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Biomedical subjects

H Olsson

Publications and source records attributed to H Olsson.

At least 55 records · Page 3Linked to original sources

Gender and time differences in initial location and histological grade of non-Hodgkin's lymphomas in Southern Sweden.

In accordance with international data, non-Hodgkin's lymphomas (NHL) in the Southern Health Care Region of Sweden were more common in men than in women and there was an inreasing incidence for both genders in the 1980s and 1990s. A study of the years 1983 and 1992, i.e. the beginning and the end of a 10-year period, was carried out. Case records for 94% of all adults diagnosed in 1983 and 1992 (220 men and 171 women) were reviewed. The sites of the lymphomas and malignancy grade (Kiel classification) were recorded. Comparisons were made between the genders and between the two years studied. Among 170 men with nodal lymphomas, 49 were localized (stage I-II) in lymphoid tissue regional to the respiratory tract, 18 were localized elsewhere and 103 were generalized (stage III-IV). The corresponding sites in 138 women were 28, 33 and 77, respectively (p = 0.002), implying a predominance of stage I-II lymphomas regional to the respiratory tract in men and a larger number of localized lymphomas elsewhere, mostly abdominal retroperitoneal with or without inguinal engagement in women. High-grade nodal lymphomas were more common in 1992 (54%) than in 1983 (34%, p = 0.01). suggesting an increasing number of mainly high-grade lymphomas. For extranodal lymphomas (50 in men and 33 in women), no clear differences were observed for gender and the years studied. Risk factors, e.g. occupational hazards, are probably different for men and women. The gender differences in initial nodal location suggest that initial lymphoma sites may be related to different risk factors. Epidemiologic studies where both malignancy grade and initial lymphoma locations are taken into account may be helpful in defining risk factors.

Adolescent↗

Prognostic factors in invasive cutaneous malignant melanoma: a population-based study and review.

A population-based study from Sweden identified 711 patients with cutaneous malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors were evaluated and a review of the literature was performed. On univariate analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.6-2.1), increasing Clark level (OR 1.8, 95% CI 1.6-2.0), ulceration (OR 1.8, 95% CI 1.6-2.0), nodular melanoma (OR 1.5, 95% CI 1.3-1.6) and increasing age (continuous variable, P < 0.0001) were associated with a shorter survival. Location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-0.9) were associated with improved survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2-1.7) and ulceration (OR 1.4, 95% CI 1.2-1.6) were independently related to a poor prognosis, while location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-1.0) were associated with improved survival. No difference in mean tumour thickness was seen over time, but there was a significant increase in the percentage of thin melanomas (< 0.8 mm) in 1985 (P = 0.01) and 1989 (P = 0.002) compared with 1965. The incidence of melanomas with inflammation increased significantly (P = 0.04), as did age at diagnosis (P = 0.005).

Adolescent↗

No support for regional selectivity in clozapine-treated patients: a PET study with [(11)C]raclopride and [(11)C]FLB 457.

OBJECTIVE: The authors' goal was to test the hypothesis of extrastriatal D(2) receptor selectivity as the mechanism of action of clozapine. METHOD: Positron emission tomography (PET) was used to examine extrastriatal as well as striatal dopamine D(2) receptor occupancy in four patients treated with clozapine and three patients treated with haloperidol. The reference radioligand [(11)C]raclopride was used for determination of D(2) receptor occupancy in the striatum. The radioligand [(11)C]FLB 457 was chosen for determination of D(2) receptor occupancy in the thalamus, the temporal cortex, and the frontal cortex. RESULTS: In patients treated with haloperidol the D(2) receptor occupancy was high in all examined brain regions. In clozapine-treated patients the D(2) receptor occupancy was relatively low in both the striatum and the extrastriatal regions. CONCLUSIONS: The results from the present study give no support for the hypothesis of regional selectivity as the mechanism of action for clozapine.

Adult↗

Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden.

