Biomedical subjects

Ovadia Abulafia

Publications and source records attributed to Ovadia Abulafia.

At least 19 recordsLinked to original sources

PubMed2006

Type 2 11beta-hydroxysteroid dehydrogenase activity in human ovarian cancer.

In the ovary cortisol-cortisone inter-conversion is catalyzed by the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD). Its role in carcinomas of human ovary is unknown. The majority of ovarian cancers are derived from ovarian surface epithelium and the inflammation caused by successive ovulation seems to a play a role in the development of cancer. Cortisol is known to act as anti-inflammatory agent and its metabolism by type 1 and type 11beta-HSD may control the inflammatory action by cortisol in ovary. We undertook this study to investigate type 2 11beta-HSD activity which functions exclusively oxidative direction, in normal ovarian tissue compared to ovarian epithelial cancer. Ovarian tissue was obtained from patients undergoing hysterectomy for both benign and malignant disease. Tissue was placed immediately on dry ice and subsequently transferred to a freezer where they were maintained at -70 degrees C. NAD dependent 11beta-HSD activity was then determined in this tissue. T-test was performed to determine statistical significance. Mean type 2 enzyme activity was 0.87 +/- 1.65 pmol/min g tissue in normal ovarian tissue versus a mean enzyme activity of 2.96 +/- 1.37 pmol/mim g tissue in from cancer specimens. This difference was statistically significant with a p-value of 0.03. Type 2 1beta-HSD activity in ovarian cancer specimens was significantly higher than enzyme activity measured in normal post-menopausal ovarian tissue. Decreased cortisol levels due type 2 1beta-HSD activity may play a role neoplastic transformation as well as tumor proliferation in ovarian cancer by eliminating anti-inflammatory action of cortisol.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2006

NAD dependent 11beta-hydroxysteroid dehydrogenase activity in human endometrium and endometrial tumors.

BACKGROUND: The isoforms of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) types 1 and 2, regulated by ovarian steroids, catalyze the interconversion of glucocorticoids and their 11-keto metabolites. The role of these enzymes in malignancies of human endometrium is unknown. We compare NAD dependent 11beta-HSD (type 2) activity levels among normal human endometrium and endometrial carcinomas of differing grades and histologies. METHODS: NAD dependent 11beta-HSD activity was determined in endometrial tissue obtained from patients undergoing hysterectomy for benign or malignant disease (endometroid, serous and carcinosarcomas). Student's t test was utilized with p < 0.05 considered significant. Data are presented as mean +/- SD. RESULTS: NAD dependent 11beta-HSD activity was present in all endometrial samples. The activities were 0.61+/- 0.27 in normal (n = 9), 0.43 +/- 0.29 in endometrioid endometrial carcinoma (n = 14), 0.50 +/- 0.26 in uterine serous carcinoma (n = 6) and 0.25 +/- 0.37 in carcinosarcomas (n = 9). NAD dependent 11beta-HSD activity was lower in the carcinosarcoma group as compared to normal endometrial tissue (p = 0.03). CONCLUSIONS: NAD dependent type 2 11beta-HSD activity was demonstrated in all normal and endometrial tumors. Enzyme activity in endometroid and uterine serious carcinoma tumors was similar to enzyme activity in normal endometrium. In contrast, carcinosarcomas show significantly lower enzyme activity compared to normal tissue.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2006

Acute onset of severe hemolysis, elevated liver enzymes, and low platelet count syndrome in a patient with a partial hydatidiform mole at 17 weeks gestation.

Preeclampsia is uncommon prior to 24 weeks gestation and has been associated with partial and complete hydatidiform moles. We present an unusual case in which a patient was diagnosed with preeclampsia at 17 weeks gestation. Ultrasound findings were consistent with a partial hydatidiform mole. Within 24 hours of the onset of symptoms, the patient developed severe hemolysis, elevated liver enzymes, and low platelet count syndrome, with a platelet count of 20 x 10 (9) cells/L. Termination of pregnancy was performed with rapid resolution of signs, symptoms, and laboratory abnormalities. Triploid 69,XXY was confirmed at karyotype analysis. This case demonstrates the acuteness in which life-threatening maternal conditions can arise with this uncommon complication of pregnancy, and the importance of correct identification of the characteristic ultrasonographic findings associated with a partial hydatidiform mole.

