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Biomedical subjects

M A Morgan

Publications and source records attributed to M A Morgan.

At least 55 records · Page 3Linked to original sources
PubMed1997

Deletion mapping of two potential chromosome 14 tumor suppressor gene loci in ovarian carcinoma.

Previous allelotyping studies of epithelial ovarian carcinoma suggest that loss of heterozygosity on chromosome 14q may be a common genetic alteration in this tumor type. The purpose of this study was to determine a precise frequency of chromosome 14q allelic loss in ovarian carcinomas and to define a minimal region(s) of deletion. Seventy-six ovarian carcinomas representative of the complete spectrum of grade, stage, and histological subtype were selected for PCR-based deletion mapping analysis using 15 highly polymorphic microsatellite markers spanning the length of this chromosome arm. Loss of heterozygosity was observed in 49% of the tumors studied, placing 14q among the most frequently affected chromosomal regions in ovarian cancer. Deletions were observed in all tumor grades and stages and in all histological subtypes except tumors of low malignant potential. Deletion of the entire chromosome arm was rare; the majority of tumors displayed partial losses, providing an informative basis for detailed deletion mapping. Two distinct minimal regions of deletion were delineated. One region was defined by markers D14S80 and D14S75 at 14q12-13, and the other region was defined by markers D14S65 and D14S267 at 14q32. These data implicate the involvement of two tumor suppressor genes on chromosome 14q in a substantial fraction of ovarian carcinomas.

Chromosome Deletion↗
PubMed1997

Effect of surgical debulking on survival in stage IV ovarian cancer.

In order to determine whether optimal surgical debulking in Stage IV epithelial ovarian cancer impacts survival, a retrospective review of patients treated at the University of Pennsylvania Cancer Center (UPCC) from 1984 to 1995 diagnosed with Stage IV epithelial ovarian cancer was performed. Data were collected regarding grade, histology, reason for allocation to Stage IV, extent of surgery performed and residual disease at initial staging procedure, major perioperative complications, first-line chemotherapy regimen, length of inpatient hospital stay, outcome at second-look laparotomy, follow-up, and survival. For the purposes of this study, optimal cytoreduction was defined as a residual disease of 2 cm or less. Forty-seven patients with Stage IV epithelial ovarian cancer identified in the Society of Gynecologic Oncologists (SGO) Database at UPCC are included. Fourteen of 47 (30%) were optimally cytoreduced at the time of their staging procedure. Twenty-six of 47 (55%) were deemed Stage IV by virtue of positive pleural effusion cytology only. Twenty-one of 47 (45%) had intraparenchymal liver involvement or metastatic disease outside of the abdomen. The median survival of the suboptimally debulked group was 17 months, while median survival in the optimal group was 37 months (P = 0.0295). These data suggest that Stage IV epithelial ovarian cancer patients with less than 2 cm residual disease have a survival advantage over patients with greater than 2 cm residual.

Female↗
PubMed1997

Cycles of dose-intensive chemotherapy with peripheral stem cell support in persistent or recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: The objective was to determine the toxicity and surgically documented response rate of sequential high-dose chemotherapy with peripheral stem cell support in patients with persistent or recurrent cisplatin-sensitive ovarian cancer. METHODS: Fourteen patients (average age, 45 years) were treated with cyclophosphamide (4.5 g/m2), followed by granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral stem cell harvests. The subsequent regimen prescribed three courses of carboplatin (1 g/m2) and cyclophosphamide (1.5 g/m2 with 2-mercaptoethanesulfonate) every 2 weeks with stem cell support. This was followed by three courses of paclitaxel at 250 mg/m2 every 2 weeks with G-CSF support only. Six patients were entered on the basis of a positive second-look laparotomy and 8 patients had a first recurrence after at least a 6-month disease-free interval. RESULTS: Fourteen patients were entered and 12 patients completed all planned courses of therapy (mean time, 13 weeks). Normal hematopoiesis was reestablished after each cycle. Hospitalization for neutropenic fever occurred in 11/93 cycles (11.8%). Thirteen patients required blood transfusions and in 12 patients platelet transfusions were given. One patient had grade 3 neurotoxicity. An initial elevated CA 125 returned to normal in 7/8 patients (88%) and 71% of patients with measurable disease responded to therapy. There were 2 pathologic complete responders (PCR), making the PCR rate 2/14 or 14% (0-35%). CONCLUSION: Although this regimen was well tolerated and clinical response rates were high, the surgically documented response rate was not clearly superior to conventional salvage regimens in platinum-sensitive patients.

