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Biomedical subjects

R J Carpenter

Publications and source records attributed to R J Carpenter.

At least 19 recordsLinked to original sources

The risk and efficacy of chorionic villus sampling in multiple gestations.

Chorionic villus sampling (CVS) in the first trimester of pregnancy provides a safe and effective method for the early prenatal diagnosis of cytogenetic abnormalities in multiple gestations. In this multicentre study involving 126 twin and 2 triplet gestations primarily at risk because of advanced maternal age, the overall success rate of obtaining an adequate villus sample from each fetus was 99.2 per cent. For women of advanced maternal age, the rate of combined losses of chromosomally normal fetuses due to spontaneous abortion, stillbirths, and neonatal deaths was 5.0 per cent, compared with a 4.0 per cent total loss rate following CVS in singleton pregnancies derived from the same population (Rhoads et al., 1989). There was a 100 per cent success rate in obtaining a cytogenetic analysis; a cytogenetic abnormality was present in five of the multiple gestations (3.9 per cent) and involved seven fetuses (2.7 per cent). There were no diagnostic errors and no cases of normal cytogenetic diagnosis followed by the birth of a cytogenetically abnormal newborn. Based on cases of XX/XY admixture, cell contamination derived either from maternal decidua or the other twin occurred in 6 of 256 samples (2.3 per cent), giving an overall estimate of the frequency of cell contamination of 4.6 per cent; these cases did not present a diagnostic problem. However, there were two cases (0.8 per cent) in which the fetal sex was incorrect, due either to complete maternal cell contamination or to the possibility that in error one twin was sampled twice.

Abortion, Induced

Prenatal diagnosis of 21-hydroxylase deficiency congenital adrenal hyperplasia using the polymerase chain reaction.

We present an improved method for the prenatal diagnosis of congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. The polymerase chain reaction (PCR) was used to analyze DNA from an affected index case, the parents, and a cultured chorionic villus sample, for point mutations in the steroid 21-hydroxylase (CYP21) gene. We can predict that the fetus is an unaffected carrier.

Adrenal Hyperplasia, Congenital

Do abnormal Starling forces cause fetal hydrops in red blood cell alloimmunization?

OBJECTIVE: The purpose of the current investigation was to ascertain whether derangements in umbilical venous pressure and plasma colloid osmotic pressure are involved in the pathophysiologic condition of immune hydrops fetalis. STUDY DESIGN: Umbilical venous pressure (corrected for ambient amniotic fluid pressure) and colloid osmotic pressure were measured during intravascular transfusion. Fetal hydrops was defined as the presence of ascites by ultrasonography. The Mann-Whitney test was used for comparison of groups; a value of p < 0.05 was considered statistically significant. RESULTS: Fifteen hydropic fetuses were matched for gestational age with 15 nonhydropic fetuses also undergoing intrauterine transfusion for anemia. On comparison with their nonhydropic counterparts, hydropic fetuses had a statistically lower colloid osmotic pressure. Umbilical venous pressure was higher and the colloid osmotic pressure--umbilical venous pressure gradient was lower in association with fetal hydrops although these differences did not achieve statistical significance. CONCLUSION: Mild abnormalities of intravascular Starling forces may play a role in the formation of hydrops in anemic fetuses.

Blood Transfusion, Intrauterine

Indomethacin for the treatment of symptomatic leiomyoma uteri during pregnancy.

Pain secondary to carneous degeneration is the most common complication of leiomyoma uteri during pregnancy. Conventional therapy utilizing bed rest and parenteral narcotic analgesics may often be ineffective. We retrospectively reviewed seven cases of degenerating fibroids complicating pregnancy where the prostaglandin synthetase inhibitor, indomethacin (25 mg orally every 6 hours), was used to treat symptoms of pain. In all cases, relief of symptoms was achieved within 48 hours of initiation of therapy. Two patients required a second course of therapy, and one patient required a third course. Mean duration of therapy was 12 days. One fetus developed transient constriction of the ductus arteriosus and transient oligohydramnios. Two pregnancies aborted, one at 22.9 and one at 22.3 weeks; however, no perinatal complications were directly attributable to indomethacin. The five term deliveries were of healthy normal infants. These retrospective data suggest that indomethacin may be effective in the treatment of pain associated with degenerating uterine leiomyomas in pregnancy.

Adult

Continuous subcutaneous terbutaline pump therapy for premature labor: safety and efficacy.

To assess the usefulness of a continuous subcutaneous pump infusion of terbutaline for long-term tocolysis, we used this modality in 13 patients in whom other tocolytic regimens had failed. The mean (+/- standard deviation) maternal age was 29.9 +/- 3.8 years. The study population included 10 singleton gestations, two sets of triplets, and one twin pregnancy. In three cases, the terbutaline pump was thought to have been successful (duration of pump therapy, 52.7 +/- 20.9 days; gestational age at delivery, 37.1 +/- 1.3 weeks), whereas in six cases marginal success was achieved (duration, 42.2 +/- 27.7 days; gestational age at delivery, 33.8 +/- 2.6 weeks). In the remaining four patients, pump therapy was discontinued after 2 to 23 days because of maternal complications. In contrast to previous reports, we achieved only limited success with the subcutaneous terbutaline pump in the small number of patients studied.

