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Testicular cancer and cryptorchidism in relation to prenatal factors: case-control studies in Denmark.

To explore prenatal risk factors that are common to testicular cancer and cryptorchidism, two parallel case-control studies were conducted in Denmark. Information about characteristics of the mother, the pregnancy, and the birth were obtained from the mothers of cases and controls, using a mailed self-administered questionnaire. A maternal age above 30 years was associated with odds ratios (OR) of 1.9 (95 percent confidence interval [CI] = 1.2-3.0) for cryptorchidism and 2.0 (CI = 1.2-3.6) for testicular seminoma; the latter effect was particularly high when the boy was the first child of the mother (OR = 4.1, CI = 1.1-14.6). Birthweights below 3,000 g or above 4,000 g were associated with increased risks of testicular cancer, with ORs up to 2.6 (CI = 1.1-5.9) for birthweight below 2,500 g. For cryptorchidism, there was a monotonous trend in the OR from 0.4 in birthweights above 4,500 g to 2.3 in birthweights below 2,500 g. The association between cryptorchidism and testicular cancer was not attenuated by adjustment for maternal age and birthweight, indicating that all three variables are independent risk factors for testicular cancer. With the exception of high maternal age, which consistently is associated more strongly with seminoma than with non-seminoma, it remains most likely that seminoma and non-seminoma have similar causes.

Adolescent↗

Cancer following breast reduction surgery in Denmark.

Intuitively, breast tissue mass should be directly related to a woman's risk of breast cancer, simply because having more cells at risk would seem to increase the potential for malignant transformation. However, studies attempting to link breast size with breast cancer risk have been inconsistent. Limitations include crude measures of breast size, the inability to distinguish glandular from adipose tissue, and the confounding influence of co-factors such as obesity. A nationwide study in Denmark was undertaken to investigate the effect of breast reduction surgery on the subsequent risk of breast cancer, including an evaluation of the patterns of risk by age and time since surgery. The Danish Hospital Discharge Registry was used to identify women who underwent reduction mammaplasty between 1977 and 1992. Linkage based on personal identification numbers with the Danish Cancer Registry provided information on cancer incidence. Expected numbers of cancers were calculated from rates in the general population. Among 7,720 women whose breasts were surgically reduced, 182 cancers were subsequently observed cf 209 expected (standardized incidence ratio [SIR] = 0.9;95 percent confidence interval [CI] = 0.7-1.0). Breast cancer was significantly reduced by nearly 50 percent (29 observed cf 53.9 expected, SIR = 0.5, CI = 0.4-0.8), and accounted for the overall deficit in cancer. The risk reductions were related inversely to age at surgery, with significant deficits apparent only among women 40 years of age and older at surgery and especially among those over age 50 (SIR = 0.3). No clear trend was apparent with increasing years post-surgery. The findings indicate that breast reduction surgery among women over age 40 is associated with a lower subsequent risk of breast cancer, but the surgery and presumably glandular mass appear less closely related to breast cancer risk among younger women.

Adolescent↗

Birth weight and risk of early-onset breast cancer (Denmark).

OBJECTIVE: To investigate if birth weight is associated with early-onset breast cancer. The mechanism behind an association with high birth weight could be the link between fetal growth and estrogens in utero. METHODS: We conducted a population-based case-control study in Denmark including 881 women with breast cancer diagnosed before the age of 40 years and 3,423 age-matched controls. Information concerning birth weight and other birth-related variables was obtained from midwife reports. RESULTS: The risk of early-onset breast cancer was increased 1.25 times (95% CI 1.00-2.51) for birth weights above 4,000 g and 1.59 times (95% CI 1.00-1.55) for birth weights below 2,500 g in comparison with birthweights of 3,000-3,499 g. CONCLUSIONS: The finding that high birth weight is associated with breast cancer is compatible with the hypothesis that level of estrogen during pregnancy is related to breast cancer in early adult life. The finding that low birth weight is also associated with breast cancer may indicate that other characteristics of the fetal environment may be important for breast cancer in early adult life.

Adult↗

Women's death in Scandinavia--what makes Denmark different?

