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Biomedical subjects

J Björk

Publications and source records attributed to J Björk.

At least 19 recordsLinked to original sources

Female fecundity before and after operation for familial adenomatous polyposis.

BACKGROUND: Knowledge about the fertility of women suffering from familial adenomatous polyposis (FAP) is scarce and inconclusive. The purpose of this study was to investigate the fecundity of women with FAP before and after operation, and to compare the findings with those of a general population database and women with ulcerative colitis. METHODS: A questionnaire concerning reproductive experiences and waiting times to pregnancy was sent to all 230 women on the polyposis registers in Denmark, Finland, Sweden and Norway in whom primary surgery had consisted of ileorectal anastomosis or ileal pouch-anal anastomosis. Data on the general population and women with ulcerative colitis came from an existing database. Cox regression and Kaplan-Meier plots were used for analysis. RESULTS: The fecundity of women with FAP before operation and after colectomy with ileorectal anastomosis was similar to that of the general population. However, fecundity dropped to 54 per cent (P = 0.015) following proctocolectomy with ileal pouch-anal anastomosis, although it was greater than the postoperative fecundity of women with ulcerative colitis. CONCLUSION: The significant reduction in female fecundity after ileal pouch-anal anastomosis should be communicated to young women with FAP before it is decided which surgical option to follow.

Adenomatous Polyposis Coli↗

Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001.

To ascertain the frequency of treatment-related acute myeloid leukemias and myelodysplastic syndromes (t-AML/t-MDS) in an unselected series, we have identified all adult cases analyzed in our department from 1976 to 1993. Further aims were to compare karyotypic features of t-AML/t-MDS with de novo AML/MDS, in our material as well as in 5098 unselected, cyto- genetically abnormal, published cases, and to analyze associations between type of prior therapy and karyotype. Among our 372 AML and 389 MDS, 47 (13%) were t-AML and 62 (16%) were t-MDS. Clonal abnormalities were significantly more common in t-AML and t-MDS than in de novo disease (68% vs 50%, P < 0.05 and 84% vs 45%, P < 0.001, respectively). Among the available 4230 AML and 1629 MDS (the present series and published cases), 14% were t-AML and 15% were t-MDS. In t-AML/t-MDS, the number of anomalies and the ploidy levels differed significantly from de novo cases, with complex and hypodiploid karyotypes being more common in t-AML/t-MDS. In t-AML, unbalanced changes in general, t(1;3), der(1;7), 3p-, -5, 5q-, -7, 7q-, t(9;11), t(11;19), t(11q23), der(12p), -17, der(17p), -18, and -21 were significantly more frequent than in de novo AML. In t-MDS, -5, -7, 7q-, 13q-, der(17p), and -18 were significantly more common. Type of prior treatment correlated significantly with number of anomalies in t-AML and with ploidy levels in t-AML/t-MDS. The frequencies of several aberrations varied with type of therapy, eg, 5q- was more frequent in radiotherapy-associated t-MDS, monosomy 7 was more common in t-AML and t-MDS after treatment with alkylators, and t(11q23) in t-AML was associated with topoisomerase II inhibitors. Abnormalities significantly more common in de novo disease were +8 as a sole anomaly, balanced changes in general, t(8;21), t(9;22), t(15;17), inv(16), and t(21q22) in AML, and -Y, 5q-, and 20q- as sole anomalies and +8 in MDS. The results emphasize the strong association between previous genotoxic exposure and karyotypic features.

Acute Disease↗

Effects of irradiation on intestinal cells in vivo and in vitro.

