Biomedical subjects

Lars Rylander

Publications and source records attributed to Lars Rylander.

32 records · Page 2Linked to original sources

PubMed2004

MDS/AML-associated cytogenetic abnormalities in multiple myeloma and monoclonal gammopathy of undetermined significance: evidence for frequent de novo occurrence and multipotent stem cell involvement of del(20q).

Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are characterized cytogenetically by 14q32 rearrangements, -13/13q-, and various trisomies. Occasionally, karyotypic patterns characteristic of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) occur in MM, often signifying therapy-related (t)-MDS/t-AML. Comparison of cytogenetic features in all published MMs (n = 993) and t-MDS/t-AML post-MM (n = 117) revealed significant differences in complexity and ploidy levels and in most genomic changes. Thus, these features often can be used to distinguish between MM and t-MDS/t-AML. Rarely, myeloid-associated aberrations are detected in MM without any signs of MDS/AML. To characterize such abnormalities in MM/MGUS, we ascertained all 122 MM and 26 MGUS/smoldering MM (SMM) cases analyzed in our department. Sixty-six (54%) MMs and 8 (31%) MGUS/SMMs were karyotypically abnormal, of which 6 (9%) MMs and 3 (38%) MGUS/SMMs displayed myeloid abnormalities, that is, +8 (1 case) and 20q- (8 cases) as the sole anomalies, without any evidence of MDS/AML. One patient developed AML, whereas no MDS/AML occurred in the remaining 8 patients. In one MGUS with del(20q), fluorescence in situ hybridization analyses revealed its presence in CD34+CD38- (hematopoietic stem cells), CD34+CD38+ (progenitors), CD19+ (B cells), and CD15+ (myeloid cells). The present data indicate that 20q- occurs in 10% of karyotypically abnormal MM/MGUS cases and that it might arise at a multipotent progenitor/stem cell level.

Aged↗

PubMed2004

Altered menstrual cycles in women with a high dietary intake of persistent organochlorine compounds.

Dietary exposure to persistent organochlorine compounds (POCs) has been found to affect the menstrual cycle in both animals and humans. In Sweden, the major exposure route for POCs is the consumption of fatty fish from the Baltic Sea. Thus, women who eat relatively large amounts of this fish constitute a suitable study group when investigating a possible association between dietary exposure to POC and menstrual cycle disruption. Questionnaires were sent to the exposed women, as well as to a socioeconomically similar cohort of controls, and information was collected on their menstrual cycles. Since the exposed women tended to smoke more than the controls, all results were adjusted for smoking habits. A cohort comparison found that the exposed women on average had 0.46 (95% confidence interval: 0.03, 0.89) days shorter menstrual cycles than controls. However, within the exposed cohort no effects were found of the proxy variables early life exposure and high consumption of Baltic Sea fatty fish. The results give some support to previous results from studies on women with similar exposure, but are not conclusive with respect to whether there is a causal association between POC exposure and menstrual cycle disruption.

Adolescent↗

PubMed2004

Polychlorinated biphenyls in serum and time to pregnancy.

Polychlorinated biphenyls (PCBs) may affect the female reproductive system in both animals and humans. In Sweden, a main exposure source to PCBs is consumption of fatty fish from the Baltic Sea. From 165 female consumers of such fish (fishermen's sisters), information on time to pregnancy (TTP) and miscarriages was collected, blood was drawn, and serum was analyzed for 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), a biomarker for total PCB exposure. TTP and miscarriage data, as well as plasma CB-153 concentrations, for 121 fishermen's wives were available from previous studies. Thus, information on 286 women was available for investigation of whether a high exposure to PCB affects fertility negatively by increasing the TTP. The concentrations of CB-153 at the time of conception were estimated and trichotomized into low, medium, and high exposure groups. When we analyzed the joint data set of fishermen's wives and fishermen's sisters, a decrease rather than an increase in TTP was indicated for women in the medium (fecundability ratio 1.27 [95% confidence interval 0.89-1.82]) and high (fecundability ratio 1.42 [0.99-2.03]) exposure groups compared to those in the low exposure group. Similar results were found when we stratified on the original data set (fishermen's wives and fishermen's sisters) or childhood exposure. Women with miscarriages had lower estimated past CB-153 concentrations than women with live births. Our data provide no evidence of a hazardous effect associated with CB-153 concentration in the exposure range assessed. The exposure levels found in the fishermen's families, although high compared to that in the general Swedish population, may not be high enough to negatively affect fertility.

