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Biomedical subjects

Stuart Ward

Publications and source records attributed to Stuart Ward.

9 recordsLinked to original sources
PubMed2005

Elevated IGFBP-1 cause high bone turnover in growth-restricted monochorionic twins with discordant birth weight.

OBJECTIVE: To test the hypothesis that low birth weight twins have a higher risk of osteoportotic fracture in later life, we investigated the association between fetal IGF axis and type-1 collagen markers of bone turnover in monochorionic (MC) twins with or without discordant birth weight of >or=20%. METHODS: Maternal and cord bloods were collected from gestational age matched MC twins of discordant (n = 16) and concordant birth weights (n = 16). The samples were assayed for cross linked carboxyl terminal telopeptide (ICTP, a marker of bone resorption) and pro-peptide (PICP, a marker of bone formation) of type I collagen, IGF-1, and IGFBP-1 by radio-immunoassay. RESULTS: The growth-restricted twins (IUGR) of discordant group had higher fetal IGFBP-1 and ICTP (P < 0.001) levels, while PICP (P < 0.001) was lower than the co-twins with normal weight (AGA). In contrast, cord blood levels of IGF-1, IGFBP-1, ICTP, and PICP in concordant twin pairs were comparable to AGA twins. The concordant and AGA twins had a positive correlation between ICTP and PICP levels (y = 23x - 711; r = 0.84; P < 0.001; n = 48) but no such association was found in IUGR twins. Instead, IGFBP-1 levels in IUGR twins had a negative association with PICP (r = 0.81; P < 0.001; n = 16) and a positive correlation with ICTP (r- = 0.51; P < 0.05; n = 16). No such association was found in concordant and AGA twins. CONCLUSION: These data suggest that growth-restricted twins had high bone turnover, due to elevated IGFBP-1. This association seems to be independent of maternal and genetic factors.

Adolescent↗
PubMed2005

Identifying and mapping surface amorphous domains.

PURPOSE: Undesirable amorphous material generation during formulation is implicated in a growing number of pharmaceutical problems. Due to the importance of interfacial properties in many drug delivery systems, it seems that surface amorphous material is particularly significant. Consequently, this study investigates a range of methods capable of detecting and mapping surface amorphous material. METHODS: A micron-sized localized surface domain of amorphous sorbitol is generated using a novel localized heating method. The domain is subsequently investigated using atomic force microscopy (AFM) imaging, nanomechanical measurements, and Raman microscopy 3-D profiling. RESULTS: AFM phase and height images reveal nanoscale-order variations within both crystalline and amorphous sorbitol domains. Nanomechanical measurements are able to quantitatively distinguish the amorphous and crystalline domains through local Young's modulus measurements. Raman microscopy also distinguishes the amorphous and crystalline sorbitol through variations in peak width. This is shown to allow mapping of the 3-D distribution of the amorphous phase and is hence complementary to the more surface sensitive AFM measurements. CONCLUSIONS: AFM and Raman microscopy map the distribution of amorphous material at the surface of a sorbitol crystal with submicron spatial resolution, demonstrating surface analysis methods for characterizing semicrystalline solids generated during pharmaceutical processing.

Chemistry, Pharmaceutical↗
PubMed2005

Prevalence of cranial scan abnormalities in preterm twins in relation to chorionicity and discordant birth weight.

OBJECTIVE: The purpose of this study was to determine the incidence of ultrasonographically detected cerebral white matter lesions (WMLs) in preterm twins at birth in relation to chorionicity, discordant weight and twin-twin transfusion syndrome (TTTS). METHODS: In this retrospective study, perinatal, neonatal, and cranial scan data of 85 monochorionic (MC) and 94 dichorionic (DC) twin pregnancies (341 infants) delivered between 24 and 34 weeks of gestation were collected. Data were analysed according to chorionicity, discordant birth weight (>20%), single intrauterine death and TTTS. RESULTS: The cerebral WML was seen in 14% of preterm twins. Monochorionic infants had higher risks of WML than DC twin (odds ratio 7.1; 95% CI 3.28-15.8). In MC group, discordant weight (37%), TTTS (38%), single intrauterine death (67%) had higher incidence of cerebral WML than concordant weight infants (7%). Similarly, incidence of WML was higher in DC discordant compared with concordant weight infants (13% versus 2%; P < 0.05). CONCLUSION: Monochorionic infants had a seven-fold higher incidence of cerebral WML than DC infants. Discordant birth weight, TTTS and survivor of co-twin demise are an independent risk of cerebral white matter lesion.

Birth Weight↗
PubMed2004

Influence of vasopressin in the pathogenesis of oligohydramnios-polyhydramnios in monochorionic twins.

