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Biomedical subjects

J Hobbins

Publications and source records attributed to J Hobbins.

12 recordsLinked to original sources
PubMed2001

In utero gene delivery by intraamniotic injection of a retroviral vector producer cell line in a nonhuman primate model.

In utero gene therapy (IUGT) offers the promise of treating a wide variety of genetic diseases before the development of disease manifestations. The most convenient and potentially easiest method of targeting the fetus is through injection into the amniotic cavity. For long-term correction of genetic defects, retroviral vectors have great potential as a tool for gene therapy strategies. However, retroviral vectors are limited by growth to low titers. In an attempt to increase the amount of vector particles delivered and assess the potential of intraamniotic administration, we injected a retroviral vector producer cell line encoding the lacZ gene into the amniotic fluid of a nonhuman primate model. After birth the infants were analyzed for vector-mediated transduction. Two of four fetuses were successfully transduced, with transgene expression detected in the esophagus, trachea, and stomach. In some sections of tissue, nearly 100% of the cells lining the lumen of these tissues were positive for transduction. Although successful, the limited number of tissues in which transduction was observed led to an in vitro analysis of the effects of amniotic fluid (AF). The presence of amniotic fluid inhibited transduction by 99%. AF affected both the transducing activity of the vector and the health of the packaging cells. The negative effects of AF were gestational age dependent; greater inhibition was observed from AF collected at later stages of pregnancy. The fact that transduction was successful despite these negative effects indicates that this approach is a promising strategy for gene therapy.

3T3 Cells↗
PubMed2000

Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group.

OBJECTIVES: Patients admitted with an acute episode of preterm labor who respond to early intravenously administered tocolysis remain at risk of having subsequent episodes of preterm labor and preterm delivery. Several pharmacologic agents have been used in an attempt to reduce subsequent episodes of preterm labor, and all are associated with significant side effects. Atosiban, an oxytocin receptor antagonist, is effective in the treatment of an acute episode of preterm labor. This study was designed to compare the efficacy and safety of atosiban with those of placebo maintenance therapy in women with preterm labor who achieved uterine quiescence with intravenous atosiban. STUDY DESIGN: A multicenter, double-blind, placebo-controlled trial was designed for patients in preterm labor who responded to early intravenous treatment with atosiban. Five hundred thirteen patients were randomly assigned to receive maintenance therapy, 252 to receive atosiban, and 251 to receive matching placebo. Maintenance therapy was administered as a continuous subcutaneous infusion, via pump, of 30 microg/min to the end of 36 weeks' gestation. The primary end point was the number of days from the start of maintenance therapy until the first recurrence of labor. A secondary end point was the percentage of patients receiving subsequent intravenous atosiban therapy. RESULTS: The time (median) from the start of maintenance treatment to the first recurrence of labor was 32.6 days with atosiban and 27.6 days with placebo (P =.02). At least one subsequent intravenous atosiban treatment was needed by 61 atosiban patients (23%) and 77 placebo patients (31%). Except for injection site reactions, adverse event profiles of atosiban and placebo were comparable. There were 4 neonatal deaths reported in the atosiban group and 5 in the placebo group after the start of maintenance therapy. Infant outcomes (including birth weight) were comparable between maintenance and treatment groups. CONCLUSIONS: Maintenance therapy with the oxytocin receptor antagonist atosiban can prolong uterine quiescence after successful treatment of an acute episode of preterm labor with atosiban. Treatment was well tolerated.

Adult↗
PubMed1999

Measuring disability and outcomes in routine practice with the FACE Core Assessment.

The authors describe the results of an outcome study of 87 psychiatric inpatients and outpatients using a generic assessment and outcome measurement tool, the FACE Core Assessment. The results suggest that the multiaxial structure of the assessment tool has the potential to be used for the routine measurement of clinical outcomes as well as for multidisciplinary assessment.

Adult↗
PubMed1997

Morphometry of fetal growth.

Intrauterine growth retardation (IUGR) complicates about 5% of all pregnancies and is responsible for substantial perinatal mortality and morbidity. With ultrasound, it is possible to assess fetal brain growth indirectly by measurement of the biparietal diameter, head circumference and transcerebellar diameter. As liver size is affected most profoundly by IUGR, measurement of the abdominal circumference of the fetus provides the earliest evidence of fetal growth restriction. Placental size, assessed with ultrasound, can also indicate the severity of the condition. Once a fetus is diagnosed as having IUGR, its well-being can be monitored with standard heart-rate testing and ultrasound assessment of fetal behaviour. Doppler analysis of the wave form of the fetal arterial and venous circulation hold the greatest promise for managing pregnancies complicated by IUGR.

Biometry↗
PubMed1995

First-trimester endocervical irrigation: feasibility of obtaining trophoblast cells for prenatal diagnosis.

We sought to determine the feasibility of obtaining trophoblast cells for first-trimester prenatal diagnosis using endocervical irrigation. We studied 20 pregnant patients between 7-10.5 weeks' gestation who presented for elective pregnancy termination. Under ultrasound guidance, a specially designed plastic catheter was advanced to the level of the internal cervical os. Gentle flushing and aspiration was performed with 3 mL of normal saline. The material obtained was fixed and stained. A placental pathologist identified trophoblast cells using light microscopy. In another five cases, we attempted to culture the endocervical washings. Trophoblast cells were identified by microscopy after staining the cultured material with an anti-alpha-hCG-antibody bound stain. In ten of 20 cases (50%), trophoblast material was retrieved on irrigation. Of the five additional cases on which culture was attempted, trophoblast was successfully cultured in one, the results were equivocal in two, and culture was unsuccessful in the other two. Trophoblast cells for prenatal diagnosis can be obtained in a significant percentage of cases by first-trimester endocervical irrigation. The advantages of irrigation include technical simplicity, brief duration (less than 3 minutes), and suitability to first-trimester diagnosis. Further testing is necessary to determine the risks.

