| 1. |
- Ludvigsson, Johnny, 1943-, et al.
(författare)
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GAD treatment and insulin secretion in recent-onset type 1 diabetes
- 2008
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Ingår i: New England Journal of Medicine. - Boston, Mass : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 359:18, s. 1909-1920
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Tidskriftsartikel (refereegranskat)abstract
- Background The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of alum-formulated GAD (GAD-alum) to reverse recent-onset type 1 diabetes in patients 10 to 18 years of age. Methods We randomly assigned 70 patients with type 1 diabetes who had fasting C-peptide levels above 0.1 nmol per liter (0.3 ng per milliliter) and GAD autoantibodies, recruited within 18 months after receiving the diagnosis of diabetes, to receive subcutaneous injections of 20 μg of GAD-alum (35 patients) or placebo (alum alone, 35 patients) on study days 1 and 30. At day 1 and months 3, 9, 15, 21, and 30, patients underwent a mixed-meal tolerance test to stimulate residual insulin secretion (measured as the C-peptide level). The effect of GAD-alum on the immune system was also studied. Results Insulin secretion gradually decreased in both study groups. The study treatment had no significant effect on change in fasting C-peptide level after 15 months (the primary end point). Fasting C-peptide levels declined from baseline levels significantly less over 30 months in the GAD-alum group than in the placebo group (−0.21 vs. −0.27 nmol per liter [−0.62 vs. −0.81 ng per milliliter], P = 0.045), as did stimulated secretion measured as the area under the curve (−0.72 vs. −1.02 nmol per liter per 2 hours [−2.20 vs. −3.08 ng per milliliter per 2 hours], P = 0.04). No protective effect was seen in patients treated 6 months or more after receiving the diagnosis. Adverse events appeared to be mild and similar in frequency between the two groups. The GAD-alum treatment induced a GAD-specific immune response. Conclusions GAD-alum may contribute to the preservation of residual insulin secretion in patients with recent-onset type 1 diabetes, although it did not change the insulin requirement. (ClinicalTrials.gov number, NCT00435981.)
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| 2. |
- Mu, Xiangkui, et al.
(författare)
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Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study.
- 2005
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:6, s. 554-62
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this treatment planning comparison study was to explore different spinal irradiation techniques with respect to the risk of late side-effects, particularly radiation-induced cancer. The radiotherapy techniques compared were conventional photon therapy, intensity modulated x-ray therapy (IMXT), conventional electron therapy, intensity/energy modulated electron therapy (IMET) and proton therapy (IMPT).CT images for radiotherapy use from five children, median age 8 and diagnosed with medulloblastoma, were selected for this study. Target volumes and organs at risk were defined in 3-D. Treatment plans using conventional photon therapy, IMXT, conventional electron therapy, IMET and IMPT were set up. The probability of normal tissue complication (NTCP) and the risk of cancer induction were calculated using models with parameters-sets taken from published data for the general population; dose data were taken from dose volume histograms (DVH).Similar dose distributions in the targets were achieved with all techniques but the absorbed doses in the organs-at-risk varied significantly between the different techniques. The NTCP models based on available data predicted very low probabilities for side-effects in all cases. However, the effective mean doses outside the target volumes, and thus the predicted risk of cancer induction, varied significantly between the techniques. The highest lifetime risk of secondary cancers was estimated for IMXT (30%). The lowest risk was found with IMPT (4%). The risks associated with conventional photon therapy, electron therapy and IMET were 20%, 21% and 15%, respectively.This model study shows that spinal irradiation of young children with photon and electron techniques results in a substantial risk of radiation-induced secondary cancers. Multiple beam IMXT seems to be associated with a particularly high risk of secondary cancer induction. To minimise this risk, IMPT should be the treatment of choice. If proton therapy is not available, advanced electron therapy may provide a better alternative.
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| 3. |
- Covacu, Ruxandra, et al.
