bluuebunny/crossref_metadata_2025 huggingface dataset:
Pro‐inflammatory Maternal Cytokine Profile in Preterm Delivery
Authors: Makhseed M. , Raghupathy R. , El‐Shazly S. , Azizieh F. , Al‐Harmi J. A. , Al‐Azemi M. M. K.
Published: December 2004

PROBLEM:  The objective of this study was to determine the levels of cytokines produced by maternal peripheral blood mononuclear cells (PBMC) upon stimulation with a mitogen, with autologous placental cells and with a trophoblast antigen extract.

METHOD OF STUDY:  Peripheral blood mononuclear cells from 54 women with a history of successful pregnancy and 30 women undergoing preterm delivery (PTD) were stimulated with the mitogen and antigens, and the cytokine levels in mitogen‐stimulated culture supernatants assessed.

RESULTS:  Significantly higher levels of the type 1 cytokines, interferon (IFN)‐γ and interleukin (IL)‐2, were produced by the PTD group than by the normal pregnancy group, which on the contrary showed significantly greater production of the type 2 cytokines, IL‐4, IL‐5 and IL‐10. A comparison of the ratios of type 2 to type 1 cytokines is indicative of a type 1 cytokine bias in PTD.

CONCLUSIONS:  These data are suggestive of a maternal type 1 cytokine bias in PTD.
Uterine Response to Infectious Bacteria in Estrous Cyclic Ewes
Authors: Seals Richard C. , Wulster‐Radcliffe Meghan C. , Lewis Gregory S.
Published: December 2004

PROBLEM:Luteal‐phase uteri are susceptible to infections, and PGE2and exogenous progesterone can down‐regulate, whereas PGF2αcan up‐regulate, uterine immune functions.

METHOD OF STUDY:Uteri of follicular‐ or luteal‐phase ewes were inoculated with either saline or bacteria (Arcanobacterium pyogenesandEscherichia coli). Vena caval blood was collected for the next 3 days, and progesterone, PGE2, and PGF2αwere measured. The effects of 10−7 mPGE2(Experiment 1), 10−7 mPGF2α(Experiment 2), 10−7 mindomethacin (INDO), and diluent on proliferation of lymphocytes from the vena caval blood in response to mitogens was quantified.

RESULTS:Experiment 1: Progesterone was greater (P < 0.01) in luteal than in follicular ewes (3.4 versus 0.4 ng/mL), and only luteal ewes inoculated with bacteria developed infections.Lymphocyte proliferation was least (P = 0.08) in follicular ewes (2.6 versus 4.5 pmol for follicular and luteal, respectively). Concanavalin A (Con A)‐stimulated proliferation was less (P < 0.05) for ewes inoculated with bacteria and for cells cultured with diluent (5.9 versus 3.1 pmol for saline and bacteria, respectively) or with INDO (6.6 versus 2.8 pmol for saline and bacteria, respectively). Also, Con A‐stimulated lymphocytes from ewes inoculated with bacteria tended to proliferate less (P < 0.1) when cultured with PGE2(4.9 versus 3.7 pmol for saline and bacteria, respectively) or PGE2 + INDO (5.5 versus 3.8 pmol for saline and bacteria, respectively). Experiment 2: Progesterone was greater (P < 0.01) in luteal than in follicular ewes (6.5 versus 1.2 ng/mL), and only luteal ewes inoculated with bacteria developed infections. Con A‐stimulated lymphocyte proliferation was greater (P < 0.001) for follicular ewes (4.1 versus 3.1 pmol for follicular and luteal, respectively). Proliferation of lymphocytes collected from follicular ewes was greater (P < 0.01) when cells were cultured with PGF2α(3.5 versus 2.7 pmol for follicular and luteal, respectively), but INDO did not affect unstimulated or mitogen‐stimulated proliferation.

CONCLUSIONS:Prostaglandin F2αenhanced lymphocyte proliferation, whereas bacterial inoculation andin vitrotreatment with PGE2suppressed lymphocyte proliferation. This may signify the involvement of bacterial products and prostaglandins in regulation of uterine immunity.
Increased T‐Cell Activation in Decidua Parietalis Compared to Decidua Basalis in Uncomplicated Human Term Pregnancy
Authors: Sindram‐Trujillo A. , Scherjon S. , Kanhai H. , Roelen D. , Claas F.
Published: December 2004

PROBLEM:  The aim of this study was to quantify and compare activated T cells in term decidua basalis and parietalis using flow cytometry.

METHOD OF STUDY:  Term decidua basalis and parietalis samples were obtained from 20 placentas collected after elective caesarean section. Percentages of leukocyte subclasses within the CD45+ cell fraction and activated T cells were determined by flow cytometry.

RESULTS:  There was no significant difference in CD45+, CD14+, CD19+, and CD3+ cell percentages. However, within the CD3+ population, there were significantly more T‐cell receptor‐γδ+ (TCR‐γδ+) and CD8+ cells in decidua parietalis compared with decidua basalis. More importantly, percentages of T cells expressing CD25, human leukocyte antigen (HLA)‐DR, CD45RO, and CD69 markers were significantly increased in decidua parietalis.

