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C Olesen

Publications and source records attributed to C Olesen.

At least 19 recordsLinked to original sources

Human FATE is a novel X-linked gene expressed in fetal and adult testis.

Previously, we identified a partial cDNA sequence of a novel human transcript, designated fetal and adult testis expressed transcript (FATE). FATE is testis-specific in fetal life and co-expressed with SRY in a 7 weeks old fetal testis, suggesting a function in early testicular differentiation. Herein, full-length cDNA clones of human and porcine FATE were isolated and the gene structure and promoter region of the human FATE gene was characterized. The human FATE gene, which maps to Xq28, consists of five exons spanning approximately 7 kb of genomic DNA. Examination of 1 kb of the FATE promoter region revealed the presence of a putative steroidogenic factor 1 (SF-1) binding site at position -79 to -71 upstream of the transcription start site. We propose that FATE might represent a novel target gene of SF-1 in human testicular differentiation and/or germ cell development.

Adult↗

Birth outcome following maternal use of fluoroquinolones.

The aim of the study was to examine fetal risk associated with intrauterine exposure to fluoroquinolones. By using on record linkage between a Prescription Database and the Birth Registry in Denmark, the offspring of 57 users of fluoroquinolones and of 17259 patients who had no prescriptive medication during pregnancy, were compared in a cohort study. Among the users, the prevalence rate ratios of congenital abnormalities, preterm birth and low birth weight were 1.30 (95% CI: 0.30-5.30),1.53 (95% CI: 0.62-3.80) and 1.17 (95% CI: 0.15-8.90), respectively. The risk of congenital abnormalities among users of fluoroquinolones during pregnancy was close to unity. Despite these limitations of statistical analysis the study suggested that the use of fluoroquinolones during pregnancy may not be a major risk factor to the foetus.

Abnormalities, Drug-Induced↗

Effect of 4-octylphenol on germ cell number in cultured human fetal gonads.

This study evaluates whether a hormone disruptor found in environment, 4-octylphenol, affects the rate of proliferation of germ cells from human fetal gonads during a 3 week culture period. Five testis and five ovaries were obtained from fetuses of women undergoing legal abortions between the 6th and 9th week of fetal life, representing the period where early gonadal differentiation takes place. Each gonad was divided into equal sized test and control tissue. The test tissue was exposed to a continued presence of 10 micromol/l 4-octylphenol in the culture medium. The cultures were terminated by fixation of the tissues, which where then processed for histology and serially sectioned. The mitotic index of the germ cells (i.e. number of mitosis per 100 germ cells) and the number of germ cells per area was determined. Each of the five testes cultured in 4-octylphenol exhibited a significantly reduced mitotic index and number of pre-spermatogonia compared to the control, whereas none of the five ovaries exposed to 4-octylphenol revealed any difference compared to the control. It is concluded that 4-octylphenol exerts a sex-specific effect on male germ cells.

Cell Count↗

Individual use of antibiotics and prevalence of beta-lactamase production among bacterial pathogens from middle ear fluid.

Prescription data and clinical laboratory data were analysed to assess the influence of previous antibiotic therapy on the prevalence of beta-lactamase in isolates of Haemophilus influenzae and Moraxella catarrhalis from primary specimens of middle ear fluid from 2129 children aged 0-5 years. The prevalence of beta-lactamase-positive H. influenzae was 6.6% [95% confidence interval (CI): 3.5-9.8%] in children who received antibiotics 5-90 days before isolation of the organism compared with 7.0% (95% CI: 3.9-10.2%) in those who did not. The prevalence of beta-lactamase-positive M. catarrhalis was 90.9% (95% CI: 84.0-97.8%) in children who received antibiotics compared with 86.7% (95% CI: 79.0-94.4%) in those who did not.

Age Factors↗

Identification of human candidate genes for male infertility by digital differential display.

