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Biomedical subjects

P Olofsson

Publications and source records attributed to P Olofsson.

At least 19 recordsLinked to original sources

Increased uterine artery vascular impedance is related to adverse outcome of pregnancy but is present in only one-third of late third-trimester pre-eclamptic women.

OBJECTIVE: Signs of increased uterine artery vascular impedance in mid-gestation are strongly related to pre-eclampsia later in pregnancy. Whether this is true for the late third trimester is, however, unclear. The aim of the present study was to analyze the frequency of increased uterine artery vascular impedance in the third trimester, and its relationship to abnormal umbilical artery Doppler and adverse outcome of pregnancy. METHODS: This was a retrospective study of uterine and umbilical artery Doppler velocimetry in 570 pregnancies complicated by pre-eclampsia. The managing clinician was informed only about the umbilical artery flow. The Doppler recordings were related to severity of pre-eclampsia, prematurity, fetal growth restriction, and rates of Cesarean section and admission to neonatal intensive care. RESULTS: Increased umbilical artery vascular impedance was seen in 59 cases (10.4%), seven having absent or reversed end-diastolic flow. Uterine artery notching was seen in 145 cases (25%), 88 (15%) having bilateral notches. Either increased uterine artery pulsatility index (PI) or notching, or both, were seen in 207 women (36.3%). In 108 women with severe pre-eclampsia, 38 (35.2%) had uterine artery notching. Signs of increased uteroplacental vascular impedance were more common in severe than in mild pre-eclampsia (57.4% vs. 31.4%), in premature than in term pregnancies (70.9% vs. 28.4%), and were more prevalent than abnormality in the umbilical artery (36.3% vs. 10.4%). CONCLUSION: Only one-third of pre-eclamptic cases showed signs of increased uterine artery vascular impedance in the third trimester. However, signs of increased vascular impedance were much more frequent in the uterine than in the umbilical arteries and were strongly related to adverse outcome of pregnancy.

Adolescent↗

Gender differences in patients treated for critical limb ischemia.

OBJECTIVE: To investigate, in patients treated for critical limb ischemia, how pre-operative conditions, localisation of lesions and outcome varied according to gender. DESIGN: Retrospective cohort study. METHODS: Medical records were analysed for all patients treated with vascular reconstruction or PTA for critical limb ischemia 1993-1994 (119 women, 115 men) at the Karolinska Hospital. All events such as secondary intervention, amputation and death occurring until 2003 were included in the analysis. RESULTS: The preoperative conditions were similar between women and men apart from higher mean age (74 years in women vs 69 in men, p=0.0002), fewer subjects with a smoking history (63 vs 82%, p=0-005) and diabetic disease (22 vs 43%, p=0.0004) among females. More interventions were performed suprainguinally in women (44% in women vs 19% in men). Amputation and survival rates were similar in women and men, even after matching for age and diabetes. CONCLUSION: Women were older, had a lower frequency of diabetes, smoked less and had more proximal lesions than treated men. Outcome was identical for both genders. Biological and anatomical differences could possibly explain several of the found gender differences. Gender differences in risk factors and possibly in the selection process also may have contributed to our findings.

Aged↗

Clinical significance of uterine artery blood flow velocity waveforms during provoked uterine contractions in high-risk pregnancy.

OBJECTIVE: To determine whether, in a group of high-risk pregnancies undergoing an oxytocin challenge test (OCT), uterine artery Doppler velocimetry will identify fetuses at risk of distress during the provoked contractions. METHODS: Bilateral uterine artery Doppler velocimetry was performed simultaneously with electronic fetal heart rate (FHR) recordings in 67 high-risk pregnancies subjected to an OCT. Flow velocity waveforms (FVWs) were classified according to pulsatility index (PI), presence of diastolic notching and a novel classification of FVW shapes. The OCT was classified as negative (normal) or positive (late FHR decelerations). Only OCT-negative cases were allowed a trial of vaginal delivery. Non-parametric statistical methods were used to test for differences between the OCT groups. RESULTS: There was no difference in prevalence of high PI or diastolic notching in OCT-positive (n = 10) and OCT-negative (n = 57) cases at basal (resting) measurements or between uterine contractions in either uterine artery (P > or = 0.3). During contractions the PI could not be used for assessment due to the biphasic shape of the FVWs, but there was no difference in distribution of FVW classes between the groups in either the placental side (P > or = 0.3) or contraplacental side (P > or = 0.6) uterine artery. No significant associations between PI or FVW class distribution and birth asphyxia or operative delivery for fetal distress in labor were found (P > or = 0.1). CONCLUSIONS: During uterine contractions there is no difference in uterine artery FVW pattern between OCT-positive and OCT-negative cases. Recording of uterine artery FVWs during the OCT seems to be of limited clinical relevance.

