Biomedical subjects

K Blakemore

Publications and source records attributed to K Blakemore.

At least 19 recordsLinked to original sources

PubMed2002

Early second trimester prenatal diagnosis of Neu-Laxova syndrome.

Neu-Laxova is a rare, uniformly lethal, autosomal recessive condition with characteristic limb posturing, facial dysmorphic features, and central nervous system abnormalities. Forty-two cases of Neu-Laxova syndrome have been reported, with only four of these diagnosed prenatally. Three of the four cases were diagnosed at or after 32 weeks' gestation. The fourth case was diagnosed at 22 weeks' gestation in a patient who was followed with serial ultrasound studies due to having a prior affected child. At 19 weeks' gestation, we present the earliest reported prenatal diagnosis of Neu-Laxova syndrome in a primigravida with a non-informative family history.

Adult↗

PubMed2001

The degree of antenatal ventriculomegaly is related to pediatric neurological morbidity.

OBJECTIVE: Our hypothesis was that the degree of antenatally diagnosed cerebral ventriculomegaly is related to aneuploidy, perinatal mortality and long-term neurological morbidity. METHODS: Ninety-one cases of ventriculomegaly identified from 1 June 1994 to 1 July 1999 were examined for prenatal, intrapartum and neonatal complications. Pediatric follow-up was reviewed for infants with ventriculomegaly from birth up to as long as 4 years. Minor neurological morbidity was defined as a score of 70-80 on the clinical adaptive test/clinical linguistic and auditory milestone scale and included mild motor or language delay. Major morbidity included a score of < 70, evidence of cerebral palsy, or seizure disorder. The incidence of neurological complications was compared, on the basis of the degree of ventriculomegaly, with group 1 being > 10-15 mm and group 2 being > 15 mm. RESULTS: Twenty-seven cases (18 with neural tube defects and nine with holoprosencephaly) were excluded. Among the remaining 64 patients, 39 had a ventricular diameter of > 10-15 mm and comprised group 1. Five of the 39 cases (12.8%), all with other ultrasound anomalies, elected to terminate. The incidence of aneuploidy in group 1 was 14.2%. Among the 19 cases with isolated ventriculomegaly, 17 (89%) were normal and two (11%) had minor neurological morbidity. In group 1 there were two cases associated with cytomegalovirus (CMV) infection. Of the 25 cases in group 2, eight (32%), all with other ultrasound anomalies, elected to terminate. The incidence of aneuploidy in group 2 was 17.4%. For the nine cases with isolated ventriculomegaly of > 15 mm, one (11%) was normal (p < 0.001), five (56%) had minor neurological morbidity requiring a ventriculoperitoneal shunt (p = 0.035), and three (33%) had major neurological morbidity (p = 0.045) when compared to cases of isolated ventriculomegaly in group 1. There was one case of CMV infection in group 2. All perinatal deaths in both groups were associated with other anomalies. CONCLUSIONS: Amniocentesis to determine karyotype and the presence of CMV is warranted for all cases of ventriculomegaly of > 10 mm. The degree of antenatal ventriculomegaly is related to pediatric neurological morbidity and, when it is > 15 mm, it is associated with an increase in abnormal neurological development.

Aneuploidy↗

PubMed2001

University hospital-based prenatal care decreases the rate of preterm delivery and costs, when compared to managed care.

OBJECTIVE: Our purpose was to compare the rate of recurrent preterm delivery and the combined costs of mother/infant care for patients with a history of preterm delivery cared for in an inner city hospital house staff (HS) clinic versus an inner city managed care organization (MCO). METHODS: A retrospective cohort study was conducted. The groups consisted of 96 patients with a history of preterm delivery who were cared for by the HS clinic and 164 patients cared for in a neighborhood MCO. All patients with a history of previous preterm delivery who delivered at the Johns Hopkins Hospital between 1 January 1994 and 31 December 1996 were included in the study. The groups were examined regarding source of prenatal care for the subsequent pregnancy (HS vs. MCO), baseline demographics, intensity of prenatal care, maternal and neonatal outcomes and total cost of the provision of care. RESULTS: There were no differences in baseline demographics between the groups. There was a higher rate of recurrent prematurity for patients cared for by the MCO (HS, 24% vs. MCO, 36%, p = 0.04). Mean total mother/infant costs were also higher in the MCO group ($13565) when compared to the HS group ($9082), (p = 0.02). CONCLUSION: While some MCOs may provide cost savings for some low-risk populations, our study demonstrates that this health-care delivery system resulted in greater total expenditures for patients with a history of preterm delivery.

