RESUMO
Hemoglobinopathies are the most common global monogenic disorders with significant mortality and morbidity of the survivors. This is due to poor understanding of the disease(s) by health care professionals and also lack of resources. We have designed a Master's degree in hemoglobinopathies course, the first of its kind, using cutting-edge lively state-of the-art media-based technology, to attain excellence in teaching and learning. The modular program is delivered by 100% virtual learning (VLE) tools. The lectures, given by international experts, are blended with interactive quizzes and assessment tools to make the program engaging. Other activities include video-based tutorials, walk-in surgeries, journal clubs and other web-based activities. We have currently received 40 intakes and the program is running successfully with excellent student feedback using quality control framework of the University College London (UCL), London, UK. In conclusion, we have shown the feasibility of VLE for knowledge and skill transfer to global healthcare professionals for a monogenic disorder.
Assuntos
Hematologia/educação , Hemoglobinopatias , Internet , Multimídia , Interface Usuário-Computador , Retroalimentação , Hemoglobinopatias/diagnóstico , Hemoglobinopatias/terapia , Humanos , Parcerias Público-PrivadasRESUMO
AIMS: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2), and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational age at delivery. METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a London University teaching hospital. Maternal IGF-1, IGF-2 and IGFBP-3 were measured in maternal blood at booking and analyzed with respect to gestational age at delivery. RESULTS: There was no significant association between maternal IGF-1 or IGF-2 and preterm birth (PTB). A significant reduction in mean IGFBP-3 levels was noted with delivery <32 completed weeks (P=0.02). CONCLUSION: Maternal mean IGFBP-3 levels are significantly reduced in cases complicated by delivery <32 completed weeks.
Assuntos
Idade Gestacional , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like I/análise , Nascimento Prematuro/sangue , Adulto , Consumo de Bebidas Alcoólicas , Estudos de Coortes , Feminino , Humanos , Gravidez , Estudos Prospectivos , FumarRESUMO
A progressive insulin resistant state develops throughout human pregnancy. Inositol phosphoglycan P-type (P-IPG), a second messenger of insulin, was reported to negatively correlate with the degree of insulin resistance in non-pregnant diabetic subjects. Urinary levels of P-IPG were assessed in insulin resistant states during pregnancy such as gestational diabetes mellitus (GDM, n=44) and type 2 diabetes mellitus (type 2 DM, n=25) and in 69 normal pregnant women. Urinary levels of P-IPG were higher in GDM than controls with a positive trend of release throughout normal pregnancy (P<0.01). P-IPG excretion was higher in diabetic (GDM and type 2 DM) than in healthy women in the second trimester (P<0.05). A higher P-IPG urinary excretion occurs during the second trimester in pregnant women with clinically evident insulin resistance with a positive association with poor glycemic control.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/urina , Diabetes Gestacional/urina , Fosfatos de Inositol/urina , Polissacarídeos/urina , Gravidez em Diabéticas/urina , Adulto , Peso ao Nascer , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Diabetes Gestacional/sangue , Diabetes Gestacional/patologia , Feminino , Humanos , Recém-Nascido , Resistência à Insulina/fisiologia , Projetos Piloto , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Gravidez em Diabéticas/sangue , Gravidez em Diabéticas/patologiaRESUMO
Fetal therapy raises ethical concerns in relation to the balance of potential benefit and harm, autonomy and informed consent, and the duties of the clinician to the pregnant women and fetus. Invasive therapy should be recommended only when it has a realistic chance of saving the life of the fetus and offspring or preventing serious and irreversible disease or disability. Clinicians should respect maternal choice and assessment of risk, particularly if the therapy might be only partially successful, leaving the offspring with a profound morbidity. Fetal therapy should not be undertaken without maternal consent; nor should it be presented coercively as an option to avoid a termination of pregnancy. Therapeutic procedures of unproven efficacy should be undertaken only with the voluntary informed consent of the pregnant woman and according to a clearly defined research protocol that has been approved by an appropriate research ethics committee and where appropriate support and counselling can be provided.
