Search PubMed⌕ Search

Biomedical subjects

A Lindgren

Publications and source records attributed to A Lindgren.

At least 91 records · Page 5Linked to original sources

Paraffin tissue block radiography of nonpalpable lesions with calcifications detected at mammography: 5-year consecutive series of surgically excised cases.

The objective of our study was to evaluate paraffin tissue block radiography following biopsy for breast calcifications at a center for population-based mammography screening. During a 5-year period, we radiographed tissue blocks from 259 breast specimens excised because of nonpalpable calcifications. A total of 124 cases were examined retrospectively and 135 cases were examined prospectively. In 34 of 94 (36 %) retrospectively examined cases with calcifications, the histopathological diagnosis was ductal cancer in situ with or without invasive cancer, compared with 3 of 30 (10 %) cases without calcifications. In 6 cases a primary benign histopathological diagnosis was changed to malignant due to the use of tissue block radiography. Tissue block radiography is a valuable adjunctive method to assure that areas containing calcifications are examined by histopathology.

Breast↗

Addition of calcium to Euro-Collins solution is essential for 24-hour preservation of the vasculature.

BACKGROUND: Genuine Euro-Collins solution is calcium free. The aim of this study was to investigate whether the addition of calcium would improve its capacity to preserve the vasculature. METHODS: The infrarenal aorta of Sprague-Dawley rats was investigated in organ baths: as fresh controls, after 24 hours of cold (4 degrees C) storage in Euro-Collins solution, or in Euro-Collins solution with the addition of calcium in amounts ranging from 0.05 to 1.5 mmol/L. The thromboxane analogue U-46619 was used to investigate contractility. Endothelium-dependent relaxation was tested by cumulative addition of acetylcholine. Papaverine was used to elicit endothelium-independent relaxation. Investigation by transmission electron microscopy was also performed. RESULTS: Storage of rat aorta for 24 hours in genuine Euro-Collins solution almost abolished smooth muscle function, and severe edema was found in the endothelial cells. However, if calcium was added, the rat aorta could be stored for 24 hours without affecting smooth muscle function, and endothelium-dependent relaxation was only slightly reduced. Furthermore, only slight edema could be demonstrated in the endothelial cells. CONCLUSIONS: If calcium is added to Euro-Collins solution in amounts ranging from 0.4 to 1.5 mmol/L, it allows good preservation of rat aorta for 24 hours. Without calcium, this solution destroys both the function and morphology of the vessels.

Animals↗

Mammographic screening for breast cancer. What cancers do we find?

The aim of this study was to compare lymph node involvement of breast cancer cases detected at mammography screening with clinically-detected cases. During a 3-year period, 273 primary breast cancers were detected in a population-based screening programme, and 149 primary breast cancers were diagnosed clinically. Lymph node involvement was evaluated in univariate and multivariate logistic regression models correcting for tumour size, histological grade, steroid receptor status and DNA-ploidy. Patients with screen-detected cancers had a low relative risk of having lymph node metastases (univariate, OR = 0.31; 95% confidence interval = 0.19-0.52). In the multivariate logistic regression model, the relative risk was halved (OR = 0.47; 0.28-0.78). The reduced risk was more pronounced for women younger than 50 years of age compared to older women. The risk for screen-detected cases of having lymph node metastases at diagnosis was statistically significantly lower than for clinically-detected cases. The marked reduction, even when correcting for tumour size, makes it less likely that factors such as detection of clinically innocent tumours, length bias sampling or clinical symptoms related to axillary metastases can explain the whole difference. The results indicate at least part of the effect may be explained by tumour progression in the late preclinical detectable phase.

Adult↗

Risk factors for local recurrence after conservative treatment in stage I breast cancer. Definition of a subgroup not requiring radiotherapy.

