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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 73 records · Page 4Linked to original sources
PubMed1999

Prevalence of postmenopausal symptoms in two age groups of elderly women in relation to oestrogen replacement therapy.

A cross-sectional study of the whole female population of ages 71 and 81 years in a defined part of Sweden was undertaken to investigate the prevalence of oestrogen treatment and postmenopausal symptoms. A questionnaire was mailed to 2245 women, of whom 1084 (87%) aged 71 years and 611 (62%) aged 81 years left evaluable responses. Of the responding 71- and 81-year-old women 25 and 16%, respectively were receiving oestrogen, and 4 and 2% of all women of the respective age groups were on systemic treatment. Nearly half of all the women reported urinary incontinence, which was considerate for approximately half of these women. Five and 11% of the respective age groups had experienced more than two urinary tract infections (RUTI) in the last year. RUTI had occurred both in the oestrogen-treated group and in the non-treated group. Vegetative symptoms were still encountered among these elderly women. Previous fractures were frequent, being experienced after menopause by 29 and 39% of the 71- and 81-year-old women respectively. Thirty-five and 39% of the women in respective age group had sought medical help for postmenopausal symptoms. Of the women with moderate, severe or unbearable urinary incontinence, 60 and 66% of the respective age groups had sought medical help. In only few of the totals of women on oestrogen had the treatment a complete effect. Only 2 and 1% of all women in respective age group had been offered and undergone surgery for their urinary incontinence.

Aged↗
PubMed1999

Mapping the ribosomal RNA neighborhood of protein L11 by directed hydroxyl radical probing.

Ribosomal protein L11 is a highly conserved protein that has been implicated in binding of elongation factors to ribosomes and associated GTP hydrolysis. Here, we have analyzed the ribosomal RNA neighborhood of Escherichia coli L11 in 50 S subunits by directed hydroxyl radical probing from Fe(II) tethered to five engineered cysteine residues at positions 19, 84, 85, 92 and 116 via the linker 1-(p -bromoacetamidobenzyl)-EDTA. Correct assembly of the L11 derivatives was analyzed by incorporating the modified proteins into 50 S subunits isolated from an E. coli strain that lacks L11 and testing for previously characterized L11-dependent footprints in domain II of 23 S rRNA. Hydroxyl radicals were generated from Fe(II) tethered to L11 and sites of cleavage in the ribosomal RNA were detected by primer extension. Strong cleavages were detected within the previously described binding site of L11, in the 1100 region of 23 S rRNA. Moreover, Fe(II) tethered to position 19 in L11 targeted the backbone of the sarcin loop in domain VI while probing from position 92 cleaved the backbone around bases 900 and 2470 in domains II and V, respectively. Fe(II) tethered to positions 84, 85 and 92 also generated cleavages in 5 S rRNA around helix II. These data provide new information about the positions of specific features of 23 S rRNA and 5 S rRNA relative to protein L11 in the 50 S subunit and show that L11 is near highly conserved elements of the rRNA that have been implicated in binding of tRNA and elongation factors to the ribosome.

Amino Acid Substitution↗
PubMed1999

Lung symptoms in pseudohypoaldosteronism type 1 are associated with deficiency of the alpha-subunit of the epithelial sodium channel.

OBJECTIVE: To study patients with autosomal recessive pseudohypoaldosteronism type 1 and to relate pulmonary disease to gene mutations of the epithelial sodium channel (ENaC). STUDY DESIGN: Clinical and laboratory data were collected from 4 Swedish patients with pseudohypoaldosteronism type 1. The genes for ENaC and cystic fibrosis transmembrane conductance regulator were analyzed for mutations with methods including DNA sequencing. RESULTS: Three novel mutations were found in the alpha-gene of ENaC, 2 frameshifts (1449delC and 729delA) and 1 missense mutation resulting in the substitution of leucine for serine 562 in the alpha-chain (S562L). The 1449delC mutation was found in all patients in either homozygous or heterozygous form and seems to be the predominant cause of pseudohypoaldosteronism in Sweden. The allele coding for S562L also contained a transition converting tryptophan 493 to arginine (W493R), which seems to be a rare polymorphism. All patients had pulmonary symptoms to various degrees. The bacterial findings resembled, to some extent, those in cystic fibrosis, but development of chronic lung disease and progressive decline in lung function were not observed. CONCLUSIONS: Genetic deficiencies of the alpha subunit of the ENaC are associated with prominent lung symptoms, which are, however, clearly different from those in cystic fibrosis.