Cells, Cultured↗
PubMed1988

Ultrasonographic assessment of gestational age with the distal femoral and proximal tibial ossification centers in the third trimester.

A prospective sonographic evaluation of the distal femoral and proximal tibial epiphyseal ossification centers in 228 normal pregnant women was carried out from 28 to 40 weeks' gestation. The mean gestational age at which the distal femoral epiphysis and proximal tibial epiphysis were imaged was 34 and 38 weeks, respectively. The distal femoral epiphysis was not identifiable before 28 weeks but was observed in 72% of fetuses at 33 weeks and in 94% of fetuses at 34 weeks' gestation. The presence of a distal femoral epiphysis measuring 1 or 2 mm was associated with a gestational age of greater than 33 weeks in 87.0% of fetuses, whereas a distal femoral epiphysis measuring greater than or equal to 3 mm was associated with a gestational age greater than 37 weeks in 85% of fetuses. The proximal tibial epiphysis, which was absent before 34 weeks' gestation, was observed in 56% of fetuses at 36 weeks, in 80% of fetuses at 37 weeks, and in 100% of fetuses at 39 weeks of gestation. The presence of a proximal tibial epiphysis of 1 or 2 mm was associated with a gestational age of greater than 36 weeks in 88% of fetuses, whereas a proximal tibial epiphysis greater than or equal to 3 mm was associated with a gestational age of greater than 38 weeks in 94% of fetuses. The sonographic evaluation of distal femoral epiphysis/proximal tibial epiphysis can be used as independent markers for estimation of gestational age during the third trimester, a period in which standard fetal biometric estimates of gestational age are least accurate.

Epiphyses↗
PubMed1987

A sonographic screening method for Down syndrome.

We describe a potential screening method for the second trimester detection of the fetus with Down syndrome by the use of standard sonographic biometry. Retrospective assessment of the biparietal diameter, femur length, and biparietal diameter/femur length ratio in 55 fetuses with Down syndrome and 544 control fetuses was performed at two medical centers. Adequate numbers of cases and controls were available to permit statistically significant comparisons between the groups at 15 to 23 weeks' gestation. Fetuses with Down syndrome displayed no statistically significant differences in the cephalic index or the biparietal diameter compared with controls at a given gestational age. Significant femur length shortening was observed, but the greatest statistical difference was noted for the biparietal diameter/femur length ratio. This ratio was found to decrease with gestational age in the normal population and was consistently elevated in the Down syndrome population (compared with control) throughout the second trimester. With a cutoff value of 1.5 SD above the normal population mean for the biparietal diameter/femur length ratio, 50% to 70% of fetuses with Down syndrome could be identified in 6% of the total population (p less than 0.0001). This preliminary study suggests that the biparietal diameter/femur length ratio may prove superior to current Down syndrome screening methods and, as a third independent variable, may significantly enhance the sensitivity and specificity of combined maternal age/maternal serum alpha-fetoprotein screening modalities.

Down Syndrome↗
PubMed1987

Sonographic features of the triploid fetus.

The sonographic characteristics of six viable triploid fetuses, with gestational ages ranging from 16 to 33 weeks, are presented. Each pregnancy was associated with decreased amniotic fluid volume, a significant lag in biparietal diameter and femur length, and severe head-to-body disproportion. No placental abnormalities were noted on ultrasound and only one placenta demonstrated hydropic change (15% to 20% of villi) on pathologic examination. Since the nonmolar triploid fetus often presents with unexplained intrauterine growth retardation, identification of its characteristic sonographic features allows for karyotype confirmation and the avoidance of inappropriate obstetric management.

Female↗
PubMed1984

Coagulopathy associated with factor VIII inhibitor. A literature review.

Coagulopathy associated with factor VIII inhibitor is a potentially serious medical condition that may mimic the hemostatic failure seen in hemophilia A. This disorder may be detected first during pregnancy or the postpartum period and may cause life-threatening hemorrhagic diathesis. Thirty-three cases of coagulopathy associated with factor VIII inhibitor in the peripartum period have been reported.

Adolescent↗
PubMedDate not supplied

Microchimerism and tolerance following intrauterine transplantation and transfusion for alpha-thalassemia-1.

A fetus homozygous for alpha-thalassemia-1 was given haploidentical paternal CD34 cells at 13, 19 and 24 weeks' gestation and supported through pregnancy by blood transfusion. The fetal hematocrit ranged between 27 and 47% and between one half and three quarters of this hemoglobin was of recipient (Bart's) type. Intrauterine growth proceeded normally and no significant fetal hydrops was detected. Tests for donor HLA antigens, and alpha-globin DNA, were negative on fetal blood samples drawn before birth. A positive signal for alpha-globin DNA was obtained from cord blood and from marrow obtained at 3 months of age, suggesting that some donor stem cells had persisted in the recipient. The infant's blood mononuclear cells showed little proliferative and no cytotoxic response to the donor while responses to a third party were present. Additional paternal CD34 cells given at 3 months age did not reduce transfusion dependency in the subsequent 6 months. Our results show that repeated transfusions can support an alpha-thalassemia-1 fetus through pregnancy, in this instance without significant birth defects or apparent hypoxic tissue injury. The donor stem cells did not have a survival advantage compared with endogenous stem cells, but appeared to survive in the recipient as judged by the persistence of an alpha-globin DNA signal. In vitro studies of alloreactivity suggest tolerization of the host to the donor's MHC disparity. Future efforts will focus on exploiting this tolerance to improve the level of donor chimerism.

Antigens, CD34↗