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Biomedical subjects

L Pedersen

Publications and source records attributed to L Pedersen.

At least 37 records · Page 2Linked to original sources
PubMed2003

Birth outcome in women exposed to 5-aminosalicylic acid during pregnancy: a Danish cohort study.

BACKGROUND: 5-Aminosalicylic acid (5-ASA) preparations are the firstline drugs in the treatment of inflammatory bowel disease. Data on the safety of these drugs in pregnancy are sparse. AIMS: To examine the risk of adverse birth outcome in women who were prescribed 5-ASA drugs during pregnancy. PATIENTS: Women were included in the study if they were prescribed 5-ASA drugs immediately before or during pregnancy. To examine the risk of malformations, we included 60 pregnancies exposed to 5-ASA drugs 30 days before pregnancy or in the first trimester. To examine stillbirths, preterm births, and low birth weight, we included 88 pregnancies exposed during the entire pregnancy. Outcomes were compared with those of 19 418 pregnancies in which no drugs were prescribed for mothers during the study period. METHODS: We conducted a Danish cohort study based on data from a population based prescription registry, the Danish Birth Registry, and the Hospital Discharge Registry in North Jutland County. RESULTS: Odds ratios for malformations, stillbirth, preterm birth, and low birth weight in women who received prescriptions for 5-ASA drugs were 1.9 (95% confidence interval 0.7-5.4), 6.4 (1.7-24.9), 1.9 (0.9-3.9), and 1.2 (0.4-3.3), respectively. The increased risk of stillbirth and preterm birth were found only in patients with ulcerative colitis. CONCLUSIONS: We found an increased risk of stillbirth and preterm birth in women who had been prescribed 5-ASA drugs during pregnancy but no substantial increased risk of malformations. It was difficult to distinguish the specific effects of disease activity and 5-ASA drugs.

Abnormalities, Drug-Induced↗
PubMed2002

Symptomatology of cancer patients in palliative care: content validation of self-assessment questionnaires against medical records.

To elucidate which symptoms or problems to measure when evaluating palliative care, we assessed the content validity of selected patient self-assessment questionnaires used to evaluate palliative care: the European Organization for Research and Treatment of Cancer-Quality of Life-Core 30 (EORTC QLQ-C30), the Edmonton Symptom Assessment System (ESAS), the Palliative Care Outcome Scale (POS), the McGill Quality of Life Questionnaire (MQOL) and the Memorial Symptom Assessment Scale (MSAS). The content of the questionnaires was compared against the symptoms and problems noted in the medical records of 171 consecutive cancer patients on their first admission to a department of palliative medicine. From the records, 63 different symptoms were listed. Two questionnaires covered almost all of the prevalent symptoms/problems: the EORTC QLQ-C30 covered 10 and the MSAS 11 of the 12 most frequent problems. Researchers selecting instruments for evaluating palliative care may use the present study and other reviews to examine to what degree a given selection of instruments cover the symptoms/problems targeted by palliative care physicians.

Adult↗
PubMed2002

Atrial fibrillation or flutter and stroke: a Danish population-based study of the effectiveness of oral anticoagulation in clinical practice.

OBJECTIVES: A pooled analysis of randomized trials has shown that oral anticoagulation therapy reduces the risk of ischaemic stroke with 68% in patients with atrial fibrillation. We examined the effectiveness of oral anticoagulation on risk of stroke of any nature (fatal and nonfatal ischaemic and/or haemorrhagic stroke) in patients with nonvalvular atrial fibrillation or flutter living in the County of North Jutland, Denmark. DESIGN: Cohort study. SUBJECTS AND METHODS: We used the Hospital Discharge Registry covering the county (490 000 inhabitants) from 1991 to 1998 to identify 2699 men and 2425 women with atrial fibrillation or flutter, aged 60-89 years. Data on prescriptions of anticoagulation were obtained from the National Health Service. We defined use of oral anticoagulation as date of prescription or reiteration plus 90 days. Patients were followed in the County Hospital Discharge Registry until a diagnosis of stroke (fatal and nonfatal ischaemic and/or haemorrhagic stroke), emigration, death or the end of 1998. We used Cox regression analyses to estimate the relative risk of stroke associated with use of oral anticoagulation compared with no use, adjusted for age, diabetes and underlying cardiovascular diseases. RESULTS: Eight hundred and thirty-eight of 2699 men (31%) and 552 of 2425 women (23%) with atrial fibrillation had one or more recorded prescriptions of oral anticoagulation. The incidence rates of stroke were 31 per 1000 person-years of follow-up in men, and 30 per 1000 person-years of follow-up in women. The adjusted relative risks of stroke during anticoagulation were 0.6 [95% confidence interval (CI) 0.4-1.0] in men, and 1.0 (95% CI 0.7-1.6) in women compared with nonuse periods. CONCLUSIONS: The effectiveness of oral anticoagulation in clinical practice may be lesser than the efficacy of oral anticoagulation reported from randomized trials.