Assuntos
Ética Clínica , Doenças Fetais/terapia , Terapias Fetais/ética , Terapias Fetais/efeitos adversos , Terapias Fetais/métodos , Terapia Genética/efeitos adversos , Terapia Genética/ética , Terapia Genética/métodos , Humanos , Consentimento Livre e Esclarecido/ética , Seleção de Pacientes/ética , Experimentação Humana Terapêutica/éticaRESUMO
Renal transplant recipients (RTRs) have a high incidence of erectile dysfunction (ED). Differentiation of penile vasculogenic impotence from other causes is important for treatment. Conventional 2-D color Doppler assessment after intracavernosal stimulant injection often fails to produce reliable results because of limited views by the cross-sectional imaging and the painful procedure. In comparison to the findings in three healthy volunteers, we determined cavernosal vascular hemodynamics in eight RTRs with ED before and after oral sildenafil by using live 3-D ultrasound and dynamic 3-D color Doppler. Results showed that, before sildenafil, penile arterial flow signals could only be reliably detected in one patient. After sildenafil, all had reliably detectable flow with grades II to III erection. Our data suggest that 3-D volumetric changes of the penis and its vasculature during erection can be studied by this technique and that this method could be useful for the evaluation of new drugs and therapeutic biofeedback.
Assuntos
Disfunção Erétil/diagnóstico por imagem , Imageamento Tridimensional , Transplante de Rim , Piperazinas/uso terapêutico , Sulfonas/uso terapêutico , Ultrassonografia Doppler em Cores/métodos , Vasodilatadores/uso terapêutico , Administração Oral , Adulto , Velocidade do Fluxo Sanguíneo , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/fisiopatologia , Estudos de Viabilidade , Humanos , Impotência Vasculogênica/complicações , Impotência Vasculogênica/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pênis/irrigação sanguínea , Pênis/diagnóstico por imagem , Purinas/uso terapêutico , Citrato de Sildenafila , Resultado do TratamentoRESUMO
INTRODUCTION: Pseudoxanthoma elasticum (PXE) is an inherited multisystem disorder of the elastic tissue and the objective of this case report is to correlate ultrasonographic and histological appearances of placental calcification in PXE. CLINICAL PICTURE: We report a case of a 37-year-old white woman with PXE, whose antenatal imaging showed a markedly echogenic placenta due to extensive calcification confirmed on postpartum placental histology. OUTCOME: There were no maternal or fetal complications in the antenatal period. A healthy baby of appropriate maturity and weight was delivered via Caesarean section and remained well at 6 months. CONCLUSION: The majority of cases of PXE is caused by mutations in the ABCC6 gene. Serious complications in pregnancy can include gastrointestinal haemorrhage, congestive heart failure and cardiac arrhythmia but has not been shown to be associated with markedly increased fetal loss or adverse reproductive outcomes as reported in previous literature. Apart from the cosmetic deterioration of the abdominal skin, there were few serious complications and most have normal pregnancies. Obstetric prognosis is dependent on the vascular damage caused by the illness. There is no basis for advising women with PXE to avoid becoming pregnant, and most pregnancies in PXE are uncomplicated.
Assuntos
Calcinose/etiologia , Doenças Placentárias/diagnóstico , Doenças Placentárias/etiologia , Pseudoxantoma Elástico/complicações , Adulto , Calcinose/diagnóstico , Cesárea , Feminino , Humanos , Doenças Placentárias/patologia , Gravidez , Resultado da Gravidez , Pseudoxantoma Elástico/diagnóstico , Fatores de RiscoRESUMO
Gene transfer early in development for the treatment of monogenetic and other diseases could overcome major obstacles of intervention in the mature individual. Early gene transfer may prevent the onset of irreversible pathological changes, predispose the individual to immunological tolerance to the introduced protein, take advantage of the high vector to cell ratio, and provide unique access to stem cell/progenitor compartments. The past few years have witnessed the publication of five studies showing long-term correction of monogenetic disorders by fetal gene transfer. Many others have examined the use of new vector systems with therapeutic transgenes, tested their potential for treating diseases in a wide range of organs (including the brain, lung and skin), and examined the hazards of fetal application. This review gives a comprehensive summary of the development of fetal gene transfer over the past few years.