Abortion, Spontaneous↗

PubMed2004

High frequencies of chromosomal aberrations in multiple myeloma and monoclonal gammopathy of undetermined significance in direct chromosome preparation.

Although many cases of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are cytogenetically normal, interphase fluorescence in situ hybridization (FISH) analyses reveal aberrations in the majority of the cases. Most likely, non-neoplastic cells are more prone to divide in culture than neoplastic cells. Direct chromosome preparations (DCP) would be one way to circumvent this methodological problem. We have investigated 47 bone marrow samples from 39 patients by DCP. A median of 58 metaphases (range 9-158) was analysed per sample. Interphase FISH analyses using probes to detect IGH rearrangements, -13/13q-, +3, +7, and +11 were also performed. Abnormal karyotypes were detected in 15 (63%) of 24 MM and in 4 (50%) of eight MGUS/smouldering MM (SMM) cases that could be successfully cytogenetically analysed. Age, sex, or degree of bone marrow plasma cell (PC) infiltration did not influence the karyotypic patterns (P > 0.05). However, the frequencies of aberrant karyotypes varied in relation to the Colcemide concentrations used - 7% (30 ng/ml) versus 69% and 67% (100 and 200 ng/ml, respectively) (P = 0.01). Combining the G-banding and FISH results, abnormalities were detected in 29 of 31 (94%) MM and in six of eight (75%) MGUS/SMM patients. Thus, cytogenetic and FISH analyses after DCP using 100-200 ng Colcemide/ml identified aberrations in most MM/MGUS/SMM, irrespective of PC percentages.

Adult↗

PubMed2004

Reproductive function during summer and winter in Norwegian men living north and south of the Arctic circle.

Seasonal, daylight-dependent variation in human spermatozoa counts, with lowest values during summer, has been suggested. To test this hypothesis, we performed a longitudinal study of semen quality and reproductive hormone levels in Norwegian men living north and south of the Arctic Circle. An ejaculate and a serum specimen were obtained both in summer and in winter from 92 volunteers in Tromsoe (69 degrees north latitude) and 112 in Oslo (60 degrees north latitude). Semen analyses were performed, and serum was assayed for FSH and inhibin B. The median spermatozoa concentration in Tromsoe after adjustment for abstinence period length was 49 x 10(6)/ml in summer and 54 x 10(6)/ml in winter. Corresponding values for Oslo were 59 x 10(6)/ml and 54 x 10(6)/ml. The seasonal differences in spermatozoa concentration were not statistically significant, nor were significant differences observed in median total spermatozoa count, semen volume, percentage progressive motile spermatozoa, or FSH. In Tromsoe, but not Oslo, inhibin B concentration was slightly, but significantly (P = 0.02) higher in winter than summer (229 ng/liter vs. 223 ng/liter). The length of the daylight period may have a slight impact on hormonal markers of spermatogenesis but does not cause substantial changes in spermatozoa numbers and motility.

Adult↗

PubMed2004

Exposure to persistent organochlorine compounds through fish consumption and the incidence of osteoporotic fractures.

