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Mark D Kilby

Publications and source records attributed to Mark D Kilby.

At least 19 recordsLinked to original sources
PubMed2026

Paediatric outcomes after maternal nipocalimab for haemolytic disease of the fetus and newborn: an open-label, single-arm study.

OBJECTIVES: To describe haemolytic disease outcomes, growth, neurodevelopment and health-related quality of life (HRQoL) through 24 months of life in infants exposed to nipocalimab in pregnancies at high risk of early-onset severe haemolytic disease of the fetus and newborn (EOS-HDFN). DESIGN: A multicentre, open-label, single-arm trial. SETTING: Centres with expertise in HDFN management. PATIENTS: Pregnant individuals with previous EOS-HDFN and maternal anti-D titres &#x2265;32&#x2009;or anti-K titres &#x2265;4. INTERVENTIONS: Weekly nipocalimab (30 and/or 45 mg/kg) from 14 to 35&#x2009;gestational weeks. MAIN OUTCOME MEASURES: Infants' cord-blood alloantibody titres at birth, HDFN management, growth through 6 months, neurodevelopment (caregiver-reported Ages and Stages Questionnaire, third edition (ASQ-3)) and HRQoL assessments through 24 months of life. RESULTS: Of 13 pregnancies, 12 resulted in live births; one fetal loss occurred due to intrauterine transfusion (IUT) complications. A single simple transfusion was administered in one of seven infants delivered after a maternal nipocalimab course without IUTs, where cord blood alloantibody titres were <8. Multiple transfusions (one to seven&#x2009;simple transfusions/infant; one exchange transfusion) were administered to five infants delivered after early nipocalimab discontinuation and IUTs, with cord-blood alloantibody titres ranging from 512 to 32 768. No unusual growth patterns were observed through 6 months. No neurodevelopmental delays were identified through 24 months of life, with mean ASQ-3 domain scores within normal ranges. HRQoL outcomes were positive across physical, emotional, social and cognitive functioning. CONCLUSIONS: Maternal nipocalimab in pregnancies at high risk of EOS-HDFN may reduce adverse neonatal outcomes correlating with low cord-blood alloantibody titres, without affecting growth through 6 months, neurodevelopment or HRQoL through 24 months of life. TRIAL REGISTRATION NUMBER: NCT03842189.

Child Health↗
PubMed2006

Functional HY-specific CD8+ T cells are found in a high proportion of women following pregnancy with a male fetus.

Recent studies have demonstrated that fetal cells can be detected in the maternal circulation during virtually all human pregnancies. These fetal cells can engraft and may be isolated for many decades after pregnancy, leading to a state that may be maintained by the passage of pregnancy-associated progenitor cells. The clinical consequences of fetal cell microchimerism are unclear but may be potentially detrimental or valuable to the mother. One possibility is the generation of an alloreactive immune response by the mother to antigens expressed by the fetus; for example, the HY protein encoded by the Y chromosome. To test this we have screened a cohort of women with a range of parity histories within 8 yr of their last pregnancy for the presence of an HY-specific CD8+ T-cell response. Fluorescent HLA-peptide (HY) tetramers were used to stain short-term T-cell cultures from these women for analysis by flow cytometry. Responses were detected in 37% of women with a history of pregnancies that produced males, and this value rose to 50% in women with two or more pregnancies that produced males. HY-specific CD8+ T cells also could be detected directly in the peripheral blood of women with a history of at least two pregnancies that produced males. These HY-specific CD8+ T cells produced interferon gamma (IFNG) following peptide stimulation, demonstrating their functional capacity. In conclusion, our data indicate that alloreactive CD8+ T cells are generated frequently following normal pregnancy and retain functional capability for years following pregnancy.

Adolescent↗
PubMed2006

Effects of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on cytokine production by human decidual cells.