CONCLUSION:  These findings suggest that there are more activated T cells in decidua parietalis than in decidua basalis. Further investigation into differences between the two decidual sites may expand our understanding of the immunology of the maternal–fetal interface.
Development of Topical Microbicides for Prevention of Human Immunodeficiency Virus and Herpes Simplex Virus
Authors: Keller M. J. , Klotman M. E. , Herold B. C.
Published: December 2004

Topical microbicides, designed for vaginal or rectal administration, are needed to prevent human immunodeficiency virus (HIV) and other sexually transmitted infections (STI). Presently marketed topical microbicides are cytotoxic and damage the vaginal epithelium with frequent use. Rational development of new candidate compounds should build on knowledge of the pathways of microbial invasion. The establishment of assays and models that predict efficacy and safety is critical. Comprehensive pre‐clinical evaluation of promising microbicides should include rigorous assessment of the effects of repeated application of topical agents on mucosal inflammatory cells, cytokines, and the genital tract virus population. These studies will lay the groundwork for future clinical trials.
MD‐1 is a Critical Part of the Mechanism Causing Th1‐Cytokine‐Triggered Murine Fetal Loss Syndrome
Authors: Clark David A. , Yu Gary , Arck Petra C. , Levy Gary A. , Gorczynski Reginald M.
Published: December 2004

PROBLEM:  Fetal loss syndrome (abortion/resorption) occurring on or after gestation day (gd) 9.5 in CBA/J×DBA/2 matings is dependent upon presence of TNF‐α + IFN‐γ, which act by increasing expression of fgl2 prothrombinase at the feto‐maternal interface. The magnitude by which the abortion rate can be boosted by an injection of these cytokines on gd 7.5 depends on endogenous rate of loss, and appears to depend on microbial flora. Is cytokine‐triggered abortion dependent upon a third signaling pathway that senses ‘danger'?

METHODS:  Female CBA/J were mated to DBA/2 males and, C57Bl/6 and C57Bl/6 TNFαR1−/−Mak were mated to C57Bl/6 control or TNFαR1−/−Mak males. LPS from Escherichia coli and Salmonella enteritidis, or the combination of TNF‐α + IFN‐γ, was injected to stimulate abortions. The effect of anti‐MD‐1, which interferes with expression of CD14 and, hence, with signaling by LPS via the CD14‐tlr4 complex, on TNF‐α + IFN‐γ was tested. The presence of MD‐1 in the uterus was evaluated by in situ hybridization, and effect of lipopolysaccharide (LPS) on mice lacking TNF‐αR1 was tested.

RESULTS:  Anti‐MD‐1 completely abrogated TNF‐α + IFN‐γ ‐induced abortions. MD‐1 was expressed on trophoblast and in deciduas on gd 8.5 but LPS could not abort mice that lacked the type 1 receptor for TNF‐α. Pregnant CBA/J females had classical resorptions (abortions) countable on gd 13.5–14.5 in response to LPS from E. coli or S. enteritidis, but C57Bl/6 strain mice resorbed only in response to the latter, and E. coli LPS appeared to induce ‘occult’ losses. ‘Occult’ loss did not require TNF‐α R1.

CONCLUSIONS:  TNF‐α + IFN‐γ could not induce murine abortions without co‐presence of a ‘danger’ signal such as LPS acting via CD14 on toll receptors, and LPS could not act without co‐signaling by TNF‐α. Classical resorptions/abortions and ‘occult’ losses have a different mechanism in these models as reflected in type of endotoxin and requirement for TNF‐αR1 signaling.
Chemokine Bioactivity of RANTES is Elevated in the Sera of Infertile Women with Past Chlamydia trachomatis Infection
Authors: Shibahara Hiroaki , Hirano Yuki ,   Ayustawati, Kikuchi Kumiko , Taneichi Akiyo , Fujiwara Hiroyuki , Takamizawa Satoru , Sato Ikuo
Published: December 2004

PROBLEM:  It has been shown that Chlamydia trachomatis infection in infertile women is highly associated with tubal pathology. Chlamydia trachomatis antibody testing is a simple screening test for tubal factor subfertility, however, it is based on the detection of previous infection. Recently, association between some inflammatory diseases and chemokines has been investigated. This study was performed to clarify the relationship between chemokines in the sera of infertile women and past C. trachomatis infection.

METHOD OF STUDY:  Serum samples were collected from 10 infertile women having C. trachomatis antibodies [immunoglobulin (Ig)G and/or IgA] in their sera and 10 infertile women without the antibodies. All patients' tubo‐ovarian structures were explored by transvaginal hydrolaparoscopy (THL). A CXC chemokine, interleukin‐8, and six CC chemokines including macrophage inflammatory protein‐1α (MIP‐1α), MIP‐1β, monocyte chemotactic protein‐1 (MCP‐1), MCP‐3, eotaxin, and regulated on activation, normal T cell expressed and secreted (RANTES) concentrations in their sera were analyzed using enzyme‐linked immunosorbent assay.

RESULTS:  The serum concentration of RANTES was significantly higher in patients with C. trachomatis antibodies than those without the antibodies (P = 0.019). However, there were no significant differences of the concentrations of other chemokines between the sera of infertile women with and without C. trachomatis antibodies. The concentration of RANTES in the sera of infertile women did not correlate with C. trachomatis antibody titers or tubal pathology diagnosed by THL.

CONCLUSIONS:  These findings might indicate significant roles of some chemokines in the pathogenesis of C. trachomatis infection. Further studies are necessary to study the usefulness of evaluations of chemokines in tubal infertility investigations.
Expression of Nuclear Factor of Activated T Cells mRNA in Maternal Peripheral Blood Cells
Authors: Kojima H. , Tamura T. , Okuda T. , Kato C. , Kinoshita Y. , Honjo H.
Published: December 2004

PROBLEM:  In T lymphocytes, nuclear factor of activated T cells (NF‐AT) regulates the induction of cytokine genes upon antigenic stimulation. This study was designed to analyse the relationship between NF‐AT and pregnancy.

METHOD OF STUDY:  With informed consent, peripheral blood cells (PBCs) were obtained from non‐pregnant (n = 114), pregnant (n = 604), and puerperal women (n = 52). The expression of NF‐AT2 and NF‐AT3 mRNAs in PBCs was measured by a quantitative reverse transcriptase‐polymerase chain reaction method.