Evidence for the importance of genetic factors in male fertility is accumulating. In the literature and the Mendelian Cytogenetics Network database, 265 cases of infertile males with balanced reciprocal translocations have been described. The candidacy for infertility of 14 testis-expressed transcripts (TETs) were examined by comparing their chromosomal mapping position to the position of balanced reciprocal translocation breakpoints found in the 265 infertile males. The 14 TETs were selected by using digital differential display (electronic subtraction) to search for apparently testis-specific transcripts in the TIGR database. The testis specificity of the 14 TETs was further examined by reverse transcription-polymerase chain reaction (RT-PCR) on adult and fetal tissues showing that four TETs (TET1 to TET4) were testis-expressed only, six TETs (TET5 to TET10) appeared to be differentially expressed and the remaining four TETs (TET11 to TET14) were ubiquitously expressed. Interestingly, the two tesis expressed-only transcripts, TET1 and TET2, mapped to chromosomal regions where seven and six translocation breakpoints have been reported in infertile males respectively. Furthermore, one ubiquitously, but predominantly testis-expressed, transcript, TET11, mapped to 1p32-33, where 13 translocation breakpoints have been found in infertile males. Interestingly, the mouse mutation, skeletal fusions with sterility, sks, maps to the syntenic region in the mouse genome. Another transcript, TET7, was the human homologue of rat Tpx-1, which functions in the specific interaction of spermatogenic cells with Sertoli cells. TPX-1 maps to 6p21 where three cases of chromosomal breakpoints in infertile males have been reported. Finally, TET8 was a novel transcript which in the fetal stage is testis-specific, but in the adult is expressed in multiple tissues, including testis. We named this novel transcript fetal and adult testis-expressed transcript (FATE).

Chromosome Mapping↗

Do pregnant women report use of dispensed medications?

Surveillance of drug safety in pregnancy often draws on administrative prescription registries. Noncompliance in the use of prescribed medication may be frequent among pregnant women owing to their fear of fetotoxic side effects. To estimate compliance in the use of prescription drugs dispensed during pregnancy, we compared prescription data from the North Jutland Prescription Database with information on drug use provided by pregnant women to the Danish National Birth Cohort (DNBC), which is a health interview survey. We used the North Jutland Prescription Database to identify all prescription drugs dispensed during pregnancy for the 2,041 women who were enrolled in the DNBC in the County of North Jutland, Denmark. Compliance was defined as the probability of reporting drug use in DNBC after purchasing a dispensed prescription drug. The overall compliance to drugs purchased within 120 days before the interview was 43% (95% confidence interval = 40-46). Drugs used for treating chronic diseases, for example, beta-blockers, insulin, thyroid hormones, and diuretic and antiepileptic drugs, were always reported to be used, but compliance was low for drugs used for local or short-term treatment such as antihistamines, antibiotics, antacids, nonsteroid anti-inflammatory drugs, and gynecologic drugs. Thus, for the latter drug groups the prescription database may provide an incomplete identification of exposure. Neither data source is unbiased regarding actual drug intake. Nevertheless, our results indicate that for some drug groups risk assessment studies based on prescription data may produce false negative results as a result of noncompliance.

Cohort Studies↗

Effect of diuretics on fetal growth: A drug effect or confounding by indication? Pooled Danish and Scottish cohort data.

AIMS: The diabetogenic effect of diuretics, as well as the indication for prescribing them, may impact on fetal growth. We analysed whether the purchase of prescription drugs for diuretics during pregnancy was associated with measures of fetal growth. METHODS: During 1991-98 all women who purchased prescription drugs for diuretics during pregnancy were identified in the Northern Jutland Prescription Database (NJDP), Denmark, and in the Medicines Monitoring Unit's Database (MEMO), Scotland. Information on birth weight and gestational age was obtained from the Danish Birth Registry, the Danish Hospital Discharge Registry and the Scottish Tayside Neonatal Database. Information on diabetes, hypertension and prepregnancy weight were obtained by hospital record review in a sample of women in the Danish cohort. Women who did not purchase prescription diuretics during pregnancy were used as a reference group in both cohorts. RESULTS: Danish women who purchased prescription loop diuretics during pregnancy gave birth to infants with higher birth weights than women who did not use diuretics; mean difference 104.7 g (95% CI; 2.6, 206.9). However, the high prevalence of diabetes (10.3%) among Danish women who purchased prescription loop diuretics during pregnancy might explain this result. Both the Danish and the Scottish women who purchased prescription diuretics during their pregnancy were at increased risk of preterm delivery (< 37 completed weeks); ORs: 1.8 (CI; 1.2, 2.7)NJDP, 1.9 (CI; 0.9, 4.3)MEMO. The proportion of hypertension among women who purchased prescription thiazides was 15.8%, and the risk of having an infant with a birth weight (BW) < 2500 g was increased; ORs: 2.6 (CI; 1.4, 5.0)NJDP, 2.4 (CI; 0.8, 7.8)MEMO. CONCLUSIONS: Prescribing diuretics during pregnancy was associated with differences in birth weight and incidence of preterm delivery. Confounding by indication may explain the findings.