Arteries↗

Acute changes of cerebral venous blood flow in growth-restricted human fetuses in response to uterine contractions.

OBJECTIVE: The fetal cerebral venous circulation during acute hypoxic stress provoked by uterine contractions has not been studied previously. The aim of this study was to explore the cerebral venous circulation during an oxytocin challenge test (OCT) in intrauterine growth-restricted (IUGR) fetuses. METHODS: Doppler recordings of blood flow in the vein of Galen (GV), straight sinus (SS) and transverse sinus (TS) before and during uterine contractions and relaxation were obtained at the same time as electronic fetal heart rate (FHR) monitoring in 44 term IUGR fetuses. The OCT was classified as negative (normal FHR) or positive (late FHR decelerations). Non-parametric statistics were used to test differences between OCT groups. RESULTS: In OCT-negative cases (n = 39), de novo pulsations occurred in the GV, and SS flow velocities increased during contractions compared with basal measurements. There were no significant differences in TS flow. Flow recordings were less often obtained from OCT-positive cases (n = 5), making comparisons with OCT-negative cases uncertain. CONCLUSIONS: In uncompromised IUGR fetuses an acute cerebral venous hyperperfusion develops in response to uterine contractions. Pulsations in the GV are detected but are unlikely to be an ominous sign in this situation. The more centrally located TS was less discriminating for acute cerebral venous blood flow changes.

Blood Flow Velocity↗

Skewed fetal gender distribution in prolonged pregnancy: a fallacy with consequences.

OBJECTIVE: Skewed gender distribution and falsely assigned gestational age lead to unnecessary or late obstetric intervention in prolonged pregnancy. The aim of this study was to examine the consequences of a fetal gender-dependent systematic 1.5-day dating error at ultrasound fetometry. MATERIAL AND METHODS: A total of 82 484 singleton deliveries >/=37 weeks at 11 hospitals in southern Sweden from 1995 to 2000 were included. Frequencies of labor induction and Apgar scores <7 at 5 min were compared with regard to fetal gender, both before and after correction of gestational age by adding 0.75 days to female-fetus pregnancies and subtracting 0.75 days from male-fetus pregnancies. RESULTS: The uncorrected odds ratio for having a male baby at >/=42 weeks was 1.41 (95% confidence interval, 1.33-1.49). After adjusting gestational age by +/-0.75 days, the odds ratio reduced to 0.90 (95% confidence interval, 0.84-0.95). The risk for labor induction was significantly above unity in male-fetus pregnancies delivered after 41 weeks when gestational age was corrected for fetal gender, while the risk for female fetuses having a low Apgar score was not significantly increased compared to male fetuses (P = 0.087). CONCLUSION: Skewed gender distribution in prolonged pregnancy results in a higher rate of labor induction in pregnancies with male fetuses at >/=41 weeks, and the risk for newborn females having a low Apgar score in prolonged pregnancy is not significantly increased compared to boys.

Diagnostic Errors↗

Uterine artery blood flow velocity waveforms during uterine contractions.