The active form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) is a potent immunomodulatory seco-steroid. We have demonstrated that several components of vitamin D metabolism and signaling are strongly expressed in human uterine decidua from first trimester pregnancies, suggesting that locally produced 1,25(OH)(2)D(3) may exert immunosuppressive effects during early stages of gestation. To investigate this further, we used primary cultures of human decidual cells from first and third trimester pregnancies to demonstrate expression and activity of the enzyme that catalyzes synthesis of 1,25(OH)(2)D(3), 1alpha-hydroxylase (CYP27B1). Synthesis of 1,25(OH)(2)D(3) was higher in first trimester decidual cells (41 +/- 11.8 fmoles/h/mg protein) than in third trimester cells (8 +/- 4.4 fmoles/h/mg protein; P < 0.05). Purification of decidual cells followed by quantitative RT-PCR analysis showed that CYP27B1 was expressed by both CD10(+VE) stromal-enriched and CD10(-VE) stromal-depleted cells, with higher levels of mRNA in first trimester pregnancies. Expression of CYP27B1 correlated with TLR4 and IDO. Functional responses to 1,25(OH)(2)D(3) were studied using CD56(+VE) natural killer (NK) cells isolated from first trimester decidua. Decidual NK cells treated with 1,25(OH)(2)D(3) or precursor 25-hydroxyvitamin D(3) (25OHD(3)) for 28 h showed decreased synthesis of cytokines, such as granulocyte-macrophage colony stimulating factor 2 (CSF2), tumor necrosis factor, and interleukin 6, but increased expression of mRNA for the antimicrobial peptide cathelicidin antimicrobial peptide. These data indicate that human decidual cells are able to synthesize active 1,25(OH)(2)D(3), particularly in early gestation, and this may act in an autocrine/paracrine fashion to regulate both acquired and innate immune responses at the fetal-maternal interface.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2006

Do screening-preventative interventions in asymptomatic pregnancies reduce the risk of preterm delivery--a critical appraisal of the literature.

Recent research has suggested that women who experience preterm delivery (PTD) may be identified earlier in pregnancy and before onset of symptoms. Interventions commenced at this earlier asymptomatic stage may offer an opportunity to prevent PTD or lengthen gestation sufficiently to reduce adverse perinatal outcome. Our objective was to examine the evidence that supports or refutes this approach to preventing PTD. We therefore conducted a systematic search and critical appraisal of the identified literature. We found evidence that introducing screening-preventative strategies for asymptomatic pregnancies may reduce the rate of PTD. Evidence for screening and selective treatment exists for: asymptomatic bacteriuria; bacterial vaginosis in low-risk population groups; elective cervical cerclage in high-risk pregnancies; indicated cervical cerclage in women with short cervical length on ultrasound; prophylactic progesterone supplementation in high-risk pregnancies, and smoking cessation. However, for most other strategies, such as increased antenatal attendance, or routine administration of prophylactic micronutrients, the evidence is inconsistent and conflicting. Information on neonatal outcomes apart from PTD (such as serious neonatal morbidity and mortality) was found to be lacking in most studies. It was therefore not possible to establish whether preventing PTD or prolonging gestation would correlate to improved perinatal outcome, and this lessened the potential clinical usefulness of any proposed preventative strategy. No studies were found that evaluated the effectiveness of combining screening-preventative strategies. The review concludes with a suggested an antenatal management plan designed to prevent PTD based on current practice and the evidence presented in this article.

Anti-Infective Agents↗
PubMed2006

An audit of outcome in intravascular transfusions using the intrahepatic portion of the fetal umbilical vein compared to cordocentesis.

