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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 181 records · Page 10Linked to original sources

The cosmetic outcome in early breast cancer treated with sector resection with or without radiotherapy. Uppsala-Orebro Breast Cancer Study Group.

In a randomised trial, the cosmetic results after sector resection and axillary dissection with or without postoperative radiotherapy for early breast cancer were evaluated. The evaluations were made at 3, 12, 24 and 36 months (357, 326, 302 and 255 women, respectively) after treatment. Good to excellent cosmetic results were achieved in 84-90% of those in the group randomised to radiation and in 91-95% in the group allocated to surgery only, as judged by the women themselves, and in 81-86% and 87-93%, respectively, according to other observers. At 12 months the results in 290 patients were photographically documented and evaluated by a panel. The results were good to excellent in 35-84% of the irradiated group and in 62-93% of the non-irradiated group. Poor results followed the development of contour differences, breast oedema and mamillary deviation, which were the most important mediators of a poor cosmetic result after radiotherapy. We conclude that sector resection and axillary dissection can be performed with good cosmetic results. Doses to 54 Gy of radiotherapy influence the result negatively, but from a clinical standpoint to a moderate extent.

Adult↗

Failure to detect early breast cancer using in vitro nuclear magnetic resonance spectroscopy of plasma.

Water suppressed proton nuclear magnetic resonance (1H NMR) spectroscopy of human plasma has been described as successful in detection of malignancy. We designed a prospective study to test the hypothesis that in vitro NMR spectroscopy has a high sensitivity for detecting early breast cancer. One hundred and thirty-five women were referred for breast biopsy due to abnormal mammograms. One hundred of these were recruited through a population-based mammography screening project. Sixty-nine of 135 women were found to have breast cancer and their average line width of the methyl and methylene resonance in the plasma were compared to those women who had a benign or normal histopathology in the biopsy and to the line width for 100 healthy subjects from the same population. The mean line width at a half-height of the methyl and methylene resonances of the serum lipoprotein lipids in the NMR spectrum did not differ appreciably between the groups. The line width correlated highly with the serum triglycerides, but correction for the level of triglycerides did not improve the diagnostic accuracy of the line width. Receiver-operating characteristic analysis revealed a sensitivity of 61% and a false positive rate of 43% at the most beneficial cut-off of line width (39.7 Hz). In vitro NMR spectroscopy in our hands was thus not a useful diagnostic tool in patients with early breast cancer.

Aged↗

Physiological deactivation after two contrasting tasks at a video display terminal: learning vs repetitive data entry .

Two contrasting 90 min VDT work situations were simulated in the laboratory: (1) a machine-paced, repetitive data entry task; and (2) a stimulating, self-paced learning task with successive feedback. Thirty non-smoking male students (20-34 years), without previous experience of VDT work, participated individually in each condition on two consecutive days (balanced order) and in a task-free baseline condition. Self-reports and successive measurements (ambulatory recordings) of systolic and diastolic blood pressure and heart rate were obtained during work and during a subsequent 60 min period of deactivation. Urine samples were obtained after each period for the determination of catecholamines and cortisol. In the baseline condition, measurements were obtained at corresponding times of the day. As expected, the data entry task was associated with self-reports of boredom, irritation, and unpleasantness; the learning task wtih alertness, interest, and ability to concentrate. Similar elevations of physiological measurements occurred in both work situations. However, differences between conditions were found after work. Following data entry, deactivation was slower in five of the six variables (significant for epinephrine).

Adult↗

von Willebrand factor mutation enhancing interaction with platelets in patients with normal multimeric structure.

Variant von Willebrand disease designated as type I New York or type Malmö is characterized by enhanced ristocetin-induced platelet agglutination with normal von Willebrand factor multimeric distribution in plasma. We have studied four such patients belonging to three unrelated families and found in all of them a unique cytosine-to-thymine transition changing the codon for Pro503 (CCG) to Leu (CTG). In three patients the mutant allele also had a silent mutation in the codon for Ser500 (TCG-->TCA). Both nucleotide changes are present in the von Willebrand factor pseudogene; however, the characterization of distinctive markers where the gene and pseudogene differ, as well as the examination of amplified cDNA derived from platelet mRNA, confirmed that the abnormality occurs in the von Willebrand factor gene of the patients. Moreover, recombinant expression of the isolated glycoprotein Ib-binding domain of von Willebrand factor provided direct evidence that the Pro503-->Leu mutation is responsible for enhanced platelet reactivity to lower ristocetin concentrations. These results define a new structural element affecting the affinity of von Willebrand factor for glycoprotein Ib and establish the molecular basis of a variant form of von Willebrand disease.

Adult↗

Prognostic factors in canine mammary tumors: a multivariate study of 202 consecutive cases.

