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Biomedical subjects

J E Ferguson

Publications and source records attributed to J E Ferguson.

At least 19 recordsLinked to original sources

Mechanisms of endothelial differentiation in embryonic vasculogenesis.

The formation of new blood vessels in the adult organism not only contributes to the progression of diseases such as cancer and diabetic retinopathy but also can be promoted in therapeutic approaches to various ischemic pathologies. Because many of the signals important to blood vessel development during embryogenesis are recapitulated during adult blood vessel formation, much work has been performed to better-understand the molecular control of endothelial differentiation in the developing embryo. In this review, we describe the current understanding of where endothelial differentiation from pluripotent progenitor cells occurs during development, how this process is controlled at the molecular level, and what model systems can be used to investigate the earliest steps of blood vessel formation.

Animals↗

Management of a parturient with a history of local anesthetic allergy.

IMPLICATIONS: The management of parturients with a strong history of allergy to local anesthetics poses significant challenges to the obstetric anesthesiologist. We recommend that when such patients have a strong desire to receive labor analgesia with local anesthetics, they undergo provocative challenge testing with preservative-free bupivacaine performed in labor and delivery with preparations for emergent cesarean delivery after 24-wk gestation.

Adult↗

Audit of admissions to dermatology beds in Greater Manchester.

We present the results of a prospective questionnaire-based audit of admissions to dermatology beds. We examined the admission practices of clinicians and the outcome in terms of benefit to patients. The majority of patients (90%) were admitted because of the severity of their skin disease but other contributing factors included: inability to cope (40%); need for further investigation or observation (33%); coexisting medical factors (17%); poor social support; transport and psychological factors. Most (87%) patients benefited from admission and the dermatology life quality index improved by 42%. We demonstrate that inpatient treatment is effective and improves patients' quality of life.

Adolescent↗

Doppler ultrasound velocimetry for timing the second intrauterine transfusion in fetuses with anemia from red cell alloimmunization.

OBJECTIVE: Middle cerebral artery peak systolic velocity has been successfully used for timing the first cordocentesis in fetuses who are at risk for anemia because of maternal red cell alloimmunization. The effects on Doppler velocimetry after the intrauterine transfusion of adult blood to these fetuses are unknown. The objective of this study was to assess the applicability of Doppler methods for the prediction of severe anemia in fetuses who had undergone 1 previous intrauterine transfusion. STUDY DESIGN: Doppler examination of middle cerebral artery peak systolic velocity was performed before cordocentesis in 64 fetuses who had undergone 1 previous intrauterine transfusion. Timing of the second intrauterine transfusion was based on traditional criteria. Anemia was defined as mild (hemoglobin value between 0.84 and 0.65 multiples of the median), moderate (hemoglobin value <0.65-0.55 multiples of the median), and severe (hemoglobin value <0.55 multiples of the median). Receiver operator characteristic curves were created to select threshold values to identify the 3 degrees of anemia with a sensitivity of 100%. RESULTS: Gestational age at the Doppler study ranged from 19 to 36 weeks. Forty-six fetuses (72%) were not or mildly anemic; 7 fetuses (11%) were moderately anemic, and 11 fetuses (17%) were severely anemic. Middle cerebral artery peak systolic velocity for the prediction of severe, moderate, and mild anemia at a sensitivity of 100% showed false-positive rates of 6%, 37%, and 70%, respectively. CONCLUSION: In fetuses who have undergone 1 previous intrauterine transfusion because of maternal red cell alloimmunization, timing the second intrauterine transfusion can be determined noninvasively by Doppler ultrasonography on the basis of an increase in the peak velocity of systolic blood flow in the middle cerebral artery.

Anemia↗

Color Doppler ultrasonography of the superior mesenteric artery for prenatal ultrasonographic diagnosis of a left-sided congenital diaphragmatic hernia.

The incidence of congenital diaphragmatic hernia (CDH) has been estimated as 1 per 2000 to 1 per 4000 births. The etiology of the malformation is unknown, but it has been reported in association with maternal administration of medications such as thalidomide or antiepileptics before closure of the pleuroperitoneal canal at 9 to 10 weeks' gestation as well as having a familial inheritance pattern. Congenital diaphragmatic hernia is associated with other congenital anomalies in 25% to 57% of cases and with chromosomal abnormalities in 10% to 20% of cases. Posterolateral, anterolateral, and pars sternalis defects of closure of the pleuroperitoneal canal encompass the 3 types of CDH. The most frequent type is the left-sided posterolateral defect or Bochdalek's hernia, which accounts for 81% of cases.