OBJECTIVES: Animal studies have shown that persistent organochlorine compounds (POC) impair normal bone metabolism and result in increased bone fragility. These findings may have health implications for POC-exposed human populations. The aim of the present study was to assess the impact of POC-contaminated fish on the self-reported fracture incidence of Swedish fishermen and their wives. METHODS: A postal questionnaire was sent to 2096 fishermen and 1602 fishermen's wives from the Swedish east (exposed) coast and 4584 fishermen and 4217 fishermen's wives from the west (unexposed) coast. Self-reported fractures, together with specified current fish consumption and information about potential confounders, were registered. The response rates varied between 50% and 59%. The age distributions of the nonrespondents and respondents were almost identical. Hip, vertebral, and wrist fractures were classified as osteoporotic. The fracture incidence rates for specific skeletal locations were based on allocated fractures and person-years under risk from the age of 25 years until the time of fracture or the end of follow-up. RESULTS: No differences in fracture incidence were observed between the east and west-coast cohorts. East-coast wives with more than one meal of fatty fish from the Baltic Sea per month had, however, an increased fracture incidence as compared with that of the east-coast wives who ate, at most, one such meal per month (age-adjusted incidence rate ratio 1.68, 95% confidence interval 1.00-2.84). No such exposure-response association was found for the fishermen. CONCLUSIONS: The present study only minimally supports an association between POC exposure through contaminated fish and an increased risk of osteoporotic fractures.

Animals↗

PubMed2003

Incidence of hospitalized osteoporotic fractures in cohorts with high dietary intake of persistent organochlorine compounds.

OBJECTIVES: Environmental factors might be of importance for the dramatically increasing incidence of osteoporotic fractures. Persistent organochlorine compounds (POCs) have, in animal studies, impaired normal bone metabolism and resulted in increased bone fragility. The goal of this study was to assess whether a high dietary intake of POCs through fatty fish from the Baltic Sea may result in an increased incidence of osteoporotic fractures. METHODS: Fishermen and their wives from the Swedish east coast on the Baltic Sea (exposed) and west coasts (unexposed) constituted the study base. Information on vital status and hospitalization of persons with fractures from 1987 to 1996, classified according to the ninth revision of the International Classification of Diseases, was retrieved for 17,823 subjects through register linkages. The impact of coastal stretch on fracture incidence was assessed by Poisson regression models, with age and calendar year also being taken into account. RESULTS: There was a significantly increased incidence rate ratio (IRR: 2.29, 95% confidence intervals (CI): 1.23-4.28) for vertebral fractures among east-coast women, and a similar, but non-significant, similar tendency in men (IRR 1.45, 95% CI 0.74-2.84). Such cohort differences were not seen for any other fracture type. CONCLUSIONS: The results give some indirect support for the notion that a high dietary intake of POCs through fatty fish from the Baltic Sea might be a risk factor for vertebral fractures, but it cannot be excluded that confounding from differences in smoking habits might explain part of the observed effects. To clarify this, detailed individual information on exposure and potential confounders has to be ascertained.

Animals↗

PubMed2003

The incidence of respiratory symptoms in female Swedish hairdressers.

BACKGROUND: Airway diseases in hairdressers are a concern. The objective of this investigation is to evaluate the risk for three respiratory symptoms, wheeze, dry cough, and nasal blockage, in hairdressers. METHODS: A questionnaire on respiratory symptoms, atopy, smoking, and work history was answered by 3,957 female hairdressers and 4,905 women from the general population as referents. Incidence rates (IR) and incidence rate ratios (IRRs) for the three symptoms were estimated. RESULTS: The IRs of all three studied symptoms were higher in the hairdressers compared with the referents. Smoking modified the effects of cohort affiliation for all three symptoms; the combined effect from hairdressing work and smoking was less than expected. In addition, the effect of cohort affiliation for wheeze was also modified by atopy, and the effect of cohort affiliation for nasal blockage was also modified by calendar year. CONCLUSIONS: Hairdressing work was associated with increased incidences of respiratory symptoms. Smoking had a negative modifying effect.

Adult↗

PubMed2003

A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences.

