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Biomedical subjects

J M Alexander

Publications and source records attributed to J M Alexander.

At least 37 records · Page 2Linked to original sources
PubMed1999

Obstetric history in women with surgically corrected adult urinary incontinence or pelvic organ prolapse.

STUDY OBJECTIVE: To compare obstetric histories of women who had surgical correction of urinary incontinence or pelvic organ prolapse with a similar group who did not. DESIGN: Case control study (Canadian Task Force classification II-2). SETTING: Urban, community-based, private practice teaching hospital. PATIENTS: Four hundred eighty women (age 51.4 +/- 13.0 yrs) who underwent corrective surgery for urinary incontinence, pelvic organ prolapse, or both, and whose obstetric history was obtainable through chart review. The control group was composed of 150 women (age 50.7 +/- 9.6 yrs) having routine screening mammography who completed a questionnaire regarding obstetric, gynecologic, and urologic history. MEASUREMENTS AND MAIN RESULTS: Patients and controls did not differ significantly in terms of age, race, height, weight, body mass index, or smoking history. Women who underwent surgery were of greater parity (2.5 +/- 1.2 vs 2.0 +/- 1.2, p <0.001), less often nulliparous (3% vs 18%, p <0.001), less likely to have had a cesarean delivery (4% vs 15%, p <0.001), and more likely to have had a vaginal delivery (94% vs 77%, p <0.001) than those with no surgery. The odds ratio of patients who had a vaginal delivery compared with controls was 4.7 (2.3-8.3), and that for cesarean delivery was 0.22 (0.11-0.43). Analysis of specific delivery information found that, compared with controls, patients were older by 4 years at time of their first delivery (28.9 +/- 4.9 vs 24.9 +/- 4.9 yrs, p <0.001) and more commonly received epidural analgesia intrapartum (87% vs 40%, p = 0.004). Comparisons within the patient group, categorized by indication for surgery, revealed that women who had surgery for either prolapse alone or for both prolapse and incontinence were most likely to have had vaginal deliveries (85% incontinence alone vs 94% prolapse alone vs 97% both, p <0.001). CONCLUSION: Increased parity, vaginal childbirth, maternal age at time of delivery, and use of epidural analgesia are associated with need for operative correction of pelvic organ prolapse or adult urinary incontinence. Conversely, cesarean delivery is associated with less need for surgical correction of incontinence or pelvic organ prolapse.

Case-Control Studies↗
PubMed1999

Epidural analgesia during labor and maternal fever.

BACKGROUND: In recent observational studies, epidural analgesia during labor at patient request has been associated with maternal fever. The authors report a secondary analysis of fever in women who were randomized to receive either epidural or patient-controlled intravenous analgesia during labor. METHODS: Maternal tympanic temperature was measured during spontaneous labor in 715 women at term who were randomized to either epidural analgesia with bupivacaine and fentanyl or to patient-controlled intravenous analgesia with meperidine. Intent-to-treat analysis of women with fever (temperature > or = 38.0 degrees C) versus those without was performed using Student t test and Fisher exact test to determine statistical significance (P < 0.05). RESULTS: Epidural analgesia was associated with maternal fever (odds ratio = 4.0; 95% confidence interval = 2.0-7.7), as was nulliparity (odds ratio = 4.1; 95% confidence interval = 1.8-9.1) and labor longer than 12 h (odds ratio = 5.4; 95% confidence interval = 2.9-9.9). These factors were all independent variables for maternal fever when analyzed using logistic regression. CONCLUSIONS: Epidural analgesia is associated with maternal fever. However, nulliparity and dysfunctional labor are also significant cofactors in the fever attributed to epidural analgesia.

Analgesia, Epidural↗
PubMed1999

Mutational analysis of activin/transforming growth factor-beta type I and type II receptor kinases in human pituitary tumors.