OBJECTIVES: The pathophysiology of oligohydramnios-polyhydramnios in monochorionic (MC) twins complicated by chronic twin-twin transfusion syndrome (TTTS) is poorly understood. We hypothesise that oliguria and oligohydramnios in the donor twin of chronic TTTS, occurs due to antidiuretic and vasoconstrictive activity of vasopressin (AVP). METHODS: We measured AVP levels in maternal, fetal and amniotic fluid samples obtained in utero and at birth from 44 MC twins with (n=27) or without chronic TTTS (n=17). Concentrations of AVP in pg/ml were determined by immuno-radiometry assay. RESULTS: In donor fetuses, plasma and amniotic fluid AVP levels were higher than those of the recipient twins in utero (P<0.001) and at birth (P<0.001). No such differences were found between the non-TTTS twins. The plasma AVP concentrations were higher in the recipient fetuses with severe hydrops than those without hydrops (2.8+/-0.7 pg/ml versus 0.3+/-0.3 pg/ml; P<0.05). Maternal AVP levels were comparable between the TTTS and non-TTTS groups. In the non-TTTS twins, both plasma and amniotic fluid AVP levels were higher than those of the recipient twins (P<0.001) but lower than those of the donor twins (P<0.001). There was a significant association between amniotic fluid and plasma AVP levels both in the TTTS (r=0.78; P<0.001) and non-TTTS (r=0.70; P<0.01) infants. CONCLUSIONS: Vasopressin concentrations in the donor twins were three times higher than their co-twins which suggests that oligohydramnios may occur as a consequence of AVP mediated reduction in fetal urine output.

Adult↗
PubMed2004

Neuromorbidity in preterm twins in relation to chorionicity and discordant birth weight.

OBJECTIVE: The purpose of this study was to determine the incidence of neurologic morbidity in preterm monochorionic (MC) and dichorionic (DC) twins. STUDY DESIGN: We collected perinatal, neonatal, and infant follow-up data of 76 MC and 78 DC twins born between 24 and 34 weeks of gestation (295 infants). Risks of neuromorbidity in the surviving infants were evaluated in relation to chorionicity, discordant birth weight (>20%), twin-twin transfusion syndrome (TTTS), and cotwin death. RESULTS: The overall incidence of cerebral palsy and minor neurologic disabilities in surviving twins was 4% and 9%, respectively. MC infants had a higher incidence of cerebral palsy (8% vs 1%, P<.05) and neurologic morbidity (15% vs 3%, P<.05) than DC infants. The risk of impaired neurodevelopment was higher in MC infants with discordant birth weight (42%, P<.01), TTTS (37%, P<.01), and cotwin death (60%, P<.01) than those with concordant birth weight (8%). In MC pregnancies, the cerebral palsy risk was higher in infants with discordant birth weight than those with chronic TTTS (19% vs 4%, P<.05). Similarly, discordant DC infants had higher neuromorbidity than concordant group (5% vs 1%, P<.05). In both MC and DC discordant infants, neurologic morbidity was independent of growth restriction. CONCLUSION: Neurologic morbidity in the preterm MC infants was 7-fold higher than DC infants because of chronic TTTS, discordant birth weight, and cotwin death in utero.

Adult↗
PubMed2003

Brain natriuretic peptide and endothelin-1 in the pathogenesis of polyhydramnios-oligohydramnios in monochorionic twins.

OBJECTIVE: We investigated the association between amniotic fluid levels of human brain natriuretic peptide, endothelin-1, and abnormal amniotic fluid volume in monochorionic twins with and without chronic twin-twin transfusion syndrome. STUDY DESIGN: Amniotic fluid and fetal blood samples were obtained in utero or at cesarean delivery from monochorionic twins with (n = 20) or without chronic twin-twin transfusion syndrome (n = 10). Concentrations of atrial natriuretic peptide, human brain natriuretic peptide, and endothelin-1 (in picograms per milliliters) were determined by radioimmunoassay. RESULTS: The amniotic fluid concentrations of human brain natriuretic peptide (P <.001) and endothelin-1 (P <.001) in the recipient fetuses were higher than the donor twins but were similar in the twins with no twin-twin transfusion syndrome. In the donor twins, amniotic fluid concentrations of human brain natriuretic peptide (P <.001) and endothelin-1 (P <.001) were lower than the twin pairs with no twin-twin transfusion syndrome. In both chronic twin-twin transfusion syndrome fetuses (P <.01) and fetuses with no twin-twin transfusion syndrome (P <.001), the amniotic fluid concentrations of human brain natriuretic peptide were high, although the concentrations of the endothelin-1 were lower than the fetal plasma concentrations. A positive association was present between amniotic fluid levels of human brain natriuretic peptide and endothelin-1 (R (2) = 0.51, P <.001, n = 60). Amniotic fluid human brain natriuretic peptide (r = 0.67, P <.001) and endothelin-1 (r = 0.57, P <.01) levels of the recipient twins correlated with the amniotic fluid index. CONCLUSION: These data suggest that amniotic fluid concentrations of human brain natriuretic peptide and endothelin-1 were highest in the twins with polyhydramnios and lowest in the twins with oligohydramnios, which suggests the importance of these hormones in the regulation of amniotic fluid volume.