The effects of irradiation on intestinal epithelial cells were analyzed in vivo and in vitro. The in vivo study was carried out on the rat small intestine and for the in vitro study the intestinal crypt cell-line IEC-6 was used. Rat intestine and IEC-6 cells were irradiated with X-ray doses ranging between 1-16 Gy. Energy-dispersive X-ray microanalysis was used for detection of the elemental changes in the cells. Cell morphology was investigated in the scanning electron microscope, DNA-synthesis by autoradiography of 3H-thymidine incorporating nuclei and proliferation by cell counting. Our results indicate that in vivo, in the crypt cells, the increasing doses of irradiation led to increased sodium and lowered potassium and phosphorus concentrations. Corresponding ion shifts were found in the irradiated IEC-6 cells. Cells continued to proliferate up to the dose of 8 Gy, although the proliferation rate became lower with increasing dose of irradiation. The increasing dose of irradiation significantly reduced DNA-synthesis (16 Gy decreased DNA-synthesis by 50%) which resulted in a complete inhibition of cell proliferation. Analysis of goblet cells also showed characteristic radiation-dependent elemental changes. Scanning electron microscopical investigation of cells in culture revealed that most of the control cells were flat and had rather smooth cell membranes. Irradiation led to the appearance of numerous different membrane manifestations (microvilli of varying length and distribution, and blebs). Frequency of differences in the topology of the cells was related to the dose of irradiation. Our study clearly demonstrates that even low doses of irradiation cause changes in the ionic composition of the cells and inhibit DNA-synthesis and cell proliferation. The effects observed in the crypt cells in vivo were the same as in the intestinal cell line in vitro, which indicates that IEC-6 cells can be used for investigation of side effects of radiation to the abdomen.

Animals↗

COL11A1 in FAP polyps and in sporadic colorectal tumors.

BACKGROUND: We previously reported that the alpha-1 chain of type 11 collagen (COL11A1), not normally expressed in the colon, was up-regulated in stromal fibroblasts in most sporadic colorectal carcinomas. Patients with germline mutations in the APC gene show, besides colonic polyposis, symptoms of stromal fibroblast involvement, which could be related to COL11A1 expression. Most colorectal carcinomas are suggested to be a result of an activated Wnt- pathway, most often involving an inactivation of the APC gene or activation of beta-catenin. METHODS: We used normal and polyp tissue samples from one FAP patient and a set of 37 sporadic colorectal carcinomas to find out if the up-regulation of COL11A1 was associated with an active APC/beta-catenin pathway. RESULTS: In this study we found a statistically significant difference in COL11A1 expression between normal tissue and adenomas from one FAP patient, and all adenomas gave evidence for an active APC/beta-catenin pathway. An active Wnt pathway has been suggested to involve stromal expression of WISP-1. We found a strong correlation between WISP-1 and COL11A1 expression in sporadic carcinomas. CONCLUSIONS: Our results suggest that expression of COL11A1 in colorectal tumors could be associated with the APC/beta-catenin pathway in FAP and sporadic colorectal cancer.

Adenomatous Polyposis Coli↗

Outcome of primary and secondary ileal pouch-anal anastomosis and ileorectal anastomosis in patients with familial adenomatous polyposis.

PURPOSE: The aim of this study was to present Swedish experiences of the ileal pouch-anal anastomosis in patients with familial adenomatous polyposis from the introduction in 1984. The study also compared the surgical and functional outcome of different anal continence preserving procedures: ileal pouch-anal anastomosis as primary surgery, ileal pouch-anal anastomosis as secondary surgery after colectomy and ileorectal anastomosis, and ileorectal anastomosis alone. METHODS: The material comprises all 120 patients with familial adenomatous polyposis reported to the Swedish Polyposis Registry who had undergone prophylactic colorectal surgery, including those operated on because of colorectal cancer from 1984 until the end of 1996. Anal continence preserving surgery was performed on 102 patients: 20 had ileal pouch-anal anastomosis as primary surgery at a median age of 24.5 years, 39 had ileal pouch-anal anastomosis as secondary surgery at a median age of 34 years, and 43 had ileorectal anastomosis alone, at a median age of 26 years, because 6 of the initially ileorectal anastomosis-operated patients were converted to ileal pouch-anal anastomosis as secondary surgery. Surgical outcome was assessed on the basis of hospital records. A questionnaire was used to evaluate the functional outcome. Fisher's exact probability test was used for statistical analysis. RESULTS: Complications occurred in 51 percent of the patients after ileal pouch-anal anastomosis: 40 percent after ileal pouch-anal anastomosis as primary surgery and 56 percent after ileal pouch-anal anastomosis as secondary surgery. When the previous ileorectal anastomosis was taken into account 67 percent of the patients suffered complications which was significantly more compared with ileal pouch-anal anastomosis as primary surgery. After ileorectal anastomosis, 26 percent had complications which was significantly less compared with all other procedures but ileal pouch-anal anastomosis as primary surgery. No cancer occurred after ileal pouch-anal anastomosis, either in the ileal pouch or in retained rectal mucosa, but two of the patients who had an ileorectal anastomosis developed rectal cancer. One pouch excision was performed compared with ten rectal excisions. Functional outcome did not differ between ileal pouch-anal anastomosis as primary surgery and ileal pouch-anal anastomosis as secondary surgery. However, ileorectal anastomosis-operated patients had significantly better bowel function with regard to nighttime stool frequency, continence and perianal soreness. CONCLUSION: These findings indicate that major advantages of ileal pouch-anal anastomosis are the low excision rate and, so far, no cancer in the ileal pouch. Moreover, the surgical outcome of ileal pouch-anal anastomosis as primary surgery is not significantly different from that of ileorectal anastomosis. However, the good surgical and functional outcome of ileorectal anastomosis, despite the long-range prognosis including rectal cancer and excision risks, has to be taken into consideration when selecting patients with familial adenomatous polyposis for primary surgery.