Assuntos
Feto , Técnicas de Transferência de Genes , Animais , Feminino , Doenças Genéticas Inatas/genética , Doenças Genéticas Inatas/terapia , Terapia Genética , Humanos , GravidezRESUMO
An association between inositol phosphoglycan P-type (P-IPG) and preeclampsia has been demonstrated over recent years. This molecule can mediate many of the metabolic and growth promoting effects of insulin. Dysregulation of the mediator family is associated with insulin resistance. An increased concentration of P-IPG has been reported in preeclamptic placenta, although its precursor (GPI) was undetectable in those placental samples. Insulin administration, that induces P-IPG release in normal human placenta, was shown not to cause production/release of the mediator from preeclamptic placental tissue as a consequence of a disturbed insulin signalling. Amniotic fluid is enriched of this mediator, with further increase during preeclampsia. We have found that the fetus released increasing amounts of P-IPG in the urine between 13 and 18 weeks of gestation, reaching a plateau beyond 20 weeks. Cord blood of infants of preeclamptic mothers showed an increased content of soluble P-IPG compared to controls and to the mother.
Assuntos
Líquido Amniótico/metabolismo , Fosfatos de Inositol/metabolismo , Polissacarídeos/metabolismo , Pré-Eclâmpsia/metabolismo , Feminino , Sangue Fetal/metabolismo , Feto/metabolismo , Humanos , Fosfatos de Inositol/sangue , Fosfatos de Inositol/urina , Insulina/metabolismo , Resistência à Insulina , Placenta/metabolismo , Polissacarídeos/sangue , Polissacarídeos/urina , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/urina , GravidezRESUMO
OBJECTIVE: To evaluate the incidence and significance of fetal anomalies and "soft markers" after screening for Down syndrome using the integrated test. METHODS: This study is a retrospective study of 2,332 women at University College London Hospitals, United Kingdom. All women were screened for Down syndrome by the integrated test. Subsequently, a detailed anomaly scan was performed. All scan reports and screening results were analyzed statistically using SPSS 11.0 software. RESULTS: Sixty-eight (2.9%) patients were categorized as high risk. There were 12 cases affected by Down syndrome, 10 (10 of 68) in the high-risk group and two (two of 2,264) in the low-risk group. Soft markers or structural anomalies were found in 13.0% of the low-risk group, in 29.4% of the high-risk group, and in 50% of the fetuses affected by Down syndrome. Multiplying the likelihood ratio of each marker with the risk of Down syndrome from the integrated test reduced the false-positive rate of the integrated test from 2.5% to 1.8%, but was accompanied by a reduction in the detection rate from 83% to 75%. CONCLUSION: Absence of structural anomalies or markers should not prevent offering karyotyping to women in the high-risk group, because this would result in a significant reduction in the detection rate of Down syndrome. Women screened as low risk by the integrated test who have isolated soft markers should not be offered an amniocentesis.
Assuntos
Síndrome de Down/diagnóstico , Ultrassonografia Pré-Natal , Adolescente , Adulto , Síndrome de Down/diagnóstico por imagem , Reações Falso-Positivas , Feminino , Humanos , Funções Verossimilhança , Pessoa de Meia-Idade , Medição da Translucência Nucal , Gravidez , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND/AIMS: The mechanisms underlying overgrowth of adipose tissue in fetuses of women with gestational diabetes mellitus (GDM) are generally unknown. Inositol phosphoglycan A-type (A-IPG), a putative second messenger of insulin, was reported to regulate lipogenesis in adipose tissue. IPGs have recently been shown to increase during normal pregnancy, in maternal and fetal compartments. METHODS: 48 women with GDM and 23 healthy pregnant women were recruited for this cross-sectional study. Levels of A-IPG were assessed enzymatically in urinary specimens and correlated with clinical parameters. RESULTS: A-IPG urinary release was lower in GDM patients (p < 0.01) and correlated positively with BMI (p < 0.01) and negatively with glycaemic control in the diabetic group (postprandial glycaemia and glycated haemoglobin, p < 0.01) in addition to a nearly significant correlation with birth weight (p = 0.08). Furthermore, a lower A-IPG urinary release was found in diabetic subjects with normal fasting glycaemia compared with those with poor fasting glycaemic control (p < 0.05). CONCLUSIONS: An altered A-IPG urinary excretion occurs in GDM with a negative correlation with poor glycaemic control. Our data suggest an interesting potential role of this molecule in maternal metabolic control during pregnancy and, possibly, in fetal growth.
