors for local recurrence. Radiotherapy to the breast and adjuvant hormone therapy were protective. Cancer in situ was not associated with a higher risk of local recurrence than invasive cancer (odds ratio 1.0, 95 per cent confidence interval 0.8 to 1.3). NHG and NPI were not helpful in determining risk of local recurrence. CONCLUSION: Margin status, age, tumour multicentricity, and use of radiotherapy and adjuvant hormone therapy were important determinants of risk of local recurrence. With the exception of surgical margin, variables related to the quality of surgical management did not predict risk of local recurrence.

Adult↗

Carotid artery stenosis: contrast-enhanced MR angiography with two different scan times compared with digital subtraction angiography.

Contrast enhanced magnetic resonance angiography (CE MRA) is a non-invasive alternative to conventional digital subtraction angiography (DSA). CE MRA is increasingly used as a complement to Duplex in the preoperative assessment of carotid artery stenosis. The purpose of this study was to determine if CE MRA could replace preoperative DSA. CE MRA with a scan time of 10 or 28 s was performed in 24 consecutive patients who were scheduled for preoperative DSA because of Duplex-verified severe carotid artery stenosis. Two neuroradiologists measured the degree of stenosis with three different methods, and the image quality was evaluated. DSA was used as the gold standard. For detection of severe stenosis (N. American symptomatic carotid endarterectomy trial (NASCET) > or =70%; European symptomatic carotid endarterectomy trial (ECST) > or =80%; common carotid artery method (CCAM) > or =80%), the sensitivity of CE MRA maximum intensity projection (MIP) compared with DSA was 82%-100 %, the specificity was 74%-93% and the accuracy was 77%-90%. The inter-observer agreement was higher, the image quality was better and the intracranial main arteries were better visualized with the 28 s than with the 10 s scan time. The enhancement of the jugular veins seen in 17% of the 10 s scans and in 58% of the patients with the 28 s scans did not interfere with the evaluation of the carotid arteries. CE MRA, preferably with a scan time of 28 s, can replace DSA in the preoperative assessment of most patients with carotid artery stenosis.

Aged↗

Discounting and clinical decision making: physicians, patients, the general public, and the management of asymptomatic abdominal aortic aneurysms.

Clinical decisions often entail in intertemporal trade-off. Moreover, they often involve physicians of different specialities. In an experiment dealing with the management of small asymptomatic abdominal aortic aneurysms (a clinically relevant problem) we find that specialists in internal medicine exhibit higher implicit discount rates than vascular surgeons, general practitioners, and actual and prospective patients. Several personal characteristics expected to be directly related to pure time-preference and risk aversion (gender, smoking habits, age, place of employment) have the hypothesised effects. Additionally, financial incentives appear to affect the estimated implicit discount rates of physicians, but are unlikely to have caused the inter-group differences. Differences in discount rates could lead to variations in clinical practice, which may conflict with equality of treatment or equal access to health care.

Aged↗

Characterization of inhibitors to FVIII with an ELISA in congenital and acquired haemophilia A.

Different methods can be used for the detection and quantification of inhibitors or antibodies to coagulation factor VIII (FVIII). Traditionally, clotting assays have been used, in particular the Bethesda assay. These assays have, however, several shortcomings, due to the complex reaction kinetics of some inhibitors and a low sensitivity to low-titre antibodies. In addition, a universal FVIII inhibitor standard is lacking. Furthermore, clotting assays do not detect noninhibitory antibodies. Use of ELISAs has been described and FVIII from various commercially available FVIII concentrates has been used as target antigen in the assays. In the present study, we systematically explored the influence of different FVIII concentrates on the performance of an ELISA for detection of FVIII antibodies. The described ELISA was also used for further characterization of FVIII inhibitors in patients with acquired and congenital haemophilia A. We found that the source of FVIII had a substantial impact on the frequency of antibody detection. Albumin-free recombinant FVIII as target antigen gave the highest sensitivity for the assay, whereas plasma-derived concentrates containing a high level of von Willebrand factor (vWF) gave the lowest sensitivity. Presumably vWF interferes with the binding of antibodies to FVIII. We suggest that albumin-free recombinant FVIII should be used as target antigen when ELISAs are used for detection of FVIII antibodies.

Antibodies↗

Demographic transition of the Swedish cystic fibrosis community--results of modern care.