Benzothiadiazines↗

A population-based prescription study of asthma drugs during pregnancy: changing the intensity of asthma therapy and perinatal outcomes.

BACKGROUND: Among the goals of gestational asthma, therapy is optimisation of pulmonary function. According to the US Food and Drug Administration, no asthma drugs can be considered 'safe' during pregnancy. Fear of adverse fetal effects may thus lead to restrictive use of asthma drugs during pregnancy, and no population-based studies concerning gestational asthma therapy exist. OBJECTIVES: To examine whether asthma drugs or changing intensity of asthma therapy during pregnancy was associated with deviations from expected values of gestational age, birth weight, length at birth, or malformations. METHODS: The Birth Registry was used to identify all 15,756 primiparous women who gave birth in the County of North Jutland between 1991 and 1996. According to the North Jutland Prescription Database, 303 of these women received prescriptions for asthma drugs during pregnancy. Women who did not purchase any prescription drugs during pregnancy constituted the reference group. CONCLUSION: Women who received prescriptions for asthma drugs during pregnancy gave birth to infants with birth weight and length at birth within the expected limits. Reducing intensity of asthma treatment during pregnancy was associated with lower birth weight and length at birth. This may indicate that pregnant women chose to discontinue therapy although their disease severity justifies continuation of treatment. However, analyses did not take into account important clinical variables, and results could also be due to confounding factors or chance.

Adult↗

Influence of day care attendance on the use of systemic antibiotics in 0- to 2-year-old children.

OBJECTIVE: To examine the association between time spent in different public day care settings and prescription of systemic antibiotics. Design. Population-based cohort study of 5035 Danish children born in 1997 followed from birth to June 30, 1999. METHODS: The study was performed by the linkage of records drawn from administrative registries. Exposure was the total time spent in a day care home or day care center. Outcome was the first prescription of a systemic antibiotic. Possible perinatal and sociodemographic confounding factors were considered by statistical analysis. RESULTS: During the first year of life, 39.8% of the girls and 51.1% of the boys received at least 1 antibiotic prescription drug. Enrollment in a day care setting doubled a child's risk of receiving a prescription drug (adjusted relative risk in day care home 1.9, 95% confidence interval: 1.7-2.0; adjusted relative risk in day care center 2.0, 95% confidence interval: 1.7-2.3). Only age confounded the analyses. Age >1 year at the starting time in day care reduced the risk of receiving antibiotic prescriptions during the first 3 months after enrollment. CONCLUSIONS: Enrollment in public day care facilities raised the risk of receiving an antibiotic prescription drug to the same extent in day care homes as well as in day care centers, so we cannot recommend one facility over the other based on the present study. Children <1 year old at enrollment were most at risk, suggesting that extension of parental leave may reduce the use of antibiotics.

Anti-Bacterial Agents↗

Pregnancy outcome following prescription for sumatriptan.

BACKGROUND: Some 2.5% of fertile Danish women use sumatriptan, and the drug is also taken during pregnancy. Although sumatriptan reacts selectively in brain vessels, the possibility of reactions with placental blood flow and uterotonic activity cannot be ruled out. The aim of our study was to examine the association between sumatriptan exposure during pregnancy and the risk of preterm delivery and low birth weight. METHODS: Data from the Pharmaco-Epidemiological Prescription Database of North Jutland county regarding all women who had given birth in the county of North Jutland from 1991 to 1996 were linked to the Danish Medical Birth Registry. Women who were exposed to sumatriptan during pregnancy were identified (n = 34), and using logistic regression models their pregnancy outcome was compared with two groups of pregnant women: (1) healthy women (n = 15 955) and (2) migraine controls (n = 89), defined as migraine patients who did not redeem prescriptions for migraine treatment during pregnancy. RESULTS: The risk of preterm delivery was elevated among women exposed to sumatriptan compared with migraine controls (odds ratio [OR] 6.3, 95% confidence interval [CI] 1.2-32.0) and healthy women (OR 3.3, 95% CI 1.3-8.5). The odds ratio for having a newborn with a low birth weight was increased (OR 3.0, 95% CI 1.3-7.0) for all migraine patients who delivered at term (n=115) compared with the outcome of healthy pregnancies. CONCLUSIONS: We found that sumatriptan exposure during pregnancy was associated with an increased risk of preterm delivery and low birth weight. These findings may be due to drug exposure, but they may also reflect the impact of disease severity rather than the treatment itself, or confounding, or chance.

