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Biomedical subjects

E K Main

Publications and source records attributed to E K Main.

At least 19 recordsLinked to original sources
PubMed2000

Prevention of early-onset invasive neonatal group B streptococcal disease in a private hospital setting: the superiority of culture-based protocols.

OBJECTIVE: In a large private tertiary care hospital we compared the two different approaches to group B streptococcal screening and intrapartum chemoprophylaxis suggested by The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention: risk factor-based protocol and culture-based protocol. STUDY DESIGN: A 2-year baseline period was followed by sequential prospective observational studies of the impacts of two different group B streptococcal management protocols, 3 years with the risk-based approach and 2 years with the culture-based approach of universal screening at 35 to 37 weeks' gestation. RESULTS: During the baseline period the rate of early-onset group B streptococcal infection was 1. 1 cases per 1000 births (n = 8 cases per 6829 births). With the risk-based strategy the rate was also 1.1 cases per 1000 births (15 cases/13,270 births). After we switched to the culture-based protocol for 2 years, there were no cases of early-onset group B streptococcal infections among 9304 births (P =.001; chi(2) = 10.9). There were no increases in other early-onset infections or in antibiotic resistance. CONCLUSIONS: In our setting, which included good prenatal care and good communication between laboratories and the hospital, the approach based on maternal culture at 35 to 37 weeks' gestation and treatment during labor of all patients with positive results significantly reduced early-onset group B streptococcal infections without increasing infections from resistant organisms.

Adult↗
PubMed2000

The relationship between maternal age and uterine dysfunction: a continuous effect throughout reproductive life.

OBJECTIVE: In a selected low-risk population with spontaneous term labor we sought to determine whether there was a continuous effect of maternal age on uterine function. STUDY DESIGN: With our comprehensive computerized database and medical record system, we identified 8496 patients who were nulliparous and in spontaneous labor at term (> or =37 weeks' gestation) with singleton fetuses in vertex presentation. This group was then analyzed according to maternal age for measures of labor dysfunction and rates of operative delivery. Analysis of variance and chi(2) statistics were used. RESULTS: Use of oxytocin, duration of second stage of labor, cesarean delivery, cesarean delivery for failure to progress, and operative vaginal delivery rates were significantly increased with advancing maternal age (P <.0001). These increases appeared to be continuous functions beginning during the early 20s rather than new phenomena beginning after age 35 years. CONCLUSION: Among nulliparous patients with uncomplicated labor there is a continuously increasing risk of uterine dysfunction related to maternal age.

Adult↗
PubMed1999

Reducing cesarean birth rates with data-driven quality improvement activities.

Reduction of cesarean section rates has been a difficult process that has not been easily accomplished by the institution of guidelines. It is more a process of changing physician behavior rather than of medical education. This article analyzed the role of intensive feedback of outcomes to bring about such changes. Two large private obstetric services in San Francisco, CA, were studied. Intensive outcomes feedback using a computerized information system, The Perinatal Data Center, regarding cesarean birth rates and a variety of obstetric outcomes was provided to the medical and nursing staff at one hospital. The other center served as a control. After the first observation period, the outcomes system was introduced to the second hospital. Finally, "open label" feedback, intradepartmental release of everyone's key statistics with names attached, was performed. Active management of labor was not practiced at either hospital. Results. Cesarean birth rates were stable in the baseline period from 1980 through 1988 at 24% to 25%. Introduction of the Perinatal Data Center outcomes system was associated with a reduction to 21% at the first hospital with no change in the control hospital. Subsequent introduction of the system 3 years later in the control hospital resulted in a decline from 25% to 20.5%. After merger of the two obstetric units and the institution of "open label" feedback, an additional decline to 18.5% was observed. Conclusion. Physician practice patterns and cesarean birth rates can be altered with the intensive use of comparative outcome data and strong physician leadership. Nonblinded, intradepartmental distribution of outcomes is an even more effective tool.

Algorithms↗
PubMed1996

The use of intravenous immunoglobulin in recurrent pregnancy loss associated with combined alloimmune and autoimmune abnormalities.