RESULTS:  In the early pregnancy period, in successful pregnancy, both NF‐AT2 and NF‐AT3 mRNAs increased significantly, whereas in cases of spontaneous abortion they did not change significantly. After peaking, they decreased gradually and were re‐elevated in the ninth and tenth gestational month. In the puerperal period, NF‐AT3 mRNAs decreased, but NF‐AT2 mRNA showed a comparatively high expression level.

CONCLUSION:  These findings suggested that in humans NF‐AT signal transduction might be involved in alloantigenic recognition and tolerance and play important roles, especially in the early and late period of pregnancy.
TNF‐α Protects Embryos Exposed to Developmental Toxicants
Authors: Torchinsky Arkady , Shepshelovich Jeanne , Orenstein Hasida , Zaslavsky Zeev , Savion Shoshana , Carp Howard , Fein Amos , Toder Vladimir
Published: December 2004

BACKGROUND:  Tumor necrosis factor α (ΤNF‐α) has been implicated in mediating post‐implantation embryo loss or the embryonic maldevelopment induced by development toxicants or maternal metabolic imbalances. In order to clarify the role of TNF‐α further, a comparative study was performed in TNF‐α knockout and TNF‐α positive mice, exposed to a reference teratogen, cyclophosphamide (CP).

METHODS:  Cyclophosphamide was injected on day 12 of pregnancy and 18‐day fetuses were examined for external structural anomalies. Apoptosis and cell proliferation were measured by TdT‐mediated biotin–dUTP nick‐end labeling and 5′‐bromo‐2′‐deoxyuridine incorporation, respectively, in the brain (an organ, sensitive to the teratogen) of embryos 24 hr after CP injection. NF‐κB DNA‐binding activity by electrophoretic mobility shift assay (EMSA) and the expression of RelA (an NF‐κB subunit) and IκBα proteins by Western blot analysis were assessed in the brain of embryos tested 24 and 48 hr after CP treatment.

RESULTS:  Surprisingly, the proportion of fetuses with craniofacial, trunk and severe limb reduction anomalies were significantly higher in TNF‐α–/– females, than in TNF‐α+/+ mice. Excessive apoptosis and suppression of cell proliferation was found in the brain, and they were more prominent in TNF‐α–/– than TNF‐α+/+ embryos, when examined 24 hr after CP injection. Finally, CP‐induced suppression of NF‐κB DNA‐binding activity was found to be enhanced in the brain of TNF‐α–/– embryos, and the restoration of NF‐κB DNA‐binding activity was compromised.

CONCLUSION:  This work demonstrates for the first time that TNF‐α may act as a protector of embryos exposed to teratogenic stress. One possible mechanism may be restoration of NF‐κB activity in embryonic cells surviving the teratogenic insult.
Hofbauer Cell Activation and its increased Glucose‐6‐Phosphate Dehydrogenase Activity in Second Trimester‐spontaneous Abortion: an Ultrastructural Dual Staining Enzyme‐cytochemical Study
Authors: Matsubara S. , Takayama T. , Yamada T. , Usui R. , Izumi A. , Watanabe T. , Ohkuchi A. , Shibahara H. , Sato I. , Suzuki M.
Published: December 2004

PROBLEM:  While activated/phagocytosing phagocytes infiltrating to the chorioamnion are considered to be one of the causal agents of preterm labor onset, whether placental villous macrophages (Hofbauer cells) are activated/phagocytosing in this condition is not known.

METHOD OF STUDY:  We concomitantly localized two important phagocytosis‐related enzymes, acid phosphatase (ACP) and glucose‐ 6‐phosphate dehydrogenase (G6PD), in Hofbauer cells in second trimester placental villi, and compared them with those from infection‐related second trimester‐spontaneous abortion (miscarriage) placentas.

RESULTS:  There were two types of Hofbauer cells. The first cells exhibited ACP stainings confined to the lysosomes, suggesting that they are dormant/non‐activated cells. Approximately two‐thirds of these cells showed weak G6PD labeling on the cytosolic side of endoplasmic reticula, and G6PD labeling was hardly recognizable in the remaining one‐third. The second cells, possessing large phagosomes, showed marked ACP labeling in the phagosomes, suggesting that they are activated/phagocytosing cells. All these cells exhibited G6PD labeling, and in ‘bursting cells’ (possibly hyperactivated cells) G6PD deposits were marked. The percentage of activated cells in miscarriage placentas was significantly higher (44.8 ± 6.0%) than that in gestational age‐matched controls (17.4 ± 5.3%).

CONCLUSIONS:  These observations indicated that (1) G6PD activity increased in activated/phagocytosing Hofbauer cells, and (2) the percentage of phagocytosing cells increased in infection‐related miscarriage placentas. Hofbauer activation and G6PD may play an role in the pathogenesis/pathophysiology of preterm labor onset.
Pre‐term Birth and Severe Pre‐eclampsia are not Associated with Altered Expression of HLA on Human Trophoblasts*
Authors: Datema Gert , Van Meir Claudia A. , Kanhai Humphrey H. H. , Van Den Elsen Peter J.
Published: December 2004

PROBLEM:  The unusual pattern of human leukocyte antigen (HLA) expression on human trophoblasts could play an important role in successful pregnancy outcome. To determine whether alterations in HLA expression are associated with pregnancy abnormalities we have investigated expression of these antigens on chorionic and extravillous cytotrophoblasts.

METHODS:  Frozen tissue sections of placenta and fetal membranes were collected after pre‐term spontaneous delivery, severe pre‐eclampsia pre‐term Caesarean section, normal term delivery and term Caesarean section. HLA expression was analyzed by immunohistochemistry.