BACKGROUND: Risk factors for local recurrence after breast-conserving treatment of early breast cancer have not previously been evaluated in settings where mammography has been a major pathway to diagnosis of both primary tumour and recurrences or in patients treated surgically by a formal sector resection. PATIENTS AND METHODS: Three hundred eighty-one women with stage 1 primary breast cancer were randomised after a standardised sector resection to either a course of postoperative radiotherapy to 54 Gy to the breast (XRT group) or to surgery alone (non XRT group). At five years, 43 local recurrences, six of them in the XRT group, appeared. Patient characteristics collected from the medical records, histopathological characteristics determined by re-examination of slides, and mammographic characteristics from the pre-operative mammograms were evaluated as risk factors for recurrence by univariate and multivariate Cox proportional hazards models. Results are reported as relative hazards (RH) with 95% confidence intervals (95% CI). RESULTS: In the univariate analysis comedo cancer, RH 3.5 (95%, CI 18 6.7), lobular cancers RH 2.8 (95% CI 1.1 7.1), mammographic appearance as circular/oval shaped density, RH 2.3 (95% CI 1.1 4.51, and mammographic appearance as a stellate lesion with microcalcifications inside the lesion, RH 3.8 (95% CI 1.1-13.0) were identified as risk factors for local recurrence. Age, with a RH of 0.97 (95% CI 0.94 0.99) for each increasing year was inversely associated with risk. A multivariate analysis, which also took postoperative radiotherapy into account, only showed comedo cancers with a RH 2.6 (95% CI 1.3-5.0) and mammographic appearance of a stellate lesion with microcalcification inside the lesion RH 4.5 (95% CI 1.1-17.6) to be statistically significant. The estimates for age RH 0.98 (95% CI 0.95 1.01 and lobular cancers RH 2.5 (95%, CI 0.98 6.6) were marginally changed, with widened CIs. Patients > 60 years of age, without comedo or lobular carcinomas were found to be at low risk 15.9% at five years in Kaplan Meyer estimate) of local recurrence, even without postoperative radiotherapy. CONCLUSION: Low age, comedo and lobular cancers and mammographic appearance of the tumour as a stellate lesion with microcalcifications inside the lesion indicate an increased risk for local recurrence after sector resection in stage 1 tumours at five years. Patients > 60 years of age without comedo or lobular cancers are at low risk for local recurrence at five years even without postoperative radiotherapy.

Combined Modality Therapy↗

Paracetamol-induced cholestatic and granulomatous liver injuries.

OBJECTIVE: To describe uncommon (previously unreported) types of adverse liver reactions to paracetamol. DESIGN: In addition to describing patients, with uncommon types of liver reactions to paracetamol, admitted to our hospitals, we surveyed all the liver reactions to paracetamol reported to the Swedish Adverse Drug Reactions Advisory Committee from 1973 to 1993. SETTING: The Swedish population of 8 million inhabitants. MEASUREMENT: Extensive medical evaluation. RESULTS: We found one case with a cholestatic liver reaction and one with granulomatous hepatitis. The reactions were probably idiosyncratic and took several months to disappear. CONCLUSION: In addition to the well-known dose-related toxic liver damage paracetamol may rarely cause non-dose-related severe, prolonged cholestasis or granulomatous hepatitis with cirrhosis.

Acetaminophen↗

The perfusion fraction in volunteers and in patients with ischaemic stroke.

The fractional volume of capillary blood, i.e. the perfusion fraction f, was measured with the aid of an echo-planar imaging protocol originally designed for the measurement of water diffusion. In healthy volunteers, reasonable f values were obtained. In patients with cerebral ischaemic stroke, a marked decrease in the f value was seen in the infarcted region as compared with corresponding values in the contralateral hemisphere. We suggest that perfusion-fraction measurements may add to the diagnostic value of water-mobility examinations in patients with ischaemic disease.

Adult↗

Schilling and protein-bound cobalamin absorption tests are poor instruments for diagnosing cobalamin malabsorption.

