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Biomedical subjects

H Olsson

Publications and source records attributed to H Olsson.

At least 91 records · Page 5Linked to original sources

Urinary incontinence: an unexpected large problem among young females. Results from a population-based study.

BACKGROUND: The International Continence Society has defined urinary incontinence as a condition in which involuntary loss of urine is objectively demonstrable and is a social or hygiene problem. Urinary incontinence is presumably a common health problem among women even in younger ages. OBJECTIVES: The primary aim was to investigate the prevalence of urinary incontinence (UI) in a female population with a special focus on younger women (18-30 years old). The secondary aim was to investigate the association between UI and number of deliveries, use of contraceptives or oestrogen substitutions, and urinary tract infections (UTIs). METHODS: A population-based study with a self-administered questionnaire was set in the community of Surahammar, Sweden. Subjects were all women (3493) aged 18-70 years living in Surahammar during 1995. The main outcome measures were the prevalence of UI and variables such as number of deliveries, use of contraceptives or oestrogen substitutions, and UTIs. RESULTS: Twenty-six per cent of the women reported problems of UI. The prevalence of UI in younger women was 12%. The number of reported complaints of UTIs was significantly higher in the women with UI compared with women without urinary incontinence (wUI). In the younger women UTI, nulliparous or having given birth to one or two children were most frequent in those with UI. The use of contraceptives was more common in younger women without UI (P < 0.05). However, the use of oestrogen was more common in older women in the age group 51-70 years with UI (P < 0.01). CONCLUSION: Our findings have shown that 26% of the women who took part in the survey reported problems of UI. Among women below 30 years of age, 12% reported complaints of UI. We found a high prevalence of UI in younger women with a UTI, not taking oestrogen, nulliparous or having given birth to one or two children. There are needs for further investigations with a special focus on younger women.

Adolescent↗

Quantification of [11C]FLB 457 binding to extrastriatal dopamine receptors in the human brain.

Positron emission tomography (PET) has hitherto been used to examine D2 dopamine receptor binding in the striatum, a region with a high density of receptors. Research has been hampered by the lack of suitable radioligands for detection of the low-density D2 dopamine receptor populations in the limbic and cortical dopamine systems that are implicated in the pathophysiology of schizophrenia. [11C]FLB 457 is a new radioligand with the very high affinity of 20 pmol/L (K(i)) for the D2 and D3 dopamine receptor subtypes. This study in eight healthy subjects was designed to evaluate the suitability of [11C]FLB 457 for quantification of extrastriatal D2/D3 dopamine receptors. PET-data were acquired in the three-dimensional mode and the arterial input function was corrected for labeled metabolites. The standard three-compartment model and four derived approaches were applied to calculate and compare the binding potentials. Besides the striatum, conspicuous radioactivity was found in extrastriatal regions such as the thalamus, the anterior cinguli, and the temporal and frontal cortices. The time activity curves could be described by the three compartment model. The different approaches gave similar binding potential values and the rank order between regions was consistent with that found in vitro. The short time of a PET measurement using [11C]FLB 457 (63 minutes) seemed not to be sufficient for reliable determination of the high binding potential in the striatum. These results are of principal importance because they show the potential for PET quantification of minute receptor populations in the human brain.

Adult↗

Clinical and histopathological characteristics in relation to aetiological risk factors in cutaneous melanoma: a population-based study.

In this population-based, case-control study from Sweden using data collected from 1988 to 1990, an increased risk of melanoma was associated with the number of sunburns, propensity to freckle, the number of raised naevi and a family history of melanoma. Furthermore, a decreased risk was associated with occupational sun exposure. The purpose of this study was to investigate whether different histopathological features of the melanoma and clinical factors were related to the different aetiological risk factor patterns. All the confirmed primary cutaneous melanomas (n = 366) were included in the study. Both univariate analyses with tests for interaction and multivariate analyses were performed. Patients with melanoma on the trunk and patients with thin melanomas had an excess of close relatives with a history of melanoma (odds ratios [ORs] = 2.7 and 2.3, respectively). A relationship was also seen between melanomas in younger persons and a family history of melanoma (OR = 2.6). The presence of raised naevi on the arm had a tendency to be closer related to melanoma of the nodular type (OR = 4.3) than melanoma of the superficial spreading type (OR = 1.6). Patients with outdoor occupations during summer had a decreased risk of developing melanoma on the extremities. Melanoma diagnosed in patients born before 1939 had an association with sunburns (OR = 1.9) and freckling (OR = 2.0), while melanomas in patients born in 1939 or later were related to a family history of melanoma (OR = 2.2). These results suggest that different histopathological and clinical features of melanoma are associated with different risk factor patterns, which may imply diverging tumour genesis.