INTRODUCTION: Maternal red cell alloimmunization is a potential cause of perinatal morbidity and mortality. The outcome of severe disease has been transformed by the use of in-utero and particularly, fetal intravascular transfusion. In the majority of instances this is performed by cordocentesis. However, this cohort study represents the experience in a large tertiary referral centre in performing fetal intravascular transfusions via the intrahepatic vein (IHV). METHODS: Over an 8-year period, 1997-2004, 221 in-utero transfusions (IUT) were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age of the cohort was 31 years (range 19-43). The median gestation at initial IUT was 25 weeks (interquartile range (IQR) 23-29 weeks). RESULTS: A median number of three IUT were performed in each fetus (IQR 2-5) with a median haemoglobin at first fetal blood sampling of 7.3 g% (IQR 4.6-8.8 g%) (73% < or =5 SD and 27% < or =2 SD). Of the total intravascular transfusions, 170 were performed via the IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%). There were 'transient' bradycardias complicating 4.1% of all transfusions and amniorrhexis following 1.4%. 92% of babies were live born at a median gestation of 34 weeks (range 21-38) with a birth weight centile of 50 (range 3-90). There was no significant difference in intravascular transfusion complication rate when the procedure was performed via the IHV (7.6%) as compared to cord root puncture (3.0%) (Fisher's exact test, p < 0.47). CONCLUSION: IUT performed by fetal IHV puncture is safe and carries no excess morbidity when performed for severe rhesus disease.

Adult↗
PubMed2005

Maternal nutrient deprivation induces sex-specific changes in thyroid hormone receptor and deiodinase expression in the fetal guinea pig brain.

Thyroid hormone deprivation during fetal life has been implicated in neurodevelopmental morbidity. In humans, poor growth in utero is also associated with fetal hypothyroxinaemia. In guinea pigs, a short period (48 h) of maternal nutrient deprivation at gestational day (gd) 50 results in fetuses with hypothyroxinaemia and increased brain/body weight ratios. Thyroid hormone action is mediated by nuclear thyroid hormone receptors (TRs) and is dependent upon the prereceptor regulation of supply of triiodothyronine (T3) by deiodinase enzymes. Examination of fetal guinea pig brains using in situ hybridization demonstrated widespread expression of mRNAs encoding TRalpha1, alpha2 and beta1, with regional colocalization of deiodinase type 2 (D2) mRNA in the developing forebrain, limbic structures, brainstem and cerebellum at gd52. With maternal nutrient deprivation, TRalpha1 and beta1 mRNA expression was significantly increased in the male, but decreased in the female fetal hippocampus and cerebellum and other areas showing high TR expression under euthyroid conditions. Maternal nutrient deprivation resulted in elevated D2 mRNA expression in males and females. Deiodinase type 3 (D3) mRNA expression was confined to the shell of the nucleus accumbens, the posterior amygdalohippocampal area, brainstem and cerebellum, and did not change with maternal nutrient deprivation. In conclusion, maternal nutrient deprivation resulted in sex-specific changes in TR mRNA expression and a generalized increase in D2 mRNAs within the fetal brain. These changes may represent a protective mechanism to maintain appropriate thyroid hormone action in the face of fetal hypothyroxinaemia in order to optimize brain development.

Animals↗
PubMed2005

Urine protein estimation in hypertensive pregnancy: which thresholds and laboratory assay best predict clinical outcome?

OBJECTIVE: To determine what threshold for proteinuria could best predict clinical outcome and whether this threshold could be applied universally to any biochemical assay. DESIGN: A prospective observational study of hypertensive pregnancies referred for further assessment after in a UK University hospital (n=197). Twenty-four hour urine protein was measured by two different assays [benzethonium chloride assay (BCA) and Bradford assay]. The differences between the two assays were calculated from Receiver Operating Characteristic (ROC) curves. Commonly used thresholds for defining preeclampsia (0.3 and 0.5 g/24 hours) were explored for both assays for the prediction of adverse clinical outcomes (severe hypertension, Birthweight<10th percentile, preterm delivery, and a composite biochemical/haematological derangement). RESULTS: The two assays are not equivalent. The prevalence of>300 mg/24 hour proteinuria and, hence, the prevalence of preeclampsia differed between the two assays. ROC curve analysis demonstrates that the two assays are similar in terms of overall performance as predictive tests. However the threshold of 300 mg/24 hours performs poorly as a predictor of clinical risk. Likelihood ratios (LR) for the BCA at the 300 mg/L threshold for each clinical outcome do not achieve statistical significance. At the 500 mg/L threshold, the LR+for the BCA assay does achieve statistical significance for severe hypertension (LR+:1.51 95% CI 0.99-2.28) and for birthweight<10th percentile (LR+:1.72 95% CI 1.11-2.66). For the Bradford assay at the 300 mg/24 hour threshold, the LR+does achieve statistical significance for birthweight<10th percentile (LR+:1.71 95% CI 1.41-4.31). However, at the 500 mg/24 hour threshold, the LR+is significant for severe hypertension (LR+:2.15 95% CI 1.07-4.34), birthweight<10th percentile (LR+:2.79 95% CI 1.4-5.54) and biochemical disease (LR+:2.47 95% CI 1.22-5.01). CONCLUSIONS: This study suggests that thresholds for proteinuria need to be higher (possibly>or=0.5 g/24 hours) and there is the need for a "gold standard" proteinuria assay against which all other measures of quantification can be assessed.

