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Biomedical subjects

A Lindgren

Publications and source records attributed to A Lindgren.

At least 109 records · Page 6Linked to original sources
PubMed1996

Hyperhomocysteinaemia--a common finding in a psychogeriatric population.

Plasma homocysteine concentration is a sensitive marker for cobalamin and folate deficiency. The previously reported high incidence of increased plasma homocysteine in psychogeriatric patients and the association between reduced concentrations of cobalamin, folate and neuropsychiatric symptoms led to the present study on 741 consecutive psychogeriatric patients. The concentrations of plasma homocysteine correlated significantly with blood folate, serum cobalamin and serum creatinine both in demented (n = 295) and in non-demented patients with other psychiatric disorders (n = 215). Plasma homocysteine concentrations were significantly increased in both the demented and the non-demented patients, whereas only the demented patients had lower blood folate and serum creatinine concentrations than 163 control subjects. Almost all of the different diagnostic groups of demented and non-demented patients exhibited significantly increased plasma homocysteine concentrations compared with control subjects. Significantly decreased blood folate concentrations were mainly found in the different diagnosis groups of demented patients. Plasma homocysteine concentrations in both demented and non-demented patients with serum cobalamin and blood folate above the lower 20th percentile of these vitamins in the control subjects were also studied. Despite these vitamin concentrations, both groups of patients still exhibited significantly higher plasma homocysteine concentrations than the control subjects, which may indicate an increased frequency of impaired genetic capacity to metabolize homocysteine in these patients. Patients with either dementia of vascular cause or a history of other occlusive arterial disease had a significantly higher plasma homocysteine concentration than those without a history of vascular disease.

Aged↗
PubMed1996

Tissue plasminogen activator and plasminogen activator inhibitor-1 in stroke patients.

BACKGROUND AND PURPOSE: Abnormal endogenous fibrinolytic activity may be a risk factor for stroke. Since the possible variation of tissue-type plasminogen activator (TPA) antigen and plasminogen activator inhibitor-1 (PAI-1) antigen concentrations over time after stroke has been rarely studied, it was examined in plasma from stroke patients in the acute and convalescent phases of the disease and in a control group. METHODS: Plasma concentrations of TPA and PAI-1 were determined in 135 stroke patients and in 77 control subjects. All but 4 patients were examined within 7 days after stroke onset, and 32 patients and 18 control subjects were reexamined 2 to 4 years later. RESULTS: In the acute phase, stroke patients had significantly higher TPA (median, 10 micrograms/L) and PAI-1 (median, 14 micrograms/L) antigen concentrations, compared with control subjects (median values, 6 micrograms/L [P = .0001] and 8 micrograms/L [P < .01], respectively); TPA levels were higher in both the cerebral infarction (n = 122) and cerebral hemorrhage (n = 12) subgroups, whereas PAI-1 levels were higher in the cerebral infarction subgroup only. Stepwise logistic regression analysis (with correction for age, sex, history of hypertension, diabetes mellitus, and heart disease) showed TPA antigen level to be an independent discriminator between the cerebral infarction subgroup and control subjects (P = .0001), whereas the corresponding difference for PAI-1 antigen levels just failed to reach significance (P = .05). TPA antigen levels were correlated with concentrations of serum cholesterol (Spearman's rho = 0.15; P < .05), serum triglyceride (rho = 0.33; P = .0001), and plasma homocysteine (rho = 0.19; P < .01). PAI-1 antigen levels were correlated with serum triglyceride levels only (rho = 0.41; P = .0001). At reexamination after 2 to 4 years, neither TPA nor PAI-1 levels had changed significantly from the baseline values. CONCLUSIONS: In stroke patients, high TPA antigen concentrations may indicate an activation of the fibrinolytic system or may be due to a delayed clearance of TPA complexed with inhibitors. High PAI-1 antigen concentrations in patients with cerebral infarction represent increased fibrinolytic inhibition. The findings in this longitudinal study suggest that TPA and PAI-1 antigen concentrations both differ little between the acute and convalescent phases after stroke.

