Biomedical subjects

M A Morgan

Publications and source records attributed to M A Morgan.

At least 19 recordsLinked to original sources

PubMed2001

Cell-cycle-dependent activation of mitogen-activated protein kinase kinase (MEK-1/2) in myeloid leukemia cell lines and induction of growth inhibition and apoptosis by inhibitors of RAS signaling.

Disruption of the RAS-to-mitogen-activated protein kinase (MAPK/ERK) signaling pathway, either directly through activating RAS gene mutations or indirectly through other genetic aberrations, plays an important role in the molecular pathogenesis of myeloid leukemias. Constitutive activation of ERK-1/2 and MEK-1/2, which elicit oncogenic transformation in fibroblasts, has recently been observed in acute myeloid leukemias (AML). In this study, the activation of the RAS-to-MAPK cascade in 14 AML and 5 chronic myeloid leukemia (CML) cell lines is examined and correlated with the effects of a panel of 9 RAS signaling inhibitors on cell viability, colony formation, cell-cycle progression, and induction of apoptosis. Activation of MEK, ERK, and the transcription factors CREB-1, ATF-1, and c-Myc is demonstrated in the majority of the cell lines (9 of 14 AML and 2 of 5 CML cell lines). Although activation of the ERK cascade did not always correlate with the presence of activating RAS mutations or BCR-Abl, it is linked to the G0/G1 and the G2/M phase of the cell cycle. In contrast to most inhibitors (eg, B581, Cys-4-Abs-Met, FPT-2, FTI-276, and FTS), a significant growth inhibition was only observed for FTI-277 (19 of 19), FPT-3 (10 of 19), and the MEK inhibitors U0126 (19 of 19) and PD098059 (8 of 19). Treatment of NB-4 cells with FTI-277 primarily resulted in a G2/M block, whereas treatment with FPT-3 and U0126 led to induction of apoptosis. FTI-277 revealed strong toxicity toward normal purified CD34+ cells. The results suggest differences in the mechanisms of action and support a potential therapeutic usefulness of these inhibitors in the treatment of myeloid leukemias.

Apoptosis↗

PubMed2001

Survival of BRCA1 negative ovarian cancer patients based on family history.

OBJECTIVE: To compare survival of ovarian cancer patients with and without a family history of breast or ovarian cancer who are known to be without mutations in BRCA1. METHODS: Patients with ovarian cancer were tested for germline mutations in BRCA1 by polymerase chain reaction amplification of DNA for single-strand conformation polymorphism and direct sequencing analysis to examine the 22 coding exons of BRCA1 in fresh and archived tumor specimens. Demographic and survival data were collected for statistical analysis. Survival data were calculated by the method of Kaplan and Meier and compared by the log-rank test. RESULTS: Of the 110 patients tested at our institution, 100 were noted to be negative for BRCA1 mutations. After exclusion of nonepithelial histologies, benign tumors, primary peritoneal carcinoma, and incomplete staging, 87 patients remained for analysis, of which 37 demonstrated a family history of breast or ovarian cancer. The two groups showed similar age at diagnosis, stage, grade, residual disease, and type of chemotherapy. Median actuarial survival was 75 months for those patients with a family history versus 70 months for those without (P = 0.73). Evaluation of patients with two or more relatives with breast or ovarian cancer also revealed no differences in survival. CONCLUSIONS: Family history of breast or ovarian cancer does not affect survival of patients with ovarian cancer in the absence of mutations in BRCA1. Previously described differences in survival among patients with BRCA1 mutations may be more related to genetic factors than to biases introduced by the presence of family history.

Actuarial Analysis↗

PubMed2001

Effects of the phytoestrogen coumestrol on locomotor and fear-related behaviors in female mice.