RESULTS:  We did not observe differences in the expression of HLA on chorionic and extravillous cytotrophoblasts in pregnancy abnormalities. However, we noted higher expression levels of HLA class Ia molecules in amnion epithelial cells in pre‐term deliveries. Furthermore, in severe pre‐eclampsia the number of extravillous cytotrophoblast islands were elevated when compared with pre‐term deliveries.

CONCLUSIONS:  No alterations in expression of HLA class Ia, HLA‐G and HLA class II on human trophoblasts in pregnancy abnormalities were seen.
Th1 Cytokines and the Prothrombinase fgl2 in Stress‐triggered and Inflammatory Abortion
Authors: Knackstedt M. K. , Zenclussen A. C. , Hertwig K. , Hagen E. , Dudenhausen J. W. , Clark D. A. , Arck P. C.
Published: December 2004

PROBLEM:  The immune system contributes to the outcome of pregnancy by complex immunological interactions. Cytokines especially influence the immune milieu pro or contra pregnancy. T helper 1 (Th1) cytokines [tumor necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ)] cause inflammation and together are thought to threaten the maintenance of pregnancy. It has been proposed that increased levels of these Th1 cytokines activate coagulation via up‐regulating the novel prothrombinase, fgl2. This study further investigates the Th1 cytokine up‐regulation of fgl2 expression in a pathophysiological, stress induced abortion model, and an inflammatory, interleukin‐12 (IL‐12) triggered abortion model.

METHOD:  The DBA/2J‐mated CBA/J female mice were exposed to sonic sound stress or were injected with IL‐12 during early gestation. On day 13.5 of pregnancy the uteri were removed and the resorption rate was calculated. We evaluated TNF‐α, IFN‐γ, fgl2 as well as IL‐12 messenger RNA (mRNA) expression in decidual samples of all mice by quantitative, real‐time polymerase chain reaction (PCR).

RESULTS:  A similar resorption rate of 24% was detected in stressed mice, as well as in IL‐12 injected mice compared with approximately 11% in non‐stressed, non‐injected control mice. In stressed mice compared with controls, we observed on day 13.5 up‐regulated TNF‐α, unchanged IFN‐γ down‐regulated fgl2, and a slightly increased levels of IL‐12. In the IL‐12 triggered abortion model, we observed up‐regulated levels of TNF‐α, IFN‐γ and fgl2.

CONCLUSION:  These novel data suggest two distinct cytokine patterns leading to similar abortion rates. A physiological cascade associated with up‐regulation of TNF‐α, and an IL‐12‐triggered cascade characterized by persistent up‐regulation of TNF‐α and IFN‐γ as well as a persistent increase in fgl2.
Antiphospholipid Antibodies in Implantation Failures*
Authors: McIntyre J. A.
Published: December 2004

PROBLEM:  The amino phospholipids (PL), phosphatidylserine (PS) and phosphatidylethanolamine (PE) are distributed asymmetrically in the plasma membranes of eucaryotic cells. This arrangement involves active transport of PS and PE from the outer to inner membrane leaflet by an aminophospholipid translocase (flipase). Cell activation, injury and programmed cell death (apoptosis) cause collapse of the PS/PE asymmetry by activation of another enzyme system, scramblase. Unlike other cells, the developing trophoblast exteriorizes PS during its differentiation.

METHODS OF STUDY:  An analysis of published and unpublished data.

RESULTS:  The trophoblast is targeted by antiphospholipid antibodies (aPL), especially to PS (aPS). Cardiolipin is not present in the trophoblast plasma membrane, nonetheless, anticardiolipin (aCL) has been implicated in trophoblast pathology. The aPS and aCL are often crossreactive. Both animal and in vitro experimental models have shown monoclonal and polyclonal aPS and aCL to specifically destroy trophoblast, inhibit syncytium formation, halt human chorionic gonadatropin (hCG) production, and limit trophoblast invasion. Antibodies to PE (aPE) have not been well characterized, however, recent reports from several independent laboratories document that aPE are associated significantly with very early (embryonic) recurrent pregnancy loss (RPL). Umeda and coworkers have shown that during cytokinesis (late telophase) of Chinese hamster ovary (CHO) cells, formation of PE rafts in cleavage furrows is required for completion of cell division and formation of daughter cells. This raises the question whether aPE might interfere with implantation and cell division during embryogenesis.

CONCLUSIONS:  A role for aPL in implantation failure and occult pregnancy loss constitutes the basis of this overview.
Feasibility to Generate Monocyte‐Derived Dendritic Cell from Coculture with Melanoma Tumor Cells in the Presence of Granulocyte / Macrophage Colony‐Stimulating Factor (GM‐CSF) and Interleukin‐4
Authors: Kim Young T. , Hersh Evan M. , Trevor Katrina T.
Published: December 2004

OBJECTIVE:  We investigated how melanoma cells and membrane‐bound granulocyte/macrophage colony stimulating factor (mbGM‐CSF) melanoma cell lines affect the differentiation of dendritic cells (DC) from CD14+ monocytes.

METHOD OF STUDY:  The malignant melanoma cell lines (Conley and Jorp) and mbGM‐CSF‐positive cell lines (Conley B‐F8 and Jorp C‐E6) were cultured and cell‐free supernatants were collected from each cell line cultures to assess the GM‐CSF level. Adherent monocytes were cocultured for 6–7 days with irradiated mbGM‐CSF and wild type melanoma cells (50 Gy) at each 1 : 1 and 0.1 : 1 ratio in six‐well culture plates in ex vivo culture medium containing interleukin (IL)‐4. Immunophenotyping was performed by triple color immunofluorescence staining with flow cytometry analysis.