Assuntos
Diabetes Gestacional/urina , Fosfatos de Inositol/urina , Polissacarídeos/urina , Adulto , Glicemia , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Índice Glicêmico , Humanos , GravidezRESUMO
CONTEXT: Preeclampsia is a severe complication of human pregnancy often associated with maternal risk factors. Insulin resistance represents a major risk for developing preeclampsia during pregnancy. OBJECTIVE: A putative second messenger of insulin, inositol phosphoglycan P type (P-IPG), was previously shown to be highly increased during active preeclampsia. Its association with insulin resistance was investigated. DESIGN AND SETTING: A cross-sectional study was carried out in a referral center. PATIENTS: Nine preeclamptic (PE) and 18 healthy women were recruited and matched for maternal age, body mass index, parity, and ethnicity in a 1:2 ratio. Placental specimens were collected immediately after delivery. INTERVENTION: Placental tissue was incubated with insulin and P-IPG production assessed. Insulin signaling proteins were subsequently studied by immunoblotting. RESULTS: P-IPG extracted from human term placentas upon incubation with insulin was found to be far lower in those with preeclampsia than controls (P < 0.001). Immunoblotting studies revealed serine phosphorylation of insulin receptor substrate-1 and -2 in PE placentas (P < 0.001) with downstream impairment of insulin signaling. The activation of the p85 regulatory subunit of phosphatidylinositol 3- kinase was markedly decreased in PE samples (P < 0.001). CONCLUSIONS: These findings highlight the importance of P-IPG in active preeclampsia and demonstrate a substantially different response to the insulin stimulus of human PE placentas. Acquired alterations in activation of proteins involved in insulin signaling may play a role in the complex pathogenesis of preeclampsia, probably as a consequence of the immunological dysfunction that occurs in this syndrome. These results seem to confirm an insulin-resistant state in PE placenta and shed a different light on its role in the pathogenesis of this disease with potential therapeutic implications.
Assuntos
Resistência à Insulina/fisiologia , Fosfoproteínas/metabolismo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Adulto , Western Blotting , Estudos Transversais , Ativação Enzimática , Feminino , Humanos , Fosfatos de Inositol/biossíntese , Proteínas Substratos do Receptor de Insulina , Peptídeos e Proteínas de Sinalização Intracelular , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Polissacarídeos/biossíntese , Gravidez , Estudos Prospectivos , Serina/metabolismo , Transdução de SinaisRESUMO
PURPOSE OF REVIEW: Over the last few years, great progress has been made in imaging technology, which is changing the way prenatal visualization of the fetal heart is used for diagnosis and therapy. RECENT FINDINGS: This paper reviews recent clinical research using these new techniques, namely dynamic three-dimensional (4D) echocardiography, myocardial Doppler imaging, B-flow ultrasonography, endoscopic ultrasound, and magnetic resonance imaging. Of them, 4D echocardiography is the most significant development and is discussed in greater detail. This includes real-time volumetric data acquisition using matrix-array transducer technology, motion artefact elimination using spatio-temporal image correlation, and various display options. The advantages and limitations of each are also addressed. SUMMARY: These techniques can provide (1) sequential assessment of the entire heart using a full 4D dataset, (2) 4D delineation of trabeculation patterns on the ventricular walls, en-face dynamic shapes of ventricular septal defects and spatially complex malformations, (3) derivation of cardiac indices to myocardial contractility and strain rate by Doppler tissue imaging, and/or (4) the use of transoesophageal ultrasound to guide in-utero cardiac intervention. All of these techniques expand our ability to evaluate the morphology and function of the in-utero heart.