PROBLEM: Several studies have evaluated the effect of intravenous gammaglobulin (IVIG) in women with unexplained recurrent spontaneous abortions (RSA). Data regarding the underlying immunologic abnormalities in these patients is scant. This study reports the pregnancy outcome and immunologic changes observed in a large group of women with RSA associated with well-defined alloimmune and autoimmune abnormalities treated with IVIG. METHODS: Thirty-five patients with three or more recurrent miscarriages were studied. None of the patients had identifiable alloimmune response to paternal lymphocytes. Twenty-four patients had anti-thyroid antibodies, ten patients had high levels of circulating immune complexes, and six patients had anti-cardiolipin antibodies. Five patients had Hashimoto's disease, one had immune thrombocytopenic purpura, and one had Crohn's disease. Twenty-three patients had more than one autoimmune abnormality. All patients received IVIG infusions (200-250 mg/kg) every 3 weeks during the first 8 months of pregnancy. RESULTS: Twenty-eight patients (80%) had a successful pregnancy. Decrease of the level of autoantibodies and circulating immune complexes was observed in all patients who had a successful pregnancy. Only three of these patients developed measurable alloimmune response to paternal antigens. CONCLUSIONS: This preliminary study suggests that IVIG may be of benefit to patients with recurrent pregnancy associated with combined alloimmune and autoimmune abnormalities. This benefit was seen in spite of lack of detectable correction of the alloimmune abnormality in the majority of patients.

Abortion, Habitual↗
PubMed1994

Expression of the nonclassic histocompatibility antigen HLA-G by preeclamptic placenta.

OBJECTIVE: Expression of the histocompatibility antigen HLA-G may be required for appropriate invasion and remodeling of uterine spiral arteries. Inappropriate expression of this antigen may result in failure of invasion, leading to partial placental ischemia and gestational disease. STUDY DESIGN: To test the hypothesis that the level of expression of HLA-G is reduced in trophoblasts from patients with gestational complications (preeclampsia, intrauterine growth retardation, or gestational hypertension) compared with patients with normal pregnancy, total ribonucleic acid was isolated from the fetal membrane or decidual interface of term placenta from several patient groups. Ribonuclease protection assay was used to determine levels of HLA-G expression, which was normalized for total ribonucleic acid input with beta-actin and for trophoblast content in the tissue by cytokeratin 8. RESULTS: When normalized for total ribonucleic acid input (beta-actin), term placental expression of HLA-G was reduced for all forms of preeclampsia but not for intrauterine growth retardation or gestational hypertension. When tissue expression of cytokeratin, an indicator of trophoblast input, was normalized for trophoblast input, was normalized for total ribonucleic acid input, primary preeclampsia and intrauterine growth retardation had reduced numbers of trophoblast per unit tissue. When controlled for trophoblast input HLA-G expression was similar to normal for all clinical groups, except for intrauterine growth retardation, which was slightly increased. CONCLUSION: Level of expression of HLA-G in placental tissue was reduced in preeclampsia. This decrease in expression appears to be related to reduced numbers of trophoblasts in placental tissue examined at term from patients with primary preeclampsia.

Adult↗
PubMed1994

Nuclear regulation of HLA class I genes in human trophoblasts.

PROBLEM: Human trophoblast expression of class I human leukocyte antigen (HLA) genes is unique in that there is no classical gene expression, but nonclassical HLA-G is expressed and only by cytotrophoblast cells. This differential expression of classical versus nonclassical class I genes suggests tissue specific regulation. Recently, a negative regulatory element (NRE), 180 bp 5' to transcription initiation was identified in a murine embryonal carcinoma cell line that markedly inhibited class I gene expression (Flanagan et al., Proc Natl Acad Sci USA 1991; 83:3145-3149). METHOD: Here we analyzed the human HLA-A2 gene for a putative NRE sequence and determined whether such a sequence is capable of binding to factors present in a variety of class I-null cell lines. RESULTS: Sequence analysis revealed that the NRE for human HLA-A2 is identical to that for mouse H-2Ld. Using gel shift assays with nuclear extracts (NE) from a variety of cell types, we demonstrated specific binding to the HLA-A2 NRE sequence. The choriocarcinoma cell lines JEG and BeWo and the F9 cells (all negative for classical gene expression) contained this DNA binding factor(s). This binding factor was not present in NE from lymphocytes or a variety of other cell lines that were positive for classical gene expression. CONCLUSION: Human trophoblasts appear to have a tissue specific nuclear binding factor that may down regulate classical class I expression upon binding to the NRE sequence. The HLA-G gene does not have this NRE region thus enabling its expression by these cells.

Base Sequence↗
PubMed1994

Detection of human leukocyte antigen class I messenger ribonucleic acid transcripts in human spermatozoa via reverse transcription-polymerase chain reaction.

