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Biomedical subjects

S M Cox

Publications and source records attributed to S M Cox.

At least 19 recordsLinked to original sources
PubMed1992

Histocompatibility screening by molecular techniques: use of polymerase chain reaction products and heteroduplex formation.

Novel molecular approaches have recently become available allowing improved major histocompatibility complex (MHC) matching of potential allogeneic bone marrow donors and recipients. Current cellular and serological assays are hindered by aberrant cell populations and limited reagents which only detect an individuals' phenotype. Therefore, a molecular screening protocol which discriminates at the genotypic level would be advantageous. Here we describe a two-step DNA-based approach that can be applied to large-scale screening of potential donors. A primary screen, utilizing polymerase chain reaction (PCR), reduces the potential donor population, whereas a secondary or fine resolution screen uses DNA heteroduplex analysis to determine identity or non-identity at specific loci. Heteroduplex analysis generates a DNA migration pattern that is unique for alleles at a given locus, and is more sensitive than serology in discriminating among individuals. Here we demonstrate the potential feasibility of this approach by analyzing results at one MHC locus, HLA-DQ. Since this method does not rely on typing sera or viable lymphocytes, it is not subject to the variability found in the traditional methods. In contrast to traditional methods, these molecular techniques can provide the critical information needed to select a potential bone marrow donor.

Base Sequence↗
PubMed1992

Serum erythropoietin quantitation in pregnancy using an enzyme-linked immunoassay.

During normal pregnancy there is a decrease in the hematocrit due to a disproportionate increase in the blood volume compared with the red cell mass. Using a new enzyme-linked immunoassay (Amgen Diagnostics), serum erythropoietin was quantified in normal nonanemic pregnancies throughout gestation and in third trimester anemic patients. We found that the mean hematocrit in normal pregnancy reached a nadir late in the second trimester and the serum erythropoietin plateaued at a 50% increase. Those pregnancies complicated by anemia defined by a hematocrit less than 30 vol% demonstrated a statistically significant increase in serum erythropoietin above those not anemic.

Adolescent↗
PubMed1992

Expectant management of preterm ruptured membranes: effects of antimicrobial therapy.

OBJECTIVE: To determine whether the addition of broad-spectrum antimicrobial therapy to traditional expectant management improves pregnancy outcome in patients with premature rupture of membranes (PROM) remote from term. METHODS: Patients with preterm PROM before 34 weeks' gestation who were not in labor and had no signs of infection or fetal distress were randomized to one of two study groups: 1) expectant management alone and 2) expectant management plus antimicrobial therapy. Women in the latter group received intravenous ampicillin, gentamicin, and clindamycin for 24 hours, followed by amoxicillin plus clavulanic acid orally for 7 days. Other than antibiotic use, management of the two groups was identical. RESULTS: Significantly more women (P < .01) treated with antibiotics (20 of 48, 42%) remained undelivered 7 days after admission compared with those managed expectantly without antibiotics (seven of 46, 15%). In addition, more neonates in the group managed with antibiotics were admitted to the routine nursery (nine of 48 versus two of 45; P = .03). However, there was no difference between the groups in the frequency of serious maternal or neonatal morbidity. CONCLUSIONS: The addition of broad-spectrum antimicrobial therapy to traditional expectant management of pregnancy complicated by preterm PROM may increase the number of gestations undelivered 7 days after admission. It may also decrease the proportion of infants admitted to special care nurseries. Whether these effects result in significant short- or long-term maternal or neonatal benefit remains to be determined.

Anti-Bacterial Agents↗
PubMed1992

The penicillins.

The penicillins have played a major role in the treatment of many obstetric and gynecologic infections. The advent of the newer broad-spectrum penicillins has allowed their use as single-agent therapy for certain infections. Although toxicity is extremely low, disadvantages of their use include superinfection and induction of resistance. The cost of therapy is comparable with other antibiotics with similar coverage.

Bacterial Infections↗
PubMed1992

Fetal fibronectin: a method for detecting the presence of amniotic fluid.