Adult↗

B-Lynch suture for postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage is a major contributor to maternal morbidity and mortality. Numerous medical and surgical therapies have been used, but none has been uniformly successful. CASE: Two women with postpartum hemorrhage due to uterine atony after cesarean for twins are presented. Neither responded to medical management. In the first subject, O'Leary uterine artery ligation and utero-ovarian branch ligations were done without benefit. The B-Lynch suture immediately sustained correction of hemorrhage in both subjects. Magnetic resonance imaging and hysterosalpingogram after the first case showed no uterine defects. CONCLUSION: The B-Lynch suture might be a valuable addition to the surgical treatment of postpartum hemorrhage due to uterine atony.

Adolescent↗

Ethical theory and principles: do they have any relevance to problems arising in everyday practice?

This review of ethical theories with application to two difficult obstetric cases will allow the practicing obstetrician and gynecologist to use these theories to help resolve difficult ethical dilemmas. In the first case a pregnant human immunodeficiency virus-infected woman refuses to take triple preventive therapy, with potential fetal harm. In the second case a couple with a quintuplet multifetal pregnancy needs assistance to decide about selective termination to effect fetal reduction.

Caregivers↗

Initial development of a system-wide maternal-fetal outcomes assessment program.

OBJECTIVE: This study was undertaken to develop a comprehensive risk-assessment approach capable of evaluating maternal and fetal outcomes. STUDY DESIGN: Data from 10,984 women and 11,066 infants delivered at 79 military treatment facilities in the United States from 1995 to 1997 were used to develop two individual but complementary risk-adjustment models for maternal and, separately, fetal outcomes. A range of maternal and delivery-related risk variables and clinically important outcomes were identified by expert opinion and selected and weighted with ordinal logistic regression analysis. Receiver operating characteristic curves for the maternal and fetal models were determined. Variation across the facilities in risk-adjusted performance was also evaluated. RESULTS: Risk factors and poor outcomes were rare for both mothers and infants, with 96.9% of infants and 97.7% of mothers having good or excellent outcomes (0.7% mortality and 0.01% mortality, respectively). Despite the low frequency of poor outcomes both models performed well, with receiver operating characteristic curves of 0.75 for maternal outcomes and 0.78 for infant outcomes. When the models were applied to the military treatment facilities, there were significant differences among facilities in risk-adjusted outcomes. Twenty-four of the facilities in the study (30%) had outcomes odds ratios that were significantly >1 or significantly <1 (P <.05). There did not appear to be any relationship between the performance of a military treatment facility for maternal outcome and that for infant outcome. CONCLUSION: Complementary risk models for maternal and infant outcomes were developed that had satisfactory discriminatory power across a variety of facilities within a large health system. With further development and refinement this approach holds promise of being able to detect variations in risk-adjusted performance that could be used to identify best practices. The results might also be used to help coordinate and improve the quality of care for the entire conception-to-delivery process.

Female↗

Insights into the pathogenesis and natural history of fetuses with multicystic dysplastic kidney disease.

To better delineate the natural history of multicystic displastic kidney disease (MCDKD) and provide insights into the pathogenesis of this condition, we report our experience in 102 prenatally detected cases. MCDKD is most commonly an incidental finding on prenatal ultrasound examination. The abnormality may be unilateral (76 per cent) or bilateral (24 per cent). In unilateral cases, abnormality of the contralateral kidney is common (33 per cent). Associated non-renal abnormalities occur frequently with both unilateral (26 per cent) and bilateral (67 per cent) MCDKD, and increase the risk for an abnormal chromosome study. Males are more likely to be affected than females with a ratio of 2.4:1, but females are twice as likely to have bilateral MCDKD and associated non-renal abnormalities, and four times more likely to have an abnormal chromosome study. We suggest that the option of chromosomal analysis should be discussed with all patients diagnosed with MCDKD in their fetus, if there is bilateral renal involvement or if an associated non-renal abnormality is present. Unilateral MCDKD without associated renal or non-renal abnormalities was not associated with an abnormal chromosome study, and resulted in favourable outcomes. While unilateral MCDKD, lack of associated anomalies, normal chromosome study and adequate amniotic fluid are all reassuring findings, a complete neonatal urologic work-up should be performed in all newborns. We believe the evaluation should include voiding cystourethrography to rule out vesicoureteral reflux. Our findings allow more precise counselling of patients regarding prognosis, and subsequent management of the fetus found to have MCDKD.