Genetic mutation or loss of activin/transforming growth factor-beta (TGFbeta) receptor function has been shown in human lymphoid, breast, and colorectal tumors as well as Hep2B and Mv1Lu cell lines. Although activin stimulates FSHbeta biosynthesis and secretion, a large percentage of human gonadotroph tumors have previously been demonstrated to be nonresponsive to characterized activin effects. This phenotype may be indicative of loss of functional cell surface receptors and/or intracellular signaling mediators of activin responses. Several studies examining the structure/function of type I and II receptors specific for ligands in the TGFbeta superfamily have delineated the critical regions for receptor intracellular kinase function. In the case of TGFbeta, inactivating mutations in these regions have been shown to render these receptors kinase deficient by a dominant negative phenotype and result in resistance to growth arrest. We therefore hypothesized that activin/TGFbeta cell surface receptors may act as tumor suppressors in human pituitary tumors, and that inactivating genetic mutations in the intracellular kinase region of this gene family may release pituicytes from normal growth suppression by activin through a similar mechanism. We used single stranded conformational polymorphism analysis to examine 2 intracellular regions required for type I receptor signaling by human Alk1-5 type I receptors as well as the entire coding region of 2 activin type II receptors and the TGFbeta type II receptor in 64 human pituitary tumors. A novel polymorphism was found in 45% of tumors at codon P117 of the ActRIIA gene and was used as a positive control for single stranded conformational polymorphism. One patient with a gonadotroph tumor had a confirmed A482V germline mutation in the Alk1 gene within kinase subdomains X-XI. No other mutations were detected in any tumor studied. These data suggest that somatic mutations within these intracellular kinase regions of type I/type II receptors are rare in human pituitary tumors.

Activin Receptors, Type I↗
PubMed1999

Managed care contracting for specialists.

Specialty managed care contracting requires specialists to understand their role in managing care, as well as carve-out and subcapitation agreements. Specialists should know their referral sources, their costs for providing care, and how to provide care that meets their referral sources' needs and the payers' requirements. Once specialists enter carve-out or subcapitation arrangements, they need to determine the best payment calculation method for their practice. Three methods to consider are resource-based relative value scale, per-referral basis, and a point system. Because each method produces different results, providers need to understand each method and the unique concerns of specialty managed care contracting to negotiate the best contracts for their situation.

Capitation Fee↗
PubMed1998

The course of labor with and without epidural analgesia.

OBJECTIVE: Our purpose was to measure effects of epidural analgesia on labor compared with boluses of meperidine in a cohort of women with similar clinical circumstances. STUDY DESIGN: One hundred ninety-nine nulliparous women who were delivered spontaneously at term and who received oxytocin for labor augmentation before the initiation of analgesia were identified for analysis. All these women were managed in a low-risk labor unit according to a standardized protocol. This management protocol encouraged early amniotomy and the use of oxytocin when ineffective labor was diagnosed. RESULTS: The demographic characteristics of the two study groups were similar with respect to age, height, weight, and maternal age. The two groups had the same cervical dilatation on admission (3.3 cm) and at the time of analgesia administration (4.1 vs 4.2 cm), indicating similar progress of labor before oxytocin administration. The length of the active phase of labor was longer in the epidural group (7.9 vs 6.3 hours, p = 0.005), as was the second stage (60 vs 48 minutes, p = 0.03). The mean and maximal rates of oxytocin infusion were similar between the two study groups; however, the amount of oxytocin required for each centimeter of cervical change was more in the epidural group (22 vs 16 mU per cm of cervical change, p = 0.009). Neonatal outcomes were unaffected by the type of labor analgesia. CONCLUSION: Epidural analgesia decreases uterine performance during oxytocin-stimulated labor, resulting in an increase in the length of the first and second stages of labor.

Adolescent↗
PubMed1998

Does magnesium sulfate given for prevention of eclampsia affect the outcome of labor?