Acute Disease↗
PubMed1996

beta-Hexosaminidase isoenzymes A and B in middle-aged and elderly subjects: determinants of plasma levels and relation to vascular disease.

Plasma/serum beta-hexosaminidase (Hex) activity is known to be increased in chronic alcoholism, liver disorders, pregnancy and diabetes mellitus. Hex activity also shows an association with risk factors for vascular disease and heredity for arteriosclerosis. There are several isoenzymes of Hex. Using an enzyme immunoassay for Hex isoenzymes (Hex A and Hex B) we studied possible determinants of Hex isoenzymes and their relation to vascular disease in randomly invited (n = 244) 35-95-year-old men and women. In both sexes there were significant age-related increases in Hex activities and men exhibited higher activity of both isoenzymes. Both Hex isoenzymes correlated with age, systolic blood pressure, serum triglycerides and liver enzymes, whereas Hex A was distinguished from Hex B by its stronger correlation with blood glucose. In multiple linear regression analysis Hex A was explained to 20.7% by blood glucose, age, serum aspartate aminotransferase and glutamyl transpeptidase. Hex B was explained to 14% by age, serum glutamyl transpeptidase and serum triglycerides. There was no significant increase in Hex isoenzymes in subjects with hypertension, diabetes mellitus or myocardial disease, nor did current smokers exhibit any increase of these enzymes compared to non-smokers. The main conclusion in that liver function, as reflected by the level of liver enzymes and glucose metabolism, is the major determinant for Hex isoenzymes in plasma.

Adult↗
PubMed1996

Can endoscopic biopsy specimens be used for reliable Laurén classification of gastric cancer?

BACKGROUND: The aim of this study was to ascertain whether routine endoscopic biopsy specimens are of sufficient quality and representative enough to enable reliable classification of histologic type, grade of differentiation, and frequency of signet ring cells. METHODS: As part of a population-based etiologic study of gastric cancer in Sweden, the histologic slides of 687 incident cases were independently reviewed by one pathologist. In 305 cases both biopsy and surgical specimens were available for assessment of sensitivity and specificity of diagnoses on the basis of biopsy specimens, with the classification based on surgical specimens as the gold standard. RESULTS: The sensitivity and specificity of the diagnoses on the basis of biopsy specimens was 86% and 82%, respectively, for detecting the intestinal type, and 87% and 90%, respectively, for the diffuse type of gastric cancer. The percentage agreement between biopsy and surgical specimens with regard to grade of differentiation was 71%. CONCLUSIONS: This study shows that misclassification of Laurén type due to random intraobserver variation needs to be taken into account in epidemiologic studies. The degree of misclassification appears to be of similar magnitude regardless of the source material.

Adenocarcinoma↗
PubMed1996

Prevalence of Crohn's disease and simultaneous occurrence of extraintestinal complications and cancer. An epidemiologic study in adults.

BACKGROUND: Very dissimilar prevalence figures for Crohn's disease (CD) have been reported from different regions of Scandinavia. There are few reports on the occurrence of liver, joint, skin, and eye disease and gastrointestinal cancer in CD. METHODS: All patients > or = 16 years old with CD living in a well-defined catchment area on 1 March 1990 were identified from the previous 10 years' registers of inpatients and outpatients. The records were screened for evidence of extraintestinal complications and fistulas. RESULTS: The prevalence of CD was 94/10(5) (95% confidence interval, 84-104) inhabitants > or = 16 years old. Signs of liver disease were encountered in 1 of 10 patients, and other extraintestinal complications and intestinal cancer occurred in 1-3%. The true prevalence of primary sclerosing cholangitis could not be assessed. CONCLUSION: The prevalence of CD was midway between recent figures from Orebro and Copenhagen. Fistulas and pathologic liver laboratory test results were more prevalent when CD involved both the large and small bowel.

Adolescent↗
PubMed1996

Overview on human breast cancer with focus on prognostic and predictive factors with special attention on the tumour suppressor gene p53.