Administration, Oral↗
PubMed2002

Secular trends in incidence and 30-day case fatality of acute pancreatitis in North Jutland County, Denmark: a register-based study from 1981-2000.

BACKGROUND: The incidence rate of acute pancreatitis has been reported as having increased during recent decades in Western countries. Reported mortality lies around 10% and has improved during the past 20 years. The incidence rate and 30-day case fatality rate of acute pancreatitis in North Jutland County, Denmark were examined for the period 1981 to 2000. METHODS: Data were collected from the Hospital Discharge Registry of North Jutland County for the period 1981-2000. Sex- and age-standardized incidence rates and 30-day case fatality rate of a first attack of acute pancreatitis were calculated. Data on endoscopic procedures were assessed for the period 1992 to 2000 and on certain drugs for 1991 to 1999. RESULTS: The incidence rate of acute pancreatitis in women increased from 17.1 per 100,000 person-years in 1981 (95% confidence interval (CI), 12.6-23.2) to 37.8 per 100,000 person-years in 2000 (95% CI, 31.0-46.1). The corresponding increase in men was from 18 per 100,000 person-years in 1981 (95% CI, 13.3-24.2) to 27.1 per 100,000 person-years in 2000 (95% CI, 21.5-34.3). The incidence rate of acute pancreatitis increased with age in both sexes. The overall 30-day case fatality rate was 7.5% (95% CI, 6.5-8.7) increasing with age, adjusted odds ratio (OR) = 6.4 (95% CI, 3.5-11.6) and decreased with time, adjusted OR = 0.7 (95% CI, 0.4-1.0). CONCLUSION: The incidence of acute pancreatitis has increased, and in women surpassed that in men in 1999 and 2000. Short-term prognosis has improved.

Acute Disease↗
PubMed2001

[Congenital malformations and fetal growth of children with intrauterine exposure to anticonvulsants].

OBJECTIVES: To examine the risk of malformations and fetal growth in the children of women treated with anticonvulsant drugs in North Jutland County, Denmark. MATERIAL AND METHODS: All women treated with anticonvulsant drugs in the county were identified in a Pharmaco-Epidemiological Prescription Database and linked to the Danish Medical Birth Registry and the Regional Hospital Information system. RESULTS: We identified 235 pregnancies where the mothers had used prescriptions for anticonvulsants around conception and/or during pregnancy, and 17,259 unexposed pregnancies where the mothers had not used prescriptions. One case of neural tube defect was found among 15 malformations in the exposed cohort. The overall odds ratio for malformations was 2.2 (95% confidence intervals 1.3-3.8). The odds ratios for low birth weight and preterm delivery were respectively 1.5 (95% confidence intervals 0.6-3.7) and 1.6 (95% confidence intervals 1.0-2.5). CONCLUSION: We found an increased risk of congenital malformations and a tendency to growth retardation in the children of women taking anticonvulsants.

Abnormalities, Drug-Induced↗
PubMed2001

Risk of hospitalization for cardiovascular disease after use of macrolides and penicillins: a comparative prospective cohort study.