Child, Preschool↗
PubMed1999

Ductal carcinoma in situ of the breast from a population-defined cohort: an evaluation of new histopathological classification systems.

The increased incidence of ductal carcinoma in situ of the breast (DCIS) in the era of mammography screening requires a deeper knowledge of the biology of the disease and calls for a suitable classification system to optimise therapy. Our aim was to evaluate the correlation to prognosis for two new classification systems of DCIS. The histopathological specimens from 195 women consecutively diagnosed between 1986 and 1994 with a primary DCIS were re-classified by two separate observers using the system proposed by an European Organization for Research and Treatment of Cancer (EORTC) working group and the Van Nuys system. The relapse-free survival (RFS) by histopathological subgroup and by nuclear grade only was estimated for women treated with breast conserving surgery (n = 149). Thirty-two local recurrences occurred among 149 women (mean follow-up time 59 months). No distant recurrences or breast cancer deaths were reported. The women in the group with the highest differentiation according to the EORTC classification had no recurrences. RFS did not differ appreciably between the two other groups. This was true also after stratification for radiotherapy. We found no statistically significant difference in RFS between the three groups in the Van Nuys classification. There was an overall agreement between the observers in 79% and 64% of the cases, according to the EORTC and Van Nuys systems, respectively. We were able to define one group with highly differentiated lesions and an excellent prognosis with the EORTC classification. Further classification into intermediate and low differentiated lesions did not help predict RFS.

Adult↗
PubMed1999

Three common CFTR mutations should be included in a neonatal screening programme for cystic fibrosis in Sweden.

Children with cystic fibrosis (CF) diagnosed by neonatal screening have a better nutritional development and other advantages compared with those in a nonscreened group. The two-tier immunoreactive trypsinogen (IRT)/DNA screening protocol has been found superior to the single-tier IRT approach, improving the positive predictive value and thus reducing the false-positive rate. However, variations of the DNA test are required for different populations. In this study we examined CFTR (cystic fibrosis transmembrane conductance regulator) mutations in 331 CF patients attending the centres in Stockholm, Lund and Uppsala, comprising about 75% of the CF population in Sweden. The frequency of deltaF508 among CF alleles was 68.3%. There were two other mutations, 394delTT and 3659delC, found to be fairly frequent, amounting to 8.5 and 7.9%, respectively. Other mutations were comparatively rare. A simple and effective method of analysing the three mutations from Guthrie cards has been developed. Assuming Hardy-Weinberg equilibrium, 90% of our CF patients will be expected to carry at least one deltaF508 allele and 97.6% to carry at least one deltaF508, 394delTT or 3659delC copy. Including the latter two in a screening programme would thus substantially reduce the risk of a false-negative outcome.

Cystic Fibrosis↗
PubMed1999

Intensified primary cancer care: a randomized study of home care nurse contacts.

Newly diagnosed cancer patients (n=527) were randomised to intensified primary care or a control group. Intensified primary care comprised routines to improve general practitioners' and home care nurses' possibilities to support and monitor patients, i.e. increased information from specialist care, education and supervision in cancer care. The aims of this paper are to evaluate the effects of intensified primary care on cancer patients' home care nurse contacts, and to study if patients' use of home care services 6 months after diagnosis can be predicted. The intervention resulted in a marked increase of follow-up contacts. About 90% of intensified primary care patients reported such contacts, compared to 26% of control patients. The results indicate that standard care does not routinely include follow-up contacts, not even for the oldest (80+ years) or those with advanced disease. Only 27% and 36% of these groups of control patients reported follow-ups. Logistic regression analysis identified intensified primary care as the strongest predictor for reporting a continuing contact 6 months after diagnosis. Intensified primary care patients were 14 times more likely than controls to report a such contact. The strongest predictor of a continuing contact in the intensified primary care group was high age. Patients with advanced disease were more likely than patients with non-advanced disease to report a continuing contact, and living in a rural district was positively associated with reporting a contact. A majority of the patients (70%) assessed the time for the first contact as the 'right time' and estimated that the nurse gave expected support to a very large or large extent (67%). The results suggest that routines like those implemented through intensified primary care may be an effective strategy to increase the accessibility and continuity of care, especially for elderly people and for patients with a need for long-term contacts.

Adult↗
PubMed1999

On the scientific inference from clinical trials.