The prognostic variables of 223 consecutively sampled spontaneous mammary tumors from female dogs were studied. These variables included flow cytometric DNA analysis and cell proliferation measured as cells in S-phase rate evaluated from DNA histograms. The dogs were surgically treated, in most cases with unilateral mastectomy (all mammary glands), and 202 of the 223 dogs were studied temporally following surgery. Univariate analysis with correction for age indicated that the variables of lymph node metastasis, elevated S-phase rate, presence of a sarcoma, DNA aneuploidy, and ulceration and infiltrative growth into underlying tissue had a statistically significant negative influence on the survival rates of dogs with a diagnosed malignant tumor. Similar results were obtained from tests on all dogs, but tumor size and its relative hazard increased with increasing size of the tumors, regardless of whether total or disease-specific mortality was considered. Using multivariate-analysis conducted Cox's proportional hazards model, elevated S-phase rate, increased age, and presence of a sarcoma remained statistically significant risk factors. The prognostic value of DNA ploidy and lymph node status varied depending on choice of end point. The study of tumor growth pattern and tumor size provided no prognostic information in the multivariate analysis. Flow cytometric cell analysis, including S-phase rate and DNA ploidy, is of value in predicting the prognosis of canine mammary tumors and can be used as a new prognostic tool to improve the preoperative diagnostics of canine mammary tumors.

Age Factors↗

Two new candidate mutations in type IIA von Willebrand's disease (Arg834-->Gly, Gly846-->Arg) and one polymorphism (Tyr821-->Cys) in the A2 region of the von Willebrand factor.

Recently, several von Willebrand factor gene mutations resulting in type IIA von Willebrand's disease have been reported. We examined 8 patients from Sweden and Denmark with this phenotype and found two new candidate mutations and a hitherto unknown amino acid polymorphism. One patient had a de novo occurring mutation resulting in substitution of glycine for arginine 834. Previous reports have demonstrated conversion of arginine 834 to tryptophan or glutamine in IIA patients. A 2nd patient had a G(4825)-->A transition, substituting arginine for glycine 846. The transition produces a sequence congruent with that of the pseudogene but several lines of evidence indicate that a sequencing error due to influence by the latter could be excluded. The remaining 6 patients had one of the earlier described substitution mutations: Ser743-->Leu and Ile865-->Thr. In addition, two sequence variations not linked to the phenotype were found, namely Tyr821-->Cys and Val802-->Leu.

Adolescent↗

Ribosome-bound eukaryotic elongation factor 2 protects 5 S rRNA from modification.

The interaction between eukaryotic elongation factor eEF-2 and reconstituted 80 S ribosomes was investigated by analyzing the accessibility of 5 S ribosomal RNA for chemical and enzymatic modification. Ribosomes reconstituted from derived subunits were modified, and the positions of the modified sites were identified by primer extension using a 5 S rRNA-specific probe. All reactive sites were located between nucleotides 38 and 99, and most of them were found in putative single-stranded regions of the 5 S rRNA. Conversion of the ribosomes to the post-translocation type of particles by treatment with the translational inhibitor ricin resulted in the exposure of 3 additional bases for chemical modification, suggesting that the 5 S rRNA was more exposed in this type of ribosome. After binding of eEF-2 in complex with the non-hydrolyzable GTP analogue guanosine 5'-(beta, gamma-methylene)-triphosphate, most of the exposed bases in the 5 S rRNA were protected against both chemical and enzymatic modification.

Animals↗

Erythrocyte sedimentation rate as a tumor marker in human prostatic cancer. An analysis of prognostic factors in 300 population-based consecutive cases.

BACKGROUND: The natural history of prostatic cancer is variable. Our knowledge of prognostic factors is limited; therefore, research is needed. METHODS: The cases of 300 population-based consecutive patients with a diagnosis of cancer of the prostate were analyzed regarding different prognostic factors (but with special reference to the erythrocyte sedimentation rate [ESR]). RESULTS: After a mean observation time of 100 months, M category, ESR, grade, performance status, hemoglobin level, and T category were found to correlate with disease-specific death using multivariate analysis. The variables correlating with progression in the multivariate model were M category, ESR, T category, grade, treatment, and age. Patients treated with estrogen had a significantly lower risk (relative hazard, 0.3) of relapse. ESR was highly statistically significant (P less than 0.0001) as a prognostic factor. With the variable in linear form, a 20-mm/h higher level suggested a 29% increased risk, on average, for dying of prostatic cancer (using a best-fit multivariate model). However, the relationship was not linear. After correcting for the effect of other factors, the risk for dying of prostatic cancer was lowest when the ESR was 40-50 mm/h and highest when its values were highest. CONCLUSIONS: ESR is an indicator of increased risk of progression and death in prostatic cancer. Other prognostic factors such as M and T categories, grade, performance status, hemoglobin level, and age currently are more important when planning treatment. It is possible that the ESR reflects aspects of tumor-host relationship and that both a low and high ESR are markers for patients with receding host defence mechanism.

Aged↗

Alcoholism and cancer risk: a population-based cohort study.