(författare)
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Nitric oxide exposure diverts neural stem cell fate from neurogenesis towards astrogliogenesis
- 2006
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1066-5099 .- 1549-4918. ; 178, s. 268-268
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Regeneration of cells in the central nervous system is a process that might be affected during neurological disease and trauma. Because nitric oxide (NO) and its derivatives are powerful mediators in the inflammatory cascade, we have investigated the effects of pathophysiological concentrations of NO on neurogenesis, gliogenesis, and the expression of proneural genes in primary adult neural stem cell cultures. After exposure to NO, neurogenesis was downregulated, and this corresponded to decreased expression of the proneural gene neurogenin-2 and beta-III-tubulin. The decreased ability to generate neurons was also found to be transmitted to the progeny of the cells. NO exposure was instead beneficial for astroglial differentiation, which was confirmed by increased activation of the Janus tyrosine kinase/signal transducer and activator of transcription transduction pathway. Our findings reveal a new role for NO during neuroinflammatory conditions, whereby its proastroglial fate-determining effect on neural stem cells might directly influence the neuroregenerative process.
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| 4. |
- Glimelius, B., et al.
(författare)
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Number of patients potentially eligible for proton therapy
- 2005
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Ingår i: Acta Oncol. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 836-49
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Tidskriftsartikel (refereegranskat)abstract
- A group of Swedish radiation oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy in a facility where one of the principal aims is to facilitate randomized and other studies in which the advantage of protons can be shown and the magnitude of the differences compared with optimally administered conventional radiation treatment, also including intensity-modulated radiation therapy (IMRT) and brachytherapy, can be shown. The estimations have been based on current statistics of tumour incidence in Sweden, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours together with information on normal tissue complication rates. In Sweden, it is assessed that between 2200 and 2500 patients annually are eligible for proton beam therapy, and that for these patients the potential therapeutic benefit is so great as to justify the additional expense of proton therapy. This constitutes between 14-15% of all irradiated patients annually.
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| 5. |
- Hogberg, Johan, et al.
(författare)
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Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:3, s. 334-339
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An important question relates to the choice of suitable biological matrices for assessing exposure during this period. OBJECTIVES: This study was designed to measure the concentrations of phthalate diesters or their metabolites in breast milk, blood or serum, and urine and to evaluate their suitability for assessing perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42 Swedish primipara provided breast milk, blood, and urine samples at home. Special care was taken to minimize contamination with phthalates (e.g., use of a special breast milk pump, heat treatment of glassware and needles, addition of phosphoric acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if detected, were present at concentrations close to the limit of detection. By contrast, most phthalate metabolites were detectable in urine at concentrations comparable to those from the general population in the United States and in Germany. No correlations existed between urine concentrations and those found in milk or blood/serum for single phthalate metabolites. Our data are at odds with a previous study documenting frequent detection and comparatively high concentrations of phthalate metabolites in Finnish and Danish mothers' milk. CONCLUSIONS: Concentrations of phthalate metabolites in urine are more informative than those in milk or serum. Furthermore, collection of milk or blood may be associated with discomfort and potential technical problems such as contamination (unless oxidative metabolites are measured). Although urine is a suitable matrix for health-related phthalate monitoring, urinary concentrations in nursing mothers cannot be used to estimate exposure to phthalates through milk ingestion by breast-fed infants.
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| 6. |
- Johansson, Stefan, et al.
(författare)
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Infection with Parvovirus B19 and Herpes viruses in early pregnancy and risk of second trimester miscarriage or very preterm birth
- 2008
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Ingår i: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 26:3-4, s. 298-302
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether infections with Parvovirus B19 and Herpes viruses in early pregnancy increase risks of second trimester miscarriage or delivery before 32 gestational weeks. Blood samples taken in early pregnancy were analyzed for Parvovirus B19 or Herpes viruses. Viremia was found in blood samples of 11 (4.7%) women with second trimester miscarriage and 10 (3.7%) women with very preterm birth, compared to 5 (1.7%) women who delivered at term, corresponding to adjusted odds ratios [95% CI] of 3.32 [0.93, 11.8] and 2.21 [0.71, 6.84], respectively. In stratified analyses, Parvovirus B19 viremia was associated with adjusted odds ratios of 3.76 [0.77, 18.3] for second trimester miscarriage and 2.66 [0.64, 11.1] for very preterm birth. Corresponding odds ratios for Human Herpes virus 6 viremia was 2.52 [0.33, 19.5] and 1.08 [0.14, 8.08], respectively. In conclusion, this study lends some support to the hypothesis that women with viremia in early pregnancy may face an increased risk of second trimester miscarriage or very preterm birth. Studies with larger sample sizes are needed.
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| 7. |
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| 8. |
- Jonas, W., et al.