A long list of potential prognostic markers has been analysed for breast cancer, some of them will be reviewed in this article. The lymph node status is still the best prognostic marker. The lymph node status combined with information on tumour size, receptor- and proliferation status of the tumour should be analysed as standard for all breast cancer patients. Prognostic information for breast cancer patients has also been described for the membrane protein c-erbB2, the protease cathepsin D, plasminogen activators and inhibitors, certain oncogenes and tumour suppressor genes. Some of these factors also give potential additional information on the response to different oncological therapies, and are better denoted predictive factors. In this overview we shortly describe the above mentioned prognostic factors with major focus on the tumour suppressor gene p53 and its prognostic value and potential predictive value.

Apoptosis↗
PubMed1995

Reproducibility in DNA flow cytometric analysis of breast cancer: comparison of 12 laboratories' results for 67 sample homogenates.

Flow cytometric (FCM) DNA analysis yields information on ploidy status and the S-phase fraction (SPF), variables of prognostic importance in breast cancer. The clinical value of the SPF is currently being evaluated in prospective randomized trials. The widespread use of FCM DNA analysis emphasizes the importance of reproducibility (both intra- and interlaboratory). In this study, 67 nuclear suspensions of breast cancer samples were analyzed by 12 laboratories routinely performing FCM DNA analysis in breast cancer. No general guidelines were imposed; each laboratory used its own standard protocols. For DNA ploidy status (diploid vs. non-diploid), agreement was complete for 79% (53/67) of the samples, compared with 64% (43/67) of samples when tetraploidy was considered [i.e., euploid (diploid+tetraploid) vs. aneuploid (the remaining non-diploid)]. For the SPF, pairwise comparison of the results of all 12 laboratories yielded a mean Spearman's rank correlation of 0.78 (range: 0.54-0.93). For those 39 samples being categorized in low or high SPF by all laboratories, all agreed in 14 samples (36%). Similar patterns were obtained with kappa measures, agreement being good for ploidy status (diploid vs. non-diploid; overall kappa = 0.87 and 0.74 for euploid vs. aneuploid), but moderate for the SPF [overall kappa = 0.47 (for low SPF vs. high SPF vs. "no SPF reported")]. Discrepancies were chiefly attributable to differences in the categorization of the S-phase values, rather than in FCM procedures, other critical differences being in the detection and interpretation of near-diploid and small non-diploid cell populations, the definition of tetraploidy, and the choice and execution of the method used for S-phase estimation. Based on the observations of this study, detailed guidelines for FCM analysis and interpretation of data are proposed in the Appendix. Some issues remain, however, e.g., to standardize a method for S-phase calculation and tetraploid definition.

Breast Neoplasms↗
PubMed1995

Prevalence of Helicobacter pylori infection in subtypes of gastric cancer.

BACKGROUND & AIMS: Although Helicobacter pylori has already been declared a human carcinogen, the exact nature of the association with gastric cancer remains to be explored. The aim of this study was to determine if the association is confined to specific types of gastric cancer. METHODS: The prevalence of H. pylori immunoglobulin G antibodies (HM-CAP immunoassay; Enteric Products Inc., Westbury, NY) was determined in prospectively collected sera from 279 patients with gastric cancer. RESULTS: The overall prevalence of H. pylori seropositivity was 77%. The prevalence of H. pylori infection was significantly lower among patients with tumors of the gastric cardia compared with those with other gastric locations. Age-adjusted H. pylori seroprevalence among patients with the intestinal type of gastric cancer tended to be higher than among those with the diffuse type according to Laurén (P > 0.05). In both histological types, the seroprevalence decreased with increasing age. Multivariate logistic regression analysis showed that high age and proximal tumor location were independent predictors of absence of H. pylori. CONCLUSIONS: The association with H. pylori infection is similar regardless of the histological features of the tumor, whereas it is stronger for noncardiac gastric cancer than for cardiac cancer. The apparent loss of H. pylori seropositivity among patients with gastric cancer is determined by age rather than tumor stage.

Age Factors↗
PubMed1995

Expression of the 85-kd membrane protein in primary human breast cancer: relationship to hormone receptor levels, DNA ploidy, and tumor grade.