Adenomatous Polyposis Coli↗

Evaluation of occupational and leisure time exposure assessment in a population-based case control study on leukaemia.

OBJECTIVES: To increase the credibility of retrospective exposure assessments. documentation of the procedures and presentation of measures on quality control is recommended. The aim of this study was to present and evaluate the procedures used in a case-control study on leukaemia. METHODS: A series of 1,087 cases and matched controls were interviewed. Exposure assessments were performed for 13 occupational agents and ten leisure-time activities and the confidence of the assessments was coded. The exposure assessments were performed blind by three occupational hygienists. Ten percent of the interviews were reassessed by two of the three occupational hygienists. RESULTS: The leisure-time activities contributed to a large extent to the overall prevalence of exposure. For organic solvents approximately 25% of the controls classified as exposed would be misclassified if leisure-time exposure were not considered. The proportions of subject assessments with low confidence were higher for next-of-kin than for in-person interviews. A negative correlation was seen between the proportions of assessments with low confidence and the reliability. A significant difference was seen in the inter-rater comparison between cases and controls when the reliability was calculated for each assessed period; no difference was seen for the subject assessments used for relative risk estimation. CONCLUSION: When low-dose exposure in epidemiological studies are being assessed there is an obvious risk of misclassification if leisure-time activities are not included. Furthermore, the reliability of the assessments may suffer if next-of-kin interviews are used to a large extent. For cancers with poor prognoses, prospective studies are preferable to minimise possible information bias.

Case-Control Studies↗

Fibre type proportion and fibre size in trapezius muscle biopsies from cleaners with and without myalgia and its correlation with ragged red fibres, cytochrome-c-oxidase-negative fibres, biomechanical output, perception of fatigue, and surface electromyography during repetitive forward flexions.

In the literature enlarged/increased cross-sectional area (CSA) of type I muscle fibres has been reported as a morphological mark of work-related localised myalgia in the descending part of the trapezius muscle of women. These studies did not use enough subjects or lacked an adequate control group. The recording of surface electromyograms (EMG) is central to the research field of work-related myalgia. However, the influence of intrinsic muscle properties such as the effect of muscle fibre distribution upon surface EMG has to be better understood in order properly to evaluate this method as a possible diagnostic and preventive tool. This study had two aims. Firstly, it investigated the muscle fibre distribution and CSA in work-related myalgia in trapezius muscles. Secondly, the multivariate relationships among muscle morphology and histochemistry [ragged-red (RR) fibres, and cytochrome-c-oxidase-negative-fibre changes] EMG, perceived fatigue, and biomechanical output of shoulder flexions were analysed. The raw data have been presented in an earlier study. The participants in this study were 25 female cleaners with work-related myalgia of the trapezius muscle and 25 female cleaners not experiencing work-related myalgia of this muscle. The control group comprised 21 healthy female teachers who had not been exposed to highly repetitive work or static muscle work. Smaller CSA of type II fibres were found in cleaners compared to teachers. In this study the CSA of type I fibres of the trapezius muscles associated with myalgia were no greater than in muscles without myalgia. The prevalence of RR fibres together with age, fibre type proportions, CSA and working as a cleaner correlated with the ability to relax as recorded electromyographically. The relative mean frequency of the EMG of the trapezius muscle correlated with the prevalence of RR fibres, but it did not correlate with the proportions and CSA of different fibre types. Low biomechanical outputs and low signal amplitude increases of the EMG during the test were associated with high proportions of type -IIB fibres. The smaller CSA of type II fibres in cleaners might have reflected a different muscle activation pattern due to different occupational demands in cleaners than in teachers. Morphological or histopathological variables can influence the three EMG variables investigated.