OBJECTIVES: To assess the advantage of a protein-bound cobalamin absorption test (PBAT) over the Schilling test in patients with suspected cobalamin (vitamin B12) malabsorption. DESIGN: Clinical study of consecutive patients referred from primary care units, medical and neurological clinics. SETTING: The catchment area of Sahlgrenska University Hospital, Göteborg. SUBJECTS: Referred patients (n = 155) with suspected cobalamin deficiency and at least one serum cobalamin value < 200 pmol L-1. INTERVENTIONS: All patients were investigated with upper gastrointestinal endoscopy with biopsies taken from the gastric body and duodenal mucosa. Serum methylmalonic acid (MMA) and homocysteine (Hcy) were determined in all 109 patients not on cobalamin substitution. A dual isotope cobalamin absorption test was then performed with the concomitant administration of crystalline (Schilling) and protein-bound cobalamin (PBAT). MAIN OUTCOME MEASURES: Number of patients with gastric body atrophy diagnosed with each absorption test and the relation between these results and functional cobalamin deficiency defined as elevated MMA and Hcy, that normalized after cobalamin substitution treatment. RESULTS: The majority of patients with abnormal absorption tests had already developed elevated MMA and/or Hcy. PBAT was more sensitive than the Schilling test in identifying patients with gastric body atrophy but the sensitivity was too low for clinical use. About 1/3 of the patients with gastric body atrophy and normal absorption tests had elevated MMA and/or Hcy, indicating cobalamin deficiency. CONCLUSION: PBAT may be somewhat more sensitive than the Schilling test but neither test is sensitive enough for diagnosing cobalamin malabsorption at an early stage.

Adult↗

Perimetric probability maps to separate change caused by glaucoma from that caused by cataract.

We describe a new method for analysis of change in glaucomatous visual fields with the object to differentiate between changes caused by glaucoma from those caused by cataract. New pattern deviation change probability maps were developed from a prospectively collected glaucoma material and designed to be sensitive to changes in localized field loss, but to be unaffected by media-induced perimetric change. We compared the new change probability maps with the commercially available total deviation change probability maps in series of Humphrey perimetric tests in a glaucoma material of 43 eyes of 35 patients, who had undergone cataract surgery. When using the total deviation maps, considerable differences were seen between fields obtained before and after cataract surgery. Much smaller differences were seen when using the new change probability maps, that almost eliminated the common and disturbing effect of increasing cataract. This new tool could be of considerable help in differentiation between progressive glaucomatous visual field loss and deterioration caused by increasing media opacities.

Aged↗

The influence of mammography screening on the pathological panorama of breast cancer.

The pathologist describes the biological domain of breast cancer in which the clinician works. Over the last 20 years there have been indications that the biological domain has shifted following the introduction of fine-needle biopsies, clinical mammography, and later screening mammography. The most commonly used parameters for staging, classification and grading of cancer in some respects probably reflect the biological domain. We describe how the pathological panorama of breast cancer has changed with the introduction of population-based mammography screening. Our experiences are based on a consecutive series of 1961 breast cancers diagnosed from 1977 to 1994 in a region where screening mammography was introduced in 1988. All results, including histological classification and grading were prospectively registered in a computerized data base. There were more comedo than tubuloductal carcinomas and there was a corresponding preponderance of grade III tumours in the youngest and a high incidence of tubuloductal, lobular and colloid cancers in the oldest age group. The proportion of women with comedo carcinoma decreased after 1987. Looking at changes in the grade distribution after 1987, the proportion of women with grade I tumours increased and grade III tumours decreased in women over 50 years of age, but in the youngest women only marginal changes were noted. Very few in situ carcinomas were diagnosed in the prescreening period. About 11% of all tumours were in situ after 1987. The percentage of node-positive cancer decreased in the screening period in all histological types of cancer regardless of tumour size. The percentage of small tumours < or = 20 mm increased with time, though less so for comedo carcinomas. Comedo carcinomas dominate among the largest cancers most frequently detected clinically. From a biological standpoint it is interesting to note that screening seems to entail a larger shift in the biological domain in older as compared to younger women. Furthermore, comedo carcinomas seem to be less well detected by the screening procedure.