Assessing the results of modern cystic fibrosis (CF)-care and estimating the future population and its demography is important to evaluate the treatment regimens and to calculate the future needs of health-care resources. This paper updates previous incidence calculations. It assesses the results of modern CF-care in terms of survival and changing demography in Sweden. The incidence of CF in Sweden was calculated as 1/5600 live-births. Of the CF-population alive in 1999, 45% were > or = 18 years old. The mean annual mortality rate since 1991 was 0.9% (+/-0.4) and the median age at death 26 years (range 0-72). Of those born > or = 1991, 95% were estimated to survive their 25th birthday. The incidence of CF in Sweden is low. Modern CF-care in Sweden shows good results. The CF-population is growing rapidly and the adult part of the population will soon be larger than the paediatric. Continuously adapted resources are required to assure the future treatment quality especially for the growing adult CF-population.

Adolescent↗

Elevated serum methylmalonic acid. How much comes from cobalamin deficiency and how much comes from the kidneys?

Serum methylmalonic acid (S-MMA) as a sensitive indicator of cobalamin deficiency was introduced more than 10 years ago. The use of this method for identifying patients with cobalamin deficiency reflects much higher prevalence figures than was previously thought. In this review, all major studies on the subject are analysed. The least common denominator that could explain the probably overrated prevalence figures is the deteriorated renal function accepted for inclusion in virtually all the studies. A strong association between S-MMA and S-creatinine, even within the normal range for creatinine. has become increasingly apparent. At present, it is impossible to estimate how much of elevated S-MMA comes from impaired renal function and how much comes from impaired cobalamin metabolism. Thus, the use of S-MMA as the sole indicator of cobalamin deficiency cannot be recommended.

Humans↗

Persistent high signal on diffusion-weighted MRI in the late stages of small cortical and lacunar ischaemic lesions.

Diffusion-weighted imaging (DWI) is very sensitive to early brain infarcts. However, the late stages have been insufficiently studied. Infarcts in small vessel disease are often multiple and of different ages, and differentiation between new and old lesions might be difficult. We have therefore studied the change with time in DWI of small (< 3 ml) ischaemic lesions. We imaged 21 patients with an acute lacunar syndrome and a lesion visible on early DWI. They all had three MRI examinations 12-58 h (early), 7-16 and 54-144 days after the onset of stroke; 10 patients with high DWI signal on the third examination had a fourth examination 12-28 months after the stroke. MRI was performed at 1.5 T, using echo-planar DWI with 7 b-values from 0 to 1200 x 10(6) s/m2 and conventional T2-weighted imaging. After 7-16 days 18 of 21 lesions gave high signal on DWI, and 12/16 measurable lesions had a decreased apparent diffusion coefficient (ADC). After 54-144 days ten lesions still gave high DWI signal and two still had an ADC below normal. On the fourth examination there was no remaining high DWI signal and all ADC were higher than normal.

Brain↗

The value of b required to avoid T2 shine-through from old lucunar infarcts in diffusion-weighted imaging.

Multiple small infarcts of different ages are common in small-vessel disease. Diffusion-weighted imaging (DWI) is a powerful method for discriminating new from chronic lesions. This can be done on the diffusion-weighted images provided that b is sufficiently high. Our purpose was to determine that critical value of b. We reviewed DWI from a previous study of acute, mainly lacunar strokes, and selected 18 old lacunar infarcts, well defined on uncoded images with b 0 s/m2 (i. e., T2-weighted images) but invisible on DWI with b 1,200 x 10(6) s/m2. We used a 1.5 tesla imager and single-shot echo-planar technique. We had seven separate acquisitions with echo time 123 ms and b in steps between 0 and 1,200 x 10(6) s/m2. Two neuroradiologists blinded to the selection of lesions carried out two different lesion-detection procedures, thereby testing each lesion four times, giving a total of 72 tests of b values. The results were consistent, indicating a level for detection of 800 x 10(6) s/m2 in two tests, 400-600 x 10(6) s/m2 in 65 tests and at lower values in the remainder. For imagers up to 1.5 tesla, at long repetition times and an echo time up to 120 ms T2-shine through of old lacunar infarcts can be avoided using b of 1,000 x 10(6) s/m2.

Brain↗

Spectroelectrochemical study of cellobiose dehydrogenase and diaphorase in a thiol-modified gold capillary in the absence of mediators.