Abortion, Induced↗

PubMed2006

Do serum beta-human chorionic gonadotropin levels on day 4 following methotrexate treatment of patients with ectopic pregnancy predict successful single-dose therapy?

The purpose of this study is to assess whether serum beta-human chorionic gonadotropin (beta-hCG) levels on day 4 following methotrexate (MTX) treatment in patients with ectopic pregnancy predict successful single-dose therapy or the need for subsequent surgical intervention. Retrospective analysis of patients with ectopic pregnancies treated with MTX (50 mg/m (2)) was conducted. Inclusion criteria for MTX management were serum beta-hCG < 15,000 mU/mL, absent fetal cardiac activity, ultrasonographic gestational sac < 3.5 cm, normal liver function tests, hemodynamically stable patient with no evidence of hemoperitoneum, and informed consent. Day 1, 4, and 7 serum beta-hCG levels were obtained. Outcome parameters included successful single-dose MTX management, the requirement for multiple treatments, and whether subsequent surgery was required. Receiver operator characteristic (ROC) curves were used. P < 0.05 was considered significant throughout. Eighty-three patients were studied. Of these, 60 patients were treated successfully with single doses, 16 patients required two doses, and two patients required three doses of MTX, and five underwent surgical management. Mean day 1 serum beta-hCG levels of patients successfully treated with single-dose MTX was 3938.5 (+/- 589.2 [standard deviation]) versus 1767.65 (+/- 1237.8) mU/mL in patients requiring multiple doses of MTX therapy, ( P < 0.0001). ROC curves for serum beta-hCG levels on days 1, 4, and 7 were 0.449, 0.592, and 0.754, respectively, indicating that only day 7 serum beta-hCG levels were associated with successful single-dose MTX therapy. Serum beta-hCG levels on day 4 of MTX in patients with ectopic pregnancy do not predict successful single-dose therapy or the need for surgery.

Abortifacient Agents, Nonsteroidal↗

PubMed2006

Haymaker gene expression in malignant and normal gynecologic tissues.

We previously reported that cell lines established from human carcinomas and leukemias/lymphomas expressed high levels of an intracellular membrane-bound protein, Haymaker, whereas cell lines derived from non-malignant connective tissue cells and lymphoid cells expressed low levels of this gene product. To determine whether these findings reflect neoplastic transformation or, alternatively, tissue specificity, we examined by immunohistochemical and molecular methods the expression of Haymaker in gynecologic organs with and without tumor. A highly specific, affinity-purified rabbit polyclonal antibody against a 25-mer Haymaker peptide was used for immunohistochemical staining and morphometric analysis of 85 tissue specimens. Immunohistochemical studies demonstrate, for the first time, that Haymaker protein is highly expressed in epithelial cells of the endometrium of the normal uterus and to a somewhat lesser extent in the mucosa of the normal vagina and cervix, but is poorly expressed or absent in cells of the connective tissue and smooth muscle strata of these organs (p < 0.005). Significant differences in Haymaker expression, as assessed by immunohistochemistry, between malignant and normal gynecologic tissues were not observed (p = 0.27). The expression of Haymaker protein does not appear, therefore, to be a marker of malignant transformation of the epithelium of gynecologic organs but rather distinguishes both normal and malignant epithelial cells from normal connective tissue and smooth muscle cells.

Animals↗

PubMed2006

Evaluation of pegylated liposomal doxorubicin (Doxil) as second-line chemotherapy of squamous cell carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group.

OBJECTIVE: Doxorubicin has reported activity in advanced and recurrent cervical cancer but hematologic toxicity has limited its use in some combinations. To determine the level of activity and potential for use in future combinations, a phase II trial of pegylated liposomal doxorubicin as second-line therapy in advanced and recurrent cervical cancer was performed. METHODS: Eligible patients had squamous cell carcinoma of the cervix, measurable disease, one prior chemotherapy regimen which did not include an anthracycline, absolute neutrophil count (ANC) > 1500/microl, platelet count > 100,000/microl, and adequate hepatic function. Pegylated liposomal doxorubicin 40 mg/m(2) was administered intravenously over 1 h every 4 weeks. RESULTS: Twenty-seven patients were entered on this study. All patients were evaluable for toxicity and 26 were evaluable for response. A median of 2 courses of therapy (range 1-10) was given. No grade 4 toxicities were noted. Three patients (11.1%) had partial responses. CONCLUSION: Liposomal doxorubicin has limited activity, at the dose and schedule employed in previously-treated cervical cancer.