The objective of this study was to identify all malignancies in an inception cohort of SLE patients in southern Sweden and compare with the observed frequencies and spectrum of malignancies in the general population. All adult incidence cases of SLE in a defined population during the period 1981-1996 were retrieved from a prospective database and the cases were followed to endpoint or through 1998. The SLE cohort registry was aggregated with the National Cancer Registry to identify all malignancies by date, type and outcome. Standardized morbidity rates (SMR) were calculated based on the sex- and age-matched general population of the region. Sixteen malignancies occurred in 13 patients out of a total of 116 SLE patients observed for 1086 patient-years. The SMR for all cancers detected was 2.24 (confidence interval 0.6-5.7) for males and 1.02 (confidence interval 0.4-2.1) for females and thus indicative of no general increase in malignancies. However, the SMR for non-Hodgkin lymphoma was 11.63 (confidence interval 1.4-42.0), for pulmonary cancer 5.55 (confidence interval 0.7-20.1) and prostatic cancer 6.41 (confidence interval 1.3-18.7) all significantly increased. The increase in prostatic carcinoma disappeared when only cases occurring after a latency period of 3y after SLE diagnosis were included. In this comprehensive inception cohort of SLE no increase in relative risk of malignancy overall was found, but the frequencies of non-Hodgkin lymphoma and pulmonary cancer were increased, possibly also the frequency of prostatic carcinoma.

Aged↗

Familial breast and ovarian cancer: a Swedish population-based register study.

A cohort of offspring of mothers with breast or ovarian cancer diagnosed in 1958-1993 was established using Swedish population-based registers. The children (n = 158,041) were born between 1941 and 1993, and their cancer incidence was followed between 1961 and 1993. A total of 3,257 tumors in 3,102 children were found. Observed numbers of cases were compared with expected numbers based on national calendar year-, age-, and sex-specific incidences. For daughters of women with breast cancer, the standardized morbidity ratios for being diagnosed with breast cancer and ovarian cancer before age 50 years were 1.99 (95% confidence interval (CI): 1.86, 2.14) and 1.28 (95% CI: 1.05, 1.54), respectively. The corresponding figures for daughters of women with ovarian cancer were 1.79 (95% CI: 1.55, 2.07) and 2.38 (95% CI: 1.77, 3.12). The risks were raised if the mother's cancer was diagnosed at a young age, the mother had multiple breast/ovarian diagnoses, or there was a sister with breast/ovarian cancer. Among all offspring, increased risks were found for thyroid cancer, testicular cancer, and malignant melanoma, while lung cancer risk was decreased if the mother had had breast cancer. The authors developed a variance estimator for the standardized morbidity ratio to cope with overdispersion due to dependency within families.

Adult↗

Tumour biology of a breast cancer at least partly reflects the biology of the tissue/epithelial cell of origin at the time of initiation - a hypothesis.

A hypothesis is presented suggesting that initiation of breast epithelial cell freezes the cell at least partly according to the development/differention of cell at the time of initiation. Tumour biology will mimic the physiology of normal cell development at the time of initiation and this is preserved at least partly onwards. Also preferentially, tumours will develop from the cell type that is proliferating at the time of initiation. This may explain the overrepresentation of different types of histology in breast cancer in relation to age of the woman. The development of each tumour may follow at least partly a distinct pathway of evolution.

Age Factors↗

MYB oncogene amplification in hereditary BRCA1 breast cancer.

Comparative genomic hybridization analysis has demonstrated that breast tumors from BRCA1 and BRCA2 germ-line mutation carriers contain a large number of chromosomal copy number gains and losses. A high regional copy number gain at 6q22-q24 was observed in one BRCA1 tumor, and fluorescence in situ hybridization analysis indicated a strong amplification of the MYB oncogene (15 copies of MYB compared with 1 copy of chromosome 6 centromere). Fluorescence in situ hybridization analysis revealed amplification of MYB in 5 (29%) of 17 BRCA1 breast tumors, whereas none of 8 BRCA2 tumors and 13 breast cancer cell lines, and only 2 of 100 sporadic breast tumors exhibited altered MYB copy numbers. Gene amplification resulted in mRNA overexpression as determined by Northern blot and cDNA microarray analysis, and protein overexpression by immunohistochemical staining. We conclude that MYB amplification is infrequent in sporadic breast cancer but common in breast tumors from BRCA1 mutation carriers, suggesting a role of this cell cycle regulator and transcription factor in the progression of some BRCA1 tumors. However, we cannot rule out the significance of other genes in the 6q22-q24 amplicon.

Blotting, Northern↗

Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus.

A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for breast cancer by using mathematical models to identify early somatic genetic deletions in tumor tissues followed by targeted linkage analysis. Comparative genomic hybridization was used to study 61 breast tumors from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations. Branching and phylogenetic tree models predicted that loss of 13q was one of the earliest genetic events in hereditary cancers. In a Swedish family with five breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared 13q21 germ-line haplotype in the family. Targeted linkage analysis was carried out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10). The multipoint logarithm of odds score under heterogeneity was 3.46. The results were further evaluated by simulation to assess the probability of obtaining significant evidence in favor of linkage by chance as well as to take into account the possible influence of the BRCA2 locus, located at a recombination fraction of 0.25 from the new locus. The simulation substantiated the evidence of linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative breast cancer predisposition locus in other populations.