Assuntos
Ecocardiografia Quadridimensional/métodos , Cardiopatias Congênitas/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Ecocardiografia Transesofagiana/métodos , Feminino , Humanos , Processamento de Imagem Assistida por Computador , GravidezRESUMO
There has been no objective means for imaging the three-dimensional (3D) morphology of the clitoris-a poorly understood, complex structure. A Live 3D ultrasound system with a matrix-array transducer was used for data acquisition from eight women. The transducer was positioned in front of and about 3 cm away from the clitoris, with a gel pad or water pad being placed in between. The pads allowed the delicate structures to be imaged without noticeable deformation. Quality images could be obtained with use of a water pad in all patients. The imaging volume was big enough to cover the clitoral glans and body simultaneously, allowing real-time 3D visualisation. To cover the entire clitoris, the probe was moved from one side of the crus to the other, or a four subvolume scan was performed. 3D clitoral anatomy was depicted from 71% of 51 water pad data-sets. The study demonstrates the feasibility of obtaining 3D clitoral ultrasound images. This will improve scientific and clinical understanding of the clitoral role in sexual activity. The minimally-compressive scanning offers an opportunity to visualise dynamic 3D (4D) morphology of other deformable body parts.
Assuntos
Clitóris/diagnóstico por imagem , Adulto , Estudos de Viabilidade , Feminino , Géis , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Fatores de Tempo , Ultrassonografia , ÁguaRESUMO
BACKGROUND: Many hormones such as insulin, insulin-like growth factors, and the glucocorticoids are involved in regulating fetal growth. Inositol phosphoglycans (IPGs), a family of putative second messengers of insulin, are reported to exert several of insulin's metabolic effects. METHODS: A prospective cross-sectional study was carried out to investigate IPG P-type (P-IPG) in human amniotic fluid and in adult urine under physiological conditions. An amniotic fluid sample was taken from 78 women undergoing early amniocentesis and a mid-stream urine specimen was collected from 109 healthy pregnant and 66 non-pregnant women. All samples were assessed using a polyclonal antibody-based ELISA. RESULTS: The P-IPG content was a thousand times higher in the amniotic fluid than in the urine (p < 0.0001). Urinary specimens showed a four-fold higher P-IPG content during pregnancy than in healthy non-pregnant women (p < 0.001). CONCLUSIONS: Under physiological conditions, human amniotic fluid was found to be enriched in P-IPG compared with maternal urine, suggesting a possible fetal origin. Therefore, IPGs may play a role in insulin sensitivity and fetal growth and, perhaps, be involved in some of its abnormalities such as macrosomia and intrauterine growth restriction.
Assuntos
Líquido Amniótico/química , Fosfatos de Inositol/análise , Polissacarídeos/análise , Adulto , Amniocentese , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Maternal smoking during pregnancy is associated with a reduction in birth size. Very few studies have collated changes in fetal biometry, neonatal anthropometry, biochemical factors involved in fetal growth, and measures of uterine and umbilical blood flow. METHODS: We related smoking status in 1650 low-risk, singleton Caucasian pregnancies delivering at term to measures of fetal growth, uterine and umbilical artery blood flow, placental appearance, birth size, and cord concentrations of IGF-I and -II and IGF binding protein (IGFBP)-3. RESULTS: Mothers who smoked in pregnancy were younger (P < 0.001) and shorter (P = 0.03) and from lower socioeconomic groups (P < 0.001). Mean umbilical artery blood flow at 20 wk gestation was not associated with smoking status but was significantly higher in smokers at 30 wk (P = 0.006). Uterine artery blood flow was unaffected. Smoking was associated with an increase in the percentage of abnormal placentas in a dose-dependent manner and with a 3.1-fold increased risk (odds ratio 3.1, 95% confidence interval 1.3-7.6) of abnormal umbilical artery blood flow (P = 0.009). Smoking was associated with a reduction in fetal femur length (P = 0.005) and abdominal circumference as well as birth weight, length, and head circumference but not skinfold thickness. Cord plasma concentrations of IGF-I and IGFBP-3 were lower in the babies of mothers who had smoked (P = 0.02 and P = 0.01, respectively). CONCLUSION: We concluded that maternal smoking is associated with an altered placental appearance on ultrasonography, increased umbilical artery blood flow resistance, and a reduction in longitudinal and intraabdominal organ growth. Circulating concentrations of IGF-I and IGFBP-3 along with measures of birth size but not markers of body fat are reduced, suggesting smoking results in a reduction in organ size and function.