Adult

Evolution of hydranencephaly following intracerebral hemorrhage.

A circumscribed hyperechoic mass in the mid-portion of the left cerebral hemisphere was the presenting ultrasonographic finding in a 30-week fetus. With repeat ultrasound studies, this echo-dense mass became more sonolucent. In addition, there was an increased fluid accumulation and loss of identifiable cerebral cortex over the left parietal and occipital lobes. The patient underwent induction of labor because of progressive intracranial fluid accumulation with subsequent macrocephaly. The infant died on the fourth day of life. At necropsy, an organizing hematoma with admixtures of fresh and moderately degraded old blood was found in the left hemisphere. There was extensive resorption of the underlying cortex, leaving only a fluid-filled cavity with a meningeal covering. We believe the progressive changes that occurred after fetal intracerebral hemorrhage ultimately resulted in hydranencephaly.

Adult

Intravascular transfusion of fetuses with rhesus incompatibility: prediction of fetal outcome by changes in umbilical venous pressure.

OBJECTIVE: We examined whether abnormal elevations in umbilical venous pressure during intravascular transfusion predict post-transfusion mortality. METHODS: Umbilical venous pressures were measured during intravascular transfusion of human fetuses with Rhesus incompatibility. Five fetuses died within 24 hours after transfusion and nine fetuses survived the procedure. RESULTS: Survivors and non-survivors were similar in demographic and clinical data, as well as in transfusion characteristics. The only difference between the groups was the change in umbilical venous pressure during the transfusion: 5.0 +/- 6.3 mmHg for survivors versus 18.1 +/- 10.4 mmHg for non-survivors (P = .01). An increase in the umbilical venous pressure of 10 mmHg or more predicted fetal death with a sensitivity of 80% and specificity of 89%. CONCLUSION: Based on these results, we have modified our transfusion technique. If the change in umbilical venous pressure during intravascular transfusion approaches 10 mmHg, we discontinue the procedure. If the change in pressure exceeds 10 mmHg during transfusion, we remove blood and replace it with an equal volume of saline.

Blood Transfusion, Intrauterine

Doppler assessment of renal blood flow velocity waveforms in the anemic fetus before and after intravascular transfusion for severe red cell alloimmunization.

Image-directed pulsed Doppler ultrasonography demonstrated a decrease in the pulsatility index of the renal artery in 9 anemic fetuses (less than 30 weeks, menstrual age) soon after intravascular transfusion. The pulsatility index returned to pretransfusion values the day following the transfusion. End diastolic blood velocity in the renal artery could not be measured before the transfusion, was detectable immediately after the procedure, and was again nonmeasurable one day after the transfusion. These data suggest an increase in renal blood flow in the anemic fetus soon after intravascular transfusion to eliminate excess fluid.

Anemia

Spontaneous rupture of liver during pregnancy: current therapy.

Spontaneous hepatic rupture secondary to severe pregnancy-induced hypertension is associated with a high rate of maternal and fetal mortality. Numerous types of surgical management have been described, but a uniform surgical approach has not been accepted. The purpose of this review was to examine modes of surgical therapy reported in the literature since 1976, as well as the 11-year experience at our institution. Twenty-eight cases were extracted from the literature and seven more were identified at our institution. The incidence in our population was one per 45,145 live births. Among 27 cases managed by packing and drainage, an 82% overall survival was achieved, whereas only 25% of eight patients undergoing hepatic lobectomy survived (P = .006). Hepatic hemorrhage with persistent hypotension unresponsive to blood products should be managed by evacuating the hematoma, packing the damaged liver, and draining the operative site. More aggressive surgical techniques, such as hepatic artery ligation or hepatic lobectomy, should be reserved for refractory cases.

Adult

Characterization of cytokines present in middle ear effusions.

Retention of inflammatory mediators and cells in the middle ear cleft during chronic otitis media with effusion (COME), results in ongoing inflammation with the potential for pathologic changes and hearing loss. Cytokines are glycoproteins produced by macrophages and other cells. Activities of cytokines include fever production, osteoclast, fibroblast, phagocyte and cytotoxic cell activation, regulation of antibody formation, and inhibition of cartilage, bone and endothelial cell growth. Using enzyme-linked immunospecific assays we measured levels of six cytokines in middle ear effusions (MEE) from children with COME. Significant levels of four cytokines: interleukin-1-beta (greater than 50 pg/ml), interleukin-2 (greater than 300 pg/ml), tumor necrosis factor-alpha (greater than 40 pg/ml), and gamma-interferon (greater than 6.25 pg/ml) were found in 51%, 54%, 63%, and 19% of MEE, respectively. In contrast, levels of a fifth cytokine, granulocyte-macrophage colony-stimulating factor, and a sixth cytokine, interleukin-4, were undetectable. Age was observed to have a significant effect on the levels of specific cytokines. Interleukin-1 (IL-1) correlated inversely (P less than .02) with age such that the younger the child, the higher the level of IL-1 in MEE. Tumor necrosis factor-alpha (TNF) correlated directly (P less than .005) with age such that the older the child, the higher the level of TNF in MEE. Children undergoing tympanostomy on multiple occasions had average MEE TNF levels (234.2 +/- 109.1 pg/mg total protein) that were nearly 14 times higher (P less than .005) than those from children undergoing their first tympanostomy (16.9 +/- 3.0 pg/mg total protein). Thus IL-1 correlated with the early stages of COME, while TNF correlated with persistence of disease. The presence of these cytokines in MEE may be responsible for the mucosal damage, bone erosion, fibrosis, and resulting hearing loss seen in some cases of COME.