Adult↗

PubMed1999

A human-murine chimera model for in utero human hematopoietic stem cell transplantation.

To date, 16 in utero hematopoietic stem cell (HSC) transplants for diseases other than immunodeficiency disorders have been reported. No therapeutic level of engraftment was detected in 15 of these transplants. To overcome engraftment failure, we transplanted a very large number (5 billion paternal CD34+ cells/kg) of HSCs to a fetus with leukodystrophy during the first trimester of gestation. As reported previously, the fetus died in utero 7 weeks after the procedure and the cause of death appeared to be overwhelming donor engraftment. In the present investigation, we developed a human-murine chimera model to test for the optimal donor cell dose for human in utero transplantation. We found a strong correlation between the level of donor engraftment in three human fetuses transplanted for leukodystrophy during the first trimester of gestation and the results of parallel xenotransplants of the same human donor cells using the NOD/SCID mouse model. This small animal model appears to predict both extremes of hyperengraftment (seen in the first human fetus transplanted) and engraftment failure (seen in the second and third human fetuses transplanted in utero). These and future correlated clinical and laboratory assay results may be useful for the development of in utero transplants for a variety of congenital disorders.

Animals↗

PubMed1998

A novel factor produced by placental cells with activity against HIV-1.

The factors controlling the dynamics of HIV-1 transmission from mother to infant are not clearly known. Previous studies have suggested the existence of maternal and placental protective mechanisms that inhibit viral replication in utero. Preliminary studies from our laboratory revealed that supernatant from placental stromal cells protected HIV-1-infected PBMC from virus-induced apoptosis and suppressed virus production. We have attempted to characterize the antiviral activity of this placental factor (PF) and delineate the stages of HIV-1 replication affected. This activity was not due to the presence of any known cytokine reported to have anti-HIV effect. Direct exposure to PF had no suppressive effect on the infectivity of cell-free HIV-1, and envelope-mediated membrane fusion appeared to be unaffected. Western blot analysis of HIV-1 from infected PBMC treated with PF revealed that expression of all viral proteins was reduced proportionately, both intracellularly and in released virions. However, exposure of HIV-1-infected cells to PF resulted in production of virions with 10-100-fold-reduced infectivity. PF-treated virions contained two- to threefold reduced ratios of cyclophilin A:Gag protein as compared with untreated virus. Reduced cyclophilin A content resulting in decreased binding of cyclophilin A to Gag could account, in part, for the observed reduction in infectivity. Our results suggest that placental cells produce an antiviral factor that protects the fetus during gestation and may have therapeutic potential.

Anti-HIV Agents↗

PubMed1998

Lack of prenatal care increases the rate of recurrent preterm delivery and health care costs when compared to university hospital-based prenatal care.

Objective: To compare perinatal outcomes and total health care costs for patients with a previous history of preterm delivery (PTD) cared for in an inner-city university hospital house staff (HS) clinic vs pregnant patients who have not received any prenatal care (NPC).Study Design: We conducted a retrospective review of pregnant women with a history of PTD delivered at our institution between January 1994 and December 1996. Inclusion criteria were a history of at least one previous PTD. Prenatal care was given in a comprehensive setting in a teaching hospital. Exclusion criteria were infants with major malformations and multiple gestations. Data were obtained on maternal demographics and history of prenatal visits.Results: The study groups consisted of 96 HS and 53 NPC patients. There were no differences in maternal demographics, however, the number of prior preterm births was greater in the NPC group (1.59 vs 1.23, P =.003). The incidence of recurrent PTD (<34 weeks) was greater in the NPC group (49% vs 13%, P = <.001). The mean gestational age at time of delivery was decreased in the NPC group (33 weeks vs 37.2 weeks, P = <.001). The length of NICU stay was greater in the NPC group (15.6 vs 3.1 days, P =.001). The mean birth weight was less in the NPC group (2172 g vs 2786 g, P = <.001). The mean total mother-infant costs were significantly less in the HS group ($7,127 vs $18,047, P =.003). Even HS patients with only one prenatal visit had a significantly lower incidence of PTD (16% vs 75%, P =.04).Conclusions: Inner-city patients with a history of PTD who received even minimal prenatal care in a university HS clinic had a significantly lower incidence of recurrent PTD than those who had no prenatal care. Prenatal care also lowers total health care costs in women with a history of PTD. The coordinated multidisciplinary aspect of care provided at academic centers may have a positive impact on the problem of PTD.