(författare)
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Effects of Intrapartum Oxytocin Administration and Epidural Analgesia on the Concentration of Plasma Oxytocin and Prolactin, in Response to Suckling During the Second Day Postpartum
- 2009
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Ingår i: Breastfeeding Medicine. - : Mary Ann Liebert. - 1556-8253 .- 1556-8342. ; 4:2, s. 71-82
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oxytocin and prolactin stimulate milk ejection and milk production during breastfeeding. The aim of the present study was to make a detailed analysis of maternal release of oxytocin and prolactin in response to breastfeeding during the second day postpartum in mothers who had received oxytocin either intravenously for stimulation of labor or intramuscularly for prevention of postpartum hemorrhage and/or epidural analgesia or those who had received no such treatment in connection with birth.Methods: In a descriptive comparative study plasma oxytocin and prolactin concentrations were measured in response to suckling during the second day postpartum in women who had received intravenous intrapartum oxytocin (n = 8), intramuscular postpartum oxytocin (n = 13), or epidural analgesia, either with (n = 14) or without (n = 6) intrapartum oxytocin infusion, and women who received none of these interventions (n = 20). Hormone levels were analyzed by enzyme immunoassay.Results: All mothers showed a pulsatile oxytocin pattern during the first 10 minutes of breastfeeding. Women who had received epidural analgesia with oxytocin infusion had the lowest endogenous median oxytocin levels. The more oxytocin infusion the mothers had received during labor, the lower their endogenous oxytocin levels were during a breastfeeding during the second day postpartum. A significant rise of prolactin was observed after 20 minutes in all women, but after 10 minutes in mothers having received oxytocin infusion during labor. In all women, oxytocin variability and the rise of prolactin levels between 0 and 20 minutes correlated significantly with median oxytocin and prolactin levels.Conclusion: Oxytocin, released in a pulsatile way, and prolactin were released by breastfeeding during the second day postpartum. Oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Furthermore, oxytocin infusion facilitated the release of prolactin. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively.
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| 9. |
- Månsson, Mattias, et al.
(författare)
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Women with polycystic ovary syndrome are often depressed or anxious--a case control study.
- 2008
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 33:8, s. 1132-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common hyperandrogenic endocrine disorder affecting women of fertile age. The aim of this study was to survey whether the rate of clinical psychiatric disorders in PCOS differs from the normal population. METHOD: Women with PCOS (n=49) meeting the Rotterdam criteria for PCOS, and 49 age-matched controls identified from the population registry, were recruited. Trained clinicians used the MINI International Neuropsychiatric Interview to establish lifetime occurrence of Axis I DSM diagnoses. Serum-testosterone and sex hormone binding globulin were analyzed. RESULTS: Women with PCOS had higher lifetime incidence of depressive episodes, social phobia, and eating disorders than controls. Suicide attempts were seven times more common in the PCOS group than in the controls. Current as well as lifetime use of antidepressants and anxiolytic drugs were more common in the PCOS group. CONCLUSIONS: Previous studies have found that PCOS is associated with decreased quality of life and self-rated mental symptoms. This study demonstrates that PCOS is also linked to psychiatric syndromes as verified by structured clinical assessments. The clinical implication of this study is that clinicians treating women with PCOS should be aware that these women are a high risk group for common affective and anxiety disorders as well as suicide attempts.
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| 10. |
- Nilsson, Lars, et al.
(författare)
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The molecular signature of MDS stem cells supports a stem-cell origin of 5q-myelodysplastic syndromes
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 110:8, s. 3005-3014
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Tidskriftsartikel (refereegranskat)abstract
- Global gene expression profiling of highly purified 5q-deleted CD34+CD38–Thy1+ cells in 5q– myelodysplastic syndromes (MDSs) supported that they might originate from and outcompete normal CD34+CD38–Thy1+ hematopoietic stem cells. Few but distinct differences in gene expression distinguished MDS and normal stem cells. Expression of BMI1, encoding a critical regulator of self-renewal, was up-regulated in 5q– stem cells. Whereas multiple previous MDS genetic screens failed to identify altered expression of the gene encoding the myeloid transcription factor CEBPA, stage-specific and extensive down-regulation of CEBPA was specifically observed in MDS progenitors. These studies establish the importance of molecular characterization of distinct stages of cancer stem and progenitor cells to enhance the resolution of stage-specific dysregulated gene expression.
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