Aging

Fetal blood sampling demonstrating chimerism in monozygotic twins discordant for sex and tissue karyotype (46,XY and 45,X)

Fetal blood sampling has been used in the genetic work-up of twin gestations for rapid karyotyping. We present a case of twins which on ultrasound evaluation revealed hydrops fetalis in one twin and a normal second twin. Fetal blood sampling revealed the presence of mosaicism for 46,XY/45,X in both twins. HLA antigen testing showed the twins to be identical. The patient elected pregnancy termination. Blood chromosomal analysis after delivery revealed both twins to have 46,XY/45,X mosaicism, but the twin with signs of hydrops fetalis had tissue chromosomes of 45,X and the normal twin had tissue chromosomes of 46,XY. Amniotic fluid chromosomal analysis revealed 46,XY in twin A and 45,X in twin B. This represents a case of identical (monozygotic) twins with sex discordance. In this case, there was the probable occurrence of post-zygotic chromosomal non-disjunction leading to the discordancy of the sex in this set of twins. With the presence of vascular communication in monozygotic twins, there is the possibility of exchange of blood in monozygotic twins and the result of blood chimerism in twins.

Adult

Placental transfer of indomethacin in the human pregnancy.

Little is known about the placental transfer of indomethacin in the human pregnancy. Twenty-six pregnant patients (gestational age, 29.4 +/- 0.5 weeks) were given a 50 mg oral dose of indomethacin 6.08 +/- 0.07 hours before 42 cordocenteses undertaken for standard indications. Maternal serum, fetal serum, and amniotic fluid levels were measured at the time of each procedure. Maternal indomethacin levels were not significantly different from corresponding fetal levels (218 +/- 21 vs 219 +/- 13 ng/ml). The maternal/fetal serum ratio (0.97 +/- 0.07) was not found to vary with gestational age (R = -0.07, p = 0.66). Fetal serum levels were significantly higher than corresponding amniotic fluid levels (219 +/- 16 vs. 21 +/- 2 ng/ml; p less than 0.001). The fetal/amniotic fluid ratio (10.0 +/- 1.2) did not vary with gestational age (R = 0.33, p = 0.11). Indomethacin crosses the human placenta easily throughout gestation; only small amounts of the unchanged drug are found in the amniotic fluid.

Amniotic Fluid

Acute fetal hemodynamic alterations after intrauterine transfusion for treatment of severe red blood cell alloimmunization.

One of the compensatory hemodynamic mechanisms seen in the anemic human fetus is an increased cardiac output. With Doppler techniques, cardiac output was measured in 21 fetuses before and immediately after 38 intrauterine transfusions for severe red cell alloimmunization. Umbilical venous pressures were measured before and after transfusion; amniotic fluid pressure was also quantitated. After subtraction of amniotic pressure, umbilical venous pressure increased by 1.7 +/- 2.8 mm Hg (p less than 0.01). Left and right ventricular output declined by 19% and 22%, respectively (p less than 0.001). Four factors are known to affect cardiac output: heart rate, cardiac contractility, preload, and afterload. Fetal heart rate and mean acceleration, a measure of myocardial contractility, were unchanged after transfusion. A calculated mean increase in the fetoplacental volume of 18% in conjunction with an increase in umbilical venous pressure would indicate that cardiac preload was increased. We propose that intravascular intrauterine transfusion leads to an increased cardiac afterload, possibly by increasing blood viscosity. The fetal heart responds to the increased afterload by a decrease in stroke volume, leading to a fall in cardiac output.

Blood Transfusion, Intrauterine

Flow velocity waveforms of the vascular system in the anemic fetus before and after intravascular transfusion for severe red blood cell alloimmunization.

Sixteen intravascular transfusions were performed in 16 anemic human fetuses. To investigate the status of the vascular system with Doppler ultrasonography before and after correction of anemia, pulsatility index values were obtained for the flow velocity waveforms of the middle cerebral artery, internal carotid artery, anterior cerebral artery, thoracic aorta, abdominal aorta, renal artery, femoral artery, and umbilical artery before and the day after the correction of anemia. The fetuses were divided into two groups: (1) fetuses with a hematocrit level between 2 and 4 SDs below the normal mean value for gestational age and (2) fetuses with a hematocrit value less than 4 SDs below the normal mean value for gestational age. No significant differences were observed in the pulsatility index values of the vessels studied before and after correction of anemia in both groups of fetuses. These data suggest that the pulsatility index cannot be used as an indicator of fetal anemia at the hematocrit values studied.

Anemia, Hemolytic, Autoimmune