Adult↗

Marginal folate deficiency as a possible cause of hyperhomocystinaemia in stroke patients.

It has been reported that patients with vascular disease seem to increase their concentration of plasma homocysteine after the acute episode, whereas reexamined control subjects do not change their concentration of plasma homocysteine over time. Since the main determinants of plasma homocysteine are serum cobalamin, blood folate and serum creatinine we measured these quantities in 20 control subjects and 49 stroke patients in the acute phase and at reexamination 1.5-2 years after acute stroke onset. There were no significant differences between the levels of blood folate, serum cobalamin and serum creatinine in the acute and convalescent phase of all 49 stroke patients. However, we noted a significant decrease of blood folate concentrations in a subgroup of patients (n = 25) who had increased plasma homocysteine concentrations. Thus the increase in plasma homocysteine concentrations in this group of patients may partly be caused by a marginal folate deficiency.

Aged↗

Cardiac changes in stroke patients and controls evaluated with transoesophageal echocardiography.

In stroke patients several cardiac changes associated with embolism can be detected with transoesophageal echocardiography. Potential major cardiac embolic sources (e.g. atrial fibrillation, thrombi of left ventricle/atrium, vegetation, myxoma, dilated cardiomyopathy) have a causal relationship to embolism. Other changes with no certain causal relationship are regarded as potential minor cardiac embolic sources (e.g. atrial septal aneurysm, patent foramen ovale, mitral annular calcification, mitral valve prolapse, protruding atheroma of the aorta). We compared the prevalences of major and minor potential cardiac embolic sources in a stroke population with that in controls. One hundred and twenty-one patients with first-ever stroke were compared with 68 randomly selected controls. All subjects underwent magnetic resonance imaging of the brain, carotid ultrasound and transthoracic/transoesophageal echocardiography. The patients were slightly older (mean age 70.7 +/- 10.3 years) than the controls (65.5 +/- 15.5 years) (p < 0.05). Potential major cardiac embolic sources were found in 27% of the patients and in 4% of the controls (p < 0.001). The most common major potential embolic source was atrial fibrillation, detected in 22/121 patients. Fifteen of these also had spontaneous echocontrast in the left atrium. Eleven left atrial thrombi were found (four of these patients had atrial fibrillation and seven had sinus rhythm). A history of heart disease was more common in patients with a potential major cardiac embolic source or a carotid artery stenosis (77%) than in those patients without (44%) (p < 0.01). After excluding subjects with a major potential cardiac embolic source and/or carotid artery stenosis, no differences in the prevalence of minor potential cardiac embolic sources were found between patients (55%) and control subjects (47%) (p = NS). Even when subjects without a major potential cardiac embolic source or a carotid artery stenosis were categorized into three age groups (35-54, 55-74 and > 74 years) the prevalence of potential minor cardiac embolic sources did not differ between patients and controls. To conclude, major potential cardiac embolic sources are more common in an older population with first-ever stroke than in a comparable control group. However, potential minor cardiac embolic sources did not differ in prevalence in the patients compared with controls. Certain changes (e.g. atrial septal aneurysm) might have a potential embolic role in younger stroke patients but in our study no difference was found between older stroke patients and controls.

Acute Disease↗

The p53 gene in breast cancer: prognostic value of complementary DNA sequencing versus immunohistochemistry.