Adult↗

[Randomization and alternatives].

The randomized clinical study is being threatened from many perspectives, and participation in such studies shows a falling tendency. Assurance of the best possible treatment for future patients will be considerably weakened if randomized studies have to be replaced by non-experimental studies. This is because the choice of treatment in itself makes ordinary control of confounders impossible both in design and analysis. The rationale of the randomized study and certain alternative study designs are explained in the article.

Case-Control Studies↗

Drug use in first pregnancy and lactation: a population-based survey among Danish women. The EUROMAP group.

OBJECTIVE: To examine the drug prescription pattern in Danish women from 12 weeks prior to conception until 12 weeks post-partum. METHOD: A drug utilization study based on The North Jutland Prescription Database. The Danish pharmacies use a computerized accounting system for all subsidized drugs and this was linked to the Danish Medical Birth Registry concerning prescription patterns for all women who had given birth in the county of North Jutland from 1991 to 1996. RESULTS: The analysis included 16,001 primiparous women, who had redeemed 34,834 prescriptions prior to, during and after pregnancy. During pregnancy 44.2% of the women received prescriptions for at least one drug. Users received 2.6 prescriptions on average during pregnancy: 5% of the users redeemed 24.2% of all prescriptions. The proportion of women who redeemed prescriptions for more than three different drugs was 2.7%. The majority of prescriptions were for antibiotics (28.7%), gynaecological drugs (13.3%) and anti-asthma drugs (7.6%). The post-partum prescription proportion was 34.0% and the majority of the prescriptions during this period were for penicillins (20.1%), ophthalmologicals (15.5%) and corticosteroids for dermatological use (5.7%). CONCLUSION: A high proportion of the women received drugs during pregnancy. The pattern of drug use within the Anatomical Therapeutical Chemical (ATC) groups changed, i.e. the amount of broad spectrum antibiotics decreased and the proportion of prescriptions for local use increased. A small proportion of women redeemed prescriptions for more than three different drugs during pregnancy.

Adult↗

Prescribing during pregnancy and lactation with reference to the Swedish classification system. A population-based study among Danish women.

AIM: To assess the current prescribing pattern for 15,756 primiparae before, during, and after their pregnancies with reference to fetal and neonatal risk. METHOD: A prescription database study with linkage to The Danish Medical Birth Registry from 1991 to 1996. The drug subsidy system in Danish retail pharmacies, made it possible to identify prescriptions by individual use. All 34,334 prescriptions were set against the Swedish classification of risk of drug use in pregnancy and lactation. RESULTS: During pregnancy, safe (group A), potentially harmful (group B3, C, and D), and non-classifiable drugs accounted for 40.9%, 26.6% and 28.7% respectively. The proportion of women who redeemed drugs was 29.2%, 8.6%, 18.7% and 0.9% from drug groups A, B, C and D respectively. The proportion of prescriptions from high risk groups declined during the course of pregnancy. Postpartum, safe drugs (group I and II), drugs with possible harmful neonatal effects (group III), and non-classifiable drugs accounted for 43.5%, 4.8%, and 35.8% of the prescriptions, respectively. CONCLUSION: According to the Swedish classification system, we found that during pregnancy and lactation a high proportion of Danish women were exposed to one or more drugs in high risk groups; furthermore, knowledge regarding their safety for the fetus and neonate was limited for a large proportion of the prescriptions. Current evidence about long-term effects of prenatal exposure stresses the need for long-term follow-up of health and development among exposed children.

Adverse Drug Reaction Reporting Systems↗

The safety of proton pump inhibitors in pregnancy.