Adult↗
PubMed2005

Are isolated facial cleft lip and palate associated with increased perinatal mortality? A cohort study from the West Midlands Region, 1995-1997.

OBJECTIVE: To investigate the association between cleft lip and/or palate and perinatal mortality. METHODS: A retrospective review was performed of cases of cleft lip/palate born to West Midlands residents from 1995 to 1997. Perinatal mortality for identified cases was compared with all births from 1995 to 1997. RESULTS: 347 cases of cleft lip and/or cleft palate were delivered from 1995 to 1997. Thirty-six pregnancies were terminated due to parental wishes--2 were registerable births. There were 310 spontaneous registerable births (stillbirths/livebirths) with cleft lip and/or palate and 1 further late fetal loss. In 220 (70.5%), the lesion was isolated. Of these, there were 7 perinatal deaths, 5 had post mortems and no additional anomalies were identified. In 92 (29.5%) cases other abnormalities were identified. The overall perinatal mortality rate (PNMR) in the West Midlands, was 10.0/1000 total births. The overall PNMR for babies with facial clefts was 89.7/1000 total births. The PNMR for those with associated anomalies was 228.3/1000 live/still births. The PNMR for isolated facial clefts was 31.8/1000 live/still births, significantly higher than the background population (OR 3.3, 95% CI: 1.5-7.0). CONCLUSION: Consideration should be given to screening the fetus at 20-24 weeks for facial deformity. This has implications for detection both of fetal anomalies and of a population at risk for adverse outcome.

Cleft Lip↗
PubMed2005

Mapping the theories of preeclampsia: the role of homocysteine.

OBJECTIVE: We conducted a systematic review to examine the hypothesized mechanism through which homocysteine could lead to preeclampsia. DATA SOURCES: We searched MEDLINE, EMBASE, BIOSIS, SciSearch, and bibliographies of primary and review articles, and we contacted experts. METHODS OF STUDY SELECTION: Of the 25 relevant primary articles, 8 studies measured total serum homocysteine concentrations before the clinical onset of preeclampsia (1,876 women), whereas 17 measured it afterward (1,773 women). Meta-analytic techniques were used to examine consistency, strength, temporality, dose-response, and plausibility of the disease mechanisms implicating folate, vitamin B(6), vitamin B(12), genetic polymorphisms, oxidative stress, and endothelial dysfunction in the pathway linking hyperhomocysteinemia to preeclampsia. TABULATION, INTEGRATION, AND RESULTS: Overall, there were higher serum homocysteine concentrations among pregnant women with preeclampsia than among those with uncomplicated pregnancies, but the results were heterogeneous (P = .12; I(2) = 38.8%). Among studies with temporality, the size of association was smaller than that among those without (weighted mean difference 0.68 mumol/L versus 3.36 mumol/L; P < .006). There was no dose-response relationship between homocysteine concentration and severity of preeclampsia. The mechanisms underlying hyperhomocysteinemia (folate and vitamin B(12) deficiency and genetic polymorphisms) were not found to be plausible, but markers of oxidative stress and endothelial dysfunction were higher in hyperhomocysteinemia. CONCLUSION: Homocysteine concentrations are slightly increased in normotensive pregnancies that later develop preeclampsia and are considerably increased once preeclampsia is established. However, because of a lack of consistency in data, dose-response relationship, and biologic plausibility, the observed association cannot be considered causal from the current literature.