OBJECTIVE: To determine whether fetal fibronectin is a sensitive test for the detection of amniotic fluid (AF) in women with rupture of the membranes. METHODS: In a multicenter clinical trial, pooling, ferning, and nitrazine tests were compared with fetal fibronectin in 339 women at term (study group) with a clinical history of rupture of the membranes and in 67 women at term receiving routine prenatal care (controls). Ruptured membranes was diagnosed if any two of the standard tests were positive. Fetal fibronectin in the cervicovaginal secretions was determined using a qualitative enzyme-linked immunosorbent assay test. Fetal fibronectin was considered positive at 50 ng/mL. RESULTS: The sensitivity of fetal fibronectin in the women with ruptured membranes was 98.2%. No controls had ruptured membranes based on standard test results, but 13 women had fetal fibronectin present. The mean (+/- standard error) interval between sampling and delivery was significantly less in the women positive for fetal fibronectin (169.3 +/- 45.8 hours) than in those with no detectable fetal fibronectin (333.4 +/- 29.0 hours). CONCLUSION: Fetal fibronectin is a sensitive test for detection of AF in the vagina and compares favorably to standard tests. Its low specificity suggests that the assay may detect an alteration in membrane integrity. In addition, in patients without rupture of the membranes, the interval between sampling and delivery is significantly shorter if fetal fibronectin is present. We speculate that the presence of fetal fibronectin in cervicovaginal secretions may be a marker for impending labor in gravidas without gross rupture of the membranes.

Adult↗
PubMed1992

Maternal and perinatal effects of hypertension at term.

This study sought to determine if selected maternal and fetal outcomes in term singleton pregnancies complicated by hypertension during labor differed from those without this complication. All pregnancies delivered at Parkland Memorial Hospital, Dallas, Texas, during 1986 were ascertained using a computerized database. A total of 11,812 term singleton pregnancies ended in delivery during the study period; 1,392 (12%) were complicated by hypertension. Women with a total of 1,383 of these hypertensive pregnancies presented to the hospital with a live fetus. Hypertension was diagnosed in 984 (19%) of the 5,060 primiparous and 399 (6%) of the 6,752 parous women. Hypertension during labor in term singleton pregnancies is associated with increased maternal risks because of the potential complications associated with interventions necessary for successful management. Moreover, hypertension in such pregnancies also increases the perinatal mortality rate. However, this increased rate results from a higher likelihood that fetal death will occur prior to the patient's presentation to the hospital. The risk of fetal morbidity and mortality appears to be low in the hypertensive woman with a term pregnancy admitted to the hospital with a live fetus.

Cesarean Section↗
PubMed1991

A randomized trial of ofloxacin versus cefoxitin and doxycycline in the outpatient treatment of acute salpingitis.

The object of this randomized study was to compare the safety and efficacy of oral ofloxacin, 400 mg twice daily for 10 days, versus intramuscular cefoxitin, 2 gm, plus oral probenecid, 1 gm, followed by oral doxycycline, 100 mg twice daily for 10 days, in the outpatient treatment of uncomplicated acute salpingitis. Thirty-eight women (53%) had Neisseria gonorrhoeae from their pretreatment endocervical or endometrial cultures, and 18 had Chlamydia trachomatis (25%). Thirty-five of 37 women (95%) treated with the ofloxacin regimen were clinically cured, and 34 of 35 (97%) were cured with the cefoxitin-doxycycline regimen (p = 0.52). One clinical failure occurred in each group with N. gonorrhoeae infection, and one failure occurred in the ofloxacin group because of side effects. The bacteriologic response for N. gonorrhoeae in both groups was 100%. The eradication of C. trachomatis was 100% (10/10) for the cefoxitin/doxycycline group and 86% (6/7) for ofloxacin. The side effects were similar in both groups of subjects. In this study both regimens were effective for the outpatient treatment of uncomplicated acute salpingitis.

Acute Disease↗
PubMed1991

Mechanisms of hemolysis and anemia associated with acute antepartum pyelonephritis.

Anemia develops in about a fourth of women whose pregnancy is complicated by pyelonephritis, although its exact mechanism has not been defined clearly. In this study of 18 women with antepartum pyelonephritis, although only a third had anemia (hematocrit less than 30 vol/dl), there was evidence for hemolysis in all 18. Specifically there was a mean decrease in hematocrit of 5 vol/dl from admission to discharge. With scanning electron microscopy, we compared erythrocyte morphologic aberrations that were found in women with renal infection with those of normally pregnant women, and the former had significantly increased proportions of echinocytes in particular, but schistocytes and spherocytes were increased also (total 10.3% vs 1.4%, p less than 0.0001). These changes, especially echinocytosis, have been induced in vitro by lipopolysaccharide, and they are known to lead to premature red blood cell destruction in vivo. We conclude that hemolysis with subsequent anemia in pregnant women with pyelonephritis is caused by lipopolysaccharide-induced red blood cell membrane damage.

Acute Disease↗
PubMed1991

Role of Neisseria gonorrhoeae and Chlamydia trachomatis in intraabdominal abscess formation in the rat.