We have not been able to describe clearly how we generalize findings from a study to our own 'everyday patients'. This difficulty is not surprising, since generalization deals with how empirical observations are related to the growth of scientific knowledge, which is a major philosophical problem. An argument, sometimes used to discard evidence from a trial, is that the patient sample was too selected and therefore not 'representative' enough for the results to be meaningful for generalization. In this paper, we discuss issues of representativeness and generalizability. Other authors have shown that generalization cannot only depend on statistical inference. Then, how do randomized clinical trials contribute to the growth of knowledge? We discuss three aspects of the randomized clinical trial (Mant 1999), First, the trial is an empirical experiment set up to study the intervention on the question as specifically and as much in isolation from other -- biasing and confounding -- factors as possible (Rothman & Greenland 1998). Second, the trial is set up to challenge our prevailing hypotheses (or prejudices) and the trial is above all a help in error elimination (Popper 1992). Third, we need to learn to see new, unexpected and thought-provoking patterns in the data from a trial. Point one -- and partly point two -- refers to the paradigm of the controlled experiment in scientific method. How much a study contributes to our knowledge, with respect to points two and three, relates to its originality. In none of these respects is the representativeness of the patients, or the clinical situations, crucial for judging the study and its possible inferences. However, we also discuss that the biological domain of disease that was studied in a particular trial has to be taken into account. Thus, the inference drawn from a clinical study is not only a question of statistical generalization, but must include a jump from the world of experiences into the world of reason, assessment and theoretical judgement.

Biometry↗
PubMed1999

10-Year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: a randomized trial.

PURPOSE: To study the long-term effectiveness of postoperative radiotherapy after sector resection for breast cancer in a randomized trial in which mammography is a major pathway to diagnosis. PATIENTS AND METHODS: Three hundred eighty-one women with a unifocal breast cancer < or = 20 mm in diameter on the preoperative mammogram and without histopathologic signs of axillary metastases were treated by sector resection plus axillary dissection. Of these patients, 184 women were randomized to receive postoperative radiotherapy to the breast (XRT group), and 197 women received no further treatment (non-XRT group). RESULTS: The local recurrence rate was 8.5% (95% confidence interval [CI], 3.9% to 13.1%) in the XRT group and 24.0% (95% CI, 17.6% to 30.4%) in the non-XRT group (P =.0001). Survival free from regional and distant recurrence was 83. 3% in the XRT group (95% CI, 77.5% to 89.1%) and 80.0% in the non-XRT group (95% CI, 73.9% to 86.1%) (P =.23). Overall survival was 77.5% in the XRT group (95% CI, 70.9% to 84.1%) and 78% in the non-XRT group (95% CI, 71.7% to 84.3%) (P =.99). A subgroup analysis suggested that women older than 55 years of age without comedo or lobular carcinomas had a low risk of local recurrence of 6.1% (95% CI, 0.1% to 9.1%) in the XRT-group and 11.0% (4.0% to 18.0%) in the non-XRT group (P =.16). CONCLUSION: Sector resection plus radiotherapy resulted in an absolute reduction in local recurrence of 16% at 10 years compared with surgery alone. Women older than 55 years of age without comedo or lobular carcinomas may have a low risk of local recurrence. Postoperative radiotherapy was not shown to reduce distant recurrences or improve overall survival.

Breast Neoplasms↗
PubMed1999

Smoking, antioxidant vitamins, and the risk of hip fracture.

Smoking increases the concentrations of free radicals, which have been suggested to be involved in bone resorption. We examined whether the dietary intake of antioxidant vitamins may modify the increased hip fracture risk associated with smoking. We prospectively studied 66,651 women who were 40-76 years of age. Forty-four of the cohort members who sustained a first hip fracture within 2-64 months of follow-up (n = 247) and 93 out of 873 age-matched controls were current smokers. Information on diet was obtained by a validated food-frequency questionnaire. The relative risk of hip fracture for current versus never smokers was analyzed in relation to the dietary intake of antioxidant vitamins stratified into two categories (low/high), where median intakes among the controls were used as cut-off points. After adjustment for major osteoporosis risk factors, the odds ratio (OR) for hip fracture among current smokers with a low intake of vitamin E was 3.0 (95% confidence interval 1.6-5.4) and of vitamin C 3.0 (1.6-5.6). In contrast, the OR decreased to 1.1 (0.5-2.4) and 1.4 (0.7-3.0) with high intakes of vitamin E and C, respectively. This effect was not seen for beta-carotene, selenium, calcium, or vitamin B6. In current smokers with a low intake of both vitamins E and C, the OR increased to 4.9 (2.2-11.0). The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers. Our results suggest a role for oxidant stress in the adverse effects on the skeleton of smoking, and that an insufficient dietary intake of vitamin E and C may substantially increase the risk of hip fracture in current smokers, whereas a more adequate intake seems to be protective.