RESULTS:  GM‐CSF was detected at low levels in the culture supernatants of Conley B‐F8 (0.48 ng/106 cells/24 hr), whereas there was no detectable GM‐CSF in that of Conley melanoma cell line. Monocytes cultured with GM‐CSF/IL‐4 generated the expression of high levels of HLA DR, CD1a and CD86, while the expression of CD14 and CD83 were in low amounts. However, the addition of GM‐CSF to these cultures resulted in an increased expression of these markers and decreased that of CD14. Monocytes cocultured with Jorp C‐E6 illustrated similar expression pattern of CD1a, HLA DR and CD14 in the presence or absence of GM‐CSF as Conley B‐F8 melanoma cell line. Monocytes cocultured with Conley B‐F8 melanoma cells at 1 : 1 and 0.1 : 1 ratio showed no significant difference in expression of CD1a, CD14 and CD83 between the two ratios.

CONCLUSION:  Our results illustrate the feasibility to generate monocyte‐derived DC from coculture with melanoma tumor cells in the presence of GM‐CSF and IL‐4. However, mbGM‐CSF tumor cells did not significantly enhance the DC differentiation through juxtacrine stimulation unless soluble GM‐CSF was added in the culture media.
Use of a Highly Specific Monoclonal Antibody Against the Central Variable Amino Acid Sequence of Mammalian Gonadotropin Releasing Hormone to Evaluate GnRH‐I Tissue Distribution Compared With GnRH‐I Binding Sites in Adult Male Rats
Authors: Khan Mohammad A. H. , Ferro Valerie A. , Stimson William H.
Published: December 2004

PROBLEM:  Recent evidence shows the existence of numerous isoforms of gonadotropin releasing hormone (GnRH), with high sequence homology and a core variable region. This raises the issue that previous GnRH distribution studies may have identified a variety of isoforms. This investigation was carried out to confirm the distribution and binding activity of GnRH‐I only.

METHOD OF STUDY:  A monoclonal antibody (7B101D10), with specificity for the core region of GnRH‐I was used to stain formalin‐fixed tissue sections from adult male Sprague–Dawley rats, while a biotinylated GnRH‐I sequence was used with avidin‐labelled HRP to evaluate regions of GnRH‐I binding.

RESULTS AND CONCLUSIONS:  GnRH‐I expression was only found in the hypothalamus, cerebellum, anterior/fore brain and in Sertoli cells, while, binding activity was only present in the pituitary, subendocardium and subepicardium, thymic lymphocytes, peripheral blood lymphocytes and neutrophils. There was overlap in the olfactory neurons, liver (Kupffer macrophages and hepatocytes), spleen (lymphocytes and dendritic cells), myocardium and testes (spermatozoa and Leydig cells) and this may be further evidence of the paracrine/autocrine activity of a neuropeptide.
The Role of Cytokines in Endometriosis*
Authors: Wu Ming‐Yih , Ho Hong‐Nerng
Published: December 2004

PROBLEM:  To review the literature on the role of peritoneal cytokines in the pathogenesis and endometriosis‐related infertility.

METHODS OF STUDY:  A MEDLINE search was conducted by the key words of cytokine and endometriosis in the English publications, and references identified within the identified papers were also reviewed.

RESULTS:  Several cytokines including interleukin (IL)‐1, 6, 8, 10, tumor necrosis factor (TNF)‐α, and vascular endothelial growth factor (VEGF) were reported to be increased in the peritoneal fluid (PF) of women with endometriosis. Those cytokines may be involved in macrophage activation, inflammatory change and enhanced angiogenesis. However, some cytokines were less expressed such as IL‐2, and interferon (IFN)‐γ. They reflect the impaired T‐ and natural killer (NK)‐cell function. Endometriotic implants produce some factors, e.g. matrix metalloproteinases (MMPs), Bcl‐2, and affect their capacity to implant into the peritoneum.

CONCLUSION:  Peritoneal cytokines, which are produced by mesothelial cells, leukocytes and ectopic endometrial cells, interwork locally and systemically in women with endometriosis. More studies about the specific role and interactions of these cytokines are needed to improve the understanding of endometriosis and to develop novel therapies.
Effects of Boar Seminal Immunosuppressive Fraction on Production of Cytokines by Concanavalin A‐Stimulated Spleen Cells and on Proliferation of B Lymphoma Cell Lines
Authors: Veselský L. , Holáň V. , Zajícová A. , Dostál J. , Železná B.
Published: December 2004

PROBLEM:  The immunosuppressive fraction (ISF) of boar seminal vesicle fluid has recently been demonstrated to inhibit mitogen‐stimulated proliferation of lymphocytes and antibody response to corpuscular and soluble antigens. The effects of ISF on in vitro and in vivo production of cytokines as well as its possible inhibitory effect on proliferation of B lymphoma cells remain to be elucidated.

METHODS:  The effect of ISF on proliferation of normal mouse spleen cells stimulated by Concanavalin A (Con A) and on mouse B lymphoma cells was measured by 3H‐thymidine incorporation. Cytokines were determined in the supernatants of mouse spleen cells stimulated with Con A in the presence or absence of ISF by enzyme‐linked immunosorbent assay (ELISA). In vivo cytokine production in the sera samples of mice treated with ISF and immunized with keyhole limpet hemocyanin (KLH) was followed by ELISA, too.

RESULTS:  We confirmed the inhibitory effect of ISF on Con A‐stimulated lymphocyte proliferation. ISF affected cytokine production in the Con A‐stimulated spleen cells: production of interleukin‐2 (IL‐2) and interferon‐γ (IFN‐γ) was lowered, but production of IL‐4, IL‐6, and IL‐10 was enhanced. Similarly, in the sera samples of mice immunized with keyhole limpet hemocyanin (KLH), IL‐2 and IFN‐γ levels were decreased by ISF. ISF inhibited proliferation of Ag 8 and X 63‐IL‐2 B lymphoma cells as well.