Our concept of the pathogenesis of acute salpingitis and advanced pelvic infection, such as tuboovarian abscess, is evolving. Although Neisseria gonorrhoeae and Chlamydia trachomatis are thought to play a significant role in acute pelvic inflammatory disease, other microorganisms, such as aerobes and anaerobes, have repeatedly been reported to play a significant role, also, particularly in the patient with advanced disease. A study was designed to evaluate the pathogenesis, and particularly any synergistic role, of some aerobes and anaerobes with N gonorrhoeae and C trachomatis abscess formation. Using the rat model developed by Weinstein and Onderdonk, the study demonstrated that N gonorrhoeae and C trachomatis alone do not produce abscesses. However, when combined with facultative or anaerobic bacteria, synergism with abscess formation is noted frequently. The data support the hypothesis that N gonorrhoeae and C trachomatis initiate infection and that aerobic and anaerobic bacteria act synergistically to produce abscesses. In addition, microorganisms not inoculated were found to be recruited into the infectious process. The organisms may gain access to the peritoneal cavity via the lower genital tract or from transmucosal migration from the intestinal flora.

Abscess↗
PubMed1991

Cerebrovascular accidents complicating pregnancy and the puerperium.

The decreasing incidence of direct causes of maternal death over the past half century has led to a heightened awareness of nonobstetric factors responsible for maternal mortality. For example, cerebrovascular accidents are an important nonobstetric cause of maternal morbidity and mortality. During the 6.5-year period from 1984 to mid-1990, we encountered 15 women in whom pregnancy or the puerperium was complicated by an acute cerebrovascular accident. Six of these women had hemorrhagic strokes and nine had ischemic strokes. During this same time, approximately 90,000 women were delivered at Parkland Memorial Hospital, and thus the incidence of stroke was about one in 6000 pregnancies. Chronic hypertension or preeclampsia was causative in three cases of hemorrhagic stroke. It is important that 20% of the women died as a result of stroke, and of the 12 survivors, 40% have residual neurologic deficits. An aggressive work-up to define the etiology of stroke is necessary in order to implement cause-specific management, with subsequent reduction in morbidity and mortality.

Cerebrovascular Disorders↗
PubMed1990

Randomized investigation of magnesium sulfate for prevention of preterm birth.

One hundred fifty-six women with preterm labor between 24 and 34 weeks' gestation were randomized to receive either intravenous magnesium sulfate or no tocolytic therapy. Magnesuim sulfate infusions of up to 3 gm/hr were used in 76 pregnancies and resulted in a mean serum magnesium concentration of 5.5 +/- 1.4 mEq/L (mean +/- SEM). Compared with 80 control pregnancies, magnesium sulfate tocolysis had no significant effect on duration of gestation, birth weight, neonatal morbidity, and perinatal mortality. We conclude that clinically safe infusions of magnesium sulfate are ineffective when used to prevent preterm birth.

Adult↗
PubMed1990

Chronic renal disease and pregnancy outcome.

During the 18-year period from 1971 through 1988, 37 women whose pregnancies were complicated by moderate or severe renal insufficiency were managed at Parkland Memorial Hospital. Common maternal complications included anemia, chronic hypertension, and preeclampsia. Perinatal complications included midpregnancy losses and low birth weight from preterm delivery, fetal growth retardation, or both. Despite the high incidence of maternal morbidity, 85% of pregnancies in the 26 women with moderate renal insufficiency resulted in a live-born infant; there was one stillbirth and no neonatal deaths. Of the 11 women with severe disease, seven were delivered of live-born infants after greater than or equal to 26 weeks' gestation. Although six of these 37 women had worsening renal function during pregnancy, it seems unlikely that pregnancy per se caused this. More importantly, in four of these six women and in four others who had stable function throughout pregnancy, end-stage renal disease developed within a mean of 4 years after delivery. In 14 women blood volume was determined during pregnancy, and whereas those with moderate disease had normal volume expansion, women with severe disease had significantly attenuated expansion. Finally, serial creatinine clearances did not increase during pregnancy in half the women with moderate insufficiency and none with severe dysfunction.

Anemia↗
PubMed1990

Ticarcillin/clavulanate in the treatment of pelvic infections.