Adult↗
PubMed1997

Predictive factors for neonatal morbidity in neonates with an umbilical arterial cord pH less than 7.00.

OBJECTIVE: Fewer than 50% of neonates with an umbilical arterial pH < 7.00 have neonatal complications. Our objective was to identify clinical predictive factors for adverse outcomes in this group of neonates. STUDY DESIGN: In this case-control study both cases and controls had an umbilical arterial cord pH < 7.00. Cases were defined as those neonates who had seizures, grade 3 to 4 intraventricular hemorrhage, gastrointestinal dysfunction, respiratory distress syndrome requiring intubation, sepsis, or death. Controls had an umbilical arterial cord pH < 7.00 and no complications. A multivariable prediction model was created, with variables having an association with adverse outcome by bivariate analyses, attempting to predict which neonates in this umbilical arterial pH range are at greatest risk for adverse outcomes. RESULTS: We identified 73 of 10,705 neonates born between July 1992 and October 1996 with an umbilical arterial cord pH < 7.00. Thirty-five neonates met our case definition, and the remaining 38 composed the control group. Cases had significantly lower arterial pH values and 1- and 5-minute Apgar scores, greater arterial base deficit values, and a higher incidence of abruptio placentae and maternal cocaine use. More cases were delivered before 34 weeks. There were three neonatal deaths, two cases of grade 3 or 4 intraventricular hemorrhage, five cases of gastrointestinal dysfunction, and four cases of neonatal seizures. In our predictive model for adverse neonatal outcome, an arterial base deficit > or = 16 mmol/L and a 5-minute Apgar score < 7 had a sensitivity and a specificity of 79% and 80.8%, respectively. CONCLUSION: Neonatal morbidity in neonates with an umbilical arterial cord pH < 7.00 can be predicted by a high arterial base deficit value and low 5-minute Apgar score.

Acidosis↗
PubMed1997

The association between maternal cocaine use and placenta previa.

OBJECTIVE: Our aim was to determine whether maternal cocaine exposure is a risk factor for placenta previa. STUDY DESIGN: In this case-control study, cases of placenta previa confirmed at delivery (ascertained by International Classification of Diseases, ninth revision, Clinical Modification, code-based search, N = 40) were compared with a random sample of patients without placenta previa (N = 80) in a ratio of two controls per case. Data on antecedent maternal cocaine use, as well as other potential risk factors for placenta previa, were obtained from a review of the prenatal chart and the hospital record. Categorization of cocaine use was based on either patient self-report or urine toxicologic testing, or both. Multiple logistic regression was performed to assess the association between cocaine and placenta previa while we controlled for other variables. RESULTS: After the effects of other variables were adjusted for, maternal cocaine use was an independent risk factor for placenta previa (adjusted odds ratio = 4.39, 95% confidence interval 1.17 to 16.4). Other significant risk factors included a history of cesarean section and prior elective abortion. CONCLUSION: These results suggest that cocaine use, as well as prior cesarean section, prior elective abortion, and parity, are associated with placenta previa.

Adult↗
PubMed1997

Intrapartum airway management for giant fetal neck masses: the EXIT (ex utero intrapartum treatment) procedure.

