Biomedical subjects

Leif Matthiesen

Publications and source records attributed to Leif Matthiesen.

10 recordsLinked to original sources

PubMed2006

A case of severe Rh (D) alloimmunization treated by intensive plasma exchange and high-dose intravenous immunoglobulin.

BACKGROUND: In extremely severe Rh (D) alloimmunization, during pregnancy, early diagnosis and treatment is essential to avoid hydrops fetalis. Intrauterine transfusion (IUT) is of utmost importance in the prevention of fetal anemia but it is usually feasible only after 20 weeks of pregnancy. Therefore, additional treatment options in early pregnancy are needed. STUDY DESIGN AND METHODS: A 27-year-old severely D+C immunized woman was admitted at 8 weeks of gestation in her fifth pregnancy with an extremely high concentration of anti-D. Her first pregnancy was uneventful but resulted in D+C alloimmunization. The next two pregnancies were unsuccessful, because of hydrops fetalis resulting in fetal death in pregnancy week 20 and 24, respectively, despite treatment with high-dose intravenous immunoglobulin (IVIG) and IUT treatment. A fourth pregnancy was terminated with legal abortion. The patient was eager and persistent to accomplish a successful pregnancy. Therefore, a combination of treatments consisting of plasma exchange (PE) three times/week and IVIG 100g/week was started in pregnancy week 12. PE was performed 53 times and totally 159L of plasma was exchanged. RESULTS: The anti-D concentration was 12mug/mL (IAT titer 2000) before start of treatment by PE and IVIG in pregnancy week 12. The concentration of anti-D was gradually reduced to approximately 3mug/mL after only two weeks of treatment and was maintained at that level until pregnancy week 22. In pregnancy week 26 and 27, signs of hydrops were detected by ultrasonography and IUT were performed at each occasion. Sectio was inevitable at pregnancy week 28+1 and a male baby was born: Hb 58g/L (cord sample) and 68g/L (venous sample); weight 1385g; Apgar score=4-5-7; Bilirubin 56-150mmol/L (4h). Exchange transfusion was performed on day two and day five. Phototherapy was also implemented for eight days. The newborn's recovery thereafter was uneventful and complete. CONCLUSION: A combination of PE and IVIG may be an efficient treatment possible to start in early pregnancy in patients with extremely severe Rh (D) alloimmunization, with a history of hydrops fetalis in previous pregnancies.

Cesarean Section↗

PubMed2006

Cytokine mapping of sera from women with preeclampsia and normal pregnancies.

INTRODUCTION: Preeclampsia is a pregnancy-specific syndrome. The immune system in preeclampsia is changed with an increased innate activity and there is a hypothesis of a shift towards Th1-type immunity. The aim of this study was to determine a spectrum of soluble immunological factors denoting different aspects of immune activation in third trimester sera from women with preeclampsia (N=15) and compare with levels in sera from normal pregnant women (N=15). MATERIAL AND METHODS: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFN-alpha, IFN-gamma, TNF-alpha, GM-CSF, MIP-lalpha, MIP-1beta, MCP-1, eotaxin and RANTES were measured in serum using multiplex bead arrays. The levels of soluble CD14 and soluble IL-4 receptor were measured by enzyme-linked immunoassay (ELISA). RESULTS: Preeclamptic women had significantly increased levels of circulating IL-6 (p=0.002), IL-8 (p=0.003) and soluble IL-4R (p=0.037), compared to women with normal pregnancies. CONCLUSION: This study supports the hypothesis of increased inflammatory responses in preeclampsia, illustrated by the increased levels of IL-6 and IL-8. The finding of increased levels of soluble IL-4 receptor is an intriguing finding with several interpretations, which may partly support the hypothesis of a Th1 shift in preeclampsia.

Adult↗

PubMed2005

Indications of an altered immune balance in preeclampsia: a decrease in in vitro secretion of IL-5 and IL-10 from blood mononuclear cells and in blood basophil counts compared with normal pregnancy.

It has been suggested that maladaptation of the maternal immune response during pregnancy might be a causal factor for preeclampsia. This study was designed to examine the systemic immune status at both the innate level and the adaptive level in pregnancies complicated by preeclampsia (n=15) and normal pregnancies (n=15). Spontaneous and in vitro-induced secretion of IL-5, IL-6, IL-10, IL-12, IL-13 and TNF-alpha, in response to paternal blood cells and the vaccination antigens purified protein derivate of tuberculin (PPD) and tetanus toxoid (TT), was detected in cell culture supernatants from blood mononuclear cells by ELISA. Preeclamptic women showed reduced numbers of basophil granulocytes in the blood (p=0.004) and lower spontaneous secretion of IL-5 from blood mononuclear cells (p=0.016). In addition, paternal antigen-induced secretion of IL-10 was decreased in preeclampsia compared with normal pregnancy (p=0.012). No further differences between preeclampsia and normal pregnancy were found for any stimuli or cytokines. The present findings of reduced basophil numbers and lower spontaneous in vitro secretion of IL-5 in preeclampsia compared with normal pregnancy indicate a decrease in systemic Th2 immunity in preeclampsia. Furthermore, the decrease in paternal antigen-induced secretion of the immunosuppressive cytokine IL-10 in preeclampsia indicates a fetus-specific decrease in immunosuppression mediated by blood mononuclear cells. Whether these systemic changes are a cause or a consequence of preeclampsia remains to be elucidated.