OBJECTIVE: The purpose of this study was to determine whether magnesium sulfate given for prevention of eclampsia affected labor outcomes compared with phenytoin, which is not known to impede uterine activity when given in anticonvulsant doses. STUDY DESIGN: Secondary analysis was performed of a study of women with pregnancy-induced hypertension who were admitted for delivery and randomly assigned to receive either magnesium sulfate or phenytoin for eclampsia prophylaxis. Nulliparous women with a singleton pregnancy in cephalic presentation at term were selected for analysis in an effort to limit the influence of confounding variables such as preterm birth and malpresentations on labor management and outcomes. Similarly, women who had severe preeclampsia and who received labor epidural analgesia were excluded. RESULTS: A total of 2138 women were randomized to receive magnesium sulfate or phenytoin in the primary study. A total of 905 nulliparous women met the inclusion criteria for this secondary analysis; 480 had been randomized to phenytoin and 425 were given magnesium sulfate. The two groups were similar demographically. Labor outcomes such as (1) oxytocin stimulation, (2) admission-to-delivery intervals, (3) prolonged second-stage labor, (4) forceps delivery, and (5) cesarean delivery were not affected by maternal treatment with magnesium sulfate. CONCLUSION: Compared with phenytoin, magnesium sulfate given for intrapartum treatment of pregnancy-induced hypertension does not significantly affect labor outcomes.

Adult↗
PubMed1998

Clinical chorioamnionitis and the prognosis for very low birth weight infants.

OBJECTIVE: To determine the effects of clinical chorioamnionitis on neonatal morbidity and mortality in very low birth weight infants. METHODS: This was an observational cohort analysis of all singleton live-born infants weighing 500-1500 g at 24 weeks' or greater gestational age and born between 1988 and 1996 at Parkland Memorial Hospital, Dallas, Texas. Chorioamnionitis was diagnosed on the basis of maternal fever of 38C with supporting clinical evidence, which included fetal tachycardia, uterine tenderness, and/or malodorous infant, and the absence of another source of infection. Multiple logistic regression analysis was used to adjust for outcomes of interest. RESULTS: Ninety-five of 1367 very low birth weight infants (7%) were exposed to chorioamnionitis. Neonatal sepsis, respiratory distress syndrome, seizure in the first 24 hours of life, intraventricular hemorrhage (grade 3 or 4), and periventricular leukomalacia were all significantly increased with chorioamnionitis, after adjusting for preterm ruptured membranes, pregnancy-associated hypertension, cesarean birth, gestational age, and birth weight. The odds ratios for intraventricular hemorrhage, periventricular leukomalacia, and seizures in the first 24 hours were 2.8 (95% confidence interval [CI] 1.6, 4.8), 3.4 (95% CI 1.6, 7.3), and 2.9 (95% CI 1.2, 6.8), respectively. CONCLUSION: Our results suggest a link between clinical chorioamnionitis and several indices of neonatal morbidity in the very low birth weight infant. Chorioamnionitis appears to make the very low birth weight infant particularly vulnerable to neurologic damage.

Cerebral Hemorrhage↗
PubMed1998

Hyperbaric oxygen and thrombolysis in myocardial infarction: the 'HOT MI' randomized multicenter study.

In a previous pilot study, we demonstrated that adjunctive treatment with hyperbaric oxygen (HBO) appears to be feasible and safe in patients with acute myocardial infarction (AMI) and may result in an attenuated rise in creatine phosphokinase (CPK), more rapid resolution of pain and ST changes. This randomized multicenter trial was organized to further assess the safety and feasibility of this treatment in human subjects. Patients with an AMI treated with recombinant tissue plasminogen activator (rTPA) or streptokinase (STK), were randomized to treatment with HBO combined with either rTPA or STK, or rTPA or STK alone. An analysis included 112 patients, 66 of whom had inferior AMIs (p = NS). The remainder of the patients had anterior AMIs. The mean CPK at 12 and 24 h was reduced in the HBO patients by approximately 7.5% (p = NS). Time to pain relief was shorter in the HBO group. There were 2 deaths in the control and 1 in those treated with HBO. The left ventricle ejection fraction (LVEF) on discharge was 51.7% in the HBO group as compared to 48.4% in the controls (p = NS). The LVEF of the controls was 43.4 as compared to 47.6 for those treated, approximately 10% better (no significant difference). Treatment with HBO in combination with thrombolysis appears to be feasible and safe for patients with AMI and may result in an attenuated CPK rise, more rapid resolution of pain and improved ejection fractions. More studies are needed to assess the benefits of this treatment.

Adolescent↗
PubMed1998

Differential expression of estrogen receptor-beta (ER beta) in human pituitary tumors: functional interactions with ER alpha and a tumor-specific splice variant.