OBJECTIVE: Our goal was to review our experience with the EXIT (ex utero intrapartum treatment) procedure in the management of five cases with life-threatening fetal neck masses. STUDY DESIGN: We present a retrospective review of prenatal presentation and course, diagnostic accuracy of imaging studies, intraoperative management, complications, and outcomes. RESULTS: Polyhydramnios was the initial presenting symptom in three of five fetuses with a mean gestational age of 25 +/- 6 weeks. Preterm labor occurred in two patients. Fetal magnetic resonance imaging provided accurate diagnosis in all four cases whereas conventional ultrasonography led to the diagnosis in four of five cases. The mean duration of EXIT was 28 +/- 22 minutes. The mean venous cord blood gas values were pH 7.22 +/- 0.05, PCO2 61 +/- 11 mm Hg, and PO2 42 +/- 8 mm Hg. In four of five cases an airway was successfully secured. CONCLUSIONS: The EXIT procedure provides up to 1 hour of good uteroplacental support and is the procedure of choice to secure an airway in the fetus with a giant neck mass.

Airway Obstruction↗
PubMed1997

Evidence for magnesium sulfate as a tocolytic agent.

The objective of our study is to quantitatively examine the available evidence regarding the efficacy and side effects of magnesium sulfate for acute tocolysis (from randomized trials) compared with placebo and beta-agonist agents. Randomized trials comparing magnesium sulfate with placebo or beta-agonists for tocolysis were identified with a MEDLINE-based search and was supplemented by a search of obstetrical textbooks and bibliographies. Trials underwent quality evaluation and data abstraction by two independent, blinded investigators. Outcomes evaluated included delivery delay of various durations as well as the frequency of major and minor side effects. Summary odds ratios and 95 percent confidence intervals for dichotomous outcomes were calculated using a random effects model. Interstudy heterogeneity for these outcomes was assessed with a Q statistic. We identified 12 randomized controlled trials of magnesium sulfate for acute tocolysis. Four studies were excluded because of either lack of comparison of magnesium sulfate to either placebo or beta-agonists or lack of reporting clinical outcomes of interest. The eight remaining randomized trials comparing magnesium sulfate with placebo or beta-agonists were included in this analysis. There was no significant difference between MgSO4 and placebo for any of the measured outcomes for delay in delivery. Comparing magnesium sulfate to ritodrine or beta-agonists did not demonstrate any differences between the agents in achieving clinically significant tocolysis. There was a significant difference between MgSO4 and beta-agonists in the frequency of medication discontinuation because of side effects, but not in the frequency of major adverse drug events. There are few data comparing magnesium sulfate with a placebo for acute tocolysis. Magnesium sulfate seems to be comparable to ritodrine and beta-agonists, although the available data are not sufficient for a rational choice between these agents.

Adrenergic beta-Agonists↗
PubMed1997

Disseminated congenital neuroblastoma involving the placenta.

Neuroblastoma, a tumor of primitive neuroectodermal cells, is one of the most common solid malignancies of neonates. Placental metastases have been described in rare cases of congenital neuroblastoma, usually in association with hydrops fetalis, placentomegaly, and widespread disease in the neonate. We report a case in which the unexpected diagnosis of neuroblastoma was made based on the postnatal finding of tumor emboli confined to fetal vessels of the placenta. Radiation and chemotherapy were given based on this diagnosis, obviating the need for an invasive diagnostic procedure.

Adult↗
PubMed1997

[Observations on pe-eclampsia-eclampsia and the advances in the evolution of some laboratory tests].

The preeclampsia-eclampsia syndrome is a vasospastic disorder and probably has a placental origin. Once the hypertensive syndrome is established the uteroplacental blood flow is reduced as well as the intervillous blood flow. Since 18-24 weeks of gestation and before the symptoms of preeclampsia become overt, changes in placental flow velocity can be detected with Doppler technics. The placental theories for the etiology of preeclampsia are focused on the hypoxic effect in the trophoblastic tissue of second trimester. The placental ischemic changes are evident and seen in the uteroplacental bed. They are interrelated with the stages of trophoblastic invasion of the spiral arteries during the 14 and 20 weeks. When the trophoblastic invasion is over, the spiral arteries become a high resistance system. The defect observed in preeclampsia is the lack of invasion of the trophoblast to the maternal arteries. The diminished placental perfusion probably creates endothelial damage. This damage has several effects: decreased prostaglandin production, activated coagulation cascade, stimulated fibrin aggregation, and increased vascular permeability. The ideal laboratory test for preeclampsia shall predict the onset of this entity. Recent findings seem promising. The fibronectin concentration increases 2-3 wks. prior to the clinical manifestation of preeclampsia. Severe hypertension shows an abnormal decrease in fibronectin levels. Hypocalciuria has been described as an early predictor in the development of preeclampsia. Other agents undergoing extensive evaluation as predictors are: uric acid, b-thromboglobin, prolactin and atrial natriuretic peptide. Recently high levels of b-HCG (human corionic gonadotrophin) have been linked to a lack of trophoblastic invasion during the second trimester, therefore this is a potential marker for those patients that will eventually develop preeclampsia.

Adult↗
PubMed1996

Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1.

BACKGROUND: We tested the hypothesis that ovarian cancers associated with germ-line mutations of BRCA1 have distinct clinical and pathological features as compared with sporadic ovarian cancers. METHODS: We reviewed clinical and pathological data on patients with primary epithelial ovarian cancer found to have germ-line mutations of BRCA1. Survival among patients with advanced-stage cancer and such mutations was compared with that in control patients matched stage, grade, and histologic subtype of the tumors. A combination of single-strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice-donor and splice-acceptor regions of BRCA1 for mutations in pathological specimens. Alternatively, some patients were known to be obligate carriers of the mutant BRCA1 gene because of their parental relationships with documented mutant-gene carriers. RESULTS: We identified 53 patients with germ-line mutations of BRCA1. The average age at diagnosis was 48 years (range, 28 to 78). Histologic examination in 43 of the 53 patients showed serous adenocarcinoma. Thirty-seven tumors were of grade 3, 11 were of grade 2, 2 were of grade 1, and 3 were of low malignant potential. In 38 patients, the tumors were of stage III; 9 patients (including those with tumors of low malignant potential) had stage I disease, 5 had stage IV, and 1 had stage II. As of June 1996, with a median follow-up among survivors of 71 months from diagnosis, 20 patients had died of ovarian cancer, 27 had no evidence of the disease, 4 were alive with the disease, and 2 had died of other diseases. Actuarial median survival for the 43 patients with and advanced-stage disease was 77 months, as compared with 29 months for the matched controls (P<0.001). CONCLUSIONS: As compared with sporadic ovarian cancers, cancers associated with BRCA1 mutation appear to have a significantly more favorable clinical course.

Actuarial Analysis↗
PubMed1996

Mutations of the BRCA2 gene in ovarian carcinomas.

Inherited mutations in the recently discovered BRCA2 gene are believed to be responsible for a significant fraction of early-onset hereditary breast cancers. Unlike BRCA1, however, which confers a high risk to both breast and ovarian cancer, the incidence of ovarian cancer appears to be much lower In BRCA2-linked families, causing uncertainty as to the relevance of BRCA2 to hereditary ovarian cancer. Numerous allelotype studies indicate that allelic deletions Including the BRCA2 locus on chromosome 13q are common in ovarian cancers in general, suggesting that somatic mutations of this gene may be involved in sporadic ovarian tumorigenesis. The purpose of this study was to test the hypothesis that germline or somatic mutations of BRCA2 are associated with hereditary and/or sporadic ovarian cancers, respectively. The entire 10.2-kb coding region of BRCA2 was screened for mutations in 130 consecutive ovarian tumors, the only selection criterion being a pathological diagnosis of epithelial ovarian carcinoma. Loss of heterozygosity at markers flanking BRCA2 was observed in 56% of the tumors. Four germline mutations and two somatic mutations were identified; two of the germline mutations are recurrent, having been previously described. Remarkably, the patients with germline mutations were late-onset cases with no medical or family histories suggestive of hereditary cancer. These data suggest that mutations of BRCA2 are rare in sporadic ovarian cancers, and that the proportion of ovarian cancers resulting from hereditary predisposition may be higher than previously suspected based on estimates derived from studies of highly penetrant genetic loci.

Aged↗
PubMed1996

Cocaine's effect on plasma oxytocin concentrations in the baboon during late pregnancy.

OBJECTIVE: The hypothesis for this investigation was that intravenous cocaine would result in an elevation of maternal plasma oxytocin levels in the baboon during late pregnancy. STUDY DESIGN: Five gravid chronically instrumented baboons had timed arterial blood samples obtained before and after an intravenous bolus cocaine infusion at least 5 days after surgery. Plasma oxytocin concentrations were measured by specific radioimmunoassays, and baseline samples were compared with postcocaine samples. RESULTS: The plasma oxytocin concentrations were significantly elevated at all sampling times after the 1.0 mg/kg cocaine dose (p<0.05). CONCLUSION: The increased oxytocin concentration after cocaine use may be responsible for the increased incidence of preterm labor.

Animals↗
PubMed1996

Decreasing the cesarean section rate in a private hospital: success without mandated clinical changes.

OBJECTIVE: We analyzed the delivery statistics from our institution to describe a successful program of cesarean section delivery reduction and to help us understand what factors explained the reduction. STUDY DESIGN: A retrospective analysis of various cesarean section rates and risk factors from a prospectively collected delivery database of all patients delivered between May 15, 1988, and June 30, 1994. During the study period we instituted a program of increasing awareness, confidential provider feedback, more aggressive laboring techniques, and other clinical guidelines. The delivery data were divided into 6-month intervals and analyzed by chi 2 tables. RESULTS: The overall cesarean section rate fell from 31.1% to 15.4%. Similar reductions were noted in the primary (17.9% to 9.8%) and repeat cesarean section rates (13.2% to 5.7%). The primary cesarean section rate fall was accompanied by a drop in abdominal delivery for cephalopelvic disproportion and fetal distress. The repeat cesarean section rate is explained by a significant increase in trial and successful vaginal birth after cesarean delivery. No increase in maternal, fetal, or neonatal morbidity or mortality was observed. CONCLUSIONS: We have demonstrated that the cesarean delivery rate can be safely lowered in a private hospital without mandated clinical changes. Our data suggest that careful and detailed feedback can lead to improved clinical practice.

Cesarean Section↗
PubMed1996

Does station of the fetal head at epidural placement affect the position of the fetal vertex at delivery?

OBJECTIVE: The objective study was to determine whether epidural placement before engagement of the fetal head is associated with an increase in the incidence of malposition at delivery. STUDY DESIGN: We performed a retrospective cohort study to ascertain the relation between station at epidural placement and malposition. Three hundred fifty-seven patient records were reviewed; 320 records of patients in spontaneous or induced labor who received epidural analgesia were included in the analysis. Patients with a contraindication to labor, antepartum fetal death, or twins were excluded. Maternal demographics, cervical examination at epidural placement, epidural medication characteristics, and labor and delivery data were abstracted from medical records. Station was characterized as high if the fetal vertex was above the level of the maternal ischial spines or low if the vertex was at or below the level of the ischial spines at the time of epidural placement. RESULTS: The relative risk of occiput malposition was significantly increased with epidural placement at high station. This risk remained after we controlled for age and birth weight. Cervical dilatation was not independently associated with occiput position at delivery. CONCLUSIONS: Epidural placement before engagement of the fetal head is associated with an increased incidence of malposition at delivery. This finding may provide an insight into the empiric observation that operative delivery is variably increased for patients laboring under epidural anesthesia.

Adult↗
PubMed1996

Reduction of right atrial peak systolic velocity in growth-restricted discordant twins.

OBJECTIVE: The objective of this study was to measure blood flow velocity changes through the tricuspid valve in intrauterine growth-restricted twins. STUDY DESIGN: Discordant twins were evaluated by measurement of tricuspid valve flow velocities. Twin pairs with one intrauterine growth-restricted fetus caused by uteroplacental insufficiency and one appropriately grown fetus were included in the analysis. Fetuses with chromosomal or structural abnormalities and confirmed twin-twin transfusion syndrome were excluded. Eighteen pairs met these criteria. Student's t test was used for comparison of flow velocities. RESULTS: Peak ventricular diastolic flow velocities through the tricuspid valve in the twin with intrauterine growth restriction and the appropriately grown twin were 35.8 +/- 4.43 cm/sec and 34.0 +/- 6.7 cm/sec, respectively (p = 0.35). The atrial peak systolic flow velocity values were 42.1 +/- 1.2 and 50.3 +/- 1.2, respectively (p = 0.049). CONCLUSIONS: The velocity of blood flow through the tricuspid valve during atrial systole is lower in growth-restricted twins than in appropriately grown cotwins when growth restriction is caused by uteroplacental insufficiency. Its potential in differentiating discordancy from the other causes remains to be explored.

Atrial Function, Right↗
PubMed1996

Racial differences in survival from gynecologic cancer.

OBJECTIVE: To determine whether survival from gynecologic cancer is different between African-American and white patients at an inner-city hospital with both a large clinic and a private service. METHODS: We studied 538 patients (89 African American, 449 white) diagnosed with cervical, uterine, or ovarian cancer at a single institution from January 1, 1989 through December 31, 1993. Information was obtained on age, stage, site of disease, histology, and type of health insurance (public or commercial). Insurance coverage was used as a proxy for socioeconomic status. Overall survival was estimated by the method of Kaplan and Meier and compared by the log-rank test. Cox proportional hazard modeling was used to evaluate the effects of multiple factors on survival. RESULTS: African-American patients were significantly older and were more likely to have cervical cancer and public insurance than white patients. Overall survival was worse for African-American patients than for white patients (P < .05). However, stage for stage, there was no significant difference in survival between the groups. There was also no difference when patients were grouped by insurance status. African Americans had a significantly worse survival for cervical cancer than whites, and African-American patients older than 65 years had a worse survival than whites of similar age. On multivariate analysis, only stage and insurance coverage were significant predictors of survival. CONCLUSIONS: African-American patients with gynecologic cancer at our institution have worse overall survival than white patients. The survival difference seems to be due predominantly to differences in socioeconomic status and stage at diagnosis.

Black People↗
PubMed1996

Dating of pregnancy by trimesters: a review and reappraisal.

Many patients and obstetricians divide the events of human pregnancy into three intervals traditionally termed "trimesters." This system presumably arose from an equal division of the "9 months of pregnancy" into 3-month intervals. There are several problems with this system that follows pregnancy by months or trimesters. First, the average human pregnancy lasting 280 days or 40 weeks is not evenly divisible by three, leaving one to wonder how long each trimester is. Second, conversion from "weeks pregnant" to "months pregnant" is often an estimate that can foster misunderstanding between the patient and her obstetrician. Last, following pregnancy by the Gregorian calendar does not reflect embryonic or fetal developmental milestones. We propose a revision of this system to one in which natural embryonic and fetal developmental landmarks are used instead of trimesters to define the progressive stages of pregnancy. These landmarks occur approximately at 5-week intervals allowing a more simple division of pregnancy into four 10-week quartiles, each with two 5-week intervals. This article reviews many of these important landmarks within this framework. This system emphasizes a developmentally based way of understanding the events of pregnancy for both the patient and the obstetrician.

Embryonic and Fetal Development↗