OBJECTIVE: To compare the mortality for women in Sweden, Norway and Denmark in order to search for clues for the low life expectancy of Danish women. METHODS: Prospective age-period-cohort study covering 40 years for all Swedish, Norwegian and Danish women aged 40-84 during the period 1960-2000, and born 1900-1950. OUTCOME MEASURES: Relative risks and 95% confidence intervals for deaths. RESULTS: The high risk of dying among Danish women was associated with being born between the two World Wars, and that a similar pattern was not found for women in Norway and Sweden. A tendency of a cohort effect was observed for Swedish women born around 1940. CONCLUSIONS: The currently low life expectancy of Danish women compared with that of women in Norway and Sweden is partly a transitional phenomenon caused by excessive death rates for women born between the two World Wars. Data on smoking prevalence by birth cohort and age indicate that a high percentage of Danish women in these cohorts were smokers throughout their adult life.

Adult↗

The epidemiology of hand injuries in The Netherlands and Denmark.

Little is known about the magnitude of hand injuries at national levels. This paper quantifies and characterises the incidence of hand injuries that require acute medical attention at Emergency Departments in The Netherlands and Denmark. Except for the incidence rate and the referral after treatment, the overall picture of hand injuries is similar for both countries: hand injuries show a peak for teenagers, result mainly from home and leisure accidents, are mainly caused by objects and falls, the majority affect fingers and result mainly in superficial injuries, open wounds and fractures, a small proportion of the victims is admitted into hospital. We conclude that hand injuries are a real burden to society and are worthwhile to be prevented with special attention for home and leisure accidents and occupational accidents. Data recording on the backgrounds of accidents and their long term consequences should be improved.

Accidental Falls↗

Complaints related to respiratory events in anaesthesia and intensive care medicine from 1994 to 1998 in Denmark.

BACKGROUND: In Denmark, a National Board of Patients' Complaints (NBPC) was founded in 1988. This study analyses anaesthetic complaints related to adverse respiratory events filed at the NBPC from 1994 to 1998 to point out directions for possible preventive measures. METHODS: All decisions made by the NBPC from 1994 to 1998 concerning personnel employed in the Danish health care system were scrutinized. Cases related to anaesthesia and intensive care medicine were reviewed. Adverse respiratory events were identified and classified by mechanism of the incident that had caused the complaint. Detailed information on anaesthetic technique, personnel involved, sequence of events, clinical manifestation of injury, and outcome was recorded. RESULTS: A total of 284 cases was identified. One-fifth (n=60) of the complaints were related to an adverse respiratory event. The overall mortality in these cases was 50% (n=30). In 19 complaints (32%), the treatment was considered substandard. CONCLUSION: Complaints related to respiratory events reveal that inadequate anaesthetic and intensive care medicine treatment leads to patient damage and death. Preventive strategies should be directed at the development of guidelines for handling the difficult airway, education in the management of the difficult airway, instruction in the correct use of anaesthetic equipment, improvement of interpersonnel communication routines, as well as implementation of simulator training.

Adolescent↗

Neurological disease among women with silicone breast implants in Denmark.

OBJECTIVES: To investigate the risk of neurological disease among women with cosmetic breast implants. MATERIAL AND METHODS: We identified 1,653 women who had undergone breast implant surgery at private clinics in Denmark and a comparison cohort of 1,736 women who underwent other types of cosmetic surgery at the same clinics. Ratios of observed-to-expected numbers of hospitalizations for neurological disease in the private implant and comparison cohorts were calculated, separately and combined with data from updated public hospital cohorts. RESULTS: The occurrence of neurological disease in the private clinic implant cohort was comparable to that in the general population. A similar risk pattern was observed in the private clinic comparison cohort. When data for these private clinic cohorts were combined with updated data for public hospital cohorts, excess risks for neurological disorders were seen in both implant and comparison cohorts, reaching statistical significance only in the comparison cohort. CONCLUSION: Our findings indicate no causal association between silicone breast implants and neurological disease.

Adult↗

Metastases in the ophthalmic region in Denmark 1969-98. A histopathological study.

PURPOSE: To evaluate the patterns of origin and anatomical localization of histologically verified metastases in the ophthalmic region in Denmark during 1969-98, and to compare the findings with those of a similar study for the period 1944-68. METHODS: All metastatic lesions presented at the Eye Pathology Institute, University of Copenhagen during the period 1968-98 were investigated. RESULTS: Metastases were found in 81 specimens from the eye and eye region in 76 patients (32 men, 44 women). Five patients had bilateral involvement. The most frequent site of involvement was the uvea (63%), followed by the orbit (26%) and the eyelids (10%). Breast cancer accounted for the most frequent primary tumour (38%), followed by lung cancer (24%) and skin melanoma (14%). CONCLUSION: The pattern of anatomical location of metastases in the ocular region has not changed since 1944. The incidence of metastases has fallen significantly throughout the period.