Journal Article↗

PubMed1997

Engraftment following in utero bone marrow transplantation for globoid cell leukodystrophy.

To date, in utero bone marrow transplantation (BMT) has had limited success, largely because of poor donor engraftment. The poor engraftment is probably the result of performing the procedure late in gestation after significant fetal immunocompetence has developed and/or transplanting insufficient numbers of donor hematopoietic stem cells for competing successfully with ongoing fetal hematopoiesis. To overcome these problems, we performed in utero BMT on a fetus with globoid cell leukodystrophy during the first trimester of gestation using selected paternal bone marrow stem (CD34+) cells. CD34 selection allowed a substantially greater number of stem cells to be transplanted. Although the fetus died 7 weeks after the procedure (during the 20th week of gestation), full donor engraftment was established. Moreover, the cause of death appeared to be overwhelming donor engraftment and leukostasis with paternal myeloid cells infiltrating most tissues. The ability of in utero BMT to produce this degree of engraftment provides great promise for the use of this approach in the treatment of a variety of inherited disorders that can be diagnosed prenatally.

Bone Marrow Transplantation↗

PubMed1997

Indicators of platelet turnover in thrombocytopenic infants.

Glycocalicin has been found to be a marker of increased platelet turnover, while interleukin-6 may be increased in response to thrombocytopenia. We used these markers to study the pathophysiology of thrombocytopenia in newborn infants. Cord blood platelet counts were obtained from 499 infants. Thrombocytopenic infants (< 100,000/mm3) and a control group had ELISA assays for interleukin-6 and glycocalicin performed. The mean levels of glycocalicin and interleukin-6 were elevated in cord blood of thrombocytopaenic infants. Infants with intrauterine growth restriction and thrombocytopaenia had no detectable glycocalicin in their plasma, despite elevated levels of interleukin-6. This probably reflects impaired thrombopoiesis in these infants.

Blood Platelets↗

PubMed1996

The role of HLA antibodies in neonatal thrombocytopenia: a prospective study.

The role of HLA antibodies in neonatal alloimmune thrombocytopenia is controversial. We prospectively studied the sera of obstetric patients at delivery for HLA antibodies and correlated their presence with umbilical cord blood platelet counts. We studied 493 births at The Johns Hopkins Hospital comprising of 357 African American, 115 Caucasian, and 21 babies of other racial groups. One hundred and thirty nine mothers had HLA antibodies. Of these HLA alloimmunized mothers, only ten infants had platelet counts of 150,000/ microL or less. Three hundred and eight mothers with no detectable antibodies gave birth to 27 infants with platelet counts of 150,000/microL or less. Yates corrected Chi square analysis showed no significant relationship between maternal HLA alloimmunization and baby platelet count (p = 0.709). Only 8 of sixty cord sera from babies of HLA alloimmunized mothers were positive for HLA antibodies. The HLA cord blood antibody results were then correlated with the neonatal platelet counts. The Fisher's exact test showed no significant relationship between the presence of HLA antibodies in cord blood samples and neonatal platelet counts (p = 0.232). Although one third (31%) of mothers have HLA antibodies, neonatal thrombocytopenia is rarely associated with this finding. However, HLA antibodies can cross the placenta, and in these unusual cases, may be associated with a higher risk of neonatal thrombocytopenia.

Female↗

PubMed1995

Adherence of human immunodeficiency virus-infected lymphocytes to fetal placental cells: a model of maternal --> fetal transmission.