Using the monoclonal antibody (MAb) MRK20 the immunohistochemical expression of the 85-kd membrane protein (MP)/cell adhesion molecule (CAM) CD36 was investigated in tumors from 41 patients with untreated breast adenocarcinoma. DNA ploidy as measured by flow cytometry and estrogen (ER) and progesterone receptor (PgR) tumor contents also were determined. Immunohistochemistry on frozen tissue showed expression of 85-kd MP localized to the carcinoma cells in tumors from 16 patients (39%). These samples also displayed variable staining of the capillary endothelium. Twenty-one samples (51%) showed 85-kd MP expression in small blood vessels. Thus, a total of 37 of 41 tumors (90%) were MAb MRK20 positive in carcinoma and/or mesenchymal cells. Expression of 85-kd MP in carcinoma cells was negatively associated with expression of ER (P < .05) and PgR (P < .01) receptors and positively associated with nondiploid tumors (P < 0.05) and tumor grade (P < .05). Axillary lymph node status, tumor size, and (patient) age were not associated with expression of 85-kd MP. In cytological smears obtained by fine-needle aspiration (FNA) cytology from 19 of the samples, expression of 85-kd MP in carcinoma cells showed a good correlation with tumor cell positivity in the corresponding histological section. Expression of 85-kd MP in breast carcinoma cells thus was associated with some recognized adverse prognostic factors. Future studies of its pathophysiological and prognostic roles in breast cancer seem warranted.

Adenocarcinoma↗
PubMed1995

Cerebral complications after cardiac surgery assessed by S-100 and NSE levels in blood.

OBJECTIVE: Assessment of the value of blood analysis of the astroglia protein, S-100, and neuron-specific enolase for the detection of nervous system dysfunction after cardiac surgery. DESIGN: Prospective study. Neurologists blinded from laboratory results. SETTING: University hospital. PARTICIPANTS: 38 patients undergoing cardiac surgery. INTERVENTIONS: 21 patients were operated for coronary artery disease; seven patients with replacement of the aortic valve of whom 2 also had coronary bypass. Four patients had mitral valve replacement of whom 2 also had coronary bypass. One patient had both aortic and mitral valve replacement and coronary bypass. Two patients were operated on because of aortic arch aneurysm. MEASUREMENTS AND MAIN RESULTS: Neurologic examinations were performed before and after surgery. General behavior of the patients was repeatedly assessed. Blood samples for analysis were collected before operation and on the second day after surgery. In 8/38 patients (21%), a neurologic complication, one of which was lethal, occurred. In 27 patients (71%), the neurologic outcome was uncomplicated, and in 3 (8%), it could not be classified. Elevated S-100 and neuron-specific enolase levels were found in 7/8 patients who endured a neurologic complication and in 4/27 free of complication. (Fisher's exact test p < 0.001). Positive and negative predictive values were 64% and 96%, respectively. S-100 (range 0.5 to 1.3 micrograms/L) and neuron-specific enolase levels (range 8.6 to 16.7 micrograms/L) were lower for the 7 patients with nonlethal complications than for the patient who died (9.5 micrograms/L and 31.3 micrograms/L, respectively). CONCLUSIONS: S-100 and neuron-specific enolase levels after cardiac surgery are associated with neurologic complications. The results have implications on patient-related treatment and prognosis as well as for the development of safer perfusion techniques.

Aged↗
PubMed1995

Complete sequencing of the p53 gene provides prognostic information in breast cancer patients, particularly in relation to adjuvant systemic therapy and radiotherapy.

The complete coding region of the p53 gene was sequenced from 316 consecutively presented breast cancers, of which 97 were lymph node positive and 206 were node negative. The p53 status was related to prognosis and effect of adjuvant therapy. In all, 69 individual mutations, 29 in node-positive tumours, were demonstrated throughout the whole coding sequence. The mutation sites were partly different for node-positive and node-negative patients. p53 mutations in the evolutionary conserved regions II and V were associated with significantly worse prognosis. Adjuvant systemic therapy, especially with tamoxifen, along with radiotherapy seemed to be of less value to p53 mutation- and lymph node-positive tumours.

Amino Acids↗
PubMed1995

Protein-losing enteropathy in an unusual form of sarcoidosis.

