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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 163 records · Page 9Linked to original sources

Sector resection with or without postoperative radiotherapy for stage I breast cancer: five-year results of a randomized trial. Uppsala-Orebro Breast Cancer Study Group.

BACKGROUND: The effectiveness of routine postoperative irradiation following breast-conserving treatment of breast cancer has not previously been assessed in randomized clinical trials that have taken place in settings where mammography has been a major pathway to diagnosis or that have followed patients treated surgically by sector resection. PURPOSE: The aim of this study was to determine if treatment of stage I breast cancer by strictly standardized surgical technique with meticulous confirmation of a complete excision can reduce the local recurrence rate to an acceptable level without routine adjuvant radiotherapy. METHODS: In this trial conducted in Sweden, 381 women with stage I breast cancer were surgically treated by sector resection plus axillary dissection; then 184 women were randomly selected to receive postoperative radiotherapy to the breast (XRT group), and 197 women received no further treatment (non-XRT group). Patient accrual started in October 1981 and ended in September 1988. Criteria for eligibility were a unifocal cancer 20 mm or less in diameter (visible on mammogram) and radical excision and no histopathologic signs of axillary metastases. RESULTS: After median follow-up times of 65 and 63 months, the 5-year local recurrence rate was 2.3% (95% confidence interval [CI] = 0.1%-4.3%) in the XRT group and 18.4% (95% CI = 12.5%-24.2%) in the non-XRT group, respectively. The life-table curves were significantly different (P = .0001). The two treatment groups did not differ in overall survival: For the XRT group, the value was 91.0% (95% CI = 86.4%-95.4%); for the non-XRT group, it was 90.3% (95% CI = 85.8%-94.8%). The same was true for survival free from regional and distant recurrence: XRT group, 90.0% (95% CI = 85.3%-94.5%); non-XRT group, 87.1% (95% CI = 82.3%-92.0%). The rate of local recurrences was significantly higher in patients treated more recently (P. = 003). CONCLUSIONS: Sector resection plus radiotherapy to the breast very effectively achieves local tumor control. Surgery alone results in similar survival prospects, but the probability of local recurrence approaches 20% at 5 years. IMPLICATIONS: The increase in recurrence rate observed over time suggests that surgical technique and patient selection should be improved. The benefits of reduced cost and patient inconvenience that would result from the elimination of postoperative radiotherapy must be carefully weighed against the disadvantages of local recurrence. Longer term follow-up must be done to estimate the risk of cancer recurrence in these women 10 and 15 years later, and methods must be developed to identify those women who have a higher risk of recurrence. Finally, economic analyses of this and similar trials are needed to give empirical underpinnings for optimal use of radiotherapy.

Adult↗

Probing the structure of mouse Ehrlich ascites cell 5.8S, 18S and 28S ribosomal RNA in situ.

The secondary structure of mouse Ehrlich ascites 18S, 5.8S and 28S ribosomal RNA in situ was investigated by chemical modification using dimethyl sulphate and 1-cyclohexyl-3-(morpholinoethyl) carbodiimide metho-p-toluene sulphonate. These reagents specifically modify unpaired bases in the RNA. The reactive bases were localized by primer extension followed by gel electrophoresis. The three rRNA species were equally accessible for modification i.e. approximately 10% of the nucleotides were reactive. The experimental data support the theoretical secondary structure models proposed for 18S and 5.8/28S rRNA as almost all modified bases were located in putative single-strand regions of the rRNAs or in helical regions that could be expected to undergo dynamic breathing. However, deviations from the suggested models were found in both 18S and 28S rRNA. In 18S rRNA some putative helices in the 5'-domain were extensively modified by the single-strand specific reagents as was one of the suggested helices in domain III of 28S rRNA. Of the four eukaryote specific expansion segments present in mouse Ehrlich ascites cell 28S rRNA, segments I and III were only partly available for modification while segments II and IV showed average to high modification.

Animals↗

NBQX, a competitive non-NMDA receptor antagonist, reduces degeneration due to focal spinal cord ischemia.

We have used the laser-induced photochemical thrombosis model in adult rats to evaluate the significance of the non-N-methyl-D-aspartate (non-NMDA) subtype of glutamate receptors in situations of focal spinal cord ischemia. The animals were pretreated with the selective non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX) or, for comparison, the NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine (MK-801). Neurological function was quantified using evaluations of motor score and inclined plane. The MK-801-treated rats had higher motor scores during the 3-week observation period while NBQX-treated rats only performed significantly better at 1 week. Both treatments caused significantly better performance in the inclined plane test. NBQX and MK-801 reduced the volume of necrosis by approximately 47% at 3 weeks postlesion. We conclude that blockade of both NMDA and non-NMDA subtypes of glutamate receptors reduces ischemic necrosis, possibly by preventing excessive stimulation of these receptors by released excitatory amino acids in the lesion area.

Analysis of Variance↗

Oral contraceptives and prognosis in breast cancer: effects of duration, latency, recency, age at first use and relation to parity and body mass index in young women with breast cancer.