A spectroelectrochemical cell was constructed from a gold capillary with 200 microm inner diameter as a working electrode. This allowed spectroelectrochemical study of liquid samples with available volumes less than 5 microl. The optical measurements were accomplished with an optical fibre spectrometer. The optical path of the cell was about 1 cm. To facilitate electrochemistry of biomolecules, the surface of the gold capillary was modified with thiols. The formal potential, E degrees', of the heme in cellobiose dehydrogenase (CDH) from Phanerochaete chrysosporium was determined by spectroelectrochemistry in the absence of redox mediators. The number of electrons per redox conversion of heme in CDH was found to be equal to 0.98 + 0.04 corresponding well to a theoretical value representing the redox reaction Fe3+ + e-= Fe2+. Similar spectroelectrochemical experiments with diaphorase from Bacillus stearothermophilus showed the redox conversion of the flavin mononucleotide in diaphorase in the absence of external redox mediators.

Carbohydrate Dehydrogenases↗

Mammographic finding as predictor of survival in 1-9 mm invasive breast cancers. worse prognosis for cases presenting as calcifications alone.

PURPOSE: To investigate breast cancer survival in small invasive breast cancers in relation to mammographic findings. MATERIALS AND METHODS: We investigated a consecutive series of 96 cases of 1-9mm small invasive breast cancers diagnosed 1988-1994. Median follow-up of the survivors was 7 years (range: 4.5-10.5). Mammographic findings were classified into rounded masses, spiculated masses, calcifications (casting or pleomorphic) and masses combined with calcifications. Lymph node status and histological malignancy grade were also evaluated. Eight year survival rate in breast cancer was estimated with the Kaplan-Meier method and risk of death with proportional-hazards regression. RESULTS: 6/96 women died from breast cancer. 3/14 had calcifications alone, 2/56 with spiculated masses, 1/12 with rounded masses. 5/78 who died were node-negative cancers and 1/4 was node-positive. The survival rate for the whole group was 93%: 77% for the calcifications alone group, 95% for spiculated masses and 91% for rounded masses. The survival rate for the node-negative cancers was 92% compared to 75% for node-positive cancers. Calcifications alone (p = 0.01) and node positivity (p =0.03) had each independent significant higher risk of death taking finding, node status and grade into account. CONCLUSION: Small invasive breast cancers mammographically presenting as casting or pleomorphic calcifications alone have a significantly worse prognosis than other types.

Adult↗

Effect of interfering substances on current response of recombinant peroxidase and glucose oxidase-recombinant peroxidase modified graphite electrodes.

Graphite electrodes have been modified with different forms of horseradish peroxidase (HRP). These included native HRP, wild-type recombinant HRP, and two single-point recombinant HRP mutants, N70V and N70D. The mediator-less response of these electrodes to H2O2 was studied indicating that electrodes modified with recombinant HRP forms are more stable than those modified with native HRP. Various interfering compounds were investigated for their effect on the current response to H2O2. It was found that interferences such as acetaminophen and dopamine affected the response by mediating the electron transfer (ET) between graphite and peroxidases. The mediating behaviour manifested itself as an increased current of the electrode to H2O2. The interfering effect was less pronounced for the electrodes modified with recombinant HRPs possessing better electronic coupling with the graphite surface. The interfering behaviour of acetaminophen on the response for glucose with the bienzyme electrode containing co-immobilised glucose oxidase and HRP was mainly ascribed to mediation of ET between graphite and HRP. It was experimentally proven that a high efficiency of direct ET between graphite and recombinant HRP substantially reduces the interfering effect of acetaminophen.

Journal Article↗

Pre-operative oestradiol levels - relation to survival in breast cancer.

AIMS: There are clinical observations that operation during the luteal phase of the menstrual cycle (with high oestradiol levels) may positively influence prognosis in breast cancer. However, few studies have information on plasma levels of hormones pre-operatively. METHODS: We studied 774 women treated for breast cancer where plasma levels of oestradiol had been measured 1-2 days pre-operatively. Date and cause of death were ascertained from the files of the Swedish Cancer Register and 5434 person-years were observed. The endpoint was death with breast cancer as the underlying cause (n=41 and n=158 in the pre- and post-menopausal group, respectively). RESULTS: In life-table analyses, only pre-menopausal patients with oestradiol 500 pmol/l and above had a tendency (not statistically significant) for better survival. Multivariate Cox models with oestradiol modelled in continuous form yielded relative hazards (RH) close to unity in all women and in strata according to menopausal status. CONCLUSIONS: When oestradiol was analysed in categorized form, only women with the highest levels had a tendency for improved prognosis (RH around 0.7; not statistically significant). Moreover, this pattern was not apparent for pre-menopausal women. Our findings contradict the notion that the pre-operative oestradiol level is independently associated with breast cancer prognosis.