Effects of the estrogenic plant isoflavonoid coumestrol (COUM) on locomotor activity and fear-related behaviors in both the absence and the presence of estradiol benzoate (EB) were examined in adult ovariectomized Swiss-Webster mice. In a running wheel paradigm conducted over 10 days, with treatment beginning 12 days prior to testing, daily subcutaneous (sc) injections of 10 microg of COUM did not influence locomotor activity, whereas even the low dose of EB supplied by sc Silastic implant (2.5 microg lasting 5 weeks) produced a significant increase in locomotor activity over animals receiving vehicle alone. In animals receiving both COUM and EB, locomotor activity was significantly diminished compared to the activity observed in animals receiving EB alone. The same animals were also tested in three behavioral paradigms having known activity and fear components (open field, dark/light transition, elevated plus-maze). COUM did not produce significant effects in these assays. However, in an associative fear learning paradigm (fear conditioning), COUM produced significantly less freezing ("fearfulness") in the conditioned fear task than with animals receiving vehicle or a low dose of EB, which did not differ from each other. Unlike EB, which has comparable affinities for estrogen receptor (ER) alpha and ER beta, COUM has a higher affinity for ER beta than for ER alpha. COUM might disrupt estrogen-enhanced locomotor activity by altering the dynamic by which EB acts on the brain through these two ER isoforms. The conditioned fear result suggests that COUM may produce additional effects through alternative pathways.

Animals↗

PubMed2000

Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies?

A series of alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation is considered to be the main cause of cancer. These mutational events include activation of oncogenes and inactivation of tumor suppressor genes. The elucidation of human cancer at the molecular level allows the design of rational, mechanism-based therapeutic agents that antagonize the specific activity of biochemical processes that are essential to the malignant phenotype of cancer cells. Because the frequency of RAS mutations is among the highest for any gene in human cancers, development of inhibitors of the Ras-mitogen-activated protein kinase pathway as potential anticancer agents is a very promising pharmacologic strategy. Inhibitors of Ras signaling have been shown to revert Ras-dependent transformation and cause regression of Ras-dependent tumors in animal models. The most promising new class of these potential cancer therapeutics are the farnesyltransferase inhibitors. The development of these compounds has been driven by the observation that oncogenic Ras function is dependent upon posttranslational modification, which enables membrane binding. In contrast to many conventional chemotherapeutics, farnesyltransferase inhibitors are remarkably specific and have been demonstrated to cause no gross systemic toxicity in animals. Some orally bioavailable inhibitors are presently being evaluated in phase II clinical trials. This review presents an overview on some inhibitors of the Ras signaling pathway, including their specificity and effectiveness in vivo. Because Ras signaling plays a crucial role in the pathogenesis of some hematologic malignancies, the potential therapeutic usefulness of these inhibitors is discussed. (Blood. 2000;96:1655-1669)

Alkyl and Aryl Transferases↗

PubMed2000

Effect of thyroid hormone administration on estrogen-induced sex behavior in female mice.

Effects of thyroid hormones on reproductive processes have been described in sheep, birds, and rats. To extend this subject to mice for eventual analysis with genetically modified animals, we looked for effects of thyroid hormone treatment on lordosis behavior of ovariectomized estrogen-treated female mice. High doses of thyroid hormones reduced lordosis behavior. Since we could not explain this result by pharmacokinetic or peripheral effects, we infer that it worked by a central mechanism. Future investigations must determine whether endogenous fluctuations within the thyroid's normal physiological range have any behavioral effects.

Animals↗

PubMed2000

Can antenatal clinical and biochemical markers predict the development of severe preeclampsia?