Amniotic Fluid↗
PubMed2002

Natriuretic peptides in the pathogenesis of cardiac dysfunction in the recipient fetus of twin-twin transfusion syndrome.

OBJECTIVE: Although serial amnioreduction has substantially improved the prognosis of twin-twin transfusion syndrome, the majority of recipient twins develop cardiac dysfunction in utero and some have structural abnormalities in the neonatal period. The mechanism of cardiac dysfunction is unclear. To test the hypothesis that this occurs as a result of preload or pressure overload, we determined atrial natriuretic peptide and brain natriuretic peptide levels and their association with endothelin-1 in monochorionic pregnancies with or without chronic twin-twin transfusion syndrome. PATIENTS AND METHODS: Matched maternal and fetal blood samples were obtained in utero from monochorial twin pregnancies complicated with (n = 14) and without twin-twin transfusion syndrome (n = 6). Serial fetal echocardiography assessment included cardiac anatomy, chamber size, cardiothoracic ratio, ventricular thickness, and the presence and severity of atrioventricular valve regurgitation. Postnatal echocardiograms were obtained on the surviving twins. The plasma levels of atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 were measured by use of radio-immunoassay. RESULTS: Levels of fetal atrial natriuretic peptide (P <.001), brain natriuretic peptide (P <.001), and endothelin-1 (P <.001) in the recipient fetuses were higher than in donor twins. Fetal concentrations of atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 in the donor twins were similar to those concentrations in twins that did not have twin-twin transfusion syndrome. Fetal brain natriuretic peptide (P <.01) and endothelin-1 (P <.01) levels were significantly higher in the recipient fetuses when compared to those without severe cardiac dysfunction. A significant positive correlation was present between levels of fetal brain natriuretic peptide and endothelin-1 (y = 230.9 LOG(x) - 264.1, r =.82; P <.01). In contrast, there was no association between levels of fetal atrial natriuretic peptide and the severity of cardiac dysfunction, or with levels of fetal brain natriuretic peptide and endothelin-1. CONCLUSION: Fetal natriuretic peptide levels were higher in the recipient twins than the co-twins, and the severity of cardiac dysfunction was related to levels of brain natriuretic peptide. These data, thereby, suggest that brain natriuretic peptide is a sensitive surrogate biochemical marker of cardiac dysfunction in the recipient twin.

Atrial Natriuretic Factor↗
PubMed2002

Placenta as a link between amino acids, insulin-IGF axis, and low birth weight: evidence from twin studies.

Current evidence suggests that reduced placental transport of amino acids regulates fetal growth. We determined the association between fetal nutrition and the insulin-IGF axis by measuring the plasma concentrations of amino acids, insulin, IGF-I and IGF-binding protein-1 (IGFBP-1) in maternal and cord blood from gestational age-matched dichorionic (DC) twins with (n = 10) and without discordant birth weights (n = 10). In the growth-restricted (IUGR) twins, fetal concentrations of total essential (P < 0.01), nonessential (P < 0.01), and branched chain amino acids (P < 0.01) were lower than those in the appropriate for gestational age co-twins and concordant twin pairs. The IUGR twins had lower fetal concentrations of insulin (P < 0.001) and IGF-I (P < 0.05) and higher concentrations of IGFBP-1 (P < 0.01) than their appropriate for gestational age co-twins. In the discordant group, fetal IGFBP-1 had a negative association with fetal insulin (r = 0.71; P < 0.001), total essential amino acids (r = 0.78; P < 0.001), and branched chain amino acids (r = 0.64; P < 0.01). There was a positive correlation between total essential amino acids (r = 0.63; P < 0.001) and branched chain amino acids (r = 0.58; P < 0.01) and plasma insulin. However, there were no associations among fetal insulin, IGFBP-1 and nonessential amino acids. These data demonstrate the link between the reduction in certain essential and nonessential amino acids and alterations in fetal circulating levels of insulin and IGFBP-1, in growth-restricted twins.

Amino Acids↗