Adolescent↗

The influence of interferon-alpha on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite in patients with multiple myeloma.

The pharmacokinetics of cyclophosphamide (CP) and its cytotoxic metabolite 4-hydroxycyclophosphamide (4-OHCP) have been studied in multiple myeloma patients treated with the CIB (CP, interferon-alpha (IFN-alpha) and betamethasone) regimen. In the present investigation we aimed to determine whether exposure to CP and its cytotoxic metabolite 4-OHCP is influenced by the concomitant administration of IFN-alpha. Ten patients with previously untreated multiple myeloma entered the study. Each patient received two courses of CIB in randomized order. Interferon was administered either 2 h before the CP infusion in one course or 24 h after the CP infusion in the other course. A cyclophosphamide dose of 750-900 mg/m2 was given as a 2 h constant infusion. Interferon-alpha (10-15 x 10(6) IE) was given subcutaneously. All patients received betamethasone 24 h after CP or later. The elimination of CP was described by monoexponential decay. The administration of IFN-alpha before CP caused a decrease in CP clearance to 63% (P=0.004), a 137% longer half-life (P = 0.004) and a 137% higher peak plasma concentration (P = 0.006) compared to the results obtained when IFN-alpha was administered 24 h after CP. The formation of 4-OHCP was also affected by the administration of IFN-alpha prior to CP, 45% less exposure to 4-OHCP expressed as AUC (P = 0.002) and a 61% lower peak plasma concentration (P = 0.002) compared with that observed when IFN-alpha was administered 24 h after CP. The administration of IFN-alpha after CP resulted in a greater (45%, P = 0.02) decrease in leukocyte count compared with results when IFN-alpha was given before CP. This study demonstrates that the administration of IFN-alpha prior to CP significantly impairs pharmacokinetics of CP and 4-OHCP. When IFN-alpha was administered after CP, a higher exposure to the cytotoxic metabolite 4-OHCP was observed and reflected by a significant decrease in leukocyte count compared to that when IFN-alpha was given before CP. In conclusion, the time of administration of IFN-alpha in relation to concomitant chemotherapy (CP) has to be considered to obtain a higher efficacy of IFN-alpha/alkylating agent combining regimens for induction in multiple myeloma and related disorders.

Aged↗

Comparison of oral bambuterol and inhaled salmeterol in patients with symptomatic asthma and using inhaled corticosteroids.

Salmeterol inhaled twice-daily is now being used more frequently as additional treatment in asthma insufficiently controlled by inhaled corticosteroids. We compared oral bambuterol in a dose of 20 mg taken once daily in the evening with inhaled salmeterol at 50 microgram taken twice daily in 126 asthmatic patients (60 bambuterol, 66 salmeterol) aged 18 to 74 yr who were treated for at least 4 wk with inhaled corticosteroids at a constant dose of 400 to 2,000 microgram/d or with oral corticosteroids at </= 20 mg/d. The patients were able to use a pressurized metered dose inhaler (pMDI) efficiently, and had an FEV1 of 40 to 85% of the predicted normal value. During a run-in period, patients had to show at least one nocturnal or early awakening caused by asthma symptoms that required rescue medication, and a >/= 15% overnight decrease in peak expiratory flow (PEF) on 3 of the preceding 7 d, in order to be randomized into this double-blind, double dummy, multicenter parallel group study (2-wk run-in period and 6 wk of treatment). There was no significant difference between bambuterol and salmeterol in morning change from baseline in PEF (p = 0.53). The median increases in morning PEF were 50 L/min for bambuterol and 55 L/min for salmeterol. Other variables (evening PEF, percent of overnight decrease in PEF, number of awakenings, percent of nights with an awakening, number of puffs of rescue medication, asthma symptoms during the day and night, and mean tremor score) also showed no significant difference between bambuterol and salmeterol. Both treatments, at the doses given, were well tolerated. Once-daily oral bambuterol is a convenient, effective, and less expensive alternative to twice-daily inhaled salmeterol for treating nocturnal asthma.

Administration, Inhalation↗

What is the role of giant cells in AL-amyloidosis?