CONCLUSIONS:  ISF inhibited production of T helper1 (Th1) cytokines (IL‐2 and IFN‐γ) and enhanced production of Th2 cytokines (IL‐4, IL‐6, and IL‐10). ISF seems to shift the Th1/Th2 pattern in favor of Th2. ISF exhibited an antiproliferative activity on mouse B lymphoma cells.
Twenty‐three years of labour floor records, Vila Central Hospital, Vanuatu
Authors: Grace Robert F , Vurobaravu Thomas S
Published: December 2004

Vanuatu is an island nation in the south‐west Pacific. Vila Central Hospital (VCH) is the country's major referral hospital. The handwritten labour floor records from VCH between 1979 and 2001 were examined and collated. During this period 28 638 women received care. The mean Caesarean section and instrumental delivery rate were 5.2% (2.1–8.2% per annum) and 1.8% (0.9–3.2% per annum), respectively. The post‐partum haemorrhage rate fell from >5% in 1979 to <1% in 2001. The overall hospital maternal mortality rate was 7/10 000. These records represent the largest published series of labour floor data collected from any Pacific island nation.
Maternal complications after Caesarean section in HIV‐infected pregnant women
Authors: Panburana Panyu , Phaupradit Winit , Tantisirin Orathai , Sriintravanit Narumon , Buamuenvai Jerdjai
Published: December 2004

A study of maternal complications after elective Caesarean section in HIV‐infected women was carried out from January 1999 to April 2001. The control group consisted of all the seronegative pregnant women who underwent the elective Caesarean section during the study period. The study group was divided into two subgroups. Subgroup 1 patients were given 600 mg zidovudine (ZDV) orally and 300 mg lamivudine (3TC) daily from 34 to 38 weeks’ gestation. Subgroup 2 patients were given 600 mg ZDV orally daily from 34 to 38 weeks’ gestation and 150 mg nevirapine orally on the morning of the Caesarean section day. In both groups, the elective Caesarean section was carried out at 38 weeks’ gestation and ZDV syrup (2 mg/kg) was given orally to the newborn immediately in the operating theatre and then every 6 h for 4 weeks. No statistically significant differences in maternal complications were found between the HIV‐infected and non HIV‐infected women.
Hepatitis B surface antigen carrier status and its correlation to gestational hypertension
Authors: To William W. K. , Cheung Wai , Mok Ka‐Ming
Published: December 2004

Objective: To determine whether chronic hepatitis B surface antigen (HBsAg) carrier status is associated with an increased incidence of gestational hypertension.

Methods: A retrospective analysis of all deliveries in a regional obstetric unit over a 4‐year period using a comprehensive obstetric database.

Results: The data of 13 792 patients were analysed, of which 1340 (9.71%) were chronic HBsAg carriers. Contrary to our hypothesis, the overall incidence of gestational hypertension was significantly lower in the HBsAg positive group (2.01%) as compared to the negative group (3.58%) (P < 0.01, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.37–0.81). When comparing the incidence of severe preeclampsia, the difference remained significant (0.22 and 0.79%, respectively, P < 0.05, OR 0.28, 95% CI 0.08–0.88). There was otherwise no difference in the incidence of other major obstetric complications between the HBsAg positive and negative groups.

Conclusion: The findings presented did not support a positive association between HbsAg carrier status and gestational hypertension. The data from the present study, and re‐evaluation of similar published data, in fact suggest the contrary observation of a lower than normal incidence of gestational hypertension in HbsAg positive mothers.
Anatomy of Complications Workshop: An educational strategy to improve performance in obstetricians and gynaecologists
Authors: Hammond Ian , Taylor John , McMenamin Paul
Published: December 2004

Many specialist obstetricians and gynaecologists feel inadequately trained to deal with certain situations such as injury to bowel, bladder, ureter and major vessels, and value further training to prevent and manage these problems. We present the structure, objectives and rationale for a surgical skills workshop, which is an intensive practical learning experience aimed to improve the performance of obstetricians and gynaecologists. The overall objective of the workshop is improvement in the prevention and management of complications in obstetric and gynaecological surgery. Over 100 participants have completed the workshop so far. Pre‐workshop preparation includes anatomical illustrations to guide reading and a training video describing surgical skills, ewe anatomy and hysterectomy in the ewe. There are four modules: anatomy includes an interactive lecture, cadaveric dissection and examination of prosections with specific learning tasks. Surgical skills involves the demonstration, practice and learning of techniques needed to deal with unexpected operative injury to bowel, bladder, ureter and major blood vessels. Live animal surgery on a ewe allows further supervised practice of the previously learned skills plus the repair of serious vascular injury. Case presentations allow each participant to present a complicated case in a facilitated group session with discussion and feedback from their peers. This session is controlled, non‐threatening and a valuable interactive learning experience. Participant feedback suggests that this workshop format is useful and appears to improve the confidence, competence and performance of the participants. This workshop is presented as a template on which other educational activities can be developed.
Serum lipid and lipoprotein changes induced by preparations containing low‐dose ethinylestradiol plus levonorgestrel
Authors: Kiran Gurkan , Kiran Hakan , Ekerbicer Hasan C.
Published: December 2004

The purpose of the present study was to evaluate the effects on lipid metabolism of a new low‐dose monophasic combination oral contraceptive with 100 µg levonorgestrel and 20 µg ethinylestradiol. Sixty healthy women aged 18–45 years were administered the medication during three cycles. The study participants were screened for lipid changes. The differences in cholesterol and triglyceride levels were not statistically significant, but high‐density lipoprotein levels were significantly lower and low‐density lipoprotein levels were significantly higher than the baseline. Women at risk of cardiovascular disease should be carefully monitored even when using low‐dose preparations.
Prophylactic and therapeutic enoxaparin during pregnancy: Indications, outcomes and monitoring
Authors: Rowan Janet A , McLintock Claire , Taylor Rennae S , North Robyn A
Published: December 2004

Objectives: To evaluate the efficacy and safety of prophylactic and therapeutic enoxaparin in pregnancy.