Biomechanical Phenomena↗

Abnormal nuclear shape in solid tumors reflects mitotic instability.

Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (<11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an osteosarcoma cell line exposed to irradiation. A linear correlation was found between the frequency of abnormalities in nuclear shape, on one hand, and cells with unstable chromosomes (r = 0.87) and anaphase bridge configurations (r = 0.98), on the other hand. The relation between nuclear shape and karyotypic pattern was investigated further in cultures from 58 tumors of bone, soft tissue, and epithelium. Blebs, strings, and micronuclei were significantly more frequent in tumors that contained rings, dicentrics, or telomeric associations than in those exhibiting only stable aberrations (P: < 0.001) and a positive correlation (r = 0.78) was found between the frequency of such nuclear abnormalities and the intratumor heterogeneity of structural chromosome aberrations. These results indicate that the formation of nuclear blebs, chromatin strings, and micronuclei in malignant tissues is closely related to the breakage-fusion-bridge type of mitotic disturbances. Abnormalities in nuclear shape may thus primarily be regarded as an indicator of genetic instability and intratumor heterogeneity, independent of cytogenetic complexity and the grade of malignancy.

Cell Line↗

Smoking and acute myeloid leukemia: associations with morphology and karyotypic patterns and evaluation of dose-response relations.

This case-control study of tobacco smoking and acute myeloid leukemia (AML), emphasizing specific associations with morphologic and cytogenetic subtypes, comprised smoking histories for 333 cases and 351 controls. Smoking status (ever smokers versus life-long non-smokers) showed no evident effect on AML risk. However, an effect of smoking was indicated at high cumulative smoking doses (pack-years), e.g. 40 pack-years was associated with an odds ratio (OR) of 1.5 [95% confidence interval (CI) 1.0-2.3]. Among morphologic subtypes, the smoking associated OR for acute erythroleukemia was 8.9 (95% CI 1.0-76). No clear associations between smoking and cytogenetic subtypes of AML were observed.

Acute Disease↗

Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations.

BACKGROUND & AIMS: Patients with familial adenomatous polyposis (FAP) have a high prevalence of duodenal adenomas, and the region of the ampulla of Vater is the predilection site for duodenal adenocarcinomas. This study assessed the risk of stage IV periampullary adenomas according to the Spigelman classification and periampullary adenocarcinomas in Swedish FAP patients screened by esophagogastroduodenoscopy (EGD). The genotype of patients with stage IV periampullary adenomas and periampullary adenocarcinomas was also investigated. METHODS: A retrospective study of 180 patients screened by EGD in 1982-1999 was undertaken. Kaplan-Meier analysis was performed to evaluate cumulative risk. Mutation analysis was carried out in patients with periampullary adenocarcinomas diagnosed outside the screening program, in addition to patients in the screening group with stage IV periampullary adenomas and adenocarcinomas. RESULTS: Periampullary adenoma stage IV was diagnosed in 14 patients (7.8%), with a cumulative risk of 20% at age 60 years. Periampullary adenocarcinoma was diagnosed in 5 patients (2.8%), with a cumulative risk of 10% at age 60. Three of the adenocarcinomas occurred in patients with stage IV periampullary adenomas compared with 2 in patients with less severe periampullary adenomatosis at screening (odds ratio, 31; 95% confidence interval, 4.6-215). Fifteen (88%) of the APC gene mutations were detected; 12 of these were located downstream from codon 1051 in exon 15. CONCLUSIONS: The life time risk of severe periampullary lesions in FAP patients is high, and an association between stage IV periampullary adenomas and a malignant course of the periampullary adenomatosis is strongly suggestive. Mutations downstream from codon 1051 seem to be associated with severe periampullary lesions.

Adenocarcinoma↗

Decision analysis in the surgical treatment of patients with familial adenomatous polyposis: a Dutch-Scandinavian collaborative study including 659 patients.