The precise timing and mechanism of in utero human immunodeficiency virus (HIV) infection are unknown, but transplacental transmission is likely. Term placentas from HIV+ pregnancies contain only rare HIV-infected cells whose origins and phenotypes remain controversial, and no correlation has been found between the presence of HIV in term placentas and transmission to offspring. Reports of trophoblast infectibility have not been reproducible and do not address the question of infection in the placental stroma, the cells in direct contact with fetal circulation. We report that primary cultures of fetal placental chorionic villus stromal cells, while not infectable in vitro, do support lethally irradiated HIV-infected peripheral blood mononuclear cells (PBMCs) in a form that permits rescue of HIV by activated PBMCs weeks later. Infected PBMCs adhere and become intimately associated with placental cells by a mechanism that is LFA-1 and CD4 independent but can be blocked by antibodies or soluble CD4 binding to cell surface-expressed HIV envelope. The ability to sustain infected irradiated cells was not shared by several trophoblast, fibroblast, or epithelial cell lines. This model has several features that are compatible with in utero transmission and allow testing of various agents proposed as interventions to block maternal-->fetal transmission. Placental stromal cells appear to inhibit apoptosis of HIV-infected, irradiated lymphocytes.

Antibodies, Monoclonal↗

PubMed1995

Gene frequencies of the five major human platelet antigens in African American, white, and Korean populations.

BACKGROUND: The study of the immunogenetics of the human platelet antigens is important to the improvement of diagnosis and genetic counseling and to the development of screening programs for women at risk of having babies with neonatal alloimmune thrombocytopenia. Description of the immunogenetics of the human platelet antigens in some racial groups has been incomplete. STUDY DESIGN AND METHODS: A reverse dot blot technique employing polymerase chain reaction-amplified genomic DNA was applied in genotyping the five major human platelet antigens in the following populations: 100 African American and 100 white women admitted to the obstetric unit at Johns Hopkins Hospital (Baltimore, MD) and 100 inpatients at Yonsei University (Seoul, Korea). RESULTS: The gene frequencies of HPA-2b (Koa) and HPA-5b (Bra) in African Americans were twice those in whites (African Americans: 0.18 and 0.21, respectively; whites: 0.09 and 0.11, respectively). There is a very low gene frequency of the HPA-1b (PIA2) allele in Koreans (0.005). No significant differences were found in the gene frequencies of the human platelet antigens in whites in this series and those in published European studies. CONCLUSION: These studies indicate a higher potential risk for alloimmunization to HPA-2 (Ko) and HPA-5 (Br) antigens in African Americans than in whites. In addition, the low gene frequency of HPA-1b (PIA2) in African Americans and Koreans suggests that alloimmunization to HPA-1a (PIA1) would be very unusual in these populations. These data may provide the basis for planning neonatal alloimmune thrombocytopenia screening programs in certain ethnic populations.

Antigens, Human Platelet↗

PubMed1995

A quantitative assay for subclassing IgG alloantibodies implicated in hemolytic disease of the newborn.

Traditionally, IgG subclassing has been performed using qualitative assays. Quantitation of IgG subclasses may have prognostic value in evaluating alloimmunized pregnancies. A quantitative enzyme-linked immunosorbent assay (ELISA) was implemented for measuring IgG subclasses of red blood cell (RBC) antibodies (AB) isolated by adsorption/elution from the sera of alloimmunized pregnant women. The assay is a sandwich enzyme immunoassay using monoclonal antibodies specific for the relevant IgG subclasses and anti-human IgG peroxidase conjugate to quantitate the amount of bound IgG. The sensitivities of the assay for IgG1, 2, 3, and 4, respectively, were 4, 23, 4 and 2 micrograms/l. The results for each subclass for a given AB were expressed as a percentage of the total. In a series of pregnant mothers with ABs: E (4), Fya (2), Jka (1) and S (1), the mean percentage +/- 1SD of each subclass was: IgG1 61 +/- 34; IgG2 14 +/- 22; IgG3 18 +/- 28 and IgG4 4 +/- 17. IgG1 or IgG3 accounted for greater than 50% of the AB subclass distribution in 5 cases that resulted in hemolytic disease of the newborn (HDN). Although only a small number of samples was studied, changes in the concentrations of IgG1 or IgG3 during gestation suggest a correlation with the presence or absence of HDN. The ELISA may be used to quantitate the IgG subclasses of RBC ABs and may be valuable in predicting the severity of HDN in alloimmunized pregnancies.