Adult↗

Vitamin B12 metabolism after urinary diversion with a Kock ileal reservoir.

OBJECTIVE: To elucidate the influence of construction of a Kock reservoir for urinary diversion using 70 cm of the distal ileum on vitamin B12 metabolism. MATERIAL AND METHODS: Blood samples for determination of cobalamin concentrations were drawn up to 18 years after construction of a Kock reservoir in 97 patients. Preoperative values were obtained in 20 of these patients. Pre- and postoperative Schilling tests and analyses of methylmalonic acid and homocysteine concentrations were performed in subgroups. RESULTS: The operation did not induce a significant decrease in cobalamin uptake as reflected in the pre- and postoperatively performed Schilling tests. No significant decline in cobalamin concentration postoperatively was noted. The value of analysis of methylmalonic acid and homocysteine concentrations in finding patients with cobalamin deficiency is limited by the fact that kidney function influences the results. Ten per cent of the patients did develop true cobalamin deficiency. A postoperative vitamin B12 value below 200 pmol/l indicates a 50% risk of later cobalamin deficiency. CONCLUSIONS: The construction of a Kock reservoir does not per se cause cobalamin deficiency. Substitution should be instituted at a postoperative concentration below 200 pmol/l.

Adult↗

Diastolic blood pressure and area of residence: multilevel versus ecological analysis of social inequity.

STUDY OBJECTIVES: To study geographical differences in diastolic blood pressure and the influence of the social environment (census percentage of people with low educational achievement) on individual diastolic blood pressure level, after controlling for individual age and educational achievement. To compare the results of multilevel and ecological analyses. DESIGN: Cross sectional analysis performed by multilevel linear regression modelling, with women at the first level and urban areas at the second level, and by single level ecological regression using areas as the unit of analysis. SETTING: Malmö, Sweden (population 250 000). PARTICIPANTS: 15 569 women aged 45 to 73, residing in 17 urban areas, who took part in the Malmö Diet and Cancer Study (1991-1996). MAIN RESULTS: In the "fixed effects" multilevel analysis, low educational achievement at both individual (beta=1.093, SE=0.167) and area levels (beta=2.966, SE=1.250) were independently associated with blood pressure, although in the "random effects" multilevel analysis almost none of the total variability in blood pressure across persons was attributable to areas (intraclass correlation=0.3%). The ecological analysis also found an association between the area educational variable and mean diastolic blood pressure (beta=4.058, SE=1.345). CONCLUSIONS: The small intraclass correlation found indicated very marginal geographical differences and almost no influence of the urban area on individual blood pressure. However, these slight differences were enough to detect an effect of the social environment on blood pressure. The ecological study overestimated the associations found in the "fixed" effects multilevel analysis, and neither distinguished individual from area levels nor provided information on the intraclass correlation. Ecological analyses are inadequate to evaluate geographical differences in health.

Age Factors↗

Cancer incidence in hypertensive patients in North Karelia, Finland.

Cancer incidence of 20 529 hypertensive patients included in the community-based hypertension register of the North Karelia Project was determined. A total of 2511 incident cancer cases were obtained among the patients in record linkage with the nationwide Finnish Cancer Registry during the mean follow-up time of 16 years. The age-adjusted incidence rates per 100 000 person-years were 248.4 for men and 171.7 for women, which correspond to that of the general population in the area. The Cox regression model was used to analyze the effect of hypertension-related variables on cancer incidence. In men, the diastolic blood pressure was associated with an increased cancer risk but only in those who smoked >10 cigarettes per day. The functional diagnosis of hypertension (stage I, hypertension with no end-organ damage; stage II, hypertension with left cardiac hypertrophy; and stage III, hypertension with extracardiac organ damage) was associated with the increased risk significantly in men who used antihypertensive drugs at baseline. In women, the diastolic blood pressure was associated with an increased cancer risk in those who did not use antihypertensive drugs at baseline. The functional diagnosis of hypertension was associated with an increased risk only in those who smoked >10 cigarettes per day, but the number of women and cancer cases in this group was small. These results indicate a complex pattern of diastolic blood pressure, functional diagnosis, use of antihypertensive drugs, smoking, and gender in the cancer risk of hypertensive patients.