OBJECTIVE: This study was undertaken to develop a multivariable clinical predictive rule for severe preeclampsia using second-trimester clinical factors and biochemical markers. STUDY DESIGN: We performed a retrospective cohort study of all pregnant patients with single gestations from 1995 through 1997 for whom we had complete follow-up data. Through medical record review we determined whether patients had severe preeclampsia develop according to American College of Obstetricians and Gynecologists criteria. Case patients with severe preeclampsia were compared with control subjects with respect to clinical data and multiple-marker screening test results. With potential predictive factors identified in the bivariate and stratified analyses both an explanatory logistic regression model and a clinical prediction rule were created. Patients were assigned a predictive score according to the presence or absence of predictive factors, and receiver operating characteristic analysis was used to determine the optimal score cutoff point for prediction of severe preeclampsia with maximal sensitivity. RESULTS: Among the 1998 patients we found 49 patients with severe preeclampsia (prevalence, 2.5%). After we controlled for confounding variables, case patients and control subjects had similar human chorionic gonadotropin and alpha-fetoprotein levels, and the only variables that remained significantly associated with severe preeclampsia were nulliparity (relative risk, 3.8; 95% confidence interval, 1.7-8.3), history of preeclampsia (relative risk, 5.0; 95% confidence interval, 1.7-17.2), elevated screening mean arterial pressure (relative risk, 3.5; 95% confidence interval, 1.7-7.2), and low unconjugated estriol concentration (relative risk, 1.7; 95% confidence interval, 0.9-3.4). Our predictive model for severe preeclampsia, which included only these 4 variables, had a sensitivity of 76% and a specificity of 46%. CONCLUSION: Even after incorporation of the strongest risk factors, our predictive model had only modest sensitivity and specificity for discrimination of patients at risk for development of severe preeclampsia. The addition of the human chorionic gonadotropin and alpha-fetoprotein biochemical markers did not enhance the model's predictive value for severe preeclampsia.

Adult↗

PubMed2000

Ultrasonographic prediction of fetal macrosomia. Association with cesarean delivery.

OBJECTIVE: To investigate whether the incorrect ultrasonographic prediction of macrosomia affects the cesarean delivery rate among nonmacrosomic neonates. STUDY DESIGN: For this retrospective, cohort study, comprehensive ultrasonographic records were reviewed at two centers. Patients with singleton, nonanomalous gestations whose ultrasonography predicted an estimated fetal weight > or = 4,000 g composed one cohort (n = 135), while the other cohort (n = 129) consisted of patients whose ultrasonography predicted an estimated fetal weight between 3,000 and 3,999 g. We compared the cesarean delivery rate in neonates falsely diagnosed with macrosomia (false positives) with the rate in those correctly diagnosed as nonmacrosomic (true negatives). RESULTS: The rate of cesarean delivery was significantly higher among those falsely diagnosed by ultrasonography with a macrosomic fetus as compared to those with a fetus truly diagnosed as nonmacrosomic (42.3% vs. 24.3%, relative risk = 1.74, 95% confidence interval 1.09-2.78). Subgroup analyses excluding diabetic mothers and multiparous women and comparing false positives with true negatives with neonatal birth weights between 3,500 and 4,000 g (birth weights similar to false positives) demonstrated significantly increased cesarean delivery rates among false positives. CONCLUSION: Even in nonmacrosomic neonates, the antenatal ultrasonographic diagnosis of suspected macrosomia is associated with a significant increase in cesarean delivery rates.

Adult↗

PubMed1999

Occult bilateral involvement in stage I epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to determine the incidence of occult bilateral involvement in Stage I epithelial ovarian cancer. METHODS: We retrospectively reviewed the records of all patients (n = 135) with Stage I epithelial ovarian cancer treated at the University of Pennsylvania Cancer Center between 1985 and 1996. A study group of patients (n = 118) who underwent a bilateral salpingo-oophorectomy as part of their staging laparotomy was identified. Operative notes, pathology reports, and discharge summaries were reviewed to document stage, grade, histology, intraoperative impression, gross pathological description, and microscopic diagnosis. Clinically occult bilateral involvement was defined as pathologically documented ovarian involvement by tumor in an ovary that appeared normal to the surgeon during staging laparotomy. RESULTS: The study group consisted of mostly Stage IA (79/118, 67%), followed by Stage IC (35/118, 30%) and Stage IB (4/118, 3%), tumors. In 9/118 (7.6%) of these cases, bilateral disease was documented in the pathology report. In 3/118 (2.5%) of these cases, the bilateral involvement by tumor was clinically occult at the time of surgery. In only 1/118 (0.85%) of these cases did a clinically abnormal appearing ovary not contain tumor. CONCLUSION: Occult involvement by early ovarian cancer is uncommon at the time of staging laparotomy. In appropriately counseled patients strongly desiring to preserve fertility, a unilateral salpingo-oophorectomy may be considered as part of a staging procedure for apparent Stage IA epithelial ovarian cancer if the contralateral ovary appears normal to the surgeon. Consideration should be given to a wedge biopsy with intraoperative frozen section to help exclude occult disease in the normal appearing ovary.