AIM: To assess the safety of proton pump inhibitors during pregnancy. METHODS: Fifty-one pregnant women exposed to proton pump inhibitors around the time of conception or during pregnancy were compared with 13 327 controls without exposure to any prescribed drug in a population-based study based on The Pharmaco-Epidemiological Prescription Database of North Jutland and the Danish Hospital Discharge Registry. RESULTS: Three babies with malformations were found among 38 women exposed to proton pump inhibitors from 30 days before conception to the end of the first trimester. No cases of stillbirth were recorded. Crude relative risks of malformation, low birth weight and preterm delivery were 1.6 (95% CI: 0.5-5.1), 1.8 (95% CI: 0.2-13.0) and 2.3 (95% CI: 0.9-6.0), respectively. CONCLUSIONS: In this population-based follow-up study, we found no substantially elevated risk in terms of malformations, low birth weight or number of preterm deliveries in pregnancies exposed to proton pump inhibitors. However, further monitoring is warranted in order to establish or rule out a potential association between the use of proton pump inhibitors and increased risk of either cardiac malformations or preterm birth.

Abnormalities, Drug-Induced↗

Low use of long-term hormone replacement therapy in Denmark.

AIMS: To examine individual use of hormone replacement therapy (HRT) in a defined population of Danish women during a 5-year period. HRT may reduce osteoporosis and cardiovascular disease in postmenopausal women, but may also have side-effects. Little is known about the use of HRT in most populations. METHODS: A Pharmacoepidemiological Prescription Database was used to identify all reimbursed prescriptions for HRT in the county during the period 1991 to 1995. The Danish retail pharmacies' drug subsidy system made it possible to identify prescriptions by individual use. RESULTS: We examined 255797 HRT prescriptions issued during the period in the County of North Jutland. Total sales reached 16.5 million defined daily doses (DDDs), purchased by 31653 women, which corresponds to 26.9% of the female population above the age of 39 years. The annual prevalence proportion of current users rose from 10.4% to 14.8% during the study period, and the therapeutic intensity (DDD/1000 women/day) increased from 20.6 to 32.0. The mean DDD sum of systemic HRT per user was 73.4 in 1991; it and the proportion of users who received less than 90 DDD per year (83.4% in 1991) remained almost constant during the study period. The amount of oestrogen unopposed by progestin was high, 28.1% of all prescriptions. CONCLUSIONS: Less than one-fifth of the study population used HRT for more than 3 months per year, and only 32.8% of the women who were new users of HRT in 1992 continued this therapy throughout the study period.

Adult↗

Risk of malformations and other outcomes in children exposed to fluconazole in utero.

AIM: Fluconazole is an active drug systematically used in the oral treatment of vaginal candidiasis and other fungal diseases. We examined the risk of malformations and other birth outcomes following pregnancy related exposures. METHOD: From 1 January 1991 to 31 December 1996 we identified 165 women who had taken fluconazole just before or during pregnancy in the Pregnancy Outcome Section of the North Jutland Pharmacoepidemiological Prescription Database, Denmark, which is linked to the Danish Medical Birth Registry. We compared their birth outcomes (malformation, low birth weight and preterm delivery) with the outcomes among 13 327 women who did not receive any prescriptions during their pregnancies. RESULTS: The prevalence of malformation was 3.3% (four cases) among the 121 women, who had used fluconazole in the first trimester, and 5.2% (697 cases) in offspring to controls (odds ratio: 0.65, 95% confidence limits: 0.24-1.77). Furthermore, we did not find any significantly elevated risk of preterm delivery (odds ratio: 1.17, 95% confidence limits: 0.63-2.17) and low birth weight (odds ratio: 1.19, 95% confidence limits: 0.37-3.79). CONCLUSION: The study showed no increased risk of congenital malformations, low birth weight or preterm birth in offspring to women who had used single dose fluconazole before conception or during pregnancy.

Abnormalities, Drug-Induced↗

Multiple prescriptions of antibiotics for children aged 0 to 5 years in relation to type of antibiotic.

The risk of receiving more than one prescription within an antibiotic course was examined for all children aged 0 to 5 years in a Danish county during 1997. We identified 29,307 prescriptions of systemic antibiotics for 16,245 children in a prescription database. Ten per cent of the prescriptions were followed by a new prescription within 10 days. In children who received two prescriptions (n = 3993), 19% redeemed the prescriptions within the same course. When the child was prescribed penicillin V, compared with broad-spectrum penicillin, the odds ratio of receiving a repeat prescription within 1-2 days was 2.9 (95% CI 2.5-3.4) and within 3-10 days 1.3 (95% CI 1.2-1.5).

Anti-Bacterial Agents↗