Chlamydia pneumoniae has been associated with cardiovascular diseases, and C. pneumoniae infection is treatable with macrolides. In this comparative cohort study, 634 users of macrolides and 3827 users of penicillins were identified from the Danish Health Service Registry of Prescriptions and followed up for an average of 6 months. The patients were then linked to the Regional Hospital Discharge Registry to assess the outcome of hospitalization for cardiovascular disease. In the first 3 months, the relative risk (RR) of admission for a cardiovascular disease was 0.48 (95% confidence interval, 0.27-0.88) in users of macrolides compared with users of penicillins. No difference was seen after 3 months. Interaction analyses indicated that the lower risk seen in users of macrolides could be more pronounced in patients without versus those with a previous cardiovascular disease (RR, 0.39 vs. 0.52), in patients >or=60 versus <60 years old (RR, 0.39 vs. 0.64), and in men versus women (RR, 0.35 vs. 0.67).

Aged↗
PubMed2001

Four loops of the catalytic domain of factor viia mediate the effect of the first EGF-like domain substitution on factor viia catalytic activity.

The presence of tissue factor is essential for factor VIIa (FVIIa) to reach its full catalytic potential. The previous work in this laboratory demonstrated that substitution of the EGF1 domain of factor VIIa with that of factor IX (FVII((IXegf1))a) results in a substantial decrease in TF-binding affinity and catalytic activity. Supporting simulations of the solution structures of Ca(2+)-bound factor VIIa and FVII((IXegf1))a with tissue factor are provided. Mutants are generated, based on the simulation model, to study the effect of EGF1 substitution on catalytic activity. The simulations show larger Gla-EGF1 and EGF1-EGF2 inter-domain motions for FVII((IXegf1))a than for factor VIIa. The catalytic domain of the chimeric factor VIIa has been disturbed and several surface loops in the catalytic domain of FVII((IXegf1))a (Loop 170s (170-182), Loop 1 (185-188) and Loop 2 (221A-225)) manifest larger position fluctuations than wild-type. The position of Loop 140s (142-152) of FVII((IXegf1))a, near the N terminus insertion site of the catalytic domain, shifts relative to factor VIIa, resulting in a slight alteration of the active site. The results suggest that these four loops mediate the effect of the EGF1 domain substitution on the S1 site and catalytic residues. To test the model, we prepared mutations of these surface loops, including four FVII mutants, D186A, K188A, L144A and R147A, a FVII mutant with multiple mutations (MM3: L144A+R147A+D186A) and a FVII mutant with Loop 170s partially deleted, Loop 170s(del). The catalytic activities towards a small peptidyl substrate decreased 2.4, 4.5 and 9-fold for Loop 170s(del)a (a, activated), L144Aa and D186Aa, respectively, while MM3a lost almost all catalytic activity. The combined results of the simulations and mutants provide insight into the mechanism by which tissue factor enhances factor VIIa catalytic activity.

Amino Acid Substitution↗
PubMed2001

Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study.

OBJECTIVE: To estimate the risk of adverse birth outcome in women who take non-steroidal anti-inflammatory drugs during pregnancy. DESIGN AND SETTING: Population based cohort study and a case-control study, both based on data from a prescription registry, the Danish birth registry, and one county's hospital discharge registry. PARTICIPANTS: COHORT STUDY: 1462 pregnant women who had taken up prescriptions for non-steroidal anti-inflammatory drugs in the period from 30 days before conception to birth and 17 259 pregnant women who were not prescribed any drugs during pregnancy. CASE-CONTROL STUDY: 4268 women who had miscarriages, of whom 63 had taken non-steroidal anti-inflammatory drugs, and 29 750 primiparous controls who had live births. MAIN OUTCOME MEASURES: Incidences of congenital abnormality, low birth weight, preterm birth, and miscarriage. RESULTS: Odds ratios for congenital abnormality, low birth weight, and preterm birth among women who took up prescriptions for non-steroidal anti-inflammatory drugs were 1.27 (95% confidence interval 0.93 to 1.75), 0.79 (0.45 to 1.38), and 1.05 (0.80 to 1.39) respectively. Odds ratios for the taking up of prescriptions in the weeks before miscarriage ranged from 6.99 (2.75 to 17.74) when prescriptions were taken up during the last week before the miscarriage to 2.69 (1.81 to 4.00) when taken up between 7 and 9 weeks before. The risk estimates were no different when the analysis was restricted to missed abortions. CONCLUSIONS: Use of non-steroidal anti-inflammatory drugs during pregnancy does not seem to increase the risk of adverse birth outcome but is associated with increased risk of miscarriage.