The aim of this study was to examine associations between oral contraceptive (OC) use, body mass index (BMI = weight/height2) and prognosis in invasive breast cancer diagnosed before the age of 45. Survival analyses of a consecutive sample of breast cancer patients were undertaken. The cases were initially registered in a nationwide case-control study of OC use and risk of premenopausal breast cancer in Sweden and Norway. All 422 cases were under 45 years of age at diagnosis, and recruited from the reports to cancer registries (Sweden) or from surgical departments (Norway) during May 1984 through May 1985. Detailed information about OC exposure was obtained in the initial face-to-face interview. With Cox's proportional hazards analyses, a significantly lower hazard rate [relative hazard (RH) = 0.54; 0.31-0.94] was seen in short-term users (< 4 years)--but not in long-term (> or = 4 years) users--than in never-users of OC. Non-significant estimates for RHs lower than 1.0, i.e. better prognosis, with long recency (> 5 years) and latency (> or = 10 years) of OC use were noted. Prognosis was not influenced by age at first OC use or of its timing in relation to the first pregnancy. A higher BMI was associated with a poorer prognosis, RH 5.9 (2.0-17.8) for BMI > or = 29 versus BMI < 19, but BMI was not a confounder or an effect modifier of the association between OC use and prognosis. This study does not indicate that OC use prior to the diagnosis of breast cancer has any adverse effect on the prognosis, at least not in women under 45 years of age at diagnosis.

Adult↗

Surgical treatment of left ventricular aneurysm--assessment of risk factors for early and late mortality.

Consecutive patients operated on for left ventricular aneurysm from 1970 through August 1989 (n = 303) were evaluated with respect to survival. Early mortality, i.e. within 30 days, was 8.9%; 23% in patients who underwent aneurysm resection alone, 8.1% in cases of aneurysm resection with coronary artery bypass grafting (CABG), and 6.3% in those undergoing CABG only. Multivariate logistic regression revealed that advanced New York Heart Association (NYHA) functional class, non-use of the internal mammary artery as a graft and thromboendarterectomy increased the early risk. The total observed survival was 86% at 1 year, 72% at 5 years and 45% at 10 years. Multivariate analysis based on observed survival, using the Cox proportional hazards model, identified advanced NYHA functional class and non-use of the internal mammary artery as independent indicators of poor survival. Relative mortality, defined as the ratio of observed mortality in the study group to mortality among comparable persons from the general Swedish population, was used as a measure of disease-specific mortality. An apparent excess mortality in patients operated on for left ventricular aneurysm was found. A notable finding was that the use of the internal mammary artery to graft the left anterior descending artery improved the outcome substantially in patients with a left ventricular aneurysm.

Adult↗

Defining a high mortality risk group among women with primary breast cancer.

Increasing interest has been focused on DNA ploidy, hormone receptor status and tumour size as prognostic factors in node-negative breast cancer. We analysed these factors in patients operated on for primary invasive breast cancer between January 1981 and December 1987 in a prospective study of 248 women with no involved axillary nodes and 188 women with positive nodes followed until 15 April 1989. Oestrogen or progesterone receptor negativity, aneuploidy and tumour diameter exceeding 20 mm were studied as negative prognostic signs in life table analyses and Cox proportional hazards models of corrected survival. Corrected survival decreased with increasing number of negative signs. Three to four signs yielded a statistically significant, two- to threefold higher risk than the others. Survival estimates by life table analyses differed by 20% at 5 years. In the whole group, women with three or four negative factors had a relative risk of dying from their disease more than twice that of the others. Women with no involved nodes and with three or four negative factors had a risk of dying from breast cancer similar to that of node-positive women with fewer than three.

Aneuploidy↗

Self-administered food frequency questionnaire: the effect of different designs on food and nutrient intake estimates.

BACKGROUND: Our objective was to determine the possible influence that different designs of a food frequency questionnaire might have on food, energy and nutrient intake estimates. METHODS: A population-based survey included 6783 women, 40-70 years old, living in central Sweden. Using a factorial study design, we compared eight different types of questionnaire covering combinations of three factors: increasing/decreasing frequency categories; addition of portion sizes; and addition of non-dietary questions. All questionnaires included the same list of 60 food items. One of the eight questionnaires was mailed to each subject according to a random assignment. The overall response rate was 77%. RESULTS: Compared with increasing frequencies, decreasing order of frequency categories entailed 3-11% higher estimates of mean intake for 7 of 14 food groups, 4% higher estimates for energy and 3-6% higher estimates for 13 of 18 nutrients. Addition of portion sizes had heterogeneous effects, both on dietary items (e.g. from -30% decrease for eggs to +76% increase for coffee) and on calculated nutrients (from -7% for beta-carotene to +19% for vitamin C). The inclusion of some additional non-dietary questions did not influence the estimated mean intake of any food or nutrient. CONCLUSIONS: The results of this study have implications for the design of questionnaires and for pooled analyses in nutritional epidemiology, when different food questionnaires are used.

Adult↗

Survival after coronary artery bypass grafting. Experience from 4661 patients.