OBJECTIVE: To determine by reverse transcription-polymerase chain reaction (PCR) whether human leukocyte antigen (HLA) class I messenger RNA (mRNA) is present in mature human spermatozoa. DESIGN: Mature human spermatozoa was isolated from donor semen using a swim-up technique. Total RNA was extracted via guanidinium isothiocyanate-cesium chloride ultracentrifugation. By the method previously validated in our laboratory, reverse transcription-PCR was performed using primers specific for HLA class I transcripts. Positive control cells included a choriocarcinoma cell line (JEG) and human fetal tissue. Transformed peripheral blood lymphocytes (PBL) were used as a negative control for somatic cellular contamination. RESULTS: Human spermatozoa were positive for HLA class I (-G and -B) mRNA by reverse transcription-PCR, consistent with the positive controls. We did not detect any mRNA for beta-actin, retinoblastoma (RB), CD4, or kappa light chain genes in the sperm complementary DNA samples, verifying that the class I mRNA detected was not due to somatic cellular contamination of the purified sperm samples. CONCLUSION: These experiments provide the first evidence that mRNA for HLA class I molecules are present in mature human spermatozoa. The physiological role of these transcripts is unknown at present. Further experiments characterizing the expression of HLA class I (-G and -B) mRNA in oocytes and preimplantation embryos are in progress.

Actins↗
PubMed1992

Severe post-partum eclampsia: response to plasma exchange.

In their severest forms, pre-eclampsia and eclampsia may be life-threatening complications of pregnancy. We describe a patient with severe post-partum eclampsia characterized by seizures, deep coma, hypertension, renal insufficiency, coagulopathy, and microangiopathic hemolysis. The patient responded to treatment that included intensive plasma exchange, and she achieved full recovery. Our case supports the use of plasma exchange in patients with severe pre-eclampsia and eclampsia.

Adult↗
PubMed1992

Evaluation of maternal fluid dynamics during tocolytic therapy with ritodrine hydrochloride and magnesium sulfate.

OBJECTIVE: The purpose of the study was to observe and compare the effects of ritodrine hydrochloride and magnesium sulfate on maternal fluid dynamics. STUDY DESIGN: Fourteen women in preterm labor were prospectively studied during tocolytic therapy with either ritodrine hydrochloride or magnesium sulfate. The cardiovascular and renal effects of a pretreatment crystalloid infusion were compared with those observed during tocolytic therapy. Profile analysis and repeated measures of variance were used to analyze the data. RESULTS: Ritodrine hydrochloride was associated with decreased colloid osmotic pressure, hematocrit, and serum proteins and increased maternal and fetal heart rates. Arginine vasopressin levels increased during the first 2 hours of therapy, then returned to baseline. Sodium excretion was reduced and there was marked fluid retention. Intravenous magnesium sulfate also resulted in a reduction of colloid osmotic pressure, but hematocrit, serum protein concentration, arginine vasopressin, maternal and fetal heart rates, and mean arterial pressure were minimally affected. Sodium excretion increased to a maximum at 6 to 8 hours of treatment, then returned to baseline. A positive fluid balance was also noted in magnesium sulfate-treated patients but to a lesser degree than with ritodrine. CONCLUSIONS: Sodium retention appears to be the primary cause of plasma volume expansion in ritodrine-treated patients, whereas volume expansion during magnesium sulfate therapy is probably related to intravenous overhydration. In the absence of risk factors for pulmonary capillary membrane injury, available evidence supports volume overload as the principal mechanism for pulmonary edema during tocolytic therapy.

Arginine Vasopressin↗
PubMed1992

Relationship of fetal macrosomia to maternal postprandial glucose control during pregnancy.

OBJECTIVE: To determine the gestational ages at which maternal hyperglycemia is most closely related to fetal macrosomia; to determine whether macrosomia is related to elevations of fasting glucose, postprandial glucose, or both; and to assess the relationship of macrosomia to maternal insulin dose and caloric intake. RESEARCH DESIGN AND METHODS: One hundred eleven consecutive pregnant women with Class B through RF diabetes were studied longitudinally from 13 to 36 wk gestation. Macrosomia was defined by birthweight greater than 90th percentile for gestational age based on California norms. Women who delivered macrosomic infants were compared with those without macrosomic infants on pre- and postprandial blood glucose, GHb, insulin dose, macronutrient intake, and several other maternal variables. RESULTS: Macrosomia occurred in 32 (29%) cases, although several measures indicated reasonable glycemic control throughout pregnancy. Women delivering macrosomic infants did not differ from those without macrosomic infants in maternal age, prepregnant weight, duration of diabetes, White class, macronutrient intake, GHb, or fasting glucose. Macrosomia was associated with higher postprandial glucose levels up to 32 wk gestation and lower insulin doses from 29 to 36 wk gestation. In multiple logistic regression, macrosomia was significantly associated with postprandial glucose only between 29 and 32 wk gestation. Postprandial glucose values less than 7.3 mM (less than 130 mg/dl) were associated with a higher risk of small-for-gestational-age infants (18%) compared with values above this level (1%). CONCLUSIONS: Because macrosomia was related to postprandial glucose but not fasting glucose, we conclude that postprandial glucose measurement should be a part of routine care for diabetes in pregnancy. A target 1-h postprandial glucose value of 7.3 mM (130 mg/dl) may be the level that optimally reduces the incidence of macrosomia without increasing the incidence of small-for-gestational-age infants.