Child↗

Attachment-based classifications of children's family drawings: psychometric properties and relations with children's adjustment in kindergarten.

Investigated an attachment-based theoretical framework and classification system, introduced by Kaplan and Main (1986), for interpreting children's family drawings. This study concentrated on the psychometric properties of the system and the relation between drawings classified using this system and teacher ratings of classroom social-emotional and behavioral functioning, controlling for child age, ethnic status, intelligence, and fine motor skills. This nonclinical sample consisted of 200 kindergarten children of diverse racial and socioeconomic status (SES). Limited support for reliability of this classification system was obtained. Kappas for overall classifications of drawings (e.g., secure) exceeded .80 and mean kappa for discrete drawing features (e.g., figures with smiles) was .82. Coders' endorsement of the presence of certain discrete drawing features predicted their overall classification at 82.5% accuracy. Drawing classification was related to teacher ratings of classroom functioning independent of child age, sex, race, SES, intelligence, and fine motor skills (with p values for the multivariate effects ranging from .043-.001). Results are discussed in terms of the psychometric properties of this system for classifying children's representations of family and the limitations of family drawing techniques for young children.

Art↗

The fetal-pelvic index has minimal utility in predicting fetal-pelvic disproportion.

OBJECTIVE: Our purpose was to evaluate the fetal-pelvic index in our patient population and to determine whether it would be predictive of route of delivery. STUDY DESIGN: One hundred seventy-six patients with a previous history or clinical findings in the current pregnancy suggestive of fetal-pelvic disproportion participated in this Human Investigation Committee-approved study. All underwent fetal ultrasonographic examinations and modified digital radiography before labor. Fetal head and abdominal circumferences and maternal inlet and midpelvic circumferences were determined, and the fetal-pelvic index was calculated. RESULTS: Ninety-one patients fulfilled all aspects of the study, including rigorous criteria pertaining to labor management. Thirty of these patients underwent cesarean delivery and 61 were delivered vaginally. The fetal-pelvic index value for the vaginal delivery group was -5.4 +/- 5.3, as opposed to -2.4 +/- 5.8 in the cesarean delivery group (P <.02). Notwithstanding this difference, the fetal-pelvic index had a low overall ability to predict fetal-pelvic disproportion (0.65) and had associated sensitivity and specificity of 0.27 and 0.84, respectively. Predictive thresholds other than zero were tested, but optimal predictive ability, at a fetal-pelvic index cutoff of 2, was only 70% (sensitivity 0.20, specificity 0.95). CONCLUSION: In our patient population the fetal-pelvic index was only moderately predictive of fetal-pelvic disproportion. Factors other than those assessed by the fetal-pelvic index are probably important in determining the route of delivery. Further studies are indicated.

Adult↗

Expression and specific immunolocalization of the human parathyroid hormone/parathyroid hormone-related protein receptor in the uteroplacental unit.

OBJECTIVE: Our purpose in these studies was to determine the expression and cellular localization of the parathyroid hormone/parathyroid hormone-related protein receptor in the human uteroplacental unit. STUDY DESIGN: Human uteroplacental tissues were obtained and ribonucleic acid was extracted. Reverse transcriptase-polymerase chain reaction was performed with use of primers for both the parathyroid hormone/parathyroid hormone-related protein receptor and human phosphoglyceraldehyde dehydrogenase. Ethidium bromide-stained gels and Southern blots were evaluated, and polymerase chain reaction fragments were sequenced. For immunohistochemistry, slides were incubated with a newly developed antibody (3D1.1) specific for the parathyroid hormone/parathyroid hormone-related protein receptor, and bound monoclonal antibody was detected by use of the avidin-biotin technique. RESULTS: Reverse transcriptase polymerase chain reaction gels and blots showed that receptor messenger ribonucleic acid was present in choriodecidua, placenta, and myometrium. Sequence analysis revealed complete identity of the receptor product and the known nucleotide sequence in the receptor. There was intense receptor staining of the myometrial smooth muscle as well as staining of the endothelium and smooth muscle of the associated vasculature. In umbilical cord immunoreactive receptor was found in the vascular endothelium and vascular smooth muscle cells and in stromal cells. In choriodecidua receptor was found in chorionic trophoblasts and decidualized endometrial stromal cells. In all tissues immunostaining was specific, as evidenced by the blocking of staining after addition of receptor peptide to the antibody (absorbed controls). CONCLUSION: The parathyroid hormone/parathyroid hormone-related protein receptor is widely expressed in the human uteroplacental unit. The cellular localizations of the receptor in smooth muscle reflect the ability of parathyroid hormone-related protein to relax both uterine and vascular smooth muscle. The presence of novel autocrine and paracrine systems in the human uteroplacental unit is suggested by the finding that the same cells or adjacent cells produce both parathyroid hormone-related protein and its receptor.