Adenocarcinoma↗

PubMed1999

Contribution of ventrolateral prefrontal cortex to the acquisition and extinction of conditioned fear in rats.

The ventrolateral, agranular insular portion of prefrontal cortex (PFC) in rats is involved in visceral functions and has been shown to be involved in emotional processes. However, its contribution to aversive learning has not been well defined. Classical fear conditioning has been a powerful tool for illuminating some of the primary neural structures involved in aversive emotional learning. We measured both the acquisition and the extinction of conditioned fear following lesions of the ventrolateral PFC of rats. Lesions reduced fear reactivity to contextual stimuli associated with conditioning without affecting CS acquisition, and had no effect on response extinction. Ventrolateral PFC may normally be involved in the processing of contextual information while not being directly involved in extinction processes within the aversive domain.

Animals↗

PubMed1999

Prediction of delivery among women with early preterm labor by means of clinical characteristics alone.

OBJECTIVE: This study was undertaken to assess whether individual clinical factors or combinations thereof could be used to accurately predict the risk of delivery within 1 week of admission among women with preterm labor and minimal cervical dilatation. STUDY DESIGN: We performed a case-control study of patients admitted to our institution with preterm labor and minimal cervical dilatation. A case patient was a patient who sought treatment with uterine contractions between 24 and 34 weeks' gestation with cervical dilatation </=2 cm, who received tocolysis with magnesium sulfate, and who was delivered within 7 days of admission. Control subjects were those who had the same presentation with preterm labor but were not delivered within the first 7 days after admission. The medical records of case patients and control subjects were then abstracted, and information on >70 potential predictors was recorded. Statistical analysis consisted of bivariate and multivariable methods. We also generated a multivariable clinical predictive model with the purpose of detecting a proportion as high as possible of those destined to be delivered within 1 week (high sensitivity). We estimated that we would need 50 case patients and 150 control subjects to detect an odds ratio of 2.5 for risk factors with a prevalence of 20%, an alpha error of.05, a beta error of.20, and a control subject/case patient ratio of 3:1. RESULTS: Three variables were eligible for inclusion in our logistic models according to the bivariate analyses-bleeding on admission, substance abuse, and admission white blood cell count >/=14,000 cells/microL. The simplest and most favorable model included only 2 variables, bleeding and substance abuse, and yielded a sensitivity of 46% and a specificity of 76%. The full 3-variable model had similar test characteristics. For no model were we able to achieve a sensitivity >/=50%. CONCLUSION: The results of this case-control study suggest that combinations of clinical factors do not yield an adequate level of discrimination to be used alone for predicting the likelihood of delivery within 1 week among patients with minimal degrees of cervical dilatation.

Adult↗

PubMed1999

Multiple courses of antenatal corticosteroids and outcome of premature neonates. North American Thyrotropin-Releasing Hormone Study Group.

OBJECTIVES: We sought to examine outcome for premature neonates after multiple courses of antenatal corticosteroids compared with a single course. STUDY DESIGN: We performed a post hoc nonrandomized analysis on 710 neonates of 25-32 weeks' gestation who were born to mothers enrolled in the North American Thyrotropin-Releasing Hormone Trial and who received 1, 2, or >/=3 courses of antenatal corticosteroids. RESULTS: There was no detectable clinical difference in incidence of respiratory distress syndrome, chronic lung disease, and intraventricular hemorrhage related to courses of antenatal corticosteroids, and outcome was similar for infants delivered at 7-13 days compared with those delivered at 1-6 days after receiving antenatal corticosteroids. Compared with those who received a single course, neonates who received >/=2 courses had lower birth weights (-39 g, P =.02), and those receiving >/=3 courses had increased risk of death (adjusted odds ratio, 2.8; 95% confidence interval, 1.3-5.9; P =.01) and lower levels of plasma cortisol at age 2 hours. CONCLUSION: In this retrospective analysis multiple courses of antenatal corticosteroids did not improve outcome and were associated with increased mortality, decreased fetal growth, and prolonged adrenal suppression.

Adrenal Cortex Hormones↗

PubMed1999

Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetal membranes.