Adult↗

PubMed2006

Glucose challenge test threshold values in screening for gestational diabetes among black women.

OBJECTIVE: The objective of the study was to assess the incidence of gestational diabetes among black women according to various cut-off values of the glucose challenge test. STUDY DESIGN: We performed a retrospective chart review of black patients who had a 50-g, 1-hour glucose challenge test between 24 and 28 weeks' gestation of 130 mg/dL or higher followed by a 100-g, 3-hour glucose tolerance test. Results were categorized in 10-mg/dL increments. Gestational diabetes was diagnosed by 2 or more abnormal values using the Carpenter-Coustan criteria. RESULTS: The study included 387 patients. The incidence of gestational diabetes diagnosed overall in all patients with a glucose challenge test of 130 mg/dL or higher was 31.2%. The incidence of gestational diabetes in individuals with a challenge test in the range of 130 to 140 mg/dL was 10.7%. The incidence of gestational diabetes with a screening test of 180 mg/dL or higher was 72.0%. CONCLUSION: Our data support the use of 130 mg/dL as the threshold for a positive glucose challenge test and suggest the use of a glucose tolerance test to confirm the diagnosis of gestational diabetes for screening values up to 200 mg/dL.

Adult↗

PubMed2006

Hyperreactio luteinalis presenting with marked hyperglycemia and bilateral multicystic adnexal masses at 21 weeks gestation.

We present an unusual case in which a 23-year-old nulliparous patient was noted to have bilateral multicystic adnexal masses at 21 weeks gestation. Subsequent severe nausea, vomiting, and hyperglycemia with a serum glucose level of 450 mg/dL led to the diagnosis of gestational diabetes. Gradual development of marked maternal virilization ensued and was associated with a serum testosterone level of 4030 ng/mL (free testosterone level of 224 pg/mL), with normal serum dehydroepiandrostendione, estriol, and cortisol levels, leading to the diagnosis of hyperreactio luteinalis. Following vaginal delivery at 38 weeks gestation, gradual and complete spontaneous resolution of signs, symptoms, adnexal masses, diabetes, and testosterone levels were documented.

Adult↗

PubMed2006

11beta-Hydroxysteroid dehydrogenase activity in pregnancies complicated by hydatidiform mole.

PROBLEM: 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) plays an important role in regulating active glucocorticoid reaching the fetus. In normal pregnancy, placental 11beta-HSD functions primarily in oxidative direction. Placental tissue of patients with pregnancies complicated by pre-eclampsia exhibit significantly lower type 1 and 2 11beta-HSD activities and significantly high cortisol level in cord blood suggesting fetal exposure to higher level of active glucocorticoids. The activity of 11beta-HSD in gestational trophoblastic disease has not been determined. The objective of this study was to assess 11beta-HSD activity in tissue from normal second trimester and pregnancies complicated by hydatidiform mole. METHOD OF STUDY: Normal placental tissues were obtained from patients undergoing termination of pregnancy, and from patients undergoing uterine evacuation for hydatidiform mole. Both nicotinamide adenine dinucleotide (NAD)- and nicotinamide adenine dinucleotide phosphate (NADP)-dependent activities were assayed in central villous tissue. Comparison of groups was performed using Student's t-test. A P-value of 0.05 was considered significant. Data are presented as mean +/- S.D. RESULTS: Tissue obtained from five patients with pathology-proven hydatidiform mole demonstrated significantly lower 11beta-HSD activities compared with placental tissue obtained from normal pregnancies. The mean NAD-dependent 11beta-HSD activity in normal placentas was 386 +/- 109 pmol/min/g placenta and in hydatidiform mole was 74 +/- 54 pmol/min/g placenta (P < 0.01). The mean NADP-dependent 11beta-HSD activity in normal placentas was 370 +/- 120 pmol/min/g placenta and in trophoblastic disease was 68 +/- 69 pmol/min/g placenta (P < 0.01). CONCLUSION: Our data indicate significant impairment in the ability of hydatidiform mole tissue to inactivate glucocorticoids.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2006