Adolescent↗

High prevalence rates of adult silent coeliac disease, as seen in Sweden, must be expected in Denmark.

AIM: To disclose the prevalence of adult "silent" coeliac disease in Denmark and Sweden. EXPERIMENTAL DESIGN: 1573 Danish and 1866 Swedish healthy blood donors were screened for the presence of serum anti-gliadin antibodies (AGA) by enzyme-linked immunosorbent assay. AGA-positive serum samples were further analysed for IgA anti-endomysium antibodies (EmA) by indirect immunofluorescence microscopy. MAIN RESULTS: The Danish donor population had a higher mean age than the Swedish (41.4 years versus 37.6 years) and a higher proportion of females (41% versus 32%), and had a lower mean level of AGA (17.3 units versus 20.6 units). Sixty-one (3.9%) Danish donors had AGA above the cut-off limit, and four of these also had positive EmA tests. Sixty (3.2%) Swedish donors had AGA above the cut-off limit, and five of these also had positive EmA. Coeliac pathology was proven by biopsy in all five coeliac disease-suspected Swedish donors. No small intestinal biopsy was performed in the coeliac disease-suspected Danish donors. CONCLUSIONS: Based upon the finding of EmA in AGA-positive serum samples, silent coeliac disease may be suspected in 1 per 394 Danish blood donors (2.5 per 1,000). A similar rate was proven in 1 per 373 Swedish blood donors (2.7 per 1,000), indicating no major differences in the prevalence of adult silent coeliac disease between the two neighbouring countries.

Adolescent↗

Survey of laboratory findings in suspected cases of bovine spongiform encephalopathy in Denmark from 1990 to 2000.

A survey of the laboratory findings in suspected cases of bovine spongiform encephalopathy (BSE) in Denmark from 1 June 1990 to 31 December 2000 is presented. During this period BSE was a notifiable disease, and the heads of suspected cases were submitted according to the legislation on BSE. A total of 176 submissions were made, mostly from bovines with neurological disorders and mainly during the last 3 years of this period. Lesions or other laboratory findings consistent with severe neurological disorders were found in 115 cases. The most frequent diagnosis was encephalic listeriosis (35.8% of submissions) followed by other forms of inflammatory lesions. A wide range of lesions were diagnosed less prevalent. BSE was diagnosed twice. The first case occurred in an imported cow in 1992, while the second confirmed case was diagnosed in a native cow in February 2000. A marked increase in the number of submissions occurred following the detection of BSE in February 2000.

Age Distribution↗

Sequence analysis of measles virus strains collected during the pre- and early-vaccination era in Denmark reveals a considerable diversity of ancient strains.

A total of 199 serum samples from patients with measles collected in Denmark, Greenland and the Faroe Islands from 1964 to 1983 were analysed by PCR. Measles virus (MV) RNA could be detected in 38 (19%) of the samples and a total of 18 strains were subjected to partial sequence analysis of the hemagglutinin gene. The strains exhibited a considerable genomic diversity, which is at odds with the assumption that one genome type prevailed among globally circulating MV strains prior to the advent of live-attenuated vaccines. Our data indicate that the similarity of the various vaccine strains is attributed to their having originated from the same primary isolate. Consequently, it is implied that a small number of clinical manifestations of MV worldwide from which strains similar to the vaccine strain were identified were vaccine related rather than being caused by members of a persistently circulating ancient genome type. The Danish pre- and early-vaccination era MV strains seem to change the evolutionary spectrum of genome types A, C2 and E into one coherent group, suggesting that the genome types of MV strains circulating in the world at present do not represent far ranging evolutionary lineages but merely members of an evolutionary continuum of pre-vaccination era MV strains which by chance or due to an improved capability survived the worldwide partial herd immunity accomplished through vaccination.

Child↗

Human immunodeficiency virus-associated malignant lymphoma in eastern Denmark diagnosed from 1990-1996: clinical features, histopathology, and association with Epstein-Barr virus and human herpesvirus-8.