Aged↗

Increased cancer risk in offspring of women with colorectal carcinoma: a Swedish register-based cohort study.

BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background. METHODS: Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-based register study. The children were born during the period 1941-1993, and the cancer incidence was observed during the period 1961-1993, with the expected national Swedish incidence used as a reference. RESULTS: A significantly increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was observed in the cohort. The cancer risk was more pronounced in children whose mothers were age < 50 years at the time of diagnosis or had developed metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied an increased risk for both colon tumors and rectal tumors, the offspring of women who were diagnosed with rectal carcinoma were at increased risk of developing rectal carcinoma, but no significantly altered risk of colon carcinoma was observed. In the cohort, the cumulative risk for colorectal carcinoma before age 50 years was increased about 3.0 times compared with the general population. CONCLUSIONS: This report shows a significant familial aggregation of colorectal carcinoma, demonstrates possible differences in hereditary pattern between colon carcinoma and rectal carcinoma, and confirms that younger age at the time of diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.

Cohort Studies↗

High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families.

BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. We analyzed families with two or more cases of melanoma for germline mutations in CDKN2A and CDK4 to elucidate the contribution of these gene defects to familial malignant melanoma and to the occurrence of other cancer types. METHODS: : The entire CDKN2A coding region and exon 2 of the CDK4 gene of an affected member of each of 52 families from southern Sweden with at least two cases of melanoma in first- or second-degree relatives were screened for mutations by use of polymerase chain reaction-single-strand conformation polymorphism analysis. Statistical tests were two-sided. RESULTS: : CDKN2A mutations were found in 10 (19%) of the 52 families. Nine families carried an identical alteration consisting of the insertion of arginine at position 113 of p16(INK4a), and one carried a missense mutation, in which the valine at position 115 was replaced with a glycine. The 113insArg mutant p16(INK4a) was unable to bind cdk4 and cdk6 in an in vitro binding assay. Six of the 113insArg families had at least one member with multiple primary melanomas; the 113insArg families also had a high frequency of other malignancies-in particular, breast cancer (a total of eight cases compared with the expected 2.1; P =.0014) and pancreatic cancer (a total of six cases compared with the expected 0.16; P<.0001). Families with breast cancer also had a propensity for multiple melanomas in females, suggesting that a sex-dependent factor may modify the phenotypic expression of CDKN2A alterations. CONCLUSIONS: : Our findings confirm that the majority of CDKN2A-associated melanoma families in Sweden are due to a single founder mutation. They also show that families with the CDKN2A 113insArg mutation have an increased risk not only of multiple melanomas and pancreatic carcinoma but also of breast cancer.

Amino Acid Sequence↗

Sunscreen use and malignant melanoma.

In a new population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma, between 1995 and 1997, and 913 healthy controls aged 16 to 80 years, the association between sunscreen use and malignant melanoma was evaluated. The median sun protection factor (SPF) used by both cases and controls was 6, range 2 to 25. Sunscreen users reported greater sun exposure than non-users. Persons who used sunscreens did not have a decreased risk of malignant melanoma. Instead, a significantly elevated odds ratio (OR) for developing malignant melanoma after regular sunscreen use was found, adjusted for history of sunburns, hair color, frequency of sunbathing during the summer, and duration of each sunbathing occasion ¿OR = 1.8, 95% confidence interval (CI) 1.1-2.9]. The OR was higher in subjects who reported that sunscreen use enabled them to spend more time sunbathing (adjusted OR = 8.7, 95% CI 1.0-75.8 for always vs. never use). The association appeared to hold for subjects who did not suffer from sunburns while using sunscreens, for subjects who used SPF of 10 or lower, and among men. The pattern of a significantly increased melanoma risk was seen only for lesions of the trunk. Our results are probably related mainly to earlier sunscreens of low SPF. They substantiate the hypothesis that sunscreen use, by permitting more time sunbathing, is associated with melanoma occurrence.

Adolescent↗

One-year safety study with bambuterol once daily and terbutaline three times daily in 2-12-year-old children with asthma. The Bambuterol Multicentre Study Group.

