| 1. |
- Ahlman, Håkan, 1947, et al.
(författare)
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Cytotoxic treatment of adrenocortical carcinoma.
- 2001
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Ingår i: World journal of surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 25:7, s. 927-33
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Tidskriftsartikel (refereegranskat)abstract
- Adrenocortical carcinoma (ACC) is a rare, aggressive tumor that is often detected in an advanced stage. Medical treatment with the adrenotoxic drug mitotane has been used for decades, but critical prospective trials on its role in residual disease or as an adjuvant agent after surgical resection are still lacking. The concept of a critical threshold plasma level of the drug must be confirmed in controlled studies. Because individual responsiveness cannot be predicted, the use mitotane is still advised for nonresectable disease. In case of cortisol or other steroid overproduction, several drugs (e.g., ketoconazole or aminoglutethimide) may be used. Chemotherapy with single agents (e.g., doxorubicin or cisplatin) have been disappointing, with low response rates (< 30%) and a short response duration. Part of this refractoriness may be explained by the fact that ACC tumors express the multidrug-resistance gene MDR-1. Chemotherapy with multiple agents has been tested in smaller series and has resulted in significant side effects. The best results were achieved by the combination of etoposide, doxorubicin, and cisplatin associated with mitotane, achieving a response rate of 54%, including individual complete responses. To be able to make progress in treating advanced ACC disease, adjuvant multicenter trials must be encouraged. When mitotane-based therapies are used, monitored drug levels are mandatory.
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| 2. |
- Aladdin Haglund, Berit, et al.
(författare)
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Unexpected out-of-hospital deliveries--experiences from the Gothenburg area. Centralized obstetrical care requires competent ambulance staff
- 2004
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Ingår i: Lakartidningen. ; 101:41, s. 3148-50
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Tidskriftsartikel (refereegranskat)abstract
- One hundred and sixty-seven women gave birth before arrival at the hospital during a six-year period in the Goteborg area. Most of these women had given birth before. The actual delivery most often started at term during the night, proceeded normally but rapidly and the neonatal outcome was good. Sixty-two per cent of the women delivered at home. Complicated lacerations or major hemorrhages were uncommon. The distance to the delivery ward was one of the risk factors for prehospital delivery. This is important to take into consideration in the ongoing process of centralizing the delivery clinics. Basic knowledge in obstetrics is mandatory for the ambulance personnel, as well as regular observation visits to the delivery ward and practice in birth simulators.
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| 3. |
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| 4. |
- Harang, Valérie, 1966-
(författare)
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Aspects of Optimisation of Separation of Drugs by Chemometrics
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Statistical experimental designs have been used for method development and optimisation of separation. Two reversed phase HPLC methods were optimised. Parameters such as the pH, the amount of tetrabutylammonium (TBA; co-ion) and the gradient slope (acetonitrile) were investigated and optimised for separation of erythromycin A and eight related compounds. In the second method, a statistical experimental design was used, where the amounts of acetonitrile and octane sulphonate (OSA; counter ion) and the buffer concentration were studied, and generation of an α-plot with chromatogram simulations optimised the separation of six analytes.The partial filling technique was used in capillary electrophoresis to introduce the chiral selector Cel7A. The effect of the pH, the ionic strength and the amount of acetonitrile on the separation and the peak shape of R- and S-propranolol were investigated.Microemulsion electrokinetic chromatography (MEEKC) is a technique similar to micellar electrokinetic chromatography (MEKC), except that the microemulsion has a core of tiny droplets of oil inside the micelles. A large number of factors can be varied when using this technique. A screening design using the amounts of sodium dodecyl sulphate (SDS), Brij 35, 1-butanol and 2-propanol, the buffer concentration and the temperature as factors revealed that the amounts of SDS and 2-propanol were the most important factors for migration time and selectivity manipulation of eight different compounds varying in charge and hydrophobicity. SDS and 2-propanol in the MEEKC method were further investigated in a three-level full factorial design analysing 29 different compounds sorted into five different groups. Different optimisation strategies were evaluated such as generating response surface plots of the selectivity/resolution of the most critical pair of peaks, employing chromatographic functions, simplex optimisation in MODDE and 3D resolution maps in DryLab™.Molecular descriptors were fitted in a PLS model to retention data from the three-level full factorial design of the MEEKC system. Two different test sets were used to study the predictive ability of the training set. It was concluded that 86 – 89% of the retention data could be predicted correctly for new molecules (80 – 120% of the experimental values) with different settings of SDS and 2-propanol.Statistical experimental designs and chemometrics are valuable tools for the development and optimisation of analytical methods. The same chemometric strategies can be employed for all types of separation techniques.