We describe a case of sarcoidosis associated with great gastrointestinal loss of proteins. It was hypothesized that the loss was caused by involvement of sarcoidosis in the gastrointestinal tract. The patient was a 39-year-old woman with sarcoidosis diagnosed at age 32 years. The protein-losing enteropathy was identified by the use of [51Cr]-albumin. An extensive investigation was performed, with biopsy specimens taken from all parts of the gastrointestinal tract, using upper gastrointestinal endoscopy, colonoscopy and the Crosby capsule technique. We could find no support for our hypothesis that the leakage of proteins was caused by involvement of sarcoidosis in the gastrointestinal tract. Thus, mechanisms other than direct inflammatory involvement of the gastrointestinal mucosa probably caused protein-losing enteropathy in this patient.

Adult↗
PubMed1995

Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid.

OBJECTIVES: Moderate hyperhomocysteinaemia is an independent risk factor for cardiovascular disease which may be causal. We investigated whether the concentration of plasma homocysteine changes between the acute phase of myocardial infarction and follow-up, and whether treatment with oral folic acid was effective in lowering homocysteine levels in patients with myocardial infarction. DESIGN AND SUBJECTS: Plasma total homocysteine levels 24-36 h (baseline) after onset of acute myocardial infarction were compared with the levels obtained at 6 weeks' follow-up and with the levels in the controls. In the same patients, we studied the effect on plasma homocysteine of 6 weeks' treatment with daily oral folic acid doses of 2.5 or 10 mg compared to no treatment. RESULTS: At baseline, 12 of 68 patients (18%) had moderate hyperhomocysteinaemia (> 17.3 mumol L-1; P < 0.05). Between baseline and follow-up, plasma homocysteine levels increased from 13.1 +/- 4.6 to 14.8 +/- 4.8 mumol L-1 (mean +/- SD; P < 0.001). Treatment with nitroglycerin, streptokinase, beta blockers, or acetylsalicylic acid seemed not to have caused this change. Folic acid lowered plasma homocysteine in all but two of 33 treated patients with a mean decrease of 4.4 mumol L-1 (-27%; P < 0.001). There was no difference between the effect of 2.5 and 10 mg of folic acid. In the untreated group (n = 20), plasma homocysteine increased with a mean increase of 0.6 mumol L-1 (+4%; P < 0.05). CONCLUSIONS: Plasma homocysteine seems to increase in the post myocardial infarction period, the cause of which warrants further study. Folic acid appears to be an effective treatment for the reduction of both normal and increased plasma homocysteine concentrations in patients with myocardial infarction. This suggests that folic acid should be used for intervention when studying the effect of homocysteine-lowering therapy on the risk on myocardial infarction.

Adult↗
PubMed1995

Plasma homocysteine in the acute and convalescent phases after stroke.

BACKGROUND AND PURPOSE: Stroke patients frequently manifest moderate hyperhomocysteinemia. In most published studies, plasma homocysteine was measured at least 1 month after stroke (or the interval was not reported). To determine whether plasma homocysteine concentrations change in the acute phase, we compared acute-phase values with both convalescent-phase and control values. METHODS: Plasma homocysteine concentrations were measured in the acute phase (mean, 2 days after stroke onset) in 162 first-ever stroke patients aged 50 years or more (median, 75 years) and again at a median interval of 583 days (range, 460 to 645 days) after stroke onset in a subgroup of 17 patients, with values for 60 age-matched subjects serving as controls. Twenty of the control subjects were reexamined 2 to 3 years after their initial examination. RESULTS: The median plasma homocysteine concentration was 13.4 mumol/L in the patient group compared with 13.8 mumol/L for control subjects (NS, Mann-Whitney U test) and increased from 11.4 mumol/L in the acute phase to 14.5 mumol/L in the convalescent phase in the subgroup of patients examined twice (P < .01, Wilcoxon signed rank test). In the 20 reexamined control subjects, no significant change over time in plasma homocysteine concentration was found. CONCLUSIONS: The post-acute-phase increase in plasma homocysteine may explain why higher values were obtained for stroke patients than for control subjects in previous studies. Possible reasons for the variation in plasma homocysteine concentrations over time are (1) an acute-phase reduction secondary to a decrease in plasma albumin and (2) an increase in plasma homocysteine during the convalescent phase due to modified vitamin intake and/or lifestyle. The timing of plasma homocysteine measurements relative to stroke onset is a factor to be considered in the interpretation of results.