OBJECTIVE: No quantitative or qualitative Doppler velocimetry classification of vascular flow resistance covering all stages of forward and reversed flows exists. The objective of this study was to characterize uterine artery (UtA) flow velocity waveforms (FVWs) obtained during an oxytocin challenge test (OCT) and compare them to FVWs in spontaneous normal labor. METHODS: Uterine artery Doppler velocimetry was performed during and between uterine contractions in 61 high-risk pregnancies subjected to an OCT and in 20 normal pregnancies undergoing spontaneous labor. FVWs were classified relative to the presence of forward/absent/reversed flow during systole and diastole, and the time-averaged flow velocity over the heart cycle. RESULTS: Eleven different FVW classes were identified. No relationship between FVWs recorded during uterine inertia and contractions was found (P >/= 0.2). In both groups, only forward FVWs were recorded between contractions, whereas during contractions flow reversal was more common in the OCT group (P </= 0.002). In cases of predominantly reversed flow, a reciprocal relationship to FVW classes recorded in the contralateral artery was found. CONCLUSIONS: UtA FVW patterns recorded during uterine contractions were not predicted by flow patterns recorded during uterine inertia. Reversal of flow direction was more common during oxytocin-induced uterine contractions than during spontaneous contractions. In cases of predominantly reversed flow, domains of the uterus may be supplied by blood from the contralateral UtA. These observations give new insights into the circulatory dynamics of the uterus during labor, and also point to a possible vasoconstrictory effect in the UtAs of oxytocin at high concentrations.

Arteries↗

Positional cloning of Ncf1--a piece in the puzzle of arthritis genetics.

Positional cloning of susceptibility genes in complex diseases like rheumatoid arthritis in humans is hampered by aspects like genetic heterogeneity and environmental variations, while genetic studies in animal models contain several advantages. With animal models, the environment can be controlled, the genetic complexity of the disease is minimized and the disease onset can be predicted, which simplify diagnosis and characterization. We use pristane-induced arthritis in rats to investigate the inheritance of arthritis. Until now, we have identified 15 loci that significantly predispose rats to the development of arthritis. One of these arthritis loci has been isolated and confirmed to be caused by a polymorphism in the Ncf1 gene. In this review, we outline the methods used to identify Ncf1 as one single susceptibility gene in a complex puzzle of inherited factors that render susceptibility to a complex autoimmune disorder like arthritis.

Animals↗

Physiological predictors of performance in cross-country skiing from treadmill tests in male and female subjects.

In order to study which parameter that best corresponds to performance during cross-country skiing, seven male and nine female cross-country skiers were tested with treadmill tests. Parameters measured or computed by metabolic gas measurements were the anaerobic threshold (AT), threshold of decompensated metabolic acidosis (TDMA), the exercise intensity where the Respiratory exchange ratio reaches 1.0 (R = 1) and peak oxygen (O2) uptake (VO2peak). Onset of blood lactate accumulation (OBLA, 4 mmol.l-1 blood lactate) was also measured. The various parameters were measured in percentage of maximal heart rate, percentage of peak O2 uptake, VO2 ml.kg-1.min-1, VO2 ml.min-1.kg-2/3 and VO2 l.min-1. Results from four large competitions were also collected to rank the subjects. With correlation analysis, it was revealed that in male subjects a high OBLA was associated with good ranking results (r = (-0.829) - (-0.964); P < 0.05-0.001). In female subjects, the best association with competition results was found for R = 1 (r = (-0.715) - (-0.810); P < 0.05). Concerning VO2 measurements, for male subjects the unit l.min-1 is suggested to be used and for female subjects either the units l.min-1, ml.min-1.kg-2/3, or ml.kg-1.min-1 could be used when predicting performance in cross-country skiing. In conclusion, treadmill tests can be used for the prediction of performance in cross-country skiing. Further, various parameters from treadmill tests in men and women are best used as predictors of performance in cross-country skiing.

Acidosis↗

Signs of platelet activation, but not lipid peroxidation, in fetal blood associated with functional and structural umbilicoplacental lesions in pregnancies complicated by impaired glucose metabolism.