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| 5. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Advanced maternal age and adverse perinatal outcome
- 2004
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Ingår i: Obstet Gynecol. - 0029-7844. ; 104:4, s. 727-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the influence of maternal age on perinatal and obstetric outcome in women aged 40-44 years and those 45 years or older and to estimate whether adverse outcome was related to intercurrent illness and pregnancy complications. METHODS: National prospective, population-based, cohort study in women aged 40-44 years and those 45 years or older and in a control group of women aged 20-29 years who delivered during the period 1987-2001. Adjusted odds ratios (OR) were calculated after adjustments for significant malformations, maternal pre-existing diseases, and smoking. Main outcome measures were perinatal mortality, intrauterine fetal death, neonatal death, preterm birth, and preeclampsia. RESULTS: During the 15-year period, there were 1,566,313 deliveries (876,361 women were 20-29 years of age, 31,662 were 40-44 years, and 1,205 were > or = 45 years). Perinatal mortality was 1.4%, 1.0%, and 0.5% in women 45 years or older, 40-44, and 20-29 years, respectively. Adjusted OR for perinatal mortality was 2.4 (95% confidence interval [CI] 1.5-4.0) in women aged 45 years or older, compared with 1.7 (95% CI 1.5-1.9) in women 40-44 years. Adjusted OR for intrauterine fetal death was 3.8 (95% CI 2.2-6.4) in women aged 45 years or older, compared with 2.1 (95% CI 1.8-2.4) in women 40-44 years. Preterm birth, gestational diabetes, and preeclampsia were more common among women 40-44 years of age and those 45 years or older. Perinatal mortality was increased in women with intercurrent illness or pregnancy complications compared with women without these conditions, but there was no evidence that these factors became more important with increasing age. CONCLUSION: Perinatal mortality, intrauterine fetal death, and neonatal death increased with age. There was also an increase in intercurrent illnesses and pregnancy complications with increasing age, but this did not entirely explain the observed increase in perinatal mortality with age. LEVEL OF EVIDENCE: II-3
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| 6. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Antenatal risk factors for cerebral palsy.
- 2004
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Ingår i: Best practice & research. Clinical obstetrics & gynaecology. - : Elsevier BV. - 1521-6934. ; 18:3, s. 425-36
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Forskningsöversikt (refereegranskat)abstract
- Two of every 1000 live-born children develop cerebral palsy (CP). The aetiology of CP is often unclear and because CP is a symptom complex rather than a disease, clinically defined at 4-5 years of age, it is not surprising that there are considerable problems associated with epidemiological studies of its aetiology. The only reason for the CP concept is that it emanates from an insult to a growing, developing brain and a dynamic clinical picture from static pathology. Evidence suggests that 70-80% of CP cases are due to prenatal factors and that birth asphyxia plays a relatively minor role (<10%). Some antenatal risk factors are repeatedly observed to be related to CP: low gestational age, male gender, multiple gestation, intrauterine viral infections and maternal thyroid abnormalities. Recently, intrauterine infection/inflammation with a maternal response (consisting of chorioamnionitis) and a fetal inflammatory response (consisting of funicitis or elevated interleukin-6 in fetal plasma) has been found to be related to white matter injury and CP. Some risk factors are associated with CP at all gestational ages whereas others mostly affect term or preterm infants, e.g. intrauterine growth restriction seems to be a risk factor in term infants. There also seems to be an association between autoimmune and coagulation disorders and CP.