BACKGROUND: Mutations in the p53 tumor suppressor gene (also known as TP53) have been detected in a wide variety of human cancers. In breast cancer, the presence of p53 gene alterations has been associated with worse prognosis. PURPOSE: We compared a complementary DNA (cDNA)-based sequencing method and an immunohistochemical (IHC) method for their abilities to detect p53 mutations in breast cancer specimens. In addition, we determined the prognostic value of information obtained when these two methods were used. METHODS: Specimens from 316 primary breast tumors were evaluated for the presence of mutant p53 protein by use of the mouse monoclonal antibody Pab 1801 (that recognizes both wild-type and mutant forms of p53) and standard IHC methods. In addition, the entire coding region of p53 genes expressed in these tumors was screened for mutations by combining reverse transcription, the polymerase chain reaction, and DNA sequencing. Probabilities for overall survival (OS), breast cancer-corrected survival (BCCS; death from breast cancer is the considered event), and relapse-free survival (RFS) were estimated by use of the Kaplan-Meier method, and survival curves for different patient subgroups were compared by use of the logrank method. All reported P values are from two-sided tests. RESULTS: Sixty-nine (22%) of 316 tumors had p53 gene mutations detected by the cDNA-based sequencing method; only 31 (45%) of these mutations were located in evolutionarily conserved portions of the p53 coding region. Sixty-four tumors (20% of the total) had elevated levels of p53 protein as detected by IHC, suggesting the presence of mutations. Of the sequencing-positive tumors (i.e., p53 mutant), 23 exhibited negative IHC reactions, indicating that IHC failed to detect 33% of the mutations. Furthermore, 19 of the IHC-positive tumors were sequencing negative (i.e., p53 wild-type), suggesting a 30% false-positive frequency with IHC. Four tumors (1.3% of the total) could not be analyzed by the cDNA-based sequencing method, and three tumors (1% of the total) could not be analyzed by IHC. The 5-year estimates for RFS, BCCS, and OS were significantly shorter for patients with p53 sequencing-positive tumors than for patients with sequencing-negative tumors (P = .001, P = .01, and P = .0003, respectively). Patients with IHC-positive tumors showed reduced survival in all three categories when compared with those with IHC-negative tumors, but the differences were not statistically significant. CONCLUSIONS: Use of a cDNA-based sequencing method to determine the status of the p53 gene in primary breast cancers yielded better prognostic information than IHC performed with the Pab 1801 monoclonal antibody.

Adult↗

Plasma beta-hexosaminidase isoenzymes A and B in patients with cerebral infarction.

We determined plasma activity of the isoenzymes of beta-hexosaminidase (Hex) in 151 patients with cerebral infarction, since earlier findings have shown a relation between Hex isoenzymes and risk factors for vascular disease in normal subjects. Compared with 206 control subjects, an elevated level of plasma Hex isoenzymes was found in patients with cerebral infarction, particularly females. However, there was no relation to the clinical subtypes of diagnosis or to the presence of any risk factors for vascular disease, such as carotid artery stenosis, major potential cardio-embolic risk factors on echocardiography, hypertension, heart disease, diabetes mellitus or tobacco smoking. Instead, our findings indicate that Hex isoenzymes in patients with cerebral infarction are more influenced by the level of serum aspartate aminotransferase and blood glucose. The main conclusion is that the liver function as reflected by the level of liver enzymes and glucose metabolism are the major determinants of Hex isoenzymes in plasma.

Aged↗

Prognostic characteristics in breast cancers after hormone replacement therapy.

We examined the influence of hormone replacement therapy (HRT) on breast tumour biology by comparing the prognostic characteristics of breast cancers and survival in 121 women prescribed replacement hormones before diagnosis with those in 1468 women without such treatment. The women receiving HRT had a lowered relative risk of being diagnosed with tumours of more than 20 mm in diameter, OR = 0.7 (CI 0.5-1.0) and axillary lymph node dissemination, OR = 0.7 (CI 0.4-1.1). These risk reductions were most pronounced and statistically significant in the women who had been prescribed a combined estradiol-progestin regimen. The patients in this compound group also had a diminished relative risk of having poorly differentiated tumours. Further, there was an indication that the women prescribed HRT, and especially those with conjugated estrogens/estradiols alone, had a decreased relative risk of developing aneuploid tumours. There was no clear pattern for women receiving the biologically weak oestriol, although risk estimates were generally higher for unfavourable tumours in comparison with those receiving the higher potency compounds. Adjustments for indications of earlier detection (i.e. lead time bias) did not influence the pattern or magnitude of the risk estimates. No association between any type of HRT and survival after breast cancer diagnosis was noted, but analyses were based only on 19 breast cancer deaths among exposed patients. We conclude that breast cancers occurring after treatment with HRT, especially the combined estrogen-progestin regimen, seem to have more favourable tumour features than tumours in non-treated women. Our findings may reflect a less aggressive biological behaviour of breast cancers in women receiving HRT, or in part be explained by the earlier detection of the tumours in these women.