Adult↗
PubMed2005

Contemporary treatments for twin-twin transfusion syndrome.

OBJECTIVE: To undertake a systematic review to determine the effects of fetal therapy interventions compared with amniodrainage for twin-twin transfusion syndrome on perinatal survival and outcome. METHODS: Searching MEDLINE (1966-2004), EMBASE (1988-2004), a hand search of specialist journals, and the Cochrane library (2004:2) identified relevant articles. Studies were selected if the effects of fetal therapeutic interventions for twin-twin transfusion syndrome (laser photocoagulation, serial amnioreduction, septostomy, and selective feticide) on perinatal survival, complications, and morbidity were compared. Study selection, quality assessment, and data abstraction were performed independently and in duplicate. RESULTS: Only 3 controlled observational studies (comparing treatment in 306 twins) and 1 randomized controlled trial (of 142 twins) were identified. Laser photocoagulation significantly improved perinatal survival of at least 1 fetus and reduced neurologic morbidity compared with serial amnioreduction. No such differences were observed in the comparison of serial amnioreduction with septostomy. CONCLUSION: In a systematic review of observational and randomized controlled studies, laser photocoagulation of chorionic plate vessels at the intertwin membrane seems to be more effective than serial amnioreduction in the treatment of twin-twin transfusion syndrome with less associated perinatal morbidity and mortality. However, septostomy and selective feticide have not been robustly evaluated.

Female↗
PubMed2005

Optimal bedside urinalysis for the detection of proteinuria in hypertensive pregnancy: a study of diagnostic accuracy.

OBJECTIVE: To compare semi-quantitative visual and automated methods of urine testing with fully quantitative point of care urinalysis for the detection of significant proteinuria (0.3 g/24 hours) in pregnancy complicated by hypertension. DESIGN: A prospective comparative study. SETTING: A large teaching maternity hospital. SAMPLE: One hundred and seventy-one pregnant women referred to the obstetric day-care unit for assessment of newly arisen hypertension. METHODS: Early morning urine specimens were tested with four dipstick techniques (Multistix 8SG visual and automated and microalbumin/creatinine ratio visual and automated; Bayer, Elkhart, USA) as well as a fully quantitative measure of the microalbumin creatinine ratio with the DCA 2000 (a point of care assay for albumin; Bayer). These results were compared to a 24-hour urine protein measurement and measures of diagnostic accuracy/prediction are reported. MAIN OUTCOME MEASURES: Significant proteinuria (> or =0.3 g/24 hours) measured by laboratory assay. RESULTS: Automated dipstick urinalysis using the Clinitek 50 has significantly better predictive values for significant proteinuria (LR(+) 4.27, 95% CI 2.78 to 6.56; LR(-) 0.225, 95% CI 0.14 to 0.37) than conventional visual dipstick urinalysis (LR(+) 2.27, 95% CI 1.47 to 3.51; LR(-) 0.635, 95% CI 0.49 to 0.82). Dipstick microalbumin/creatinine ratio testing did not improve overall detection rates with automated or visual testing. Fully quantitative point of care measurement of albumin/creatinine ratio (ACR) was significantly better than any dipstick technique (LR(+) 14.6, 95% CI 6.74 to 31.8; LR(-) 0.069, 95% CI 0.030 to 0.16). CONCLUSIONS: This study confirms that in pregnancy automated dipstick urinalysis is a more accurate screening test for the detection of proteinuria than visual testing. ACR testing can offer a significant improvement over conventional urinalysis if a fully quantitative method of detection is employed that uses pregnancy-specific thresholds. Dipstick assessment of ACR does not improve the detection rate of significant proteinuria.

Adult↗
PubMed2004

A comparative study of prenatal ultrasound findings and post-mortem examination in a tertiary referral centre.