OBJECTIVES: To study the influence of platelet activation and lipid peroxidation in fetal blood on umbilical vascular prostanoid synthesis and placental morphology in diabetic pregnancy. METHODS: The concentrations of thromboxane A2 (TxA2) and malondialdehyde (MDA) were determined in umbilical cord plasma in 21 women with diabetes mellitus/impaired glucose tolerance (DM/IGT) and ten healthy women. Segments from the umbilical artery and vein were incubated and prostacyclin (PGI2) and TxA2 metabolites were determined. Prostanoid synthesis was stimulated with calcium ionophore at a second incubation. Histological examination was carried out in samples from the umbilical cord, membranes and placental parenchyma. Non-parametric statistical analysis was used, with a two-tailed p < 0.05 considered statistically significant. RESULTS: Cord plasma TxA2, but not MDA, was higher among DM/IGT women (p = 0.07). There were indications that cord plasma TxA2, but not MDA, was positively correlated with vascular prostanoid synthesis and synthesis capacity. In the umbilical vein, both the basal and stimulated PGI2 production and the stimulated TxA2 production were lower in the DM/IGT group. Ischemic placental lesions were associated with a high TxA, and a low MDA concentration in cord plasma. CONCLUSIONS: Even in less severe forms of impaired glucose metabolism, disturbances in platelet activation significantly affect both biochemical and morphological vessel wall and tissue functions in the umbilicoplacental unit. This could indicate an abnormal programming of fetal cell functions and designate cases at increased risk of developing cellular and organ damage.

6-Ketoprostaglandin F1 alpha↗

An application of a general branching process in the study of the genetics of aging.

A general branching process model is developed to analyse familial dependence in longevity data. A general formula for the survival function of a randomly chosen sibling of an individual of a specified age is derived. The branching process model takes into account that siblings' ages may be censored. This is applied to a data set consisting of lifelengths of siblings of centenarians. Age distributions used in the branching process model are estimated from US Census data from the relevant period. It is demonstrated that there is a marked difference in the survival function according to the formula assuming no familial effect and the empirical survival function estimated from the data; thus, indicating a strong familial component.

Adolescent↗

Lactate concentrations in human skeletal muscle biopsy, microdialysate and venous blood during dynamic exercise under blood flow restriction.

The intramuscular microdialysate lactate concentration during dynamic exercise with various degrees of blood flow restriction and its relation to lactate concentration in skeletal muscle biopsy and venous blood were studied. Nine healthy males performed three one-legged knee extension exercises (Ex 1-3). Blood flow was restricted stepwise by applying supra-atmospheric pressure over the working leg. Microdialysate mean (range) lactate concentrations at the end of the exercise periods were 3.2 (0.5-6.6), 4.4 (1.1-9.8) and 7.9 (1.1-11.6) mmol.l(-1)during unrestricted, moderately restricted and severely restricted blood flow respectively. There was a significant correlation between microdialysate and venous lactate concentrations at the end of all three exercise periods. Microdialysate lactate concentration correlated significantly to skeletal muscle biopsy lactate concentration at the end of Ex 1. In conclusion, microdialysate lactate concentration in the working muscle increased step-wise with increasing blood flow restriction. It showed a better correlation to venous than to muscle biopsy lactate, which is possibly partly explained by the characteristics of diffusion between body compartments and differences in time resolution between the methods used.

Adult↗

Cardiotocography only versus cardiotocography plus ST analysis of fetal electrocardiogram for intrapartum fetal monitoring: a Swedish randomised controlled trial.

BACKGROUND: Previous studies indicate that analysis of the ST waveform of the fetal electrocardiogram provides information on the fetal response to hypoxia. We did a multicentre randomised controlled trial to test the hypothesis that intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis results in an improved perinatal outcome compared with cardiotocography alone. METHODS: At three Swedish labour wards, 4966 women with term fetuses in the cephalic presentation entered the trial during labour after a clinical decision had been made to apply a fetal scalp electrode for internal cardiotocography. They were randomly assigned monitoring with cardiotocography plus ST analysis (CTG+ST group) or cardiotocography only (CTG group). The main outcome measure was rate of umbilical-artery metabolic acidosis (pH <7.05 and base deficit >12 mmol/L). Secondary outcomes included operative delivery for fetal distress. Results were first analysed according to intention to treat, and secondly after exclusion of cases with severe malformations or with inadequate monitoring. FINDINGS: The CTG+ST group showed significantly lower rates of umbilical-artery metabolic acidosis than the cardiotocography group (15 of 2159 [0.7%] vs 31 of 2079 [2%], relative risk 0.47 [95% CI 0.25-0.86], p=0.02) and of operative delivery for fetal distress (193 of 2519 [8%] vs 227 of 2447 [9%], 0.83 [0.69-0.99], p=0.047) when all cases were included according to intention to treat. The differences were more pronounced after exclusion of 291 in the CTG+ST group and 283 in the CTG group with malformations or inadequate recording. INTERPRETATION: Intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis increases the ability of obstetricians to identify fetal hypoxia and to intervene more appropriately, resulting in an improved perinatal outcome.