Adult↗
PubMed1991

Preconception care of diabetes. Glycemic control prevents congenital anomalies.

To test the value of intensive management of diabetes before and during early pregnancy, 84 women recruited prior to conception were compared with 110 women who were already pregnant referred at 6 to 30 weeks' gestation. All underwent daily measurement of fasting and postprandial capillary blood glucose levels. Mean blood glucose levels during embryogenesis and organogenesis were within 3.3 to 7.8 mmol/L in 50% of preconception subjects and exceeded 10 mmol/L in 6.5%. One major congenital anomaly occurred in 84 infants (1.2%) of women treated before conception compared with 12 anomalies in 110 infants (10.9%) of mothers in the postconception group. Transient symptomatic hypoglycemia occurred during embryogenesis in 60% of women in the preconception group, with a median frequency of 2.7 episodes per week, but was not associated with excess malformations. We conclude that education and intensive management for glycemic control of diabetic women before and during early pregnancy will prevent excess rates of congenital anomalies in their infants.

Adult↗
PubMed1990

A class I antigen, HLA-G, expressed in human trophoblasts.

The alpha chain of the human histocompatibility antigen HLA-G was identified as an array of five 37- to 39-kilodalton isoforms by the use of two-dimensional gel electrophoresis. Both cell-associated and secreted HLA-G antigens are prominent in first trimester villous cytotrophoblasts and are greatly reduced in third trimester cytotrophoblasts. Allelic variation was not detected, an indication that HLA-G is not obviously polymorphic in cytotrophoblasts. Among the following choriocarcinoma cell lines studied, HLA-G is expressed in JEG but not in Jar or BeWo. Expression of endogenous HLA-G genes has not been found in normal lymphoid cells. Thus, HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts.

Antibodies, Monoclonal↗
PubMed1990

Role of the placenta in perinatal transmission of HIV.

The role of the placental tissue in the perinatal transmission of HIV is still far from being understood. Significant data regarding transplacental infection have been collected, but differences in technique have led to controversy. It appears clear that many Hofbauer cells are CD4+ and can become infected with HIV. Less certain but probable is infection of trophoblasts themselves. Whether infection is CD4 mediated or via cell-cell fusion is not established. Transplacental traffic of virus and cells remains a little-studied possibility. Further data are needed regarding the fascinating concept of the placenta as a modulator of infection.

Female↗
PubMed1988

IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity.

Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.

Cell Adhesion↗
PubMed1988

Fetal bradycardia associated with maternal hypothermia.

A case of fetal bradycardia associated with severe maternal hypothermia (92.9F) is reported. Until maternal temperature was corrected, the baseline fetal heart rate (FHR) remained between 90-110 beats per minute without other evidence of fetal distress and despite normal maternal blood pressure and pulse. With rewarming, the FHR gradually returned to normal. Upon return of maternal hypothermia, fetal bradycardia recurred, again responding only to rewarming. This evidence suggests that low maternal temperature alone may lead to alterations of FHR.

Adolescent↗
PubMed1987

Lymphocyte function-associated antigen 1 (LFA-1) and natural killer (NK) cell activity: LFA-1 is not necessary for all killer: target cell interactions.

A panel of five monoclonal antibodies detecting human lymphocyte function-associated antigen 1 (LFA-1) was generated and shown by competitive binding studies to react with at least four distinct epitopes on this molecule. The antibodies were then tested for their ability to inhibit the lytic activity of a variety of different human natural killer (NK) populations on a panel of four NK-susceptible target cells (K562, MOLT-4, HSB-2, and Jurkat). When heterogeneous NK populations derived from fresh peripheral blood and mixed-lymphocyte culture (MLC)-generated lines were used, these anti-LFA-1 monoclonal antibodies (MAbs) inhibited lysis of all four NK targets; this finding supports the notion that LFA-1 molecules play an important role in NK-mediated lysis. When tested on a cloned line of NK cells (NK 3.3), lysis of K562 was inhibited by these MAbs, but lysis of the other three targets was not affected. This represents an instance where a MAb specific for LFA-1 inhibits the lytic activity of NK cells against some but not all targets; thus the LFA-1 molecule cannot be considered under all circumstances to be an absolute requirement in NK-mediated lysis.

Antibodies, Monoclonal↗