Assuntos
Peso ao Nascer , Desenvolvimento Fetal , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fumar/fisiopatologia , Adulto , Feminino , Sangue Fetal/química , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Gravidez , Cordão Umbilical/irrigação sanguínea , Útero/irrigação sanguíneaRESUMO
In rodents and humans there is a sexually dimorphic pattern of GH secretion that influences the serum concentration of IGF-I. Pattern differences can be identified in children, but it is not known how early this difference is established. We studied the plasma concentrations of IGF-I, IGF-II, IGF-binding protein-3 (BP-3), and GH in cord blood taken from the offspring of 1650 singleton Caucasian pregnancies born at term and related these values to birth weight, length, and head circumference. Pregnancies complicated by preterm delivery, antepartum hemorrhage, pregnancy-induced hypertension, preeclampsia, or gestational diabetes and where cigarette smoking continued were excluded, resulting in a cohort of 987. Cord plasma concentrations of IGF-I, IGF-II, and IGFBP-3 were influenced by factors influencing birth size: gestational age at delivery, mode of delivery, maternal height, and parity of the mother. Plasma GH concentrations were inversely related to the plasma concentrations of IGF-I and IGFBP-3; 10.2% of the variability in cord plasma IGF-I concentration and 2.7% for IGFBP-3 was explained by sex of the offspring and parity. None of the factors, apart from maternal height, influenced cord serum IGF-II concentrations (adjusted r(2) = 1%). Sex of the baby, mode of delivery, and parity influenced cord serum GH concentrations (adjusted r(2) = 2.6%). Birth weight, length, and head circumference measurements were greater in males than females (P < 0.001). Mean cord plasma concentrations of IGF-I (males, 66.4 +/- 1.2 micro g/liter; females, 74.5 +/- 1.3 micro g/liter; P < 0.001) and IGFBP-3 (males, 910 +/- 13 micro g/liter; females 978 +/- 13 micro g/liter; P < 0.001) were significantly lower in males than females. Cord plasma GH concentrations were higher in males than females (males, 30.0 +/- 1.2 mU/liter; females, 26.9 +/- 1.1 mU/liter; P = 0.05), but no difference was noted between the sexes for IGF-II (males, 508 +/- 6 micro g/liter; females, 519 +/- 6 micro g/liter; P = NS). After adjustment for gestational age, parity, and maternal height, cord plasma concentrations of IGF-I and IGFBP-3 along with sex explained 38.0% of the variability in birth weight, 25.0% in birth length, and 22.7% in head circumference. These data demonstrate that in a group of singleton Caucasian babies born at term, cord plasma IGF-I, IGFBP-3, and GH concentrations relate to birth size, with evidence for sexual dimorphism in the GH-IGF axis.
Assuntos
Hormônio do Crescimento Humano/metabolismo , Somatomedinas/metabolismo , Adulto , Peso ao Nascer/fisiologia , Estatura/fisiologia , Feminino , Sangue Fetal/metabolismo , Idade Gestacional , Hormônio do Crescimento Humano/sangue , Humanos , Lactente , Recém-Nascido , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Paridade , Gravidez , Análise de Regressão , Caracteres SexuaisRESUMO
Metabolic compensatory mechanisms may partly account for the decreased vulnerability to hypoxia observed in the developing brain. We used proton magnetic resonance spectroscopy and diffusion-weighted imaging to measure the cerebral concentrations of lactate and other metabolites, as well as the apparent diffusion coefficient (ADC) of tissue water, before, during and after hypoxia in anaesthetised chick embryos in ovo. Reducing the inspired oxygen concentration to 8% for 40 min caused a significant rise in both mean (+/-S.D.) lactate:creatine and alanine:creatine ratios from 0.58 (0.41) to 1.56 (0.56) and 0.14 (0.14) to 0.29 (0.17), respectively. Under similar hypoxic conditions, ADC did not change from a mean baseline value of 0.95 (0.09), but did fall to 0.40 (0.12) x 10(9) mm(2) s(-1) with further stepwise reductions in oxygenation. Moderate hypoxia increases lactate concentration in the developing chick brain without compromising cellular energy metabolism.