Acidosis↗

Gender and referral to cataract surgery in Sweden.

PURPOSE: To investigate how cataract surgery was initiated and analyse possible gender difference in referral to surgery. METHODS: Consecutive patients scheduled for first eye cataract surgery at three Swedish community-run eye departments were interviewed concerning how surgery was initiated. RESULTS: 649 patients were interviewed and 63.2% were female. The number of patients referred to surgery by an earlier contact with a health care provider was 271 (41.8%) and the remaining 378 (58.2%) patients had actively requested advice or help because of visual problems caused by cataract and without a prior regular contact. 44.7% of female patients were referred through a health care provider they visited for reasons other than cataract and the corresponding number for male patients was 36.8%. This gender difference is statistically significant at the 5% level. CONCLUSION: A health care provider that patients visited for other problems than cataract referred female patients to cataract surgery to a significantly higher degree than male patients.

Cataract Extraction↗

Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis.

Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.

Adjuvants, Immunologic↗

Gender differences in vascular interventions for lower limb ischaemia.

OBJECTIVES: to investigate changes in intervention for lower limb ischaemia with regard to gender. MATERIAL AND METHOD: type of procedure, the age and gender of all patients (8687) undergoing interventions (12 295) for lower limb ischaemia in Stockholm 1970-1994, were obtained from the National Board of Health and Welfare. RESULTS: interventions rose from 18 per million inhabitants in 1970 to 786 in 1994. The proportion of women treated grew from 34% to 48%. The number of embolectomies decreased from 80 to 69 per million. Infrainguinal reconstructions increased most from 38 in 1980-1984 to 186 per million inhabitants in 1990-1994, with the proportion of women increasing from 33 to 43%. Mean age increased from 63 to 71 years. CONCLUSIONS: there was a marked increase in the number of procedures, the proportion of female patients and mean age.

Age Factors↗

[Iatrogenic vascular injuries demand a lot from the surgeon. Better to prevent--errors and lack of knowledge can have serious consequences for the patient].

To investigate causes and consequences of iatrogenic vascular injuries requiring surgical repair, we retrospectively reviewed 18 cases during a ten year period between 1989 and 1999 at Karolinska sjukhuset. We hoped to identify specific injury patterns in these cases, which were found in all operating specialties. Inattention to vascular structures was the single most common cause of iatrogenic vascular injury. The second most common context was radical operations of cancers in which the tumor was adjacent to the vessel. A third cause was misunderstanding of the specific anatomy of the area. This study demonstrates that serious iatrogenic vascular injuries pose a great challenge for the surgeon. Representing a significantly increased risk for the patient, these serious incidents should be preventable through modifications in surgical technique.

Adult↗

Complex genetic control in a rat model for rheumatoid arthritis.

We have defined previously five quantitative trait loci controlling development of pristane-induced arthritis in a cross between E3 and DA rats. To define new loci controlling the disease we have mapped three recombinant inbred strains between DA and E3 and analysed an F2 cross between DA rats and one of these RI strains. Two novel loci affecting disease severity are identified on chromosome 1 (Pia8) and chromosome 4 (Pia7) respectively. We could also reproduce the earlier identified Pia3 locus on chromosome 6 associated with arthritis onset. In the original E3xDA F2 cross, neither of the loci Pia7, Pia8, or Pia1 showed any association with arthritis. To investigate the possibility of interacting loci preventing the phenotypic expression of other loci, the E3xDA F2 cross was re-analysed with a model for a two locus interaction, knowing the presence of these newly identified loci. We found suggestive evidence for an interaction where an effect of Pia7 and Pia1 on disease severity depends on DA homozygosity at specific loci, which themselves do not confer susceptibility. This shows that additional disease associated loci can be identified if other loci are neutralized. This will be of importance for understanding the complex genetics controlling rheumatoid arthritis.

Animals↗