Female↗

Pure motor stroke from presumed lacunar infarct: long-term prognosis for survival and risk of recurrent stroke.

UNLABELLED: BACKGROUND AND PURPOSE A low risk of recurrent stroke and death after lacunar infarction has previously been reported, but follow-up has been limited to </=5 years. METHODS: One hundred eighty patients with pure motor stroke, collected between 1983 and 1986 from a hospital-based stroke registry, were followed up until at least 10 years after the index stroke. Two patients were lost to follow-up. Survival status was determined from the official population registry and compared with survival rates of the Swedish population, matched for age and sex. Cox proportional hazards regression analyses were used to identify independent prognostic predictors. RESULTS: During follow-up 106 (60%) of the 178 patients died, most commonly as a result of coronary heart disease. During the first 5 years after the stroke, survival rates were similar to those of the general population. Beyond this time the risk of death was increased among patients with pure motor stroke, with an excess of 10 to 15 percent units compared with the general population. Independent determinants for death were age (P<0.01), male sex (P<0.01), and nonuse of acetylsalicylic acid (P=0.02). Recurrent stroke occurred in 42 (23.5%) of the patients, corresponding to an annual risk of 2.4%. Hypertension (P=0.025) and diabetes (P=0.024) were independent risk factors for recurrent stroke. CONCLUSIONS: For the first few years after lacunar infarct, the risk of death was similar to that of the general population, but later a clear excess of death was observed. The long-term prognosis in lacunar infarction appears less favorable than previously reported.

Adult↗

Management and prognostic features of intracerebral hemorrhage during anticoagulant therapy: a Swedish multicenter study.

BACKGROUND AND PURPOSE: Patients treated with oral anticoagulants (ACs) have an increased risk of intracerebral hemorrhage (ICH), which is more often fatal than spontaneous ICH. Options to reverse the AC effect include intravenous administration of vitamin K, plasma, and coagulation factor concentrate. However, the optimal management of AC-related ICH has not been determined in any randomized trial. In this study, the present management of AC-related ICH was surveyed, and determinants of survival were assessed. METHODS: We retrospectively reviewed the medical records of all AC-related ICHs at 10 Swedish hospitals during a 4-year period, 1993 to 1996. Survival status after the ICH was determined from the Swedish National population register. RESULTS: We identified 151 patients with AC-related ICH. Death rates were 53.6% at 30 days, 63.6% at 6 months, and 77.5% at follow-up (mean 3.5 years). The case fatality ratio at 30 days was 96% among patients unconscious on admission (n=27), 80% among patients who became unconscious before active treatment was started (n=15), 55% among patients in whom no special action was taken except withdrawal of AC treatment (n=42), and 28% among patients given active anti-coumarin treatment while they were still conscious (n=64). The case fatality ratio at 30 days was 11% in the group treated with plasma (n=18), 30% in the group treated with vitamin K (n=23), and 39% in the group treated with coagulation factor concentrate (n=23). Within the first 24 to 48 hours after admission, 47% of the patients deteriorated. Choice of therapy to reverse the AC effect differed substantially between the hospitals (P<0.0001), as did the time interval from symptom onset to start of treatment. Multiple logistic regression analysis showed only 2 factors (intraventricular extension of bleeding and ICH volume) that were independently related to case fatality at both 30 days and 6 months. The results were similar when the analysis was restricted to patients who were conscious on admission. CONCLUSIONS: In AC-related ICH, a progressive neurological deterioration during the first 24 to 48 hours after admission is frequent, and the mortality is high. Choice of therapy to reverse the AC effect differed considerably between the hospitals. There was no evidence that any treatment strategy was superior to the others. A randomized controlled trial is needed to determine the best choice of treatment.

Adult↗

Hyperhomocysteinemia and changed plasma thiol redox status in chronic obstructive pulmonary disease.

Reduced and total homocysteine, cysteine, glutathione and cysteinylglycine in plasma were investigated in 19 patients with chronic obstructive pulmonary disease and in 29 healthy subjects. The purpose was to examine the influence of pro-oxidant activity caused by the lung disease on the metabolism of homocysteine and other plasma thiols. We observed a decreased concentration of reduced glutathione and a decreased ratio of reduced/total glutathione in the patients compared to the healthy individuals, which supports the hypothesis of an association between free radicals and pathogenesis in some lung diseases. We also observed an increased total plasma homocysteine. The influence of a possible extracellular pro-oxidant activity on the concentration of total plasma homocysteine is discussed.

Aged↗