The mitogenic and regulatory effects of estrogen (E2) in adenohypophysial cells are known to be mediated through the nuclear estrogen receptor (ER alpha). Expression of ER alpha and several of its messenger ribonucleic acid (RNA) alternate splice variants has been shown to be restricted to prolactinomas and gonadotroph tumors. However, little is known about gene expression patterns of the novel nuclear hormone receptor ER beta in the neoplastic pituitary. ER beta has high homology to ER alpha in the DNA- and ligand-binding domains, but encodes a distinct transcriptional activating function-1 (AF-1) domain. Using RT-PCR analysis of total RNA from 38 human pituitary adenomas, we found that ER beta messenger RNA was coexpressed with ER alpha and its splice variants in 60% of prolactinomas, 100% of mixed GH/PRL tumors, and 29% of gonadotroph tumors. ER beta gene expression was not limited to ER alpha-positive tumor subtypes, however, and was also found in 100% of null cell tumors, 80% of somatotroph tumors, and 60% of corticotroph tumors. Because ER beta is coexpressed with ER alpha and its splice variants in prolactinomas and gonadotroph tumors, we functionally characterized the potential interactions between ER beta and ER alpha. We also examined the potential cooperative effects on ER beta-mediated gene expression of a tumor-specific truncated delta 5ER alpha splice variant that has been shown to be coexpressed in the majority of ER alpha-positive tumors. This exon 5 splice variant encodes the AF-1 domain as well as regions critical for DNA binding and nuclear localization, but lacks the ligand-binding and AF-2 domains. Mammalian expression vectors encoding ER alpha, delta 5ER alpha, and/or ER beta complementary DNAs were transiently transfected along with an E2 response element promoter-luciferase (ERELuc) reporter into human ER alpha/ER beta-negative osteosarcoma U2-OS cells. ER beta was less potent than ER alpha in activating E2-stimulated ERELuc activity (4-vs. 14-fold relative to basal control levels). However, when delta 5ER alpha was coexpressed with ER beta or ER alpha, E2-stimulated ERELuc activity was markedly increased to 8- and 57-fold, respectively, relative to basal control levels when each full-length isoform was expressed alone. Finally, coexpression of ER beta with ER alpha did not significantly alter the E2-stimulated ERELuc activity induced by ER alpha alone. Cotreatment with tamoxifen markedly inhibited all E2-stimulated ERELuc responses to baseline levels. Together, these data suggest that ER beta has a minor role in mediating E2 responses in ER alpha-positive tumors, but may be the main mediator of E2-stimulated gene expression when expressed alone in somatotroph, corticotroph, and null cell tumors. This low, but significant, level of ER beta trans-activation potential may be enhanced by coexpression of delta 5ER alpha in neoplastic pituitary. Therefore, E2-mediated gene expression in normal and neoplastic pituitary appears to be highly dependent on the expression of ER alpha and ER beta isoforms, which have varying transcriptional activities.

Adenoma↗
PubMed1998

A tumor-specific truncated estrogen receptor splice variant enhances estrogen-stimulated gene expression.