The duration of the reduction of mortality after coronary artery bypass grafting (CABG) is an important issue and this study was undertaken to evaluate time in relation to excess mortality among CABG patients compared with the general population. Survival was analysed in 4661 patients who had undergone their first isolated CABG. Observed survival was related to that expected among subjects from the general Swedish population stratified by age, sex and 5-year calendar period, to calculate relative survival and estimate disease-specific survival. Relative survival (including all deaths) was 94.6% at 5 years, 82.5% at 10 years, and 59.9% at 15 years. A multivariate model based on relative survival rates adjusted for age, year of surgery, severity of coronary disease, left ventricular function, and smoking habits was used. Compared with the first year of follow-up, the relative hazard (a measure of the risk of death) was at a minimum 2 years after surgery, but was dramatically increased after about 8 years. Relative survival was worsened by smoking at the time of operation and by moderate or severe left ventricular dysfunction pre-operatively. The survival rate was higher among patients operated on after 1985 than among those operated on earlier.

Adult↗

Psychosocial adjustment among women with breast cancer stages I and II: six-year follow-up of consecutive patients.

PURPOSE: To evaluate, in a long-term follow-up study of consecutive patients (N = 99), the impact of surgery--breast-conserving treatment (BCT) versus mastectomy (MT)--on psychosocial adjustment among women with breast cancer, pTNM stage I/II. PATIENTS AND METHODS: Semistructured interviews were conducted at a median of 6 years (range, 5.8 to 8.1) after primary surgery. Sixty-six women were available for the long-term follow-up study. Twenty-six women had been treated with BCT and 40 with MT. RESULTS: No statistically significant differences were found between the two groups concerning psychosocial adjustment, as measured by the Social adjustment Scale (SAS). In general, the levels of maladjustment were lower than at 13 months postoperatively, but 10% still showed maladjustment. Sixty percent of the women were unwilling to show themselves naked, and 22% felt that they had become less attractive because of the surgical treatment. In an explorative part of the interview, 68% of the women complained about how they had been informed of the diagnosis. A tendency toward a significant difference was found in the relation between previous maladjustment and a negative experience at the time of diagnosis (P = .07). CONCLUSION: Few data are available on long-term follow-up results with regard to psychosocial adjustment among women after breast cancer surgery. This study provides the important information that there are no differences in patient psychosocial adjustment that can be ascribed to the type of surgery at 6-year follow-up evaluation.

Adaptation, Psychological↗

Five year follow-up after radical prostatectomy for localized prostate cancer--a study of the impact of different tumor variables on progression.

Fifty-one patients with clinically localized prostate cancer stages A and B, who underwent radical prostatectomy have been followed for a minimum of 5 years. The impact of age, stage, capsular penetration, total tumor volume, Gleason score, seminal vesicle invasion and lymph node metastases on progression has been evaluated. Progression free survival was calculated according to the Kaplan-Meier method. Uni- and multivariate analyses were performed according to the Cox proportional hazards model. During the observation period 16 patients (31%) experienced progression. Tumor volume, grade and seminal vesicle invasion emerged as statistically significant predictors of tumor progression in the survival analyses while age at surgery, preoperative stage and different levels of capsular penetration were not statistically significant. The findings in the Cox models were in accordance with those at actuarial survival analyses though tumor volume was the only variable proven to have an independent statistically significant influence on progression.

Aged↗

Role of marrow microenvironment in engraftment and maintenance of allogeneic hematopoietic stem cells.

Following allogeneic marrow transplantation a competent marrow microenvironment consists of a complex mixture of both donor and host derived cells. Clearly some forms of genetic disparity between donor and host can compromise appropriate interactions and function of these cells. The competency of the microenvironment can also be compromised by viral infections, and the underlying disease process as in rare cases of aplastic anemia. As we come to precisely define each component of the microenvironment, it will become possible to accurately diagnose causes of poor marrow function and develop methods for prevention and treatment.

Adipose Tissue↗

Psychosocial adjustment among husbands of women treated for breast cancer; mastectomy vs. breast-conserving surgery.

Psychosocial adjustment was measured among 56 spouses of women operated for breast cancer. Of 69 eligible husbands, 56 participated. Twenty women underwent breast-conserving surgery (BCT) and 36 had a mastectomy (MT). An interview was conducted with each woman and her husband separately, 4 and 13 months after surgery. Two instruments were used; SBAS (Social Behaviour Assessment Schedule) and a scale (TB) constructed specifically for the study. The husbands of the women in the MT group were significantly more depressed after 4 months and reported complaints related to their wive's disease more often than did those in the BCT group. After 4 months, the marital relation was assessed as more positive in the MT group. A total of 48% of the husbands in the sample expressed some emotional distress during the investigation period, which is similar to levels seen among breast cancer-operated women themselves. Overall, only marginally better scores were seen for husbands married to women who had undergone breast-conserving surgery. Few researchers have studied psychosocial reactions in the breast cancer patient's family. Since patterns of social support empirically influence the rehabilitation of the cancer patient, this field of investigation is important.

Adaptation, Psychological↗