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| 7. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Cerebral palsy in preterm infants: a population-based case-control study of antenatal and intrapartal risk factors.
- 2002
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - 0803-5253. ; 91:8, s. 946-51
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have indicated that foetomaternal infection increases the risk of spastic cerebral palsy (CP) in term infants, whereas this association appears to be less evident in preterm infants. The aim of this study was to analyse infection-related risk factors for spastic CP in preterm infants. A population-based series of preterm infants with spastic CP, 91 very preterm (<32 wk) and 57 moderately preterm (32-36 wk), born in 1983-90, were included and matched with a control group (n = 296). In total, 154 maternal, antenatal and intrapartal variables were retrieved from obstetric records. In the entire group, histological chorioamnionitis/pyelonephritis, long interval between rupture of membranes and birth, admission-delivery interval <4 h and Apgar scores of <7 at 1 min just significantly increased the risk of CP, and Apgar scores of <7 at 5 and 10 min were strongly associated with an increased risk. Abruptio placentae, Apgar scores <7 at 1 min and pathological non-stress test (reason for delivery) were significant risk factors of CP only in the moderately preterm and hemiplegic groups, whereas fever before delivery was a significant risk factor in the very preterm and spastic diplegic groups. Antibiotics during pregnancy was associated with CP only in the spastic diplegic CP group. Conclusion: Antenatal infections marginally increased the risk of CP. Low Apgar score and abruptio placentae were associated with CP, especially in moderately preterm infants with hemiplegic CP.
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| 8. |
- Jacobsson, Bo, 1960
(författare)
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Infectious and inflammatory mechanisms in preterm birth and cerebral palsy
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: International studies of women in preterm labor (PTL) and preterm pre-labor rupture of the membranes (pPROM) have shown a significant association between microbial invasion of the amniotic cavity (MIAC), some cytokines and chemokines and preterm birth (PTB). These studies have been performed in countries with higher incidence of PTB than that in Sweden. Cerebral palsy (CP) has also been shown to be associated with infectious and inflammatory mechanisms in international epidemiological studies. Our aim was to examine the role of inflammatory mechanisms in PTB and CP in a setting with a low incidence of PTB and perinatal infections.Material and Methods: Amniotic fluid (AF) was retrieved transabdominally from 61 patients in PTL and 47 patients with pPROM, before 34 weeks of gestation in both groups. Forty-five women at term (= 37 weeks) were included. These women were scheduled for elective cesarean section after uncomplicated pregnancies. Cervical fluid was obtained from the external cervical os in all patients in PTL and in all term patients. Polymerase chain reaction analyses for Ureaplasma urealyticum and Mycoplasma hominis and culture for aerobic and anaerobic bacteria were performed. Interleukin (IL)-6, IL-8, IL-18 and monocyte chemotactic protein (MCP)-1 were analyzed with enzyme-linked immunosorbent assay.In order to examine inflammatory mechanisms in CP, a population-based series of 148 preterm infants with spastic CP, born 1983-90, were included and matched with a control group (n=296). Subgroup analyses of patients with spastic diplegia and hemiplegia and those born at <32 and =32 weeks were performed. Maternal, antenatal and intrapartal variables were retrieved from obstetric records. Results: MIAC was detected in 16% of women in PTL and 25 % of women with pPROM. Patients in PTL with MIAC had significantly elevated levels of IL-6, IL-8 and IL-18. The levels of IL-6, IL-8 and MCP-1 were elevated in MIAC cases in women with pPROM. There was also a significant association between elevated levels of IL-6, IL-8, IL-18 and MCP-1 and short amniocentesis-delivery interval (= 7 days) and PTB (< 34 weeks) in women in PTL, whereas this association was less evident in women with pPROM. A receiver-operator-characteristic curve was used to identify the best cut-off levels of IL-6 and IL-8 in AF for delivery within 7 days. This value was used to define an inflammatory response. The inflammatory response rate was 46 % in the PTL group and 51% in the pPROM group. Elevated IL-18 and MCP-1 were related to an inflammatory response in the women in