AL-amyloidosis is one of the most common amyloidoses and can be found in a localized and a systemic form. The precursor protein is an immunoglobulin light chain which as AL-protein in both localized and systemic AL-amyloidosis shows the same pattern of fragmentation and changes of primary structure. In this work it is shown that that there is a difference between localized and systemic amyloidosis in respect to accompanying giant cells which constantly are found associated with amyloid deposits in localized AL-amyloidosis. In addition, giant cells were found together with amyloid deposits in lymph nodes of some cases of systemic AL-amyloidosis. Based on these findings and electron microscopic studies, it is discussed whether the giant cells actively participate in amyloid fibril formation by uptake and modification of the precursor protein or the giant cells are part of a foreign body reaction. Included in this work are two new cases of localized lung (lambda I) and ureteric (kappa I) AL-amyloidosis.

Amino Acid Sequence↗

Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group.

BACKGROUND: Women with mutations in either the BRCA1 or the BRCA2 gene have a high lifetime risk of ovarian cancer. Oral contraceptives protect against ovarian cancer in general, but it is not known whether they also protect against hereditary forms of ovarian cancer. METHODS: We enrolled 207 women with hereditary ovarian cancer and 161 of their sisters as controls in a case-control study. All the patients carried a pathogenic mutation in either BRCA1 (179 women) or BRCA2 (28 women). The control women were enrolled regardless of whether or not they had either mutation. Lifetime histories of oral-contraceptive use were obtained by interview or by written questionnaire and were compared between patients and control women, after adjustment for year of birth and parity. RESULTS: The adjusted odds ratio for ovarian cancer associated with any past use of oral contraceptives was 0.5 (95 percent confidence interval, 0.3 to 0.8). The risk decreased with increasing duration of use (P for trend, <0.001); use for six or more years was associated with a 60 percent reduction in risk. Oral-contraceptive use protected against ovarian cancer both for carriers of the BRCA1 mutation (odds ratio, 0.5; 95 percent confidence interval, 0.3 to 0.9) and for carriers of the BRCA2 mutation (odds ratio, 0.4; 95 percent confidence interval, 0.2 to 1.1). CONCLUSIONS: Oral-contraceptive use may reduce the risk of ovarian cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene.

Adult↗

Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen.

Cartilage and tendon extracellular matrices are composed of collagens, proteoglycans, and a number of noncollagenous proteins. Cartilage oligomeric matrix protein (COMP) is a prominent such protein, structurally related to the thrombospondins. We found that native COMP binds to collagen I/II and procollagen I/II and that the interaction is dependent on the divalent cations Zn2+ or Ni2+, whereas Ca2+, Mg2+, and Mn2+ did not promote binding. Using a solid phase assay, Scatchard analysis identified one class of binding site with a dissociation constant (Kd) close to 1.5 nM in the presence of Zn2+. The results were confirmed by studies using surface plasmon resonance. Furthermore, metal chelate chromatography demonstrated that COMP bound Zn2+ and Ni2+. Electron microscopy showed that the interaction occurred at four defined sites on the 300-nm collagen and procollagen molecules. Two were located close to each end, and two at 126 and 206 nm, respectively, from the C-terminal. COMP interacted via its C-terminal globular domain and significantly only in the presence of Zn2+.

Binding Sites↗

Purification and characterization of a protein binding to the SP6 kappa promoter. A potential role for CArG-box binding factor-A in kappa transcription.

A protein interacting with an A-T-rich region that is a positive control element within the SP6 kappa promoter was purified and identified as CArG-box binding factor-A. The purified protein was shown to interact specifically with the coding strand of single-stranded DNA and, with lower affinity, with double-stranded DNA. A mutation that inhibited binding of the protein to the A-T-rich region also aborted the transcriptional stimulatory effect of the region. Two Ets proteins, PU.1 and elf-1, that have previously been shown to bind to an adjacent DNA element were shown to physically interact with CArG-box binding factor-A. An antiserum raised against the protein recognized two different forms indicating either that different splice-forms of CArG-box binding factor-A are expressed, or that the protein is subject to post-translational modification.

Alternative Splicing↗

A PET study of D2 dopamine receptor density at different phases of the menstrual cycle.

Behavioral and biochemical studies in animals indicate that central dopaminergic neurotransmission may be modulated by sex steroids. This may be the mechanism underlying the suggested association between estrogen and schizophrenia. The aim was to examine if different levels of sex steroids during the menstrual cycle are associated with variations in D2 dopamine receptor density as measured with positron emission tomography (PET) and [11C]raclopride. Five healthy women were examined, one during two subsequent follicular phases and four during two different phases of their menstrual cycle. In none of the women did the difference in putamen to cerebellum (P/C) ratios (-11 to 10%) exceed the difference in P/C ratios previously reported in test-retest analyses in men (-11 to 9%). The findings do not support the conclusion that there is a menstrual-cycle-dependent variation in D2 receptor density detectable with single PET examinations and [11C]raclopride. Furthermore, a stable P/C ratio throughout the menstrual cycle indicated a stable D2 receptor occupancy in schizophrenic women treated with antipsychotic drugs. Repeated PET examinations of schizophrenic women known to deteriorate during particular phases of their menstrual cycle may further contribute to our understanding of the association between schizophrenia and sex steroids.