This retrospective study compares the findings of prenatal ultrasound, performed in a tertiary fetal medicine centre, with the results of post-mortem examination in pregnancies complicated by suspected fetal abnormality that results in fetal loss. The study was carried out over a year at a teaching hospital, Fetal Medicine Centre and Regional Centre for Perinatal Pathology. Results were directly compared and the level of agreement between the ultrasound and post-mortem findings described. These were classified as having complete agreement; major agreement or major disagreement. The group of cases with major agreement between findings was further divided into those with significant, or minor, additional findings at post-mortem examination. Over the 12-month period, 153 ultrasound cases were identified, of which 47 were also examined by autopsy and were thus suitable for comparison in this study (30.7%). Complete agreement between ultrasound and post-mortem findings was found in 22 cases (46.8%). In 24 cases (51.1%), major agreement between ultrasound and post-mortem findings was seen. Of these, 11 had minor additional findings at post-mortem examination and 13 were found to have significant additional findings at post-mortem (27.7%), adding to the eventual diagnosis. In 12.8% of cases, post-mortem examination provided a definitive diagnosis. Only in one case was there complete discordance in the findings of the ultrasound examination and the autopsy (2.1%). No major disagreement between ultrasound and post-mortem findings was seen in 98% of cases. This study confirms the accuracy of prenatal ultrasound diagnosis in specialist centres, whilst emphasising the continuing importance of post-mortem examination in cases of fetal malformation to refine and, in some cases, define the diagnosis.

Abnormalities, Multiple↗
PubMed2004

Vitamin D and placental-decidual function.

The active form of vitamin D (1,25-dihydroxyvitamin D(3), 1,25[OH](2)D(3)) has well-established effects on bone metabolism and mineral homeostasis. However, recently it has become clear that 1,25(OH)(2)D(3) has potent antiproliferative and immunomodulatory actions that are not immediately linked to its role as a skeletal regulator. Both the nuclear receptor for 1,25(OH)(2)D(3) (vitamin D receptor, VDR) and the vitamin D-activating enzyme 1alpha-hydroxylase are expressed in a wide variety of nonclassic tissues, highlighting the potential for local autocrine-paracrine responses rather than traditional endocrine effects. Prominent among the tissues that express 1alpha-hydroxylase is the placenta-decidua, and this has raised important questions concerning the potential role of locally generated 1,25(OH)(2)D(3) as a modulator of fetal-placental development and function. When bound to the VDR, 1,25(OH)(2)D(3) regulates key target genes associated with implantation, such as HOXA10, whereas the potent immunosuppressive effects of 1,25(OH)(2)D(3) suggest a role in implantation tolerance. These observations are further supported by data from our group showing increased expression of 1alpha-hydroxylase and VDR in first-trimester trophoblast and decidua from human pregnancies. Studies by other groups have reported abnormal expression of 1alpha-hydroxylase in preeclamptic pregnancies, revealing a potential role for 1,25(OH)(2)D(3) as a regulator of placentation. The effect of vitamin D on reproduction has been further endorsed by murine gene knockout models for 1alpha-hydroxylase and VDR, both of which are infertile. These observations and others are discussed in this article in which we postulate an active role for 1,25(OH)(2)D(3) in placenta-decidua. In particular, we describe how induction of the vitamin D-activating enzyme 1alpha-hydroxylase in early gestation might provide a mechanism by which environmental or dietary vitamin D can influence fetal-placental development.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2004