Abnormalities, Drug-Induced↗
PubMed2001

Does the medical record cover the symptoms experienced by cancer patients receiving palliative care? A comparison of the record and patient self-rating.

The aim of this study was to investigate the extent to which the symptoms experienced by advanced cancer patients were covered by the medical records. Fifty-eight patients participated in the study. On the day of first encounter with our palliative care department, a medical history was taken, and on this or the following day, the patients completed the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), Edmonton Symptom Assessment System (ESAS), and Hospital Anxiety and Depression Scale (HADS). The symptomatology reported in the patient-completed questionnaires was compared with the symptomatology mentioned by the physician in the medical record. The analysis revealed good concordance concerning pain, but most other symptoms or problems were reported much more often by patients than by their doctors. Reasons for these discrepancies are discussed. It is suggested that the doctor's knowledge of the patient's symptomatology might gain from more systematic screening and transfer of information from patient self-assessment questionnaires to the medical records.

Adult↗
PubMed2001

Expression of type III sodium-dependent phosphate transporters/retroviral receptors mRNAs during osteoblast differentiation.

Inorganic phosphate (Pi) is essential for the formation of bone. Pi transport in osteoblastic cells is mainly handled by sodium-dependent Pi (NaPi) transporters, different from the renal type I and II transporters; their molecular identities are, however, still subject to investigation. Recently, two type III NaPi transporters, Pit1 and Pit2, were identified, both of which exhibit some of the biochemical and regulatory characteristics of osteoblastic cell-associated NaPi transporters. Here, we have investigated the Pit1 and Pit2 steady-state mRNA levels during the osteoblast differentiation in cultures of the nontransformed MC3T3-E1 cell line. While Pit2 mRNAs were invariably expressed at low levels, Pit1 mRNA levels were found to increase during osteoblast differentiation concomitantly with osteocalcin mRNA. Moreover, the increase in Pit1 mRNA levels also correlated with the time in culture at which mineralization could be observed. The increase in Pit1 mRNA levels over time in culture was only observed in cultures grown under conditions allowing for osteoblast differentiation. This is the first time that osteoblast differentiation-dependent regulation of expression of a NaPi transporter has been demonstrated. Moreover, we show here for the first time the presence of Pit1 and Pit2 mRNAs in undifferentiated and differentiated nontransformed osteoblastic cells. Our data suggest that both Pit1 and Pit2 NaPi transporters are involved in Pi transport in preosteoblastic and osteoblastic cells, and they represent the first evidence consistent with a potential role for Pit1, but not for Pit2, in differentiation-dependent Pi transport. The observed upregulation of Pit1 mRNA levels during osteoblast differentiation suggests that Pit1 might be used as a marker for osteoblast maturation.

Alkaline Phosphatase↗
PubMed2001

Crystal structures of nucleotide exchange intermediates in the eEF1A-eEF1Balpha complex.

In the elongation cycle of protein biosynthesis, the nucleotide exchange factor eEF1Balpha catalyzes the exchange of GDP bound to the G-protein, eEF1A, for GTP. To obtain more information about the recently solved eEF1A-eEF1Balpha structure, we determined the structures of the eEF1A-eEF1Balpha-GDP-Mg2+, eEF1A-eEF1Balpha-GDP and eEF1A-eEF1Balpha-GDPNP complexes at 3.0, 2.4 and 2.05 A resolution, respectively. Minor changes, specifically around the nucleotide binding site, in eEF1A and eEF1Balpha are consistent with in vivo data. The base, sugar and alpha-phosphate bind as in other known nucleotide G-protein complexes, whereas the beta- and gamma-phosphates are disordered. A mutation of Lys 205 in eEF1Balpha that inserts into the Mg2+ binding site of eEF1A is lethal. This together with the structures emphasizes the essential role of Mg2+ in nucleotide exchange in the eEF1A-eEF1Balpha complex.

Amino Acid Substitution↗
PubMed2001

Recall bias in a case-control surveillance system on the use of medicine during pregnancy.