The aim of this study was to compare bambuterol oral solution (10 mg) administered once daily in the evening with terbutaline oral solution (0.075 mg/kg body weight) administered three times daily in 2-5-year-old children and to compare bambuterol tablets (10 mg or 20 mg) administered once daily in the evening with terbutaline tablets (2.5 mg) administered three times daily in 6-12-year-old children with asthma. The study was of an open, randomized, parallel-group design, and lasted 1 year. The primary objective was to evaluate safety (pulse rate, blood pressure, adverse events, hematology, and clinical chemistry). Plasma terbutaline concentrations were also measured. Evaluation of efficacy (FEV(1)) was a secondary objective. A total of 141 patients (83 boys, 58 girls) were randomized and treated with the study drugs, i.e., 43 patients in the terbutaline group (30 on oral solution and 13 on tablets) and 98 patients in the bambuterol group (62 on oral solution and 36 on tablets). A total of 11 patients discontinued the study: 3 were on terbutaline, and 8 were on bambuterol. There were no clinically important differences between treatment groups regarding pulse rate, or systolic or diastolic blood pressure. There were no clinically important findings in the laboratory tests (hematology and clinical chemistry). Both terbutaline and bambuterol were well-tolerated, and the reported adverse events were mostly mild or moderate. Mean steady state plasma terbutaline concentrations at the visits ranged between 8.0-11.5 nmol/L in the bambuterol tablet group and between 10.6-15.2 nmol/L in the terbutaline tablet group. The corresponding values in children on oral solution were 10.3-11.3 nmol/L in the bambuterol group and 7.5-9.7 nmol/L in the terbutaline group. FEV(1) measured in the 6-12-year-old children increased by more than 0.2 L in both treatment groups during the year in the study. In conclusion, bambuterol tablets or oral solution once daily and terbutaline tablets or oral solution three times daily showed a comparable and favorable safety profile.

Administration, Oral↗

Somatic frameshift alterations in mononucleotide repeat-containing genes in different tumor types from an HNPCC family with germline MSH2 mutation.

Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a germline mutation in one of several DNA repair genes, which in the tumors is reflected as microsatellite instability (MSI). MSI+ tumors have been found to carry somatic frameshift mutations in mononucleotide repeats within the coding regions of several genes involved in growth control, apoptosis, and DNA repair, e.g., TGFBRII, BAX, IGFIIR, TCF4, MSH3, and MSH6. We have studied the occurrence of somatic frameshift alterations in these mononucleotide repeat-containing genes in 24 tumors (15 colorectal cancers, 1 colon adenoma, 4 endometrial cancers, 1 ovarian cancer, 1 gastric cancer, 1 urothelial cancer, and 1 duodenal cancer) from 14 individuals in an HNPCC family with germline hMSH2 mutation. Such somatic frameshift mutations occurred at a variable frequency; the long mononucleotide repeats that characterize intronic MSI markers were mutated in the majority of tumors, 13 of the tumors displayed alterations in the (A)(10) tract of TGFBII, eight tumors (all of gastrointestinal origin) had alterations in the (A)(9) repeat of TCF4, and one to five tumors had somatic frameshift alterations in the shorter mononucleotide repeats of IGFIIR, BAX, MSH3, and MSH6. Thus, longer mononucleotide repeats were more frequently affected by somatic frameshift mutations. The pattern of alterations varied between the tumors from different family members as well as between different tumors from the same individual. To what extent this variable pattern depends on the widespread mismatch repair deficiency induced by the underlying MSH2 mutation, or represents alternative ways whereby the tumors can achieve a tumorigenic phenotype, is unknown. We suggest, however, that the accumulation of somatic frameshifts, rather than the specific loci in which these occur, drives the development of the tumorigenic phenotype in HNPCC.

Aged↗

Prognosis and clinical presentation of BRCA2-associated breast cancer.

54 female breast cancer patients from 22 families with BRCA2 germ line mutations from Sweden and Denmark were compared with 214 age- and date of diagnosis-matched controls identified among breast cancer patients from South Sweden. At diagnosis, BRCA2-associated cases were more often node-positive (N+). OR=1.9 (95% confidence interval (CI)=1.0-3.6; P=0.036), and were more often clinical stage IV: OR=4.6 (95% CI=1.3-17; P=0.021) than the controls. Bilateral disease was also more common among the BRCA2-associated cases: OR=2. 4 (95% CI=1.1-5.3; P=0.027). Breast cancer-specific survival (BCSS) was significantly worse among the BRCA2-associated cases: RR=2.0 (95% CI=1.2-3.4; P=0.010). When stage was corrected for in a multivariate analysis, BCSS was no longer significantly worse for the BRCA2-associated cases: RR=1.6 (95% CI=0.85-3.1). The corresponding effect after correction for bilateral disease was: RR=1.8 (95% CI=1.0-3.1; P=0.034). The unfavourable prognosis in BRCA2-associated breast cancer seems, to a great extent, to be a consequence of the higher clinical stage at diagnosis. The increased presence of bilateral cancers appears to have less impact on survival in this group of hereditary breast cancer. Data presented here needs to be taken into account when counselling healthy carriers of BRCA2 germ line mutations.