PTL; MCP-1 was also related to an inflammatory response in women with pPROM. There were higher levels of IL-18 and MCP-1 in the cervical fluid of women in PTL, compared with non-laboring women at term. There were elevated levels of MCP-1 in the cervical fluid of women in PTL who gave birth within 7 days or before 34 weeks of gestation, who had MIAC or had intra-amniotic inflammation.In the case-control study of CP, clinical chorioamnionitis/pyelonephritis, long interval between rupture of membranes and birth and admission-delivery interval <4 hours just significantly increased the risk of CP. Apgar scores of <7 at 5 and 10 minutes were strongly associated with an increased CP risk. Abruptio placentae and pathological non-stress test (reason for delivery) were significant risk factors for CP only in the moderately preterm and hemiplegic groups, whereas fever prior to delivery was a significant risk factor in the very preterm and spastic diplegic groups. Conclusion: The occurrence of intra-amniotic microbial invasion and inflammation in this population of Swedish women in PTL and pPROM was similar to that reported in data from populations with a higher incidence of PTB. In addition, our data support an association between antenatal infection/inflammation and CP.
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| 9. |
- Jacobsson, Bo, 1960
(författare)
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Infectious and inflammatory mechanisms in preterm birth and cerebral palsy.
- 2004
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Ingår i: European journal of obstetrics, gynecology, and reproductive biology. - : Elsevier BV. - 0301-2115. ; 115:2, s. 159-60
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Forskningsöversikt (refereegranskat)abstract
- In a thesis examine infectious and inflammatory mechanisms involved in preterm birth and cerebral palsy.Four cross-sectional studies and a case control study.Microbial invasion of the amniotic cavity and inflammation in this population of Swedish women in preterm labor and preterm prelabor rupture of membranes was similar to that reported in data from populations with a higher incidence of preterm birth. Our data support an association between antenatal infection/inflammation and cerebral palsy.Infectious and inflammatory mechanisms are involved in preterm birth and cerebral palsy in a population with low incidence of preterm birth.
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| 10. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Interleukin-18 in cervical mucus and amniotic fluid: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation and preterm delivery.
- 2003
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Ingår i: BJOG : an international journal of obstetrics and gynaecology. - 1470-0328. ; 110:6, s. 598-603
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the relationship between interleukin (IL)-18 in cervical mucus and amniotic fluid and microbial invasion of amniotic fluid, preterm delivery and intra-amniotic inflammation in women in preterm labour, with preterm prelabour rupture of membranes and at term. DESIGN: A prospective follow up study. SETTING: Sahlgrenska University Hospital, Göteborg, Sweden. SAMPLE: Women with singleton pregnancies (<34 weeks) presenting with preterm labour (n = 87) or preterm prelabour rupture of membranes (n = 47) and women, not in labour, at term (n = 28). METHODS: Amniotic fluid was retrieved transabdominally. Cervical mucus was taken from the uterine cervix of women in preterm labour and at term. IL-18 was analysed with enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: IL-18 in relation to microbial invasion of the amniotic fluid, delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. RESULTS: The levels of IL-18 in cervical mucus and amniotic fluid were higher in women with preterm labour than in those not in labour at term. In the preterm labour group, significant associations were found between elevated IL-18 in amniotic fluid and microbial invasion of the amniotic fluid, as well as between delivery within seven days or <34 weeks of gestation and intra-amniotic inflammation. Delivery was delayed longer in the preterm prelabour rupture of membranes subgroup with IL-18 >or=1.0 ng/mL than in that with IL-18 <1.0 ng/mL. CONCLUSIONS: In the preterm labour group, high IL-18 in amniotic fluid (but not in the cervix) was associated with microbial invasion of the amniotic fluid, intra-amniotic inflammation and prompt delivery. On the other hand, elevated IL-18 in preterm prelabour rupture of the membranes group correlated with a longer interval to delivery.
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