OBJECTIVE: The rarer allele of a polymorphism within the promoter region at position -308 of the gene for tumor necrosis factor alpha is associated with increased gene transcription. In this study we tested the hypothesis that this rarer allele is associated with spontaneous preterm birth. STUDY DESIGN: We conducted a case-control study of women admitted to our labor and delivery unit. To assess data from a single racial group with a high incidence of preterm birth we restricted our analysis to African American women, who contributed 73.6% of the samples collected during the study period. Case patients (n = 55) were defined as women who were delivered before 37 weeks' gestation after idiopathic preterm labor or preterm premature rupture of membranes. Control subjects (n = 110) included women who were delivered after 37 weeks' gestation and had no history of preterm delivery. We also performed subgroup analyses of women with idiopathic preterm labor and delivery (n = 29) and women who were delivered preterm after preterm premature rupture of the fetal membranes (n = 26). RESULTS: Although carriers (homozygotes plus heterozygotes) of the rarer allele of the polymorphism at position -308 in the gene for tumor necrosis factor alpha were not significantly more common among women who were delivered preterm (n = 24/55, 44%) than among control subjects (n = 33/110, 30%, P =.08, odds ratio 1.81, 95% confidence interval 0.92-3.54), carriers of the rarer allele were more common among women who were delivered preterm after preterm premature rupture of membranes (n = 15/26, 58%) than among control subjects (P =.008, odds ratio 3.18, 95% confidence interval 1.33-7.83). CONCLUSIONS: Our results demonstrate an association between allelic variants of the polymorphism at position -308 in the gene for tumor necrosis factor alpha and preterm birth after preterm premature rupture of the fetal membranes. We hypothesize that host susceptibility to environmental factors, such as hyperresponsiveness of the gene for tumor necrosis factor alpha to genital tract infection, may promote preterm premature rupture of the fetal membranes and subsequent preterm delivery.

Adolescent↗

PubMed1999

Predicting delivery within 48 hours in women treated with parenteral tocolysis.

OBJECTIVE: To develop a prediction rule using clinical admission characteristics for women treated with parenteral tocolysis for preterm labor who are at highest risk of delivery within 48 hours. METHODS: We performed a case-control study of patients treated with magnesium sulfate for idiopathic preterm labor. A case was defined as a patient who received magnesium sulfate tocolysis and delivered within 48 hours of admission. We selected a 48-hour delay to delivery as a clinically relevant endpoint for the maximization of steroid benefit. Controls were patients who received magnesium sulfate tocolysis and remained undelivered 48 hours after admission. Cases and controls were identified by merging a pharmacy billing database with International Classification of Disease codes for premature labor. Medical records were reviewed and risk factor information was obtained. We focused on risk factors within the first hour of admission, because our goal was to identify patients at high risk of delivery early in their hospital course. Backward stepwise logistic regression was used to develop explanatory and predictive models. The focus of the predictive model was to maximize the test's sensitivity and negative predictive value. RESULTS: We identified 50 cases and 150 controls. The following six variables were included in the initial multivariable models based on bivariate analyses: white blood cell count at least 14.0 (1000/microL), cervical dilation at least 2 cm, bleeding, substance abuse, parity, and previous abortion. A two-variable model containing cervical dilation and bleeding had an overall accuracy of 73%, sensitivity of 62%, and specificity of 76%, and it was as sensitive and specific as more complex models. CONCLUSION: Cervical dilation of at least 2 cm and bleeding on admission had an overall accuracy of 73% in predicting the likelihood of delivery within 48 hours in women receiving magnesium sulfate.

Case-Control Studies↗

PubMed1999

High deferral rate for maternal-neonatal donor pairs for an allogeneic umbilical cord blood bank.