Adult↗
PubMed1999

Prognosis in women with a carcinoma in situ of the breast: a population-based study in Sweden.

We studied the risk of invasive breast cancer and breast cancer death after a breast carcinoma in situ during a period when mammography screening became a nationwide practice and when breast conservation was introduced. In a study base including all 4661 women registered to the Swedish Cancer Registry for a first carcinoma in situ between 1960 and 1992, we selected a cohort of 3398 women diagnosed between 1980 and 1992. The recruitment period was chosen according to the reporting routines for the registry. The corrected survival was 97.4% after 10 years. The risk of invasive cancer was similar in the ipsilateral and contralateral breast. Women diagnosed between 1989 and 1992 ran a relative risk of 0.1 (95% confidence interval, 0.0-0.9) of dying of breast cancer, as compared with women diagnosed from 1980-1982. Residence in counties where mammography screening was available was associated with a relative risk of 0.2 (95% confidence interval, 0.0-2.1) for breast cancer death in the age groups screened. Screening mammography may have contributed to the improvement of prognosis over this time period. This study cannot distinguish between lead time effects and a "true" improvement in prognosis. The increased use of breast conservation was not associated with a worse prognosis in the group as a whole. The study indicates that at least 50% of invasive cancers occurring after treatment for in situ lesions may be new cancers.

Adult↗
PubMed1999

Beta-carotene intake and risk of postmenopausal breast cancer.

We assessed the relation between beta-carotene consumption at various times in life and breast cancer risk by conducting a case-control study nested within a population-based cohort of women screened for breast cancer in Sweden. We conducted a telephone interview with 273 incident breast cancer cases and 371 controls about their diet at various ages throughout their lifetime. Controls were frequency matched to cases on age, month and year of mammography, and county of residence. We used unconditional logistic regression to measure the association between beta-carotene intake and breast cancer risk while adjusting for total energy intake, recency of intake, and the matching variables. Women were at lower risk with increasing levels of reported intake of beta-carotene. This pattern of association between breast cancer and beta-carotene intake was similar at various times before screening. These findings indicate that although diets high in beta-carotene may be associated with lower breast cancer risk, there does not seem to be evidence of a critical time period during which such diets are more relevant.

Breast Neoplasms↗
PubMed1998

Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture.

BACKGROUND: The highest incidence of osteoporotic fractures is found in northern Europe, where dietary intake of vitamin A (retinol) is unusually high. In animals, the most common adverse effect of toxic doses of retinol is spontaneous fracture. OBJECTIVE: To investigate whether excessive dietary intake of vitamin A is associated with decreased bone mineral density and increased risk for hip fracture. DESIGN: A cross-sectional study and a nested case-control study. SETTING: Two counties in central Sweden. PARTICIPANTS: For the cross-sectional study, 175 women 28 to 74 years of age were randomly selected. For the nested case-control study, 247 women who had a first hip fracture within 2 to 64 months after enrollment and 873 age-matched controls were selected from a mammography study cohort of 66,651 women 40 to 76 years of age. MEASUREMENTS: Retinol intake was estimated from dietary records and a food-frequency questionnaire. Bone mineral density was measured with dual-energy x-ray absorptiometry. Hip fracture was identified by using hospital discharge records and was confirmed by record review. RESULTS: In multivariate analysis, retinol intake was negatively associated with bone mineral density. For every 1-mg increase in daily intake of retinol, risk for hip fracture increased by 68% (95% CI, 18% to 140%; P for trend, 0.006). For intake greater than 1.5 mg/d compared with intake less than 0.5 mg/d, bone mineral density was reduced by 10% at the femoral neck (P = 0.05), 14% at the lumbar spine (P = 0.001), and 6% for the total body (P = 0.009) and risk for hip fracture was doubled (odds ratio, 2.1 [CI, 1.1 to 4.0]). CONCLUSION: High dietary intake of retinol seems to be associated with osteoporosis.