Cells, Cultured↗

Mechanical stretch increases secretion of parathyroid hormone-related protein by cultured bladder smooth muscle cells.

Parathyroid hormone-related protein (PTHrP) immunoreactivity has been detected in the bladder and increases in response to dilatation secondary to obstruction. The hypothesis that PTHrP could be increased solely by stretch rather than other possible in vivo variables was tested by stretching cultured bladder smooth muscle cells and analyzing the culture medium for this protein. In response to mechanical stretch, PTHrP was increased in smooth muscle cell cultures. Immunoradiometric assay revealed maximal rates of secretion for the first eight hours. Comparison of percent change in PTHrP secretion of flexed cells for the various flex parameters revealed a difference (p = .006) when the degree of stretch (i.e. percent elongation) was altered. The protein synthesis inhibitor cycloheximide inhibited basal and stretch-induced PTHrP secretion. PTHrP (1-100 nM) relaxed carbachol-contracted bladder body and base by 15% and 45% respectively. PTHrP did not affect bladder contractions induced by potassium (124 mM) or alpha-beta MeATP (10 microM). Increased PTHrP secretion in response to stretch of smooth muscle raises the possibility of an autocrine action to relax the bladder during filling. PTHrP may also exert a paracrine action on vessels regulating blood flow during bladder filling or it may modulate neural activity.

Animals↗

Developmental outcomes of children with myelomeningocele: prenatal predictors.

OBJECTIVE: The purpose of the current investigation was to determine cognitive developmental outcomes for a cohort of children with prenatally detected myelomeningocele and to determine whether the variables of (1) severity of ventriculomegaly and (2) anatomic level of lesion were predictive of cognitive development. STUDY DESIGN: Prenatal ultrasonographic examinations were reviewed by a single perinatologist to determine the degree of ventriculomegaly and the anatomic level of the lesion. Ventriculomegaly was defined as a lateral ventricular atrial width > 10 mm. Anatomic level of lesion was defined as (1) thoracic, (2) high lumbar, (3) midlumbar, (4) low lumbar-high sacral, or (5) sacral. Cognitive developmental quotients for surviving children were determined by one of two developmental pediatricians with use of a modified version of the Clinical Adaptive Test/Clinical Linguistic Auditory Milestone Scale, a measure of visual-motor and language abilities. RESULTS: The mean cognitive developmental quotient for subjects with absent to mild ventriculomegaly was 90.3 (range 54 to 120, SD 17.4), whereas the mean cognitive developmental quotient for those with moderate to severe ventriculomegaly was 74.0 (range 65 to 100, SD 17.1) (p < 0.01). There was a negative correlation between the degree of ventriculomegaly and the cognitive developmental quotient (r = -0.43, p < 0.025) and a positive correlation between the level of the lesion and the cognitive developmental quotient (r = 0.50, p < 0.01). CONCLUSIONS: The degree of ventriculomegaly determined on high-resolution prenatal ultrasonography is predictive of early cognitive development in children with myelomeningocele, with worsening ventriculomegaly being associated with lower cognitive developmental quotients. The anatomic level of the lesion also has predictive value, with lower level lesions being associated with more favorable cognitive outcomes. However, because of the high degree of variance in developmental quotients within the two ventriculomegaly groups, we advise clinicians to use caution in the interpretation and use of our data.

Cerebral Ventricles↗