Adult↗

Steroid receptors in hereditary breast carcinomas associated with BRCA1 or BRCA2 mutations or unknown susceptibility genes.

BACKGROUND: The expression of steroid receptors is a common feature of both male and female breast carcinomas and is also one of the most important prognostic factors for patients with this disease. Steroid receptor levels in BRCA1-related breast carcinoma have reportedly been low. Little data on steroid receptor levels have been reported with regard to BRCA2. METHODS: Steroid receptor levels were analyzed in 27 breast carcinomas associated with BRCA1 mutations, 14 associated with BRCA2 mutations, and 32 from individuals who had hereditary breast carcinoma but no detectable mutations of either BRCA1 or BRCA2. Breast carcinomas from 32 consecutive male patients, 6 of whom had mutations of BRCA2, were also examined for steroid receptors. Estrogen receptor (ER) and progesterone receptor (PgR) analyses were performed with radioligand or enzyme immunoassay techniques on tumor cytosol preparations. Germline mutation screening and detection were performed using the protein truncation test, single strand conformation polymorphism, and direct sequencing on DNA from normal tissue. RESULTS: The BRCA1-related tumors expressed significantly lower levels of ER than tumors from the other hereditary groups. The PgR levels were significantly lower in the BRCA1-related cases than in the hereditary cases not related to BRCA1 or BRCA2, but not significantly lower than in the BRCA2-related cases. Fourteen of 32 (44%) of the hereditary tumors not related to BRCA1 or BRCA2 had PgR levels exceeding 100 fmol/mg of protein. The tumors from male patients with BRCA2-related disease did not have receptor levels that differed from those in non-BRCA2-related tumors. CONCLUSIONS: BRCA1- and BRCA2-related breast tumors were distinct in their expression of steroid receptors. Moreover, a subgroup of tumors not related to BRCA1 or BRCA2 manifested a strongly positive PgR phenotype rarely seen in BRCA1- and BRCA2-related tumors. These characteristics may be of relevance to the treatment and follow-up of high risk individuals in these families and may help identify a homogeneous category of hereditary breast carcinomas not related to BRCA1 or BRCA2 in which new susceptibility genes may be sought.

Adult↗

BRCA2 germ-line mutations are frequent in male breast cancer patients without a family history of the disease.

Breast cancer is a rare disease in men, affecting less than 0.1% of the male population. Two heritable gene defects have been associated with a predisposition to male breast cancer development, ie., germ-line mutations in the breast cancer susceptibility gene BRCA2 and the androgen receptor (AR) gene. In this study, the entire coding regions of BRCA2 and AR were screened for mutations in 34 consecutive male breast cancer patients. Five different truncating BRCA2 mutations were identified in 7 (21%) of the 34 cases, with all mutations being of germ-line origin. Three of the mutated cases carried the same mutation (4186delG), which has been found earlier in two Swedish families with multiple female breast cancer cases. Haplotype analysis supported a common ancestry of 4186delG. One mutation, 6503delTT, was found in a male carrying also a previously identified COOH-terminal polymorphic stop codon (Lys3326ter). No differences were seen between mutation carriers and noncarriers with respect to clinical stage and estrogen or progesterone receptor status. Mutation carriers tended to be younger at diagnosis. No germ-line AR mutations were found in the present material, but the number of AR polyglutamine repeats tended to be lower among mutation carriers. Most surprisingly, only one of the seven BRCA2 mutation carriers had a positive family history of breast cancer, suggesting a lower penetrance of some BRCA2 mutations or an influence of modifying factors for disease development in males and females. The present study implies that approximately one-fifth of all male breast cancer cases in the Swedish population are due to germ-line BRCA2 mutations.

Aged↗

Analysis of Swedish male breast cancer family data: a simple way to incorporate a common sibling effect.

Based on a population-based cohort study, Olsson et al. [1993] found significant evidence for elevated incidence of breast and ovarian cancers among female first-degree relatives of men with breast cancer. Using an extension of logistic regressive models we investigate whether, after allowing for multifactorial familial correlations, single locus segregation could be the cause of the elevated incidence in these families. The logit for a given sib in the class D logistic regressive model depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as being computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sibling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysis. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the models we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This could either be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.

Adult↗