BACKGROUND AND AIMS: The choice of colorectal surgery in patients with familial adenomatous polyposis lies between the morbidity of proctocolectomy and ileum-pouch-anal anastomosis (IPAA) and the mortality from rectal cancer after total colectomy and ileorectal anastomosis (IRA). The aims of the present study were: (1) to assess the risk of dying from rectal cancer after IRA, (2) to compare the life expectancy between patients with an IRA and those with an IPAA, and (3) to investigate whether regular endoscopic examination of the rectum leads to detection of cancer at an earlier stage. METHODS: Clinical and pathological data on 659 patients who underwent colectomy and ileorectal anastomosis were collected from four national polyposis registries-that is, in Denmark, Finland, Sweden, and the Netherlands. Data were analysed using survival analysis methods. Decision analysis was used to compare the life expectancy between patients with an IRA and those with an IPAA. RESULTS: A total of 47 patients developed rectal cancer after IRA. The risk of dying from rectal cancer was 12.5% (95% confidence interval 7.1--17.9%) by age 65. Compared with IRA, IPAA would lead to an increase in life expectancy of 1.8 years. Seventy five per cent of patients with rectal cancer had a negative rectoscopy within 12 months before the diagnosis. CONCLUSION: IRA is associated with substantial mortality due to rectal cancer. Follow up examinations of the rectum does not have sufficient preventive effect on morbidity and mortality of rectal cancer.

Adenomatous Polyposis Coli↗

Are occupational, hobby, or lifestyle exposures associated with Philadelphia chromosome positive chronic myeloid leukaemia?

OBJECTIVES: To investigate a broad range of occupational, hobby, and lifestyle exposures, suggested as risk factors for Philadelphia chromosome positive (Ph+) chronic myeloid leukaemia (CML). METHODS: A case-control study, comprising 255 Ph+CML patients from southern Sweden and matched controls, was conducted. Individual data on work tasks, hobbies, and lifestyle exposures were obtained by telephone interviews. Occupational hygienists assessed occupational and hobby exposures for each subject individually. Also, occupational titles were obtained from national registries, and group level exposure-that is, the exposure proportion for each occupational title-was assessed with a job exposure matrix. The effects of 11 exposures using individual data and two exposures using group data (organic solvents and animal dust) were estimated. RESULTS: For the individual data on organic solvents, an effect was found for moderate or high intensity of exposure (odds ratio (OR) 3.4, 95% confidence interval (95% CI) 1.1 to 11) and for long duration (15-20 years) of exposure (OR 2.1, 95% CI 1.1 to 4.0). By contrast, the group data showed no association (OR 0.69, 95% CI 0.27 to 1.8; moderate or high intensity versus no exposure). For extremely low frequency electromagnetic fields (EMFs), only individual data were available. An association with long occupational exposure to EMFs was found (OR 2.3, 95% CI 1.2 to 4.5). However, no effect of EMF intensity was indicated. No significant effects of benzene, gasoline or diesel, or tobacco smoking were found. OR estimates below unity were suggested for personal use of hair dye and for agricultural exposures. CONCLUSIONS: Associations between exposure to organic solvents and EMFs, and Ph+CML were indicated but were not entirely consistent.

Adult↗

Mechanical performance and electromyography during repeated maximal isokinetic shoulder forward flexions in female cleaners with and without myalgia of the trapezius muscle and in healthy controls.

This cross-sectional study aimed at investigating the influence of occupational exposure to static and highly repetitive work involving the neck and shoulder muscles, myalgia of and tender point in the trapezius muscle on biomechanical output, and electromyogram (EMG) variables (mean frequency MNF, signal amplitude and ability to relax) during maximal forward flexions of the shoulder muscles. Groups of 25 cleaners suffering from chronic myalgia of the trapezius muscle, 25 cleaners free from myalgia of the trapezius muscle and 21 teachers performed 150 forward flexions using an isokinetic dynamometer. Perception of fatigue was reported and surface EMG was recorded from four muscles during the endurance test. The cleaners were stronger than the teachers. Myalgia was associated with lower levels of endurance and a high degree of perceived fatigue. The ability to relax the trapezius muscle decreased with age and was even lower in cleaners with and without myalgia. Higher MNF of the deltoid muscle but not of the trapezius muscle was found in the group suffering from myalgia compared to the groups free from myalgia. This cross-sectional study indicated that myalgia of the trapezius muscle did not influence the strength but did influence the endurance of the forward flexor muscles of cleaners. The observed decrease in the ability to relax the trapezius muscle in cleaners compared to healthy teachers might be indicative of a future insufficiency in the muscle. Prospective studies are needed to define the significance of the results presented here.