Basophils↗

PubMed2005

Obstetric anal sphincter injury ten years after: subjective and objective long term effects.

OBJECTIVE: To establish the long term effects of obstetric anal sphincter rupture. DESIGN: Prospective observational study. SETTING: University hospital in Sweden. POPULATION: Eighty-two women from a prospective study from 1990 to compare anorectal function after third degree tear. METHODS: Women completed a structured questionnaire, underwent a clinical examination and anorectal manometry, endoanal ultrasound (EAUSG) with perineal body measurement. MAIN OUTCOME MEASURES: Symptoms of anal incontinence, sexual symptoms, anal manometry scores and evidence of sphincter damage on EAUSG. RESULTS: Five women had undergone secondary repair and three were lost to follow up. Fifty-one women (80%) completed the questionnaire. Twenty-six out of 46 (57%) of the original study group and 6/28 (20%) of the original controls were examined. Incontinence to flatus and liquid stool was more severe in the study group than in controls. Flatus incontinence was significantly more pronounced among women with subsequent vaginal deliveries. Mean maximal anal squeeze pressures were 69 mmHg in the partial rupture group and 42 mmHg in the complete rupture group (P= 0.04). Study group women with signs of internal sphincter injury reported more pronounced faecal incontinence and had lower anal resting pressures (24 mmHg) than those with intact internal sphincters (40 mmHg) (P= 0.01). Perineal body thickness of less than 10 mm was associated with incontinence for flatus and liquid stools, less lubrication during sex and lower anal squeeze pressures (58 mmHg vs 89 mmHg, P= 0.04). CONCLUSIONS: Subjective and objective anal function after anal sphincter injury deteriorates further over time and with subsequent vaginal deliveries. Thin perineal body and internal sphincter injury seem to be important for continence and anal pressure.

Adult↗

PubMed2005

Immunology of preeclampsia.

Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine NK cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.

Cytokines↗

PubMed2004

Systemic Th1/Th2 cytokine responses to paternal and vaccination antigens in preeclampsia: no differences compared with normal pregnancy.

PROBLEM: A Th1-shift has been suggested to be involved in the pathogenesis of preeclampsia. This study was designed to compare Th1/Th2 related cytokine secretion in blood between women with preeclampsia (n = 15) and normal pregnancies (n = 15), using a high-sensitivity technique for cytokine detection. METHODS OF STUDY: Spontaneous as well as 'fetus-specific' and recall antigen-specific (purified protein derivate of Mycobacterium tuberculosis, tetanus toxoid and lipopolysaccharide) secretion of interferon-gamma, interleukin (IL)-4, IL-10 and IL-12 in peripheral blood mononuclear cells (PBMC) was detected by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT). Fetus-specific secretion was induced by stimulation with paternal PBMC in a mixed leukocyte culture assay. RESULTS: All cytokines were secreted by PBMCs both from women with preeclampsia and women with normal pregnancies. No differences in the number of cytokine-secreting cells were found between the two groups. CONCLUSIONS: No evidence was found for a shift in the systemic Th1/Th2 responses, in preeclampsia compared with normal pregnancy. This does, however, not exclude differences in the local immune responses related to the fetoplacental unit.

Adult↗

PubMed2003

In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy.

INTRODUCTION: Local and possibly systemic curtailment of the maternal immune response is important for a successful pregnancy. Although the local milieu at the utero-placental interface is likely to harbor the most prominent alterations, it is suggested, at least in mice, that systemic immunity is also tolerized during pregnancy. In the present study, we investigated mRNA expression of the key immunomodulatory cytokines; interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma during normal pregnancy. MATERIAL AND METHODS: In-situ hybridization (ISH) of cytokine mRNA in resting peripheral blood mononuclear cells (PBMCs) was used to detect the number of cells spontaneously expressing cytokines. Eleven women with normal gestations were followed during pregnancy as well as 8 weeks postpartum, and compared with 10 non-pregnant healthy controls. RESULTS: The numbers of IFN-gamma and IL-4 mRNA expressing cells were found to be significantly increased during pregnancy and postpartum compared with non-pregnant controls. Pregnant women and non-pregnant controls did not differ in their expression of TNF-alpha and IL-10. CONCLUSION: Our studies demonstrated increased numbers of both IFN-gamma and IL-4 mRNA expressing cells in blood suggesting that systemic immunomodulation, albeit partial, takes place during normal pregnancy. It is proposed that enhanced IL-4 expression, possibly in concert with other elevated anti-inflammatory immunomodulatory cytokines, curtail the potentially hazardous effects of IFN-gamma on systemic immunity during pregnancy.