The clinicopathological features of human immunodeficiency virus (HIV)-associated lymphoma were investigated in a retrospective study of 85 adult patients in eastern Denmark diagnosed during the period 1990-1996. The possible pathogenetic role of Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8) in these tumours was also studied. Seventy patients (82%) presented with extranodal disease and 26 (31%) had CNS involvement at diagnosis. Diffuse large cell B-cell lymphoma was the most frequent histological subtype, comprising 65 of 79 cases available for microscopic re-evaluation (82%) and including 20 of 23 evaluable patients with CNS lymphoma (87%). EBV RNA was demonstrated by in situ hybridization in 51 of 65 evaluable tumours (79%) and in 14 of 16 cases (88%) with CNS-lymphoma. Three cases showed a T-cell phenotype. The presence of HHV-8 DNA was analysed by PCR in 32 cases. A strong band consistent with tumour cell infection was detected in only one case, weaker bands being seen in 4 cases. None of these patients had primary effusion lymphomas. In conclusion, Danish AIDS-related lymphomas are of predominantly high-grade B-cell type with extranodal localization and atypical presentation. Our results provide further evidence that EBV plays a major role in the pathogenesis of large cell AIDS-related lymphoma, whereas HHV-8 does not appear to contribute significantly to the development of solid lymphomas in this group of patients.

Adult↗

Flashbulb memories and posttraumatic stress reactions across the life span: age-related effects of the German occupation of Denmark during World War II.

A representative sample of older Danes were interviewed about experiences from the German occupation of Denmark in World War II. The number of participants with flashbulb memories for the German invasion (1940) and capitulation (1945) increased with participants' age at the time of the events up to age 8. Among participants under 8 years at the time of their most traumatic event, age at the time correlated positively with the current level of posttraumatic stress reactions and the vividness of stressful memories and their centrality to life story and identity. These findings were replicated in Study 2 for self-nominated stressful events sampled from the entire life span using a representative sample of Danes born after 1945. The results are discussed in relation to posttraumatic stress disorder and childhood amnesia.

Age Factors↗

Extraterrestrial amino acids in Cretaceous/Tertiary boundary sediments at Stevns Klint, Denmark.

Since the discovery nearly a decade ago that Cretaceous/Tertiary (K/T) boundary layers are greatly enriched in iridium, a rare element in the Earth's crust, there has been intense controversy on the relationship between this Ir anomaly and the massive extinction of organisms ranging from dinosaurs to marine plankton that characterizes the K/T boundary. Convincing evidence suggests that both the Ir spike and the extinction event were caused by the collision of a large bolide (greater than 10 km in diameter) with the Earth. Alternative explanations claim that extensive, violent volcanism can account for the Ir, and that other independent causes were responsible for the mass extinctions. We surmise that the collision of a massive extraterrestrial object with the Earth may have produced a unique organic chemical signature because certain meteorites, and probably comets, contain organic compounds which are either rare or non-existent on the Earth. In contrast, no organic compounds would be expected to be associated with volcanic processes. Here we find that K/T boundary sediments at Stevns Klint, Denmark, contain both alpha-amino-isobutyric acid [AIB,(CH3)2CNH2COOH] and racemic isovaline [ISOVAL, CH3CH2(CH3)CNH2COOH], two amino acids that are exceedingly rare on the Earth but which are major amino acids in carbonaceous chondrites. An extraterrestrial source is the most reasonable explanation for the presence of these amino acids.

Amino Acids↗

A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in Denmark.

The purpose of this cohort study is to shed further light on the potential carcinogenic effect indicated by a Swedish case control study of the 2,4-dichlorophenol and 4-chloro-ortho-cresol based phenoxy herbicides, unlikely to be contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). In the present study it was the intention to include all persons employed in manufacture of phenoxy herbicides in Denmark before 1982. The predominant product was MCPA and only a very limited amount of 2,4,5-T was processed in one of the two factories included in the study. Registration of the cohort was based on company records, supplemented with data from a public pension scheme from 1964 onwards. Ninety-nine percent of registered employees could be followed up. Cancer cases were identified by linkage with the National Cancer Register. Totals of 3,390 males and 1,069 females were included in the study. In the analysis special attention was given to soft tissue sarcomas (STS) and malignant lymphomas (ML) which are the diagnostic groups indicated to be associated with exposure to phenoxy herbicides in the Swedish studies. Five cases of STS were observed among male employees in contrast to 1.84 expected cases. This result supports the Swedish observation of an increased risk of STS following exposure to phenoxy herbicides unlikely to be contaminated with 2,3,7,8-TCDD. However, several potential biases have to be taken into account in interpretation of this observation and these are discussed. Seven cases of ML were observed among male employees in contrast to 5.37 expected which does not support the Swedish observation of an excess risk. The total cancer risk among persons employed in manufacture and packaging of phenoxy herbicides was equivalent to the cancer risk in the Danish population. Among males thus employed 11 lung cancer cases were observed in contrast to 5.33 expected. Attention should be given to exposure to spray dried MCPA-sodium salt in the plants, but other work place exposures and tobacco consumption may have contributed to the increased risk. The tabulation of data by many diagnostic groups may explain the excesses observed for rectum cancer among males and cervical cancer among females. The study has revealed that several potential biases have to be taken into account when the Swedish observations are tested in other settings.