Cross-Sectional Studies↗

The prevalences of cytochrome c oxidase negative and superpositive fibres and ragged-red fibres in the trapezius muscle of female cleaners with and without myalgia and of female healthy controls.

The association of cytochrome c oxidase negative fibres (COX-negative) and ragged-red fibres (RR-fibres) with work related trapezius myalgia has been proposed. Hitherto studies have been small or without control groups. The aim of the present study was to investigate the prevalences of RR-fibres and COX-negative fibres in female cleaners with (n=25) and without (n=23) trapezius myalgia and in clinically healthy female teachers (n=21). The cleaners did mainly floor cleaning requiring monotonous loading on the trapezius muscle. A questionnaire covering background data and aspects of pain (prevalence, duration, intensity and influence on daily living) was answered. Biopsies were obtained from the trapezius muscle by an open surgical technique. The three groups did not differ in prevalence of COX-negative or COX-superpositive (i.e. type-I fibres with extremely strong brownish reaction in both the COX and SDH/COX stainings) fibres. The prevalence of COX-negative fibres was age dependent. Two subgroups of RR-fibres were present when stained for COX; COX-negative (73%) and COX-superpositive (26%) fibres. Forty-two percent of the COX-negative fibres were RR-fibres and 79% of the COX-superpositive were RR-fibres. A significantly (P=0.002) higher proportion of the COX-superpositive fibres in the cleaners were RR-fibres compared to the teachers. Multivariate regression analysis revealed that age, occupation as cleaner and a tender point in the trapezius were significantly associated with increased prevalences of RR-fibres; a cleaner with a tender point had a 4.35 higher prevalence of RR-fibres compared to a teacher without a tender point. No correlations between other pain related variables and prevalence of RR-fibres were noted. In conclusion, RR-fibres but not COX-negative or COX-superpositive fibres were correlated with cleaning work tasks and with a tender point in the trapezius.

Activities of Daily Living↗

Ileorectal anastomosis is appropriate for a subset of patients with familial adenomatous polyposis.

BACKGROUND & AIMS: This study reevaluates the risk of rectal cancer and the frequency of subsequent proctectomy for nonmalignant causes in patients with familial adenomatous polyposis (FAP) who have undergone colectomy with ileorectal anastomosis (IRA). Potential risk factors for rectal cancer in this setting are also examined, and recommendations for the choice of surgical procedure are made. METHODS: The national polyposis registries in Denmark, Finland, The Netherlands, and Sweden included 659 patients undergoing surgery with IRA in 1940-1997. Kaplan-Meier analysis and Cox regression analysis were performed to evaluate cumulative risk, survival, and predictive risk factors. RESULTS: Rectal carcinoma was diagnosed in 47 patients, with a cumulative 40-year risk of 0.32. The cumulative risk according to chronologic age was 0.30 at age 60, and higher in patients undergoing surgery above age 25 (P = 0.0016). Chronologic age was the only independent risk factor (P = 0.0016). The cumulative 5-year survival rate after rectal carcinoma was 0.60. The apc mutation was known in 167 patients, of whom 7 had rectal cancer. The cumulative 40-year risk of secondary proctectomy was 0.70, and higher in patients with a mutation in codon 1250-1500 than outside this region (P = 0.005). However, all 7 rectal cancers were found in the latter group. None of the 18 patients with attenuated FAP (mutation in codon 0-200 or >1500) had a secondary proctectomy. CONCLUSIONS: IRA is recommended in (1) young patients with few rectal adenomas and a family history of a mild phenotype and (2) patients with attenuated FAP (a mutation in codon 0-200 or >1500), provided there is acceptance of life-long rectal surveillance. Patients with many rectal polyps and/or a family history of severe polyposis should be offered a restorative proctocolectomy with an ileal pouch-anal anastomosis.

Adenoma↗

Smoking and myelodysplastic syndromes.