Adult↗

PubMed2002

T and B lymphocyte subsets in patients with unexplained recurrent spontaneous abortion: IVIG versus placebo treatment.

PROBLEM: To investigate circulating lymphocyte subsets in women with recurrent spontaneous abortion (RSA) in relation to pregnancy outcome and to treatment with intravenous immunoglobulin (IVIG). METHOD OF STUDY: Forty-one women with a history of unexplained RSA were examined during first trimester of pregnancy before IVIG or placebo treatment and after pregnancy. The results were compared with five healthy, non-pregnant women and five women in the first trimester of normal pregnancy. Circulating lymphocyte subsets with focus on T-cell subpopulations were determined by flow cytometry. RESULTS: The proportions of human leukocyte antigen (HLA)-DR positive T cells (CD3+ HLA-DR+), T-killer/effector cells (CD8+ S6F1+) and B cells (CD19+) were increased, whereas the proportion of T-suppressor/inducer cells (CD4+ CD45RA+) was decreased during first trimester pregnancy of RSA women compared with pregnant normal controls. T and B lymphocyte subsets did not correlate with pregnancy outcome on either IVIG or placebo group. CONCLUSIONS: In RSA patients, the immune system seems to be activated in contrast to the suppression noted in normal pregnancy.

Abortion, Habitual↗

PubMed2002

Deficiency of decidual IL-10 in first trimester missed abortion: a lack of correlation with the decidual immune cell profile.

PROBLEM: To determine if first trimester missed abortion decidua is characterized by an altered immune cell profile and/or a modified interleukin (IL)-10 and interferon (IFN)-gamma production pattern compared with decidua from elective termination. METHOD OF STUDY: Flow cytometry and immunohistochemistry techniques were used to determine the decidual immune cell phenotypic profile and production pattern of IL-10 and IFN-gamma in cases of elective termination (n = 14) and missed abortion (n = 12). RESULTS: Both groups had a similar proportion of CD56+ CD16-, CD56+ CD16+, CD19+, CD3+, CD4+, CD8+, alphabeta T cells and gammadelta T cells. The majority of alphabeta and gammadelta positive T cells in both groups coexpressed the natural killer (NK) cell marker CD56, but lacked cell surface expression of CD3. Diminished decidual IL-10 staining was noted in 7/10 missed abortion cases compared with none of the elective termination cases (n = 12) (P = 0.007). A uniform decidual IFN-gamma staining pattern was observed in both groups. CONCLUSION: Decreased IL-10 production coupled with a sustained IFN-gamma presence noted in missed abortion compared with elective termination cases suggest that these cytokines may be important determinants in pregnancy outcome. In contrast, differences in the proportion of immune cells between both groups may not be a critical factor in early pregnancy loss. In normal pregnancy, decidual alphabeta and gammadelta positive T cells with reduced CD3 on their cell surface may be intrinsically restricted in T-cell receptor (TCR)-mediated activation.

Abortion, Induced↗

PubMed2002

Cytokine changes in postmenopausal women treated with estrogens: a placebo-controlled study.

PROBLEM: Hormone replacement therapy (HRT) is being increasingly used in postmenopausal women. Sex steroids are known to affect the immune system in several ways, although this is mainly based on clinical observations and experimental studies. METHOD OF STUDY: We studied the in vivo effects of transdermal estrogens (50 microg 17 beta-Estradiol/24 hr) on cytokine production in postmenopausal women. A total of 17 women were randomized to either placebo (n = 7) or active estrogen therapy (n = 10) for 14 weeks, with addition of oral medoxyprogesterone acetate 10 mg daily during the last 2 weeks in both groups. Secretion of the cytokines IFN-gamma, IL-4, IL-10 and IL-6 in blood mononuclear cells was determined, spontaneously and after stimulation with common vaccination antigens and mitogen, using the cell ELISA technique. RESULTS: IL-6 production after stimulation with purified protein derivate (PPD) decreased in the estrogen treated group (P < 0.01). Mitogen-induced IL-6 production was reduced in the estrogen treated group in contrast to an increase in the placebo group, leading to a significant difference (P < 0.01) between the groups after 12 weeks of treatment. This difference was eliminated after an addition of progestagens for 2 weeks. No significant changes were noted for IFN-gamma, IL-4 or IL-10 in relation to estrogen or placebo treatment. CONCLUSIONS: In the present controlled study, the main in vivo effect of estrogens was a decrease in IL-6 production, indicating a possible beneficial effect of estrogen therapy.

Cytokines↗