Aged↗

Potential cardioembolic sources in an elderly population without stroke. A transthoracic and transoesophageal echocardiographic study in randomly selected volunteers.

Transoesophageal echocardiography renders a better image than transthoracic echocardiography of cardiac changes especially at the atrial level, and of atherosclerotic changes in the aorta. Although several studies on stroke patients have included transthoracic and transoesophageal echocardiography, the relevance of the reported findings remains unclear because of limited information on the prevalence of cardiac changes related to cardioembolism in a control population without stroke. In order to define a non-hospitalized group of volunteers without previous stroke or transient ischaemic attack, we randomly selected a group of 68 volunteers (mean age 65.4 years). These volunteers were divided into two groups: the elderly group, 65 years or older (n = 38) and the younger group, younger than 65 years (n = 30). The subjects underwent transthoracic and transoesophageal echocardiography, sonography of the carotid arteries, and magnetic resonance imaging of the brain. The prevalences of atrial septal aneurysm, patent foramen ovale, mitral annulus calcification, and protruding plaque in the aorta were investigated. We found atrial septal aneurysm in 13%, patent foramen ovale in 22%, protruding plaque in the aorta in 7%, and mitral annular calcification in 22% of the 68 subjects. No significant differences were found between the two age groups with the exception of mitral annular calcification, which was seen more often in the older group (P < 0.001). Total cardiac changes related to thromboembolism (including three cases with atrial fibrillation in the older group and other less common cardiac embolic sources) were more common in the older than in the younger group (23/38 vs 9/30; P < 0.05). If mitral annular calcification was excluded, no difference was found between the elderly and the younger group, 14/38 vs 8/30; ns. Even when subjects with a history of heart disease or a pathological ECG were omitted, no differences between the two age groups were found. The causal relationship between a possible embolic source and a clinical embolic event remains unsettled. The high prevalence of cardiac changes in a control population has to be considered when evaluating the significance of similar findings in patients with stroke.

Adult↗

Carcinoma of the endometrium: do the nuclear grade and DNA ploidy provide more prognostic information than do the FIGO and WHO classifications?

The aim of this study was to compare the World Health Organization (WHO), the International Federation of Gynecology (FIGO), and nuclear grading systems and to evaluate their reproducibility, as well as their prognostic impact, in relation to clinical variables and DNA ploidy. The study comprised 266 women with endometrial carcinoma in clinical stages I-IV. Low-risk patients, i.e., patients with grade 1-2 tumors in clinical stage I, were generally not included. In univariate Cox analyses, WHO, FIGO, and especially nuclear grading (p < 0.001), as well as age, stage, and ploidy, were prognostic regarding survival. In the multivariate Cox analyses, WHO and FIGO grades yielded little further independent information beyond nuclear grade. When DNA ploidy was added to the analyses, nuclear grade lost most of its impact because aneuploidy was a powerful factor (p < 0.001) that covaried with nuclear grade. The WHO, FIGO, and nuclear grading systems were found to be subjective, with correlation coefficients of approximately 0.60 between different pathologists. Age, stage, and aneuploidy were the most important predictors of outcome in the multivariate analyses. Nuclear grade was a strong prognostic factor in the univariate analyses and a more important indicator than the commonly used histopathological grading systems.

Adult↗