The purpose of this case-control study was to investigate tobacco smoking as a risk factor for myelodysplastic syndromes, emphasizing karyotypic aberrations as markers for exposure and risk differentiation with respect to morphology. We obtained smoking history by interview of 330 cytogenetically investigated adult myelodysplastic syndrome cases and 337 controls, matched with respect to sex, year of birth, and county of living. Smoking for at least 1 year at some time 20 years or less before diagnosis was associated with an elevated relative risk (RR) for primary myelodysplastic syndromes (odds ratio (OR) 1.8; 95% confidence interval (CI) = 1.2-2.7). The results indicated a relation with intensity and duration of smoking as well as a decrease in risk a few years after cessation of smoking. Smoking was associated with an increased RR for primary myelodysplastic syndromes with chromosome 7 abnormalities (OR 5.0; 95% CI = 1.1-23). Elevated RRs were also seen for refractory anemia (OR 2.5; 95% CI = 1.2-5.6) and for refractory anemia with ringed sideroblasts (OR 3.2; 95% CI = 0.88-12). The findings suggest that smoking is a risk factor for myelodysplastic syndromes.

Aged↗

Influence of the consumption of fatty Baltic Sea fish on plasma levels of halogenated environmental contaminants in Latvian and Swedish men.

We examined the influence of widely varied consumption of fatty fish from the Baltic Sea and of age on plasma concentrations of polychlorinated biphenyls (PCBs), polychlorobiphenylols (OH-PCBs), 2, 2-bis(4-chlorophenyl)-1,1,1-trichloroethane (4,4'-DDT), 2, 2-bis(4-chlorophenyl)-1,1-dichloroethane (4,4'-DDE), 2,2',4, 4'-tetrabromodiphenyl ether (BDE-47), hexachlorobenzene (HCB), and pentachlorophenol (PCP) in Latvian and Swedish men. Both age and fish consumption were significantly correlated with the concentrations of [sigman]PCB, [sigman]OH-PCB, 4,4'-DDE, 4,4'-DDT, and HCB. In the case of BDE-47, no significant relationship with age was observed, and fish consumption had the largest relative effect on plasma concentrations of this contaminant. This relationship may be a result of exposure to BDE-47 having been more recent than that of PCBs and DDE, or because the half-life of BDE-47 may be shorter than that of PCB and DDE. Latvian men demonstrated higher plasma levels of DDE and DDT but lower levels of [sigman]PCB and PCP than did Swedish men. The corresponding levels of HCB and BDE-47 were similar in both countries. The Spearman's rank correlation coefficient obtained by comparing the level of the metabolite 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to the combined levels of its parent compounds, 2,3,3',4, 4'-pentachlorobiphenyl (CB-105) and 2,3',4,4',5-pentachlorobiphenyl (CB-118), was higher than the median correlation coefficient obtained upon comparing the level of this metabolite to all other possible combinations of two PCB levels. No other increased correlation between metabolite and parent PCB concentration was observed.

Adult↗

Acute myeloid leukemia and clonal chromosome aberrations in relation to past exposure to organic solvents.

OBJECTIVES: The effects of occupational and leisure-time exposures on the risk of acute myeloid leukemia (AML) were investigated with emphasis on clonal chromosome aberrations (CCA) and morphological subtypes. METHODS: Consecutively diagnosed cases of AML (N=333) and 1 population referent per case were retrospectively included in the study. Information on worktasks, companies, and leisure-time activities was obtained with telephone interviews. Exposure probability and intensity were assessed by occupational hygienists. Associations were evaluated with logistic regression. RESULTS: Exposure to organic solvents was associated with an increased risk of AML [low exposure: OR 1.5 (95% confidence interval (95% CI) 1.0-2.3, moderate-high exposure: OR 2.3 (95% CI 1.0-5.0)]. For exposure to solvents, but not to benzene, the OR was 1.2 (95% CI 0.69-2.0) for "low" and 2.7 (95% CI 1.0-7.3) for "moderate-high" exposure. The observed effects increased with intensity and duration of exposure. The estimated effects were higher for patients >60 years of age at the time of diagnosis. The effect of exposure to organic solvents was not differential with regard to morphology [except possibly erythroleukemia: OR 4.2, 95% CI 1.0-17 or the presence of CCA in general]. No increased risk for AML with complex CCA or with total or partial losses of chromosomes 5 or 7 were observed, but a higher risk was found for AML with trisomy 8 (OR 11, 95% CI 2.7-42) as the sole aberration. CONCLUSIONS: Exposure to organic solvents was associated with an increased risk of AML. This association was not due to benzene exposure alone and may be modified by age. Furthermore, specific associations with trisomy 8, and possibly also erythroleukemia, were suggested.

Acute Disease↗