Study design: Three‐year prospective audit.

Setting: Tertiary level obstetric hospital.

Population: Fifty‐two women who received subcutaneous enoxaparin, either a prophylactic dose (40 mg daily) in 26 pregnancies or therapeutic dose (1 mg/kg twice daily) in 32 pregnancies.

Materials and methods: Pregnant women treated with enoxaparin were prospectively entered into a register. Data were retrieved by case note review.

Main outcome measures: Pregnancy outcomes, treatment complications and anti‐Xa levels.

Results: In the prophylactic group there were no fetal losses, thromboembolic events or complications related to enoxaparin. In the therapeutic group there were four first trimester miscarriages, a termination and 27 live births. Therapeutic enoxaparin prevented further thromboembolism without complications. One woman was treated with intermediate dose enoxaparin when she presented at 5 weeks’ gestation on warfarin and 7 weeks after a venous thromboembolism. She developed a recurrent pulmonary embolus 3 weeks later and was subsequently treated with therapeutic enoxaparin. In the therapeutic group the enoxaparin dose/kg correlated poorly with anti‐Xa levels, and dose adjustments were made. Therapeutic mean (SD) trough and peak anti‐Xa levels were 0.33 U/mL (0.14) and 0.86 U/mL (0.24) in the first trimester and 0.48 U/mL (0.19) and 0.84 U/mL (0.23) in the third trimester.

Conclusions: In the present series, prophylactic and therapeutic enoxaparin treatment during pregnancy was effective and safe. Studies are required to determine the optimal duration of treatment with therapeutic enoxaparin following venous thromboembolism in pregnancy and the clinical relevance of anti‐Xa monitoring.
Value of a structured participant evaluation questionnaire in the development of a surgical education program
Authors: Hammond Ian , Taylor John , McMenamin Paul
Published: December 2004

Objective: To describe how the summative evaluation of attitudes and perceptions of participants at a surgical skills workshop influences and contributes to the development of the workshop.

Materials and methods: One hundred participants from 11 workshops were invited to complete a structured scored anonymous questionnaire with 18 statements, at the end of each workshop. Space was provided for free comment next to each statement. The questionnaire covered all aspects of the workshop including the practical modules, learning materials, organisation, facilitators and the relevance of the workshop to their needs. Ninety‐eight of the 100 participants returned the questionnaire and this analysis is based on their responses.

Results: All respondents considered the workshop content, structure and facilities enabled the educational objectives to be achieved. The scored responses to the structured statements helped to determine the degree of satisfaction with the workshop domains, but did not give direction for change. The informal ‘free’ comments gave insight as to how improvements could be achieved in specific domains. Numerous changes suggested by participants have been included in subsequent workshops.

Conclusion: Summative evaluation of an educational program is important to determine participant satisfaction and to determine areas needing improvement. Structured scored questionnaires are helpful in determining levels of satisfaction with the various domains of the program. Informal written comments allow insight into specific areas requiring improvement and may provide guidance as to how improvement can be achieved. Space for such comment should be encouraged in any program evaluation questionnaire.
National audit of women with abnormal cervical smears in New Zealand
Authors: Sarfati Diana , Cox Brian , Jones Ronald W. , Sopoaga Tai , Rimene Christine , Paul Charlotte
Published: December 2004

Objective: To evaluate the follow‐up of women with abnormal cervical smears identified by the National Cervical Screening Programme (NCSP) in New Zealand.

Design: Survey and clinical audit.

Setting: The study took place in New Zealand.

Population: The population included women aged 20–69 years enrolled on the NCSP with first abnormal smear recorded in 1999.

Methods: Participants were interviewed, and clinical data collected from the NCSP‐register, and from clinicians.

Main outcome measures and results: The overall response rate was 57%. The proportions of women whose initial assessment, treatment or follow‐up fell outside recommended times were between 17 and 35%. Of women with high‐grade smears, 72% underwent a treatment procedure. Of these, 91% were excision biopsies, 6% hysterectomies and 4% ablation procedures. Approximately 10% of women had persistent or recurrent abnormalities at 6 and 12 months after treatment.

Conclusions: Overall, results were largely reassuring, but limited by the low response rate. Most women were managed within current clinical guidelines. Areas requiring improvement were identified, in particular in relation to longer than recommended waiting times for assessment and treatment.
Effect of a ginger extract on pregnancy‐induced nausea: A randomised controlled trial
Authors: Willetts Karen E. , Ekangaki Abie , Eden John A
Published: December 2004

Objective: To investigate the effect of a ginger extract (EV.EXT35) on the symptoms of morning sickness.

Design: Double‐blind randomised placebo‐controlled trial.

Setting: A tertiary metropolitan teaching hospital, March 1999–November 1999.

Participants: The participants included 120 women less than 20 weeks pregnant, who had experienced morning sickness daily for at least a week and had had no relief of symptoms through dietary changes.

Intervention: Random allocation of 125 mg ginger extract (EV.EXT35; equivalent to 1.5 g of dried ginger) or placebo given four times per day for 4 days.

Main outcome measures: Nausea, vomiting and retching as measured by the Rhodes Index of Nausea, Vomiting and Retching.