This study examines the cooperative effects of a human estrogen receptor-alpha (ERalpha) isoform on estrogen (E2)-mediated gene activation in U2-OS osteosarcoma cells. Delta5ERalpha, an alternatively spliced ERalpha variant lacking exon 5, is coexpressed with normal ERalpha in several E2-responsive neoplastic tissues. However, the potential interactions of delta5ERalpha with normal ERalpha have not been functionally characterized. Delta5ERalpha encodes the hormone-independent trans-activating function (AF-1), as well as the constitutive receptor dimerization and DNA-binding domains. It is generated by an alternate splice event that omits exon 5 and alters the reading frame of the resulting mRNA. The delta5ERalpha protein is prematurely truncated and lacks the majority of the hormone-binding and activating function-2 (AF-2) domains. When delta5ERalpha mammalian expression vector was transfected alone in human ERalpha/ERbeta-negative osteosarcoma U2-OS cells, it had no effect on either basal or E2-mediated EREtk81Luc reporter transcriptional activity, while transfected cells expressing control normal ERalpha increased EREtk81 Luc activity up to 20-fold in response to 10 nM E2. However, when delta5ERalpha was cotransfected with normal ERalpha, both basal and E2-stimulated EREtk81Luc reporter activation were increased approximately 500% over levels observed when cells were transfected with ERalpha alone. Similar effects of delta5ERalpha and normal ERa coexpression were observed using an E2-responsive human C3 promoter/luciferase reporter construct. The effects of delta5ERalpha on normal ERalpha were further assessed in U2-OS cells stably transfected with normal ERalpha. Transfection of increasing amounts of delta5ERalpha expression vector into [ERalpha+]OS cells resulted in potentiation of E2-stimulated ERELuc activity in a synergistic, dose-dependent manner. Moreover, coexpression of delta5ERalpha in [ERalpha+]OS cells improved E2 sensitivity 100-fold over cells expressing ERalpha alone. Proliferation rates of stable U2-OS cell lines expressing delta5ERalpha were significantly increased (P < 0.05), with cell doubling times reduced from 35 h in control parental U2-OS cells to 28 h in [delta5ERalpha]OS cells. However, growth rates were not affected by either E2 or tamoxifen treatment. Electromobility shift/supershift assays using nuclear extracts of U2-OS cells stably transfected with ERalpha and delta5ERalpha confirmed the constitutive binding of delta5ERalpha and ERalpha protein to estrogen-response element (ERE) sequence independent of E2 and also showed an increase in delta5ERalpha/ERalpha-ERE complexes with E2 treatment. These data are consistent with interactive effects of normal ERalpha and delta5ERalpha on transcription from classic ERE gene promoters. Delta5ERalpha appears to therefore act as a dominant positive receptor that increases both basal and E2-stimulated gene transactivation of normal ERalpha.

Alternative Splicing↗
PubMed1997

Decreased sensitivity to adriamycin in cadmium-resistant human lung carcinoma A549 cells.

Cross-resistance presents an obstacle in cancer chemotherapy. Cadmium is a potential carcinogen whose exposure has been shown in epidemiological and laboratory experiments to cause lung cancer. Cadmium also induces various forms of resistance in human lung carcinoma cells. This resistance may be shared by antineoplastic agents, which should be a concern for chemotherapy of cadmium-induced lung cancer. In the present study, two subpopulations of human lung carcinoma A549 cells with a different magnitude of resistance to cadmium toxicity were shown to have a parallel resistance to the cytotoxic action of Adriamycin (ADR), an important anticancer drug. Several factors were examined to investigate the mechanism(s) for the cross-resistance, including cellular metallothionein and glutathione (GSH) concentrations, glutathione S-transferase activity, mdr1 expression, and antioxidant enzyme activities including superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Only cellular GSH content was elevated consistently in the cadmium/ADR-resistant cells relative to the cadmium/ADR-sensitive cells. Treatment with buthionine sulfoximine, a specific inhibitor of GSH synthesis sensitized both cell lines to ADR only when the cellular GSH levels were depleted to about 5% of control. This BSO treatment, however, did not affect cell viability. Further study revealed that the cadmium/ADR-resistant cells have a greater capacity in recovery of cellular GSH content following BSO treatment. The results demonstrate that cross-resistance to ADR exists in cadmium-resistant human lung carcinoma A549 cells, and enhanced GSH synthesis capacity, rather than elevated levels of cellular GSH, may be related to this resistance.

Antibiotics, Antineoplastic↗
PubMed1997

The benefits of peer collaboration on strategy use, metacognitive casual attribution, and recall.

This study examined the benefits of a peer collaborative activity on cognitive strategy use and effectiveness, and on metacognitive understanding of strategy use. Children's knowledge about the effectiveness of the sorting strategy grouped them into lower and higher metacognitive understanding. Treatment group triads, consisting of children with lower and higher levels of metacognitive understanding, were given a collaborative recall task. Results indicated that interaction with children working at a higher level of metacognitive knowledge, in conjunction with directions to explicitly discuss strategies, increased strategy use and induced higher levels of metacognitive thinking in children who had been operating at lower levels of metacognitive thinking. overall, children's use of the sorting strategy and recall performance improved as a function of treatment group membership. Implications for future research are discussed.

Child↗
PubMed1997

The relationship of infection to method of delivery in twin pregnancy.

