Synergistic activity of recombinant human endostatin in combination with adriamycin: analysis of in vitro activity on endothelial cells and in vivo tumor progression in an orthotopic murine mammary carcinoma model.

PURPOSE: Current combination treatment strategies in malignancy are designed to evaluate the use of cytotoxic drugs and antiangiogenic agents. Endostatin, a fragment of collagen XVIII, specifically inhibits proliferation, migration, and differentiation of endothelial cells in vitro as well as angiogenesis and tumor progression in in vivo models. In this study, we determine the antitumor effect of rhEndostatin administered alone or in combination with Adriamycin against established orthotopic murine mammary carcinoma. EXPERIMENTAL DESIGN: Mice bearing orthotopically established DA-3 mammary adenocarcinoma tumors received varying doses of rhEndostatin alone and in combination with Adriamycin to assess tumor growth inhibition. Additional studies of this in vivo combination included a determination of Adriamycin-induced cardiotoxicity and in vitro effects on human umbilical vein endothelial cell proliferation and cord formation. RESULTS: For single-agent activity, optimal tumor growth inhibition was observed after s.c. administration of 50 mg/kg/day rhEndostatin or 5 mg/kg Adriamycin injected i.v. every 4 days. Combination of Adriamycin with optimal or suboptimal doses of rhEndostatin resulted in synergistic inhibition of DA-3 tumor growth. Importantly, unlike other antiangiogenic agents, rhEndostatin did not exacerbate the cardiotoxicity of Adriamycin. The synergistic interaction between rhEndostatin and Adriamycin was also observed in vitro for inhibition of human umbilical vein endothelial cell proliferation and inhibition of cord formation. CONCLUSIONS: These data suggest that the synergy observed with rhEndostatin in combination with Adriamycin is exerted at the level of the endothelial cell and can result in enhanced tumor growth inhibition. The potential benefit of Adriamycin used in combination with rhEndostatin is being considered for clinical evaluation.     

Oocyte quality in polycystic ovaries revisited: Identification of a particular subgroup of women

Purpose: Our purpose was to assess the endocrine status of women with polycystic ovaries (PCO) undergoing IVF, and to compare oocyte quality with endocrine markers of the syndrome, in an attempt to define a subpopulation with poor quality oocytes. Methods: This was a retrospective study. Patients were first endocrinologically analyzed: serum levels of androgens (T, androstenedione, DHEAS), FSH, and LH as well as glucose and insulin after an oral glucose tolerance test (OGTT) were recorded and are expressed as absolute values and area under the curve (AUC). Subsequently, they were followed over a 2-year period in which patients underwent several attempts of IVF as well as serving as oocyte donors. Patients were divided into three groups: group I (n=4) was women who displayed embryos unable to implant in 15 IVF cycles and 10 ovum donation cycles in which they served as donors; group II (n=16) was PCO patients in whom IVF (n=38) and/or oocyte donation cycles (n=42) resulted in pregnancies; and group III (n=13) was IVF patients with normal appearance of the ovaries by ultrasound. The endocrine status was compared with the IVF results. Results: There was no difference among groups in the endocrinological parameters tested, except for the OGTT which identified women in group I as having higher serum glucose and insulin levels than patients in groups II and III. Similarly, the OGTT showed higher serum glucose values in group II compared to group III. Women in