Results: The nausea experience score was significantly less for the ginger extract group relative to the placebo group after the first day of treatment and this difference was present for each treatment day. Retching was also reduced by the ginger extract although to a lesser extent. No significant effect was observed on vomiting. Follow‐up of the pregnancies revealed normal ranges of birthweight, gestational age, Apgar scores and frequencies of congenital abnormalities when the study group infants were compared to the general population of infants born at the Royal Hospital for Women for the year 1999–2000.

Conclusion: Ginger can be considered as a useful treatment option for women suffering from morning sickness.
Aetiology and prevalence of lower limb lymphoedema following treatment for gynaecological cancer
Authors: Ryan Mary , Stainton M. Colleen , Slaytor Emma K. , Jaconelli Carmel , Watts Sally , MacKenzie Patricia
Published: December 2004

Objective: To determine the prevalence and incidence of lower limb lymphoedema (LLL) in a cohort of women who had treatment for gynaecological cancer between May 1995 and April 2000.

Design: A retrospective survey.

Setting: The study took place at an urban referral centre in an Australian tertiary referral women's hospital.

Sample: The data collection was based on 66% of 743 women on the database of the Gynaecological Cancer Centre.

Methods: Interviews and assessments were conducted to determine the status of lower limbs; medical records were reviewed for age, weight, site and type of cancer and treatment.

Main outcome measures: Leg swelling, diagnosed lower limb lymphoedema, no swelling of the legs and type of surgery were determined as the main outcome measures.

Results and conclusions: The diagnosis of lower limb lymphoedema was made in 18% of the total sample: 53% of these were diagnosed within 3 months of treatment, a further 18% within 6 months, 13% within 12 months and the remaining 16% up to 5 years following treatment. Women most at risk for developing LLL were those who had treatment for vulvar cancer with removal of lymph nodes and follow up radiotherapy. For this subsample, the prevalence was 47%. The finding that LLL occurs within the first year is earlier than hitherto generally believed. It is therefore imperative for all health professionals to include care and assessment of the legs particularly during the immediate pre‐ and postoperative period.
Survey of the knowledge, attitudes and experiences of Western Australian women in relation to prenatal screening and diagnostic procedures
Authors: Rostant Kristie , Steed Lyndall , O'Leary Peter
Published: December 2004

Objective: To determine the knowledge, attitudes and experiences of women in Western Australia (WA) regarding prenatal procedures.

Design: A self‐administered mail survey.

Sample: The survey was sent to all women who gave birth during July 2001 (n = 1801). The participants were 633 women aged 15–45.

Results: The mean total knowledge score was 16 out of a possible 26 (62%). The average score for all three attitude factors was four, ‘agree’, on a Likert scale of five. Women who reported they had private health insurance and women in the metropolitan area had significantly higher knowledge levels and had significantly more positive attitudes towards the adequacy of information. Those who did not have a screening test had less positive attitudes towards the value of the tests and had less confidence in results. Those with higher educational attainments had higher knowledge and less positive attitudes towards the value of the tests.

Conclusions: Women felt positive towards the value of the tests, were confident in their results and felt positive towards the adequacy of information; however, their understanding of this information seems to be poor. It seems that the choice to undergo testing is not well informed. It was clear women need more support, information, explanations, and more time to absorb the information.
Is amniotic fluid volume status predictive of fetal acidosis at delivery?
Authors: Magann Everett F. , Chauhan Suneet P. , Martin James N.
Published: December 2004

Objective: To ascertain if dye‐determined amniotic fluid volume just prior to delivery correlates with fetal acidosis at delivery.

Design: The present was a prospective observational study.

Setting: The study took place at the University of Mississippi Medical Center, Jackson MS, USA.

Population: The population included 100 unlaboured women undergoing an amniocentesis for the assessment of fetal lung maturity before an elective Caesarean delivery between January 1997 and December 2000.

Main outcomes measured: The amniotic fluid volume was estimated by ultrasound measurement and quantified by dye‐determined methodology immediately prior to Caesarean delivery. Umbilical cord artery pH was collected at the time of Caesarean delivery.

Results: The predictive accuracy of an amniotic fluid index ≤ versus >5 to identify an umbilical artery pH of <7.20 had a sensitivity of 0%, a specificity of 84%, and a likelihood ratio of zero. None of the dye‐determined low amniotic fluid volumes were identified using the single deepest pocket technique. Dye‐determined low, normal, and high amniotic fluid volume groups contained a similar number of fetuses with umbilical cord arterial pH <7.20 (P = 0.371), <7.10 (P = 0.460), and <7.00 (P = 0.614). Receiver‐operating characteristic curves could not identify any amniotic fluid index from 0 to 18, single deepest pocket from 0 to 12, or dye‐determined amniotic fluid volume 100–1900 mL to differentiate between the two newborns with an umbilical cord artery pH <7 from 98 babies with cord pH ≥7.0.

Conclusions: Neither ultrasound estimates nor dye‐determined amniotic fluid volumes are predictive of a low umbilical artery pH at delivery.
Quest for patient safety in a challenging environment
Authors: Court Denys
Published: December 2004

We are unable to guarantee our patients that the care we provide will do no harm. Up to 16% of hospital admissions will be associated with an adverse event, approximately half of which are preventable. It is a clinical imperative that we must strive to improve patient safety by improving the systems in which we work, such that they support us in providing better and safer care. For this to occur, an environment must develop where clinicians feel safe to report and allow analysis of adverse events and near misses. The greatest inhibitor of a reporting culture is the prevailing legal climate with its associated blame culture. A new social contract is required whereby systems analysis will predominate over the previous presumption that individual clinicians must be held responsible for each and every adverse outcome. Individual responsibility should be reserved for events where it becomes evident during the course of systems analysis that an individual's behaviour is truly blameworthy.