The cytogenetic features (ploidy, complexity, breakpoints, imbalances) were ascertained in 783 abnormal multiple myeloma (MM) cases to identify frequently involved chromosomal regions as well as a possible impact of age/sex. The series included MM patients from the Mitelman Database of Chromosome Aberrations in Cancer and from our own laboratory. Hyperdiploidy was most common, followed by hypodiploidy, pseudodiploidy and tri-/tetraploidy. Most cases were complex, with a median of eight changes per patient. The distribution of modal numbers differed between younger and older patients, but was not related to sex. No sex- or age-related differences regarding the number of anomalies were found. The most frequent genomic breakpoints were 14q32, 11q13, 1q10, 8q24, 1p11, 1q21, 22q11, 1p13, 1q11, 19q13, 1p22, 6q21 and 17p11. Breaks in 1p13, 6q21 and 11q13 were more common in the younger age group. The most frequent imbalances were + 9, - 13, + 15, + 19, + 11 and - Y. Trisomy 11 and monosomy 16 were more common among men, while -X was more frequent among women. Loss of Y as the sole change and + 5 were more common in elderly patients, and - 14 was more frequent in the younger age group. The present findings strongly suggest that some karyotypic features of MM are influenced by endogenous and/or exogenous factors.

Age Factors↗

PubMed2003

Serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in relation to markers of reproductive function in young males from the general Swedish population.

A time-related deterioration in male reproductive function caused by exposure to endocrine disrupters, including persistent organochlorines (POCs), has been hypothesized. In animal studies, POCs were found to have adverse effects on male reproductive function. However, little is known about the impact of POC exposure on reproductive parameters in men. In a study of 305 young Swedish men 18-21 years old from the general population, we correlated lipid-adjusted serum levels of 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153)--an index substance for POC exposure--to markers of male reproductive function: testis size assessed by ultrasound, sperm concentration, total sperm count, sperm motility assessed manually and with a computer-aided sperm analyzer (CASA), and serum levels of follicle-stimulating hormone, inhibin B, testosterone, sexual hormone-binding globulin (SHBG), luteinizing hormone, and estradiol. We found weak but statistically significant, negative correlations between CB-153 levels and both the testosterone:SHBG ratio (r = -0.25, p < 0.001)--a measure of the biologically active free testosterone fraction--and CASA sperm motility (r = -0.13, p = 0.02). No statistically significant association with other seminal, hormonal, or clinical markers of male reproductive function was found. In previous studies of more highly POC-exposed groups of adult men, the correlation between POC exposure, including CB-153, and free testosterone levels was not statistically significant. The present study gives some tentative support for weak negative effects of CB-153 exposure on sperm motility and free testosterone levels in young men, but further semen studies on more highly exposed groups may give more firm conclusions on the hazard for male reproductive function from dietary POC exposure.

Adolescent↗

PubMed2003

Exposure-response relationships for hexahydrophthalic and methylhexahydrophthalic anhydrides with total plasma protein adducts as biomarkers.

OBJECTIVES: This study investigated the exposure-response relationships of hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydride (MHHPA) and evaluated the applicability of the total plasma protein adducts (TPPA) of these anhydrides as biomarkers of exposure and risk. METHODS: In a cross-sectional study of 139 workers in a plant manufacturing electrical capacitors, the long-term exposure to HHPA and MHHPA was assessed through the quantification of TPPA using gas chromatography-mass spectrometry. Smoking and medical histories were obtained through questionnaires. Work-related symptoms of the eyes and airways were recorded. Specific immunoglobulin (Ig) E (radioallergosorbent test) and IgG (enzyme-linked immunosorbent assay) were determined in serum. RESULTS: The mean level of the TPPA of HHPA was 840 fmol/ml and that of the TPPA of MHHPA was 1700 fmol/ml. There was no correlation between the TPPA of HHPA and the TPPA of MHHPA. Of all the workers, 19% were found to be positive for specific IgE and 17-19% for IgG. Positive associations were observed between HHPA exposure and specific IgE and IgG and between MHHPA exposure and specific IgG. Regarding work-related symptoms, 27% of the workers had symptoms of the nose, 21% had symptoms of the eyes, 11% had symptoms of the lower airways, and 8% had nose bleeding. There were significant exposure-response relationships for symptoms of the eyes and nose for HHPA exposure. CONCLUSIONS: The results show that there is an exposure-response relationship for HHPA both with specific antibodies and with work-related symptoms and down to adduct levels of 40 fmol/ml plasma. In addition, the results elucidate the potential power of TPPA as a relevant index of exposure and risk.