BACKGROUND: To fully evaluate the safety and efficacy of umbilical cord blood (UCB) as a source of hematopoietic progenitor cells, UCB banks are being established worldwide to provide a readily accessible resource of stem and progenitor cells for allogeneic transplantation. Guidelines for UCB donor criteria have been proposed to minimize the possibility of disease transmission to UCB recipients. STUDY DESIGN AND METHODS: In preparation for the establishment of an allogeneic UCB bank, 285 maternal-neonatal donor pairs were evaluated in our tertiary-care hospital, which was chosen because of the high percentage of African Americans among the maternal population. Maternal, neonatal, and family histories were obtained by confidential interview and medical record review to determine the number of eligible donor pairs on the basis of a conservative interpretation of proposed donor criteria. RESULTS: Only 44 percent of donor pairs were considered eligible. The most common deferral factors were maternal, and they included fever at delivery, history of chronic disease, and history of sexually transmitted disease. In most cases, more than one deferral factor was identified. CONCLUSIONS: High-risk maternal populations, which may provide access to ethnic minorities targeted for some UCB banks, may contain low percentages of eligible donors. Further refinement of donor criteria will be important in the evolution of UCB banking and transplantation.

Blood Banks↗

PubMed1999

Multicenter evaluation of the BACTEC MGIT 960 system for recovery of mycobacteria.

We evaluated the BACTEC MGIT 960 system, which is a fully automated, noninvasive system for the growth and detection of mycobacteria with a capacity to incubate and continuously monitor 960 7-ml culture tubes. We studied 3,330 specimens, 2,210 respiratory and 1,120 nonrespiratory specimens, collected from 2,346 patients treated at six sites. Processed specimens were inoculated into the BACTEC MGIT 960 and BACTEC 460 TB systems, as well as onto Lowenstein-Jensen slants and Middlebrook 7H11/7H11 selective plates. From all culture systems, a total of 362 isolates of mycobacteria were recovered; these were recovered from 353 specimens collected from 247 patients. The greatest number of isolates of mycobacteria (289, or 80% of the 362 isolates) was recovered with the BACTEC MGIT 960, followed by the BACTEC 460 TB (271, or 75%) and solid media (250, or 69%). From all culture systems a total of 132 isolates of Mycobacterium tuberculosis complex were recovered. The greatest number of isolates of M. tuberculosis complex was recovered when liquid medium was combined with conventional solid media; the number recovered with BACTEC 460 TB plus solid media was 128 (97%), that recovered with BACTEC MGIT 960 plus solid media was 121 (92%), that recovered with BACTEC 460 TB was 119 (90%) and that recovered with all solid media combined was 105 (79%). The recovery with BACTEC MGIT 960 alone was 102 (77%). The mean times to detection (TTD) for M. tuberculosis complex were 14.4 days for BACTEC MGIT, 15.2 days for BACTEC 460 TB, and 24.1 days for solid media. The numbers of isolates of Mycobacterium avium complex (MAC) recovered were 172 (100%) for all systems, 147 (85%) for BACTEC MGIT 960, 123 (72%) for BACTEC 460 TB, and 106 (62%) for all solid media combined. The TTD for MAC in each system were 10.0 days for BACTEC MGIT 960, 10.4 days for BACTEC 460 TB, and 25.9 days for solid media. Breakthrough contamination rates (percentages of isolates) for each of the systems were 8.1% for BACTEC MGIT 960, 4.9% for BACTEC 460 TB, and 21.1% for all solid media combined.

Automation↗

PubMed1998

Allelotype analysis of uterine leiomyoma: localization of a potential tumor suppressor gene to a 4-cM region of chromosome 7q.

Uterine leiomyoma is a benign smooth muscle tumor of the myometrium and is the most commonly encountered neoplasm in women of reproductive age. As for most benign tumors, the pathogenesis of leiomyoma remains obscure, especially at the molecular genetic level. The purpose of this study was to perform a genome-wide allelotype analysis to identify potential sites of tumor suppressor gene inactivation. Fifty-two cases of uterine leiomyoma were subjected to allelotype analysis by using matched pairs of tumor and blood DNA. Loss of heterozygosity (LOH) was assessed at 61 microsatellite markers distributed throughout the genome and representing all 41 chromosome arms. In general, LOH was very rare except on chromosome 7q, where LOH was observed in 34% of all informative tumors. Fine-deletion mapping with 25 microsatellite markers from the 7q22 region revealed a minimal deletion unit of approximately 4 cM, bounded by the markers D7S2453 proximally and D7S496 distally, that probably harbors a novel tumor suppressor gene involved in the etiology of this tumor.