Aged↗
PubMed1995

p53 Status predicts survival in breast cancer patients treated with or without postoperative radiotherapy: a novel hypothesis based on clinical findings.

PURPOSE AND METHODS: Primary breast cancer tumors without axillary metastases from 206 consecutive patients in a population-based cohort were investigated with regard to the presence of an intact p53 gene using a cDNA-based sequencing method. Clinical follow-up data and outcome of node-negative patients without any adjuvant systemic therapy (n = 168) were related to locoregional radiotherapy and p53 status. RESULTS: Mutations in p53 occurred in 31 node-negative breast cancer patients who did not receive any systemic adjuvant treatment, but were treated with postoperative locoregional radiotherapy or nothing. Node-negative breast cancer patients with p53 mutations had significantly improved relapse-free survival (P = .0007), breast cancer-corrected survival (P = .01), and overall survival (P = .02) rates when treated with locoregional radiotherapy. In node-negative breast cancer patients with wild-type p53, there was no statistically significant difference in outcome between patients who received locoregional radiotherapy and those who did not. Cox proportional hazards models indicate that mutant p53 is associated with worse prognosis independent of response to radiotherapy and that response to radiotherapy is qualitatively different in tumors with p53 mutations compared with those with wild-type p53. CONCLUSION: Our clinical findings define a group of breast cancer patients in whom locoregional radiotherapy improves relapse-free, breast cancer-corrected, and overall survival. The outcome for irradiated node-negative breast cancer patients with p53 alterations indicates that irradiation can induce cell death even in the presence of p53 mutations.

Adult↗
PubMed1995

Determination of cause of death among breast cancer cases in the Swedish randomized mammography screening trials. A comparison between official statistics and validation by an endpoint committee.

Between 1976 and 1982, four randomized mammography screening trials started in five screening centres in Sweden, involving 282,777 women (156,911 invited and 125,866 controls) with the aim to study if invitation to screening reduced the breast cancer mortality. An overview of the trials was performed to reduce the confidence intervals for the relative risk estimates. All 1,296 deaths occurring in women with breast cancer detected after randomization were evaluated by an independent endpoint committee (EPC), consisting of four physicians who reviewed collected medical information that was blinded regarding mammography screening. If there was disagreement between the EPC members at the initial individual evaluation the final classification was made at consensus meetings. In only 6.9% (n = 89) of the cases was there disagreement as to whether breast cancer was or was not the underlying cause of death. It was also found that 'breast cancer as underlying cause of death' and 'breast cancer as underlying or contributory cause of death' according to Statistics Sweden resulted in relative risk estimates very similar to those based on the classification by the EPC. The study thus supports the use of official health statistics in the evaluation of randomized breast screening trials in Sweden.

Adult↗
PubMed1995

Effect of thiol oxidation and thiol export from erythrocytes on determination of redox status of homocysteine and other thiols in plasma from healthy subjects and patients with cerebral infarction.

Changes in concentration of reduced and oxidized low-M(r) thiols were measured in blood and plasma before and after the separation of blood cells. If centrifugation of blood was postponed, the reduced form of homocysteine in plasma increased with time at 22 degrees C; in contrast, the concentrations of other reduced thiols (cysteine, glutathione, and cysteinylglycine) decreased. In plasma the reduced forms of all thiols disappeared at a rate that followed first-order kinetics. The rates of disappearance ("half-lives") were temperature-dependent; they were about the same for glutathione and homocysteine (11.7 and 14.3 min, respectively, at 22 degrees C) and somewhat higher for cysteinylglycine and cysteine. After establishing proper sampling conditions for reduced thiols, we measured this thiol fraction as well as free (non-protein-bound) and total thiols in 10 reference subjects and 19 patients with cerebral infarction. Mild but significant hyperhomocysteinemia involving total and free homocysteine (but not reduced homocysteine) was found in the patients.

Aged↗