Adult↗

PubMed2002

Physical workload on neck and upper limb using two CAD applications.

The aim was to evaluate (1) the physical workload on neck and upper limb in computer-aided design (CAD) work; (2) the impact of two applications (PROFESSIONAL-CADAM and PRO/Engineering) and (3) two input devices (computer mouse and keyboard), as well as (4) sitting and standing work positions. Fifteen CAD operators were interviewed and examined physically. For nine subjects, the physical workload was measured: electromyography (EMG) of trapezius and forearm extensor muscles, inclinometry of the head, the upper back and upper arms, as well as wrist goniometry. The muscular load was low in CAD work, but the inter-individual variation was considerable. Neither the positions were extreme, nor the movements. The applications, per se, did not have a large impact on the workload, but because of the need for different input devices the effect was strong. Using a keyboard meant higher angular velocities than using a mouse. Hence, when choosing a new software, which requires mainly a mouse as input device, this has to be balanced against the risk of disorders.

Adult↗

PubMed2002

Exposure to polybrominated diphenyl ethers and tetrabromobisphenol A among computer technicians.

This study investigates exposure to polybrominated diphenyl ethers (PBDEs) and tetrabromobisphenol A (TBBPA), which are used as flame retardants in electronic equipment, in a group of technicians with intense computer work. Thirteen PBDE congeners and TBBPA were quantified in serum from 19 computer technicians. Previously investigated groups of hospital cleaners with no computer experience, and clerks working full-time at computer screens were used for comparison. The computer technicians had serum concentrations of BDE-153, BDE-183 and BDE-209 that were five times higher than those reported among hospital cleaners and computer clerks. The median levels observed among the computer technicians were 4.1, 1.3, and 1.6 pmol/g lipid weight, respectively. In contrast, for BDE-47 there was no difference between the computer technicians and the others. BDE-100, BDE-203, and three structurally unidentified octa-BDEs and three nona-BDEs, were present in almost all samples from the computer technicians. Further, TBBPA was detected in 8 out of 10 samples. The levels of BDE-153, BDE-183, and one of the octa-BDEs were positively correlated with duration of computer work among technicians. On a group level an exposure gradient was observed, from the least exposed cleaners to the clerks, and to the highest exposed group of computer technicians. A dose (duration of computer work)-response relationship among computer technicians was demonstrated for some higher brominated PBDE congeners. Thus, it is evident that PBDEs used in computers and electronics, including the fully brominated BDE-209, contaminate the work environment and accumulate in the workers tissues.

Adult↗

PubMed2002

Female fertility in relation to the consumption of fish contaminated with persistent organochlorine compounds.

OBJECTIVES: The purpose of the study was to assess the effect of exposure to presistent organochlorine compounds through the consumption of fatty fish from the Baltic Sea on human fertility. METHODS: Information on time to pregnancy, miscarriages, and subfertility was collected retrospectively by self-administered questionnaires in two cohorts of fishermen's sisters from the Swedish east coast, by the Baltic Sea, and the west coast, where fish are less contaminated. Along with cohort affiliation, fish consumption and growing up in a fishing village or fisherman's family were used as measures of exposure within the eastcoast cohort (ie, the exposed cohort). RESULTS: There was no support for a negative effect of the consumption of fatty Baltic Sea fish on time to pregnancy, miscarriages, or subfertility. On the contrary, some evidence pointed towards a protective effect of fatty fish consumption within both cohorts. CONCLUSIONS: No evidence of reduced fertility was found for women who could be assumed to have a high lifetime consumption of fatty fish contaminated by persistent organochlorine compounds. A possible explanation for this finding is that a positive effect of some of the constituents in fatty fish could be strong enough to disguise the hazardous effects of exposure to persistent organochlorine compounds.

Abortion, Spontaneous↗