Ticarcillin/clavulanate was used to treat 130 women with pelvic infections. The 129 who completed an initial course of treatment with ticarcillin/clavulanate were analyzed according to type and clinical severity of infection, and pretreatment and posttreatment endometrial bacteriology. There were 26 cases of pelvic inflammatory disease and 103 puerperal infections, 61 of which occurred in women who had delivered by cesarean section (46 elective with no antibiotic prophylaxis at the time of surgery). Of the 129 patients treated, 124 were clinically cured, and one improved (97%). There were four treatment failures, all of which were among a total of 20 cases classified as clinically severe. All the patients designated as treatment failures required prolonged treatment with other antibacterials to achieve a clinical cure, but a longer duration of treatment with ticarcillin/clavulanate might have effected a clinical resolution even in these cases. In vitro examination of endometrial isolates revealed a significant reduction of the minimum inhibitory concentrations (MICs) of beta-lactamase-producing bacteria with the addition of clavulanate to ticarcillin. The relationship of non-beta-lactamase-producing enterococci having relatively high MICs to clinical failure was examined.

Bacteria↗
PubMed1990

The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy.

Thirty-three gravidas with syphilis were monitored with hourly vital signs and examinations for 24 hours after treatment with benzathine penicillin G. Fifteen (45%) of the subjects had a Jarisch-Herxheimer reaction, including all three, 12 of 20 (60%), and none of ten of those with primary, secondary, and latent syphilis, respectively. The most common symptoms were fever (73%), uterine contractions (67%), and decreased fetal movement (67%). The signs or symptoms began 2-8 hours after treatment; fevers peaked at 6-12 hours post-therapy and the events usually abated by 16-24 hours after treatment. Uterine contractions and decreased fetal activity began concurrent with maternal fever in eight of ten women reporting contractions. Transient late decelerations were detected in three of 11 monitored patients. Three of the women with Jarisch-Herxheimer reactions delivered infants with congenital syphilis, including one stillbirth, but none of those without a detectable reaction had fetal treatment failures. Prostaglandin F2 alpha and prostacyclin metabolites were elevated transiently in the one subject studied, suggesting their role in mediating the cardiovascular and uterine events in the post-treatment period. The Jarisch-Herxheimer reaction in pregnancy is similar in frequency, character, and intensity to that in nonpregnant adults, but gravidas may have increase uterine activity and transient alterations in fetal well-being. The pregnant patient with a severely affected fetus with congenital syphilis may experience preterm labor, preterm delivery, or fetal death in association with the Jarisch-Herxheimer reaction.

Adult↗
PubMed1989

The importance of the orientation of the C9 substituent to cannabinoid activity.

We have found a correlation between cannabinoid psychopharmacological activity and the orientation of the C9 substituent in one class of cannabinoid derivatives. We report here a study of the active cannabinoids delta 9-tetra-hydrocannabinol (delta 9-THC), delta 8-tetrahydrocannabinol (delta 8-THC), and 11 beta-hexahydrocannabinol (11 beta-HHC); the minimally active cannabinoid 11 alpha-hexahydrocannabinol (11 alpha-HHC); and the inactive cannabinoids delta 7-tetrahydrocannabinol (delta 7-THC) and delta 9,11-tetrahydrocannabinol (delta 9,11-THC). Our working hypothesis is that there are two components of cannabinoid structure which confer upon these compounds reactivity characteristics crucial to activity: the directionality of the lone pairs of electrons of the phenyl group hydroxyl oxygen and the orientation of the carbocyclic ring relative to this oxygen. The structures of these six molecules were optimized by using the method of molecular mechanics as encoded in the MMP2(85) program. Other possible minimum-energy conformations of the carbocyclic ring were calculated by driving one torsion angle in this ring by use of the dihedral driver option in MMP2(85). The rotational energy behavior of the phenyl group hydroxyl in each molecule was studied also by using the dihedral driver option in MMP2(85). We found that the carbocyclic ring in 11 alpha-HHC can exist in either a chair or a twist conformation. The carbocyclic ring in delta 9-THC, in delta 8-THC, and in delta 7-THC was found to exist only in a half-chair conformation, while the carbocyclic ring in 11 beta-HHC and in delta 9,11-THC was found to exist only in a chair form. The results of the rotational energy profiles indicated that the minimum-energy positions of the phenyl group hydroxyls are nearly identical in all molecules. These molecules, then, were found to differ only in the conformation of the carbocyclic ring in each. This conformation, in turn, determines the orientation of this ring and its C9 substituent relative to the oxygen of the phenyl group hydroxyl. In order to assess the orientation of the carbocyclic ring with respect to the phenyl group hydroxyl oxygen in each optimized structure, the following nonbonded torsion angles were measured: C10-C10a-C1-O, C8-C7-C1-O, C11-C9-C1-O, and C9-Q-C1-O (where Q is a dummy atom placed midway between C8 and C10).(ABSTRACT TRUNCATED AT 400 WORDS)

Cannabinoids↗