OBJECTIVE: Our purpose was to determine whether manipulation of the second twin increases the risk of postpartum infection. STUDY DESIGN: Medical records of all twin deliveries between January 1991 and December 1994 were reviewed. The route of delivery (vaginal vs cesarean section) was examined. The vaginal group was further divided into those delivered in the vertex/vertex position (i.e., no uterine manipulation) versus those delivered vertex/breech extraction (i.e., manipulation). The chi 2 and Student t test were used where appropriate. RESULTS: A total of 718 twins were identified, and maternal age, parity, gestational age at delivery (36 weeks), and birth weight (2278 gm) were similar among groups. The metritis rate was higher in the cesarean group (74/447 or 18%) than in the vaginal group (17/299 or 5.7%, p < 0.001). In comparing the vaginal group delivered without uterine manipulation with the vaginal group delivered with manipulation (i.e., breech extraction), there was no difference in the incidence of metritis (10/147 or 6.8% vs 7/152 or 4.6%, not significant). The length of time between delivery of twin A and twin B did not affect the metritis rate. Neonatal outcomes including sepsis, neonatal death, and length of hospitalization were similar among groups (not significant). CONCLUSION: Uterine manipulation of the second twin does not increase the risk of postpartum metritis or neonatal sepsis. In addition, the time interval between delivery of twins A and B has no effect on the rate of metritis. Although the rate of endometritis has been reported to be higher with twins delivered by cesarean section compared to singletons, the 18% rate of endometritis in twins delivered by cesarean section in this study is slightly lower than in our general population of cesarean deliveries (22%).

Adult↗
PubMed1997

Outcome of twin gestations with a single anomalous fetus.

OBJECTIVE: Our goal was to determine whether the presence of one anomalous fetus in a twin gestation affects pregnancy outcome when compared with twin pregnancies without fetal anomalies. STUDY DESIGN: Maternal and neonatal data from 970 twin pregnancies delivered from 1988 to 1995 were collected. Three groups of twin gestations were identified: one fetus with a major anomaly (n = 18), one fetus with a minor anomaly (n = 38), and both fetuses without anomalies (n = 914). RESULTS: Maternal demographic characteristics (age, race, and antepartum complications) were similar among the groups. There was no difference in neonatal outcome (gestational age at delivery, birth weight, cord pH, sepsis, and death) in the minor anomaly and no anomaly groups. There were significant differences between the major anomaly group and the no anomaly group in gestational age at delivery (32.9 vs 35.6 weeks, p < 0.05), birth weight at delivery (1759 vs 2291 gm, p < 0.05), hospital days (41 vs 13 days, p < 0.05), and perinatal death of the anomalous fetus (278/1000 vs 10/1000). Except for total days in the hospital, there was no difference in neonatal morbidity or mortality for the normal fetus when compared with the minor group or the no anomaly group. CONCLUSION: The presence of a fetus with a major anomaly in a twin gestation increases the risk of preterm delivery. The neonatal outcome of the nonanomalous fetus does not appear to be affected by the anomalous fetus.

Cesarean Section↗
PubMed1997

Tumor-specific expression of alternatively spliced estrogen receptor messenger ribonucleic acid variants in human pituitary adenomas.

The well documented mitogenic and hormone regulatory effects of estrogen (E2) on pituitary cells are mediated via its nuclear receptor (ER), a cellular homolog of v-erbA oncogene. ER isoforms generated by alternative exon splicing, termed ER variants delta 2ER to delta 7ER, have been identified in breast cancer and have been postulated to have important pathogenetic and clinical implications in tumorigenesis and/or development of hormone resistance. Because pituitary tumors, particularly prolactinomas, are known to be E2-dependent, we investigated alternatively spliced ER variant messenger ribonucleic acid expression in 40 human pituitary tumors of various phenotypes and normal pituitary tissues, using reverse transcription-PCR and Southern blot analyses. Nine of 11 prolactinomas readily expressed multiple ER variants (delta 2ER, delta 4ER, 5ER, and delta 7ER), whereas 6 of 11 tumors showed faint expression of delta 3ER. Four of 7 glycoprotein hormone-producing tumors that synthesized FSH beta expressed delta 2ER, delta 5ER, and delta 7ER. In 9 GH- and 10 ACTH-secreting tumors examined, the expression of normal and variant ER was restricted to tumors that also exhibited scattered PRL immunoreactivity. Variant and normal ER were not found in three null cell tumors (oncocytomas) that showed negative immunoreactivity for all pituitary hormones or their subunits. In contrast, only delta 4ER and delta 7ER were uniformly detected in normal pituitaries. delta 6ER was not detected in any normal or neoplastic pituitary specimen studied. We conclude that multiple alternatively spliced ER variants are coexpressed with normal ER in a tumor phenotype-specific manner. In addition, ER variants delta 2ER and delta 5ER were found to be tumor specific. Future functional studies will be required to determine whether coexpression of multiple ER variants along with normal ER confers a pathophysiological role in pituitary hormone regulation and/or tumor cell proliferation.