The incidence of cancer was studied in a population-based cohort of 9,353 individuals (8,340 men and 1,013 women) with a discharge diagnosis of alcoholism in 1965-83, followed up for 19 years (mean 7.7). After exclusion of cancers in the first year of follow-up, 491 cancers were observed cf 343.2 expected through 1984 (standardized incidence ratio [SIR] = 1.4, 95 percent confidence interval [CI] = 1.3-1.6). A similar excess risk of cancer was seen among men (SIR = 1.4, CI = 1.3-1.6) and among women (SIR = 1.5, CI = 1.1-2.0). We observed the established associations with cancers of the oral cavity and pharynx (SIR = 4.1, CI = 2.9-5.7), esophagus (SIR = 6.8, CI = 4.5-9.9), larynx (SIR = 3.3, CI = 1.7-6.0), and lung (SIR = 2.1, CI = 1.7-2.6), although confounding by smoking likely increased these risk estimates. While there was evidence of increased risk for pancreatic cancer (SIR = 1.5, CI = 0.9-2.3), alcoholism did not elevate the incidence of cancer of the stomach (SIR = 0.9, CI = 6-1.4), large bowel (SIR = 1.1, CI = 0.8-1.5), prostate (SIR = 1.0, CI = 0.8-1.3), urinary bladder (SIR = 1.0, CI = 0.6-1.5), or of malignant melanoma (SIR = 0.9, CI = 0.3-1.9). Among women, the number of breast cancers observed was close to expected (SIR = 1.2, CI = 0.6-2.2), although a significant excess number of cervical cancers occurred (SIR = 4.2, CI = 1.5-9.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Survival and causes of death in patients with inflammatory bowel disease: a population-based study.

Relative survival up to December 31, 1986 was analyzed for all patients diagnosed with ulcerative colitis (UC) (n = 2,509) and Crohn's disease (CD) (n = 1,469) within the Uppsala Region, Sweden 1965-1983. After 10 years survival was 96% of that expected for UC and CD. Patients with ulcerative proctitis, left-sided colitis, and pancolitis at diagnosis had relative survival rates of 98%, 96%, and 93% respectively. Survival did not differ by extent at diagnosis for patients with CD. After including prevalent cases, 684 deaths occurred compared with 481.1 expected deaths [standardized mortality ratio (SMR) = 1.4; 95% confidence interval (CI) = 1.3-1.5]. Inflammatory bowel disease was the main reason for this excess mortality. Colorectal cancer increased mortality (50 deaths observed vs. 15.2 expected). Death from other cancers were not greater than expected. Obstructive respiratory diseases, especially bronchitis, emphysema, and asthma increased mortality SMR = 1.5 (95% CI = 1.1-2.2) in UC. Cerebrovascular disease mortality occurred less often than expected (SMR = 0.7; 95% CI = 0.5-1.0). Mortality for other diseases and groups of diseases was close to that expected.

Cause of Death↗

Determinants of the psycho-social outcome after operation for breast cancer. Results of a prospective comparative interview study following mastectomy and breast conservation.

In a prospective interview study, designed to compare the psycho-social outcome after a breast-conserving vs. a mastectomy operation, we analysed possible predictors of the psycho-social adjustment. 99 women with breast cancer histopathological TNM stages I and II were consecutively admitted to the study. Half-structured interviews, based on the Social Adjustment Scale and a scale by P. Maguire, were performed 4 and 13 months after the operation. Living together with the spouse seems to protect women from developing psycho-social problems postoperatively. Women who were gainfully employed or who were given radiotherapy had a higher risk of poor adjustment after 4 months. At 13 months, the scorings indicate that radiotherapy has a reassuring effect. Type of surgery was controlled for in the analysis and showed that, of the risk factors studied, the most consistent trend for an overall better outcome was in the breast-conserved group except for sexual disturbances.

Adult↗

Effects of different designs and extension of a food frequency questionnaire on response rate, completeness of data and food frequency responses.

The authors studied how the introduction of several modifications to a basic food frequency questionnaire can influence the results of dietary surveys. Modifications covered eight combinations based on three levels: increasing versus decreasing order of frequency categories; questionnaires without versus with questions about portion sizes, and questionnaires without versus with extra non-dietary questions. The sample included 6783 women between the ages of 40 and 70 years who took part in mammography screening. The women were randomly assigned to one of the eight study groups. All of the women in each group received one of the eight differently modified questionnaires. The forms extended in length by extra non-dietary questions and portion size categories resulted in a 20% higher total non-response compared to the shorter basic form. Partial non-response was significantly lower for all four questionnaire types that included portion sizes. When portion sizes were included in the questionnaire, the reported mean frequency of consumption was significantly reduced for fat (-10 times per month), milk (-6), bread (-5), vegetables (-2) and fish (-0.4). The decreasing order of responses to the frequency categories was associated with a statistically significant increase in the frequency responses for bread (2.6 times per month), vegetables (2) and fish (0.6). These data provide evidence that the design and extension of food frequency questionnaires influence the results of dietary studies.

Adult↗