Chemical Industry↗

Risk of contralateral breast cancer in Denmark 1943-80.

The incidence of a second primary breast cancer in the contralateral breast among 56,237 women with a first primary breast cancer diagnosed between the years 1943-80 in Denmark was established. The relative risk (RR) for a breast cancer patient to get yet another breast cancer was studied, taking account of age, stage and treatment of the first primary breast cancer. Based on 345,573 women years at risk and 1,840 non simultaneous contralateral breast cancer cases the overall relative risk (RR) of invasive cancer in the contralateral breast following a first primary breast cancer, was found to be 2.8 (95% Confidence Interval (CI); 2.7-3.0). Among women who survived 10 or more years the risk was higher among those irradiated for the primary breast cancer (RR = 2.6) than among non-irradiated (RR = 2.0). In the large group of patients with localized disease the association with radiation was obvious for all ages combined (irradiated RR = 3.0, not irradiated RR = 1.6), but not obvious among premenopausal (age less than 45 years) and perimenopausal (age 45-54 years) women at primary breast cancer until followed for 20 years. The RR was higher among irradiated than non-irradiated post-menopausal (age greater than 55 years) women from the time of diagnosis of the first cancer, but was not significant after 14 years of follow-up. The probability for a woman diagnosed with breast cancer at 45 years of age or younger, of developing a contralateral breast cancer if surviving to the age of 75 years, is 25%. Close surveillance of the remaining breast of breast cancer patients is advised, especially if young or following an irradiated localized primary breast cancer.

Adult↗

Epidemiological investigations on neuroblastomas in Denmark 1943-1980.

During the period 1943-1980 a significant increase in the incidence of neuroblastoma was seen in Denmark. The incidence increased from a level corresponding to that in Finland to a level corresponding to that in the USA, and the increase appears to be continuing. The increase relates to children aged under 5 years, and is most pronounced in infants under 1 year. The incidence in the first year of life has, however, not yet reached the level of the USA. The increase in incidence is most likely a result of improved diagnosis, changes in the social composition of the population, and an increase in environmental carcinogens of importance in the induction of neuroblastomas. The incidence is lower in children of self-employed parents, and higher in infants of mothers aged under 20 or over 34 years. Aside from lower socio-economic circumstances for mothers under 20 years, no specific risk factors were revealed in this study. The observations of a family in which the mother has ganglioneuroma and both daughters have developed neuroblastoma, of a child who suffered from both neuroblastoma and neurofibromatosis von Recklinghausen, and of a significantly higher frequency of infants with signs of multicentric tumours in the offspring of mothers aged under 20 and over 34 years of age, is consistent with the two-hit theory of Knudson et al. (1972).

Adolescent↗

Diverging trends in incidence and mortality of testicular cancer in Denmark, 1943-1982.

Between 1943 and 1982, 5,140 new cases of testicular cancer were diagnosed in Denmark. The age-standardized incidence rate more than doubled in the period. Striking variations is seen in the age-relationship over time with a four-fold increase in incidence for men aged 15-24 years while no increment was observed for those above 65 years of age. The increase with time in the risk could be accounted for by a cohort effect. The mortality rate did not parallel the incidence rate and a 50% decrease in mortality rate appeared in the period 1978-1982. Introduction of combination chemotherapy including cis-platinum is one of the main factors responsible for this beneficial development. The observed pattern of diverging trends in incidence and mortality of testicular cancer implies that mortality rates do not reflect the incidence and will accordingly be unsuited as a basis for aetiological considerations based on trends. The brisk increase in the risk of testicular cancer, especially among young men is in accordance with trends in other western countries, and prompts an enforced search for suspected or new risk factors.

Adolescent↗