Blood Group Antigens↗

PubMed1993

Cook obstetrics and gynecology catheter multicenter chorionic villus sampling trial: comparison of birth defects with expected rates.

OBJECTIVE: The null hypothesis was that offspring of women undergoing first-trimester chorionic villus sampling do not experience a rate of birth defects exceeding background rates. STUDY DESIGN: Follow-up information regarding major malformations was prospectively sought on offspring of 4105 women undergoing first-trimester chorionic villus sampling from nine centers participating in a collaborative study with the Cook obstetrics and gynecology catheter. These data were compared with data from the Collaborative Perinatal Project and other registries. RESULTS: A total of 84 offspring with major malformations was identified (2.36%). Compared with background rates, there was no increase in the incidence of total malformations or specific malformations (including limb reduction defects) in the subjects. One institution experienced all three limb reduction defects in this series; the probability of this occurring by chance alone is < 1%. CONCLUSION: Chorionic villus sampling was not found to result in an increase in major birth defects or in specific categories of birth defects in this series.

Catheterization↗

PubMed1992

Chorionic villus sampling for fetal Rh typing: clinical implications.

OBJECTIVE: The prenatal Rh typing of red blood cells obtained by chorionic villus sampling was performed with an immune rosette technique. STUDY DESIGN: Ten Rh-negative pregnant women undergoing chorionic villus sampling at 9 to 11 weeks' gestation were studied at a large referral hospital. RESULTS: Accurate Rh phenotyping may be done on red blood cells obtained from chorionic villi weighing 2 to 8 mg. The preparations were shown to be greater than 90% fetal in origin as demonstrated by radial immunodiffusion quantitation of fetal hemoglobin-containing cells. Of the 10 fetuses typed in the first trimester nine of the pregnancies were carried to term. In all cases typing of red blood cells confirmed the antenatal fetal red cell typing. CONCLUSIONS: This study shows that antenatal Rh phenotyping may be performed as early as 9 to 11 weeks' gestation. This technique may be used in the management of pregnancies complicated by Rh incompatibility.

Blood Grouping and Crossmatching↗

PubMed1990

Fetal genitourinary tract anomalies: evaluation, operative correction, and follow-up.

The prenatal diagnosis of a genitourinary anomaly was made in 53 fetuses. Sonographic findings, antenatal course, and postnatal treatment and outcomes were examined. No interventional therapy was undertaken in utero, and the natural history could be examined in the 44 of 53 (83%) who did not electively terminate their pregnancies. Twenty-three of the total 53 (43%) had unilateral disease and 30 (57%) had bilateral involvement. Thirty-five of 53 (66%) survived, with 22 undergoing operative therapy postnatally. In all but one of the 35 survivors, the anomaly was isolated to the genitourinary tract, and the majority of surviving fetuses had unilateral disease. Oligohydramnios was present in only three of 35 survivors, and none had severe oligohydramnios. Nine of 53 women underwent termination of pregnancy and nine others experienced a neonatal death. All 18 of their fetuses had bilateral disease, with oligohydramnios present in 14 (78%). All five fetuses with chromosomal abnormalities were found in this group of 18. The majority of fetuses with a genitourinary anomaly will do well postnatally. Pulmonary hypoplasia, extrarenal anomalies, and chromosomal defects are frequent findings in the minority with poor outcomes. A multidisciplinary approach to management of the pregnancy with a fetal genitourinary tract anomaly is essential to optimize outcome.

Abortion, Eugenic↗

PubMed1989

Lethal fetal anomalies: sonographic demonstration.

Sonographic demonstration of a lethal fetal anomaly may dramatically alter obstetrical management. For example, cesarean section for fetal distress may not be performed if it is known that the fetus will not survive outside the uterus. The author describes the common fetal anomalies that are predictably fatal.

Bone and Bones↗

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↗

PubMed1983

Ethnicity, self-reported illness and use of medical services by the elderly.

Analysis of ethnic differences in disease is complicated by the fact that culture has an effect on whether people identify themselves as ill and how often they use medical services. This paper cities evidence to show that use of selected medical services by older members of ethnic groups appears to be high. Although a relatively high amount of disease among minority ethnic groups partly accounts for this, additional explanations--notably, cultural perceptions of doctors and aspects of the ageing migrant's position in society--are suggested.

Aged↗