Assuntos
Adaptação Fisiológica/fisiologia , Encéfalo/embriologia , Encéfalo/metabolismo , Embrião de Galinha/metabolismo , Metabolismo Energético/fisiologia , Hipóxia Encefálica/metabolismo , Alanina/metabolismo , Animais , Água Corporal/metabolismo , Encéfalo/anatomia & histologia , Embrião de Galinha/anatomia & histologia , Creatina/metabolismo , Imagem de Difusão por Ressonância Magnética , Hipóxia Encefálica/patologia , Hipóxia Encefálica/fisiopatologia , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Modelos Animais , Oxigênio/metabolismo , Consumo de Oxigênio/fisiologiaRESUMO
A total of 15 fetuses were scanned using 2-D array volumetric ultrasound (US). Acquired cardiac data were converted for rendering dynamic 3-D surface views and reformatting cross-sectional views. The image usefulness was compared between the data obtained from subcostal/subxiphoid and other imaging windows; the former are usually free of acoustic shadowing. Of 60 data sets recorded, 12 (20%) were acquired through subcostal windows in 6 (40%) patients. Subcostal windows were unavailable from the remaining patients due to unfavourable fetal positions. Of the 12 sets, 6 (50%) provided the dynamic 3-D and/or cross-sectional views of either the entire fetal heart or a great portion of it for sufficient assessments of its major structures and their spatial relationships. Of 48 data sets from other windows, only 9 (19%) provided such 3-D and/or cross-sectional views; the lower rate being due to acoustic shadowing. Real-time 3-D US is a convenient method for volumetric data acquisition. Through subcostal windows, useful information about the spatial relationships between major cardiac structures can be acquired. However, to offer detailed information, considerable improvement in imaging quality is needed.
Assuntos
Ecocardiografia Tridimensional/métodos , Coração Fetal/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Ultrassonografia Pré-Natal/métodos , Artefatos , Ecocardiografia Quadridimensional , Feminino , Coração Fetal/fisiologia , Humanos , Contração Miocárdica , Gravidez , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Hypertensive disorders represent the most common complications of human pregnancy with substantial impact on fetal and maternal outcomes. Inositol phosphoglycan P-type has recently been identified as a novel marker of preeclampsia, the most severe form of hypertension during pregnancy, with a significant increase in urinary excretion preceding the clinical diagnosis. METHODS: A prospective, longitudinal study was carried out to assess the potential of urinary levels of inositol phosphoglycan P-type as a screening test for preeclampsia. A specific ELISA-based test was used to assess urinary levels of P-IPG. RESULTS: Nine patients out of 93 women recruited (496 urinary samples were collected) went on to develop preeclampsia in a cohort of women with high-risk pregnancies. A cut-off value of urinary inositol phosphoglycan P-type was identified by ROC analysis providing a sensitivity and specificity for the current protocol of 88.9% and 62.7%, respectively. Twenty-three women with healthy pregnancies had sporadic episodes of increased excretion of inositol phosphoglycan P-type during pregnancy that consistently resolved back to normal baseline without development of preeclampsia. There was no correlation of urine levels of inositol phosphoglycan P-type and urine protein and patients with gestational hypertension had normal levels of urine inositol phosphoglycan P-type. CONCLUSIONS: These findings suggest that, given the rapid raise of P-IPG before the onset of the disease, multiple assessments may help at identifying women at risk of developing preeclampsia.
Assuntos
Fosfatos de Inositol/urina , Polissacarídeos/urina , Pré-Eclâmpsia/urina , Gravidez de Alto Risco/urina , Análise de Variância , Biomarcadores/urina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To investigate the relationship between levels of insulin-like growth factors 1 and 2 (IGF-1, IGF-2) and insulin-like growth factor binding protein 3 (IGFBP-3) in antenatal maternal serum and gestational hypertension and pre-eclampsia (PET). METHODS: Prospective cohort study of 1650 low-risk Caucasian women in a University teaching hospital in London. Statistical analysis was performed using commercial software (SPSS for Windows, version 6.1, SPSS, Chicago, IL), with P < 0.05 as significant. Maternal IGF 1, IGF 2 and IGF BP-3 were assessed on maternal blood at booking. Blood pressure was checked at each visit in conjunction with urine analysis. The Davey & MacGillivray 1988 classification system was used in making the diagnosis of PET. RESULTS: There was no significant correlation between maternal IGF-1 or IGFBP-3 levels and gestational hypertension or PET. However, a significant positive correlation does exist between maternal IGF-2 levels and PET. CONCLUSIONS: Maternal IGF-2 has a significant positive correlation with PET.