Increased expression of 25-hydroxyvitamin D-1alpha-hydroxylase in dysgerminomas: a novel form of humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy (HHM) is a common paraneoplastic disorder usually associated with increased synthesis of parathyroid hormone-related peptide (PTHrP). Unlike non-cancer forms of hypercalcemia, HHM does not routinely involve increased circulating levels of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Dysgerminomas are a notable exception to this rule, previous reports having described hypercalcemia with elevated serum 1,25(OH)2D3. To investigate the etiology of this form of HHM we have characterized expression and activity of the enzyme that catalyzes synthesis of 1,25(OH)2D3, 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-hydroxylase), in a collection of 12 dysgerminomas. RT-PCR analyses indicated that mRNA for 1alpha-hydroxylase was increased 222-fold in dysgerminomas compared to non-tumor ovarian tissue. Parallel enzyme assays in tissue homogenates showed that dysgerminomas produced fivefold higher levels of 1,25(OH)2D3 compared to normal ovarian tissue. Immunolocalization studies indicated that 1alpha-hydroxylase was expressed by both tumor cells and by macrophages within the inflammatory cell infiltrate associated with dysgerminomas. The immunological nature of the increased 1,25(OH)2D3 production observed in dysgerminomas was further emphasized by correlation between expression of 1alpha-hydroxylase and the endotoxin recognition factors CD14 and toll-like receptor 4 (TLR4). These data suggest that inflammatory mechanisms associated with dysgerminomas are the underlying cause of the increased expression and activity of 1alpha-hydroxylase associated with these tumors. We further postulate that this autocrine/paracrine action of 1alpha-hydroxylase may lead to increased circulating levels of 1,25(OH)2D3 and a form of HHM which is distinct from that seen with PTHrP-secreting tumors.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed2004

Accuracy of urinalysis dipstick techniques in predicting significant proteinuria in pregnancy.

OBJECTIVE: To estimate the accuracy of point-of-care dipstick urinalysis in predicting significant proteinuria in pregnancy. DATA SOURCES: Literature from 1970 to February 2002 was identified via 1). general bibliographic databases, that is, MEDLINE and EMBASE, 2). Cochrane Library and relevant specialist register of the Cochrane Collaboration, and 3). checking the reference lists of known primary and review articles. METHODS OF STUDY SELECTION: Studies were selected if the accuracy of dipstick urinalysis techniques in predicting total protein excretion was estimated compared with a reference standard (laboratory estimation of protein excretion). The tests included visually read color-change dipsticks and automated dipstick urinalysis. Study selection, quality assessment, and data abstraction were performed independently and in duplicate. TABULATION, INTEGRATION, AND RESULTS: Data from selected studies were abstracted as 2 x 2 tables comparing the test result with the reference standard. Test accuracy was expressed as likelihood ratios. Summary likelihood ratios were generated as measures of diagnostic accuracy to determine posttest probabilities. The electronic search produced 1543 citations. After independent review of published articles, a total of 34 articles was obtained for further scrutiny, and 7 studies were considered eligible for inclusion in the review. The 6 studies evaluating visual dipstick urinalysis produced a pooled positive likelihood ratio of 3.48 (95% confidence interval 1.66, 7.27) and a pooled negative likelihood ratio of 0.6 (95% confidence interval 0.45, 0.8) for predicting 300 mg/24-hour proteinuria at the 1+ or greater threshold. CONCLUSION: The accuracy of dipstick urinalysis with a 1+ threshold in the prediction of significant proteinuria is poor and therefore of limited usefulness to the clinician. Accuracy may be improved at higher thresholds (greater than 1+ proteinuria), but available data are sparse and of poor methodological quality. Therefore, it is not possible to make meaningful inferences about accuracy at higher urine dipstick thresholds. There is an urgent need for research in this area of common obstetric practice.

Female↗
PubMed2004

Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset.

Summary CD4+ CD25+ T regulatory cells (TReg), suppress antigen-specific immune responses and are important for allograft tolerance. During pregnancy the mother tolerates an allograft expressing paternal antigens (the fetus) requiring substantial changes in immune regulation over a programmed period of time. We analysed whether immune-suppressive TReg cells were altered during pregnancy and therefore might play a part in this tolerant state. The presence of TReg cells was assessed in the blood of 25 non-pregnant, 63 pregnant and seven postnatal healthy women by flow cytometry. We observed an increase in circulating TReg cells during early pregnancy, peaking during the second trimester and then a decline postpartum. Isolated CD25+ CD4+ cells expressed FoxP3 messenger RNA, a marker of TReg cells, and suppressed proliferative responses of autologous CD4+ CD25- T cells to allogeneic dendritic cells. These data support the concept that normal pregnancy is associated with an elevation in the number of TReg cells which may be important in maintaining materno-fetal tolerance.

Adult↗