Adult↗

Risk perception, screening practice and interest in genetic testing among unaffected men in families with hereditary prostate cancer.

Approximately 5-10% of prostate cancer cases are caused by dominantly inherited susceptibility to the disease. Although advances have been made in research concerning the genetic mechanisms of hereditary prostate cancer, little is known about the psychological consequences for men at high risk of developing the disease. The aims of the present study were to examine risk perception, interest in genetic investigations, cancer-specific worry, and screening practice among unaffected men, aged 40-72 years old, with a pedigree consistent with hereditary prostate cancer and an estimated lifetime risk of prostate cancer of 35-45%. A questionnaire was sent by mail to 120 subjects, of whom 110 responded. Most of the men (n = 90, 82%) worried about having an inherited susceptibility to prostate cancer, and 34 (31%) claimed that worry about prostate cancer affected their daily life (3 (3%) fairly much, 31 (28%) slightly). As many as 40% of the study subjects perceived their lifetime risk of prostate cancer as 67% or more. Perceived high risk was associated with symptoms of depression and with cancer worry affecting daily living. Two-thirds of the men aged 50 years old or more were regularly screened for prostate cancer. Subjects with high levels of cancer-specific stress, as measured by the avoidance subscale of the Impact of Event Scale, were less likely to opt for screening. Almost all of the men (94%) were interested in presymptomatic genetic testing (84 (76%) "definitely yes" and 20 (18%) "probably yes"). We conclude that hereditary susceptibility to prostate cancer has significant psychological consequences although it rarely causes psychiatric morbidity. The present study underlines the importance of giving thorough, repeated information to men at high risk of prostate cancer.

Adult↗

Estrogen receptor content in malignant breast tumors in men--a review.

Male breast cancer is a rare disease and clinical or epidemiological data are available from only a relatively few cases. Nonetheless, both similarities and discrepancies are apparent between breast cancer in men and women. For example, lobular and mucinous carcinomas are seldom seen in men. Tumors in men more often display neuroendocrine differentiation, with an average age at diagnosis ten years later than in women. A high proportion of breast tumors in men are estrogen receptor-alpha positive (in this review 77%) and progesterone receptor positive (76%). Breast tumors in men often respond favorably to endocrine manipulation, including testicular ablation or antiestrogen therapy. Thus, the hormone receptors in these tumors can be functionally active and used for therapeutic intervention. This proposal has been questioned in some studies because estrogen dependent proteins are expressed to a lesser degree in men. Furthermore, men do not have a better overall breast cancer prognosis compared with women, after adjustments have been made for age and tumor stage. While the androgen receptor content has been assessed in a few studies, there are no studies on the estrogen receptor-beta content of breast tumors in men.

Adult↗

Naive empiricism and dogmatism in confidence research: a critical examination of the hard-easy effect.

Two robust phenomena in research on confidence in one's general knowledge are the overconfidence phenomenon and the hard-easy effect. In this article, the authors propose that the hard-easy effect has been interpreted with insufficient attention to the scale-end effects, the linear dependency, and the regression effects in data and that the continued adherence to the idea of a "cognitive overconfidence bias" is mediated by selective attention to particular data sets. A quantitative review of studies with 2-alternative general knowledge items demonstrates that, contrary to widespread belief, there is (a) very little support for a cognitive-processing bias in these data; (b) a difference between representative and selected item samples that is not reducible to the difference in difficulty; and (c) near elimination of the hard-easy effect when there is control for scale-end effects and linear dependency.

Cognition↗

Visual perception of dynamic properties: cue heuristics versus direct-perceptual competence.

Constructivist and Gibsonian approaches disagree over the possibility of direct perceptual use of advanced information. A trenchant instance concerns visual perception of underlying dynamic properties as specified by kinematic patterns of events. For the paradigmatic task of discrimination of relative mass in observed collisions, 2 mathematical models are developed, 1 model representing a direct, invariant-based approach, and 1 representing a cue-heuristic approach. The models enable a critical experimental design with distinct predictions concerning performance data and confidence ratings. Although pretraining results were mixed, the invariant-based model was empirically confirmed after a minimal amount of training: Competence entails the use of advanced kinematic information in a direct-perceptual ("sensory") mode of apprehension, in contrast to beginners' use of simpler cues in an inferential ("cognitive") mode.

Biomechanical Phenomena↗