It is important to study possible teratogenic effects of drugs used during pregnancy. Many studies of this type rely upon case-control designs in which drug intake is recalled by the mothers after having given birth. Recall bias in this situation may lead to spurious associations. We looked for indicators of recall bias by comparing self-reported drug intake with medically notified intake for specific diseases in the Hungarian Case-Control Surveillance System of Congenital Abnormalities, which includes 22,865 cases with congenital abnormalities and 39,151 controls. Recall error was present, especially for drugs used for a short time period. Furthermore, the timing of drug intake was reported slightly closer to the time of interview for cases compared than for controls. Severe or visible congenital abnormalities did not appear to be more conducive to recall bias than other abnormalities under study. A case-control surveillance system of this type may frequently cause spurious associations, with biased odds ratios up to a factor of 1.9.

Abnormalities, Drug-Induced↗
PubMed2001

Crystallization of the yeast elongation factor complex eEF1A-eEF1B alpha.

Crystals of the Saccharomyces cerevisiae elongation factor eEF1A (formerly EF-1 alpha) in complex with a catalytic C-terminal fragment of the nucleotide-exchange factor eEF1B alpha (formerly EF-1 beta) were grown by the sitting-drop vapour-diffusion technique, using polyethylene glycol 2000 monomethyl ether as precipitant. Crystals diffract to better than 1.7 A and belong to the space group P2(1)2(1)2(1). The unit-cell parameters of the crystals are sensitive to the choice of cryoprotectant. The structure of the 61 kDa complex was determined with the multiple anomalous dispersion technique using three selenomethionine residues in a 11 kDa eEF1B alpha fragment generated by limited proteolysis of full-length eEF1B alpha expressed in Escherichia coli.

Chromatography, Gel↗
PubMed2001

Impact of payment method on behaviour of primary care physicians: a systematic review.

OBJECTIVE: To review the impact of payment systems on the behaviour of primary care physicians. METHODS: All randomised trials, controlled before and after studies, and interrupted time series studies that compared capitation, salary, fee-for-service or target payments (mixed or separately) that were identified by computerised searches of the literature. Methodological quality assessment and data extraction were undertaken independently by two reviewers using a data checklist. Study results were qualitatively analysed. RESULTS: Six studies met the inclusion criteria. There was considerable variation in the quality of reporting, study setting and the range of outcomes measured. Fee-for-service resulted in a higher quantity of primary care services provided compared with capitation but the evidence of the impact on the quantity of secondary care services was mixed. Fee-for-service resulted in more patient visits, greater continuity of care, higher compliance with a recommended number of visits, but lower patient satisfaction with access to a physician compared with salary payment. The evidence of the impact of target payment on immunisation rates was inconclusive. CONCLUSIONS: There is some evidence to suggest that how a primary care physician is paid does affect his/her behaviour but the generalisability of these studies is unknown. Most policy changes in the area of payment systems are inadequately informed by research. Future changes to doctor payment systems need to be rigorously evaluated.

Capitation Fee↗
PubMed2000

Oncostatin M and interleukin 6 inhibit cell cycle progression by prevention of p27kip1 degradation in HepG2 cells.

We analysed the regulation of G1-phase progression in relation to cytokine receptor signalling in HepG2 hepatoma cells, stably transduced with the IL-10 receptor after stimulation with Oncostatin M (OSM), IL-6, Leukaemia Inhibitory Factor (LIF) and IL-10. All cytokines induced STAT3 phosphorylation to approximately the same level, but only OSM, and to a lesser extent IL-6, induced STAT5 phosphorylation. The cytokines also stimulated phosphorylation of ERK in the order of decreasing effectiveness: OSM > IL-6 > LIF > IL-10. The same order of activity of the cytokines was observed on inhibition of DNA synthesis and accumulation of cells in the G1-phase of the cell cycle. These processes were accompanied by a decrease in cyclin A expression and CDK2 activity, and enhanced accumulation of p27kip1. The level of p27kip1 mRNA expression was unaffected by the cytokines, and maintenance of the elevated level of p27kip1 occurred independently of de novo protein synthesis. Furthermore, inhibition of proteasomal activity increased the level of p27kip1 in the unstimulated cells to the same level as in OSM-treated cells. Inhibition of MEK activation completely abrogated OSM and IL-6 induced p27kip1 accumulation, while expression of dominant negative STAT5 decreased the OSM and IL-6 mediated inhibition of DNA-synthesis and partially inhibited p27kip1 accumulation.

Animals↗