Adenoma↗
PubMed1996

Alterations of the glutathione redox cycle status in fumonisin B1-treated pig kidney cells.

Fumonisin B1 (FB1) causes equine leukoencephalomalacia, porcine pulmonary edema, and liver tumors and chronic nephritis in rats. To investigate mechanisms by which FB1 induces toxicity, effects of FB1 on cellular glutathione (GSH) redox status and GSH depletion on FB1 toxicity in pig kidney (LLC-PK1) cells were studied. Treatment of LLC-PK1 cells with 50 microM FB1 for 24 hours significantly decreased cellular GSH contents from 56 +/- 3.2 to 42.7 +/- 4.4 nmol/mg protein (p < 0.05) and increased the activities of glutathione reductase (GR) from 25.7 +/- 2.4 to 35.7 +/- 5.0 mumol NADPH/mg protein (p < 0.05). The activities of glutathione peroxidase (GSHpx), catalase, and Cu,Zn-superoxide dismutase (SOD) were not changed by this treatment. Treatment of LLC-PK1 cells for 12 hours with 0.1 mM buthionine sulfoximine (BSO), a selective inhibitor of the enzyme gamma-glutamylcysteine synthetase that catalyzes the rate-limiting reaction in de novo GSH synthesis, decreased cellular GSH levels to about 20% of that found in the control cells. The cells pretreated with 0.1 mM BSO for 12 hours were significantly sensitized to the FB1 cytotoxicity as determined by a long-term survival assay (p < 0.05). The results demonstrate that FB1 changes GSH redox cycle status in LLC-PK1 cells, and GSH may play a role in cytoprotection against FB1 toxicity.

Acetylcysteine↗
PubMed1996

Treatment of the small unruptured ectopic pregnancy: a cost analysis of methotrexate versus laparoscopy.

OBJECTIVE: To compare the economic costs between two strategies for management of the small unruptured ectopic pregnancy: initial treatment with methotrexate versus initial treatment with laparoscopic salpingostomy. METHODS: We assumed that both treatment strategies would result in identical clinical outcomes: resolution of the ectopic pregnancy without maternal mortality or long-term morbidity. Based on a literature review, estimates were derived for the likely clinical outcomes of a single injection of methotrexate (50 mg/m2) and for the likely clinical outcomes of the laparoscopy strategy. A range of values was evaluated for the initial success rate of each strategy and varying assumptions made about the type of treatment modality used for initial treatment failures. Direct medical costs of each strategy were estimated based on actual reimbursement rates of a third-party payer for the components of each strategy. The treatment strategies were compared in best-case/worst-case scenarios to determine the potential range of differences in costs between the two strategies. RESULTS: The cost of the methotrexate strategy ranged from $438 to $1390, and the cost of laparoscopic salpingostomy ranged from $2506 to $2974; therefore, the methotrexate strategy was less costly than laparoscopy, with a cost difference ranging from $1124 (best-case laparoscopy-worst-case methotrexate scenario) to $2536 (worst-case laparoscopy-best-case methotrexate scenario). Sensitivity analyses demonstrated that initial therapy with methotrexate was less costly over a wide range of probability and cost estimates. CONCLUSION: Initial methotrexate is a cost-effective alternative to laparoscopic salpingostomy in the treatment of the small unruptured ectopic pregnancy.

Costs and Cost Analysis↗