Adult↗
PubMed1998

Population based case-control study of sick leave in postmenopausal women before diagnosis of hyperparathyroidism.

OBJECTIVE: To analyse sick leave in women at risk of primary hyperparathyroidism before its diagnosis. DESIGN: Case-control study nested within a screened cohort of postmenopausal women. Cases were women with hyperparathyroidism without prior knowledge of their disease and no traditional symptoms or complications. Controls were women from the screened population without hyperparathyroidism. SETTING: Population based screening within a Swedish community. SUBJECT: 48 case-control pairs of women aged 55-70 years. MAIN OUTCOME MEASURE: Sick leave during the 5 years before diagnosis. RESULTS: Total duration of sickness benefits was longer in the cases than controls, and this discrepancy included sick leave on full time or half time and for periods of longer than a week. Cases had an increased risk of sick leave more than half of the investigated time compared with controls (odds ratio 12). Doctors' certificates showed that the overrepresented sick leave in the cases related mainly to cardiovascular diseases. CONCLUSION: Asymptomatic mild primary hyperparathyroidism in postmenopausal women is accompanied by a previously unrecognised morbidity, which has consequences for clinical management of the disorder and its impact on the health economy.

Aged↗
PubMed1998

Alcohol and breast cancer in women: a pooled analysis of cohort studies.

OBJECTIVE: To assess the risk of invasive breast cancer associated with total and beverage-specific alcohol consumption and to evaluate whether dietary and nondietary factors modify the association. DATA SOURCES: We included in these analyses 6 prospective studies that had at least 200 incident breast cancer cases, assessed long-term intake of food and nutrients, and used a validated diet assessment instrument. The studies were conducted in Canada, the Netherlands, Sweden, and the United States. Alcohol intake was estimated by food frequency questionnaires in each study. The studies included a total of 322647 women evaluated for up to 11 years, including 4335 participants with a diagnosis of incident invasive breast cancer. DATA EXTRACTION: Pooled analysis of primary data using analyses consistent with each study's original design and the random-effects model for the overall pooled analyses. DATA SYNTHESIS: For alcohol intakes less than 60 g/d (reported by >99% of participants), risk increased linearly with increasing intake; the pooled multivariate relative risk for an increment of 10 g/d of alcohol (about 0.75-1 drink) was 1.09 (95% confidence interval [CI], 1.04-1.13; P for heterogeneity among studies, .71). The multivariate-adjusted relative risk for total alcohol intakes of 30 to less than 60 g/d (about 2-5 drinks) vs nondrinkers was 1.41 (95% CI, 1.18-1.69). Limited data suggested that alcohol intakes of at least 60 g/d were not associated with further increased risk. The specific type of alcoholic beverage did not strongly influence risk estimates. The association between alcohol intake and breast cancer was not modified by other factors. CONCLUSIONS: Alcohol consumption is associated with a linear increase in breast cancer incidence in women over the range of consumption reported by most women. Among women who consume alcohol regularly, reducing alcohol consumption is a potential means to reduce breast cancer risk.

Alcohol Drinking↗
PubMed1998

A prospective study of association of monounsaturated fat and other types of fat with risk of breast cancer.

BACKGROUND: Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer. METHODS: We performed a population-based prospective cohort study, including 61,471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs). RESULTS: After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer. CONCLUSIONS: Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.

Adult↗
PubMed1998

NMDA and AMPA receptors evoke transmitter release from noradrenergic axon terminals in the rat spinal cord.

N-methyl-D-aspartate (NMDA) stimulated release of [3H]noradrenaline (NA) from prelabelled rat spinal cord slices. The release was partially insensitive to tetrodotoxin (TTX) and was inhibited by the NMDA antagonist MK-801. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) also evoked release of [3H]NA, which was enhanced by blocking AMPA receptor desensitization with cyclothiazide. AMPA-evoked release was inhibited by the non-NMDA antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)-quinoxaline (NBQX) but was not affected by TTX. NMDA and AMPA showed synergistic effects, indicating co-existence of NMDA and AMPA receptors on noradrenergic terminals. Kainate evoked [3H]NA release only at high concentrations and the release was not potentiated by blocking kainate receptor desensitization with concanavalin A. Thus, the results indicate that there are stimulatory presynaptic NMDA and AMPA receptors on noradrenergic axon terminals in the spinal cord and that they interact synergistically to evoke release of [3H]NA.

Animals↗