Alleles↗

PubMed1998

Clinical characteristics of clear cell carcinoma of the ovary.

OBJECTIVE: The aim of this study is to evaluate the clinical characteristics of clear cell carcinoma of the ovary. METHODS: Between 1986 and 1996, 45 patients with clear cell carcinoma of the ovary were identified by scanning the medical records department and the tumor registry at our institution. RESULTS: Median age was 55 years (range 31-80 years). Tumors were 60% (27/45) stage I, 11% (5/45) stage II, 20% (9/45) stage III, and 9% (4/45) stage IV. All patients presented with a pelvic mass ranging in size from 2 x 3 to 20 x 30 cm and all except 1 had optimal cytoreduction. All patients received postoperative platinum-based chemotherapy, 47% (21/45) in combination with paclitaxel. One stage Ia patient refused therapy. Of the 6 stage III/IV patients with measurable residual tumor, 67% (4/6) partially responded to first line chemotherapy by CT scan or second look laparotomy. Recurrences occurred in 37% (10/27) stage I patients, including 18% (2/11) stage Ia, 33% (1/3) stage Ib, and 54% (7/13) stage Ic. Time to recurrence was 16 and 38 months for the two stage Ia patients and 35 months (median, range 18-56 months) for the stage Ic patients. Survival after recurrence was significantly related to disease-free interval after primary chemotherapy. With a median follow-up of 40 months (range 4-145 months), 93% (25/27) of stage I patients are alive, 20% (5/25) with disease, while 46% (6/13) of stage III/IV patients are alive. Median survival for the stage III/IV patients was 22 months (range 4-70 months). CONCLUSIONS: Clear cell tumors of ovary frequently present at early stages. However, these tumors have a propensity for recurrence even after primary chemotherapy in early stage tumors.

Adenocarcinoma, Clear Cell↗

PubMed1998

Recurrence of gestational diabetes: who is at risk?

OBJECTIVE: The object was to determine the recurrence rate of gestational diabetes mellitus and to find various risk factors that might increase this rate. STUDY DESIGN: Seventy-eight patients with gestational diabetes mellitus in their index pregnancies were evaluated in subsequent pregnancies. Medical records for the index and subsequent pregnancies were abstracted for age, parity, body mass index, birth weight, gestational age of gestational diabetes mellitus diagnosis, insulin requirement, weight gain, and interval between pregnancies. These variables were then compared between patients with and without gestational diabetes mellitus in their subsequent pregnancies. RESULTS: Fifty-four of 78 patients (69%) had gestational diabetes mellitus in a subsequent pregnancy. The recurrence of gestational diabetes mellitus was more common when the following variables were present in the index pregnancy: parity > or = 1 (P < .004; odds ratio 3.0, 95% confidence interval 1.4-4.8), body mass index > or = 30 kg/m2 (P < .04; odds ratio 3.6, 95% confidence interval 1.1-25.9), gestational diabetes mellitus diagnosis at < or = 24 gestational weeks (P < .0003; odds ratio 20.4, 95% confidence interval 2.5-444), and insulin requirement (P < .0002; odds ratio 2.3, 95% confidence interval 1.3-3.4). A weight gain of > or = 15 pounds (P < .003; odds ratio 2.9, 95% confidence interval 1.0-5.3) and an interval between pregnancies < or = 24 months (P < .03; odds ratio 1.6, 95% confidence interval 1.1-2.2) were also associated with a recurrence of gestational diabetes mellitus. A multiple logistic regression analysis revealed that an interval of < or = 24 months and a weight gain of > or = 15 pounds between pregnancies were most strongly correlated with a recurrence of gestational diabetes mellitus. CONCLUSIONS: Gestational diabetes mellitus is more likely to recur in parous, obese women who had an early gestational diabetes mellitus diagnosis and required insulin in the index pregnancy. In addition, a shorter interval (< or = 24 months) and a larger weight gain (> or = 15 pounds) between pregnancies appear to be the most significant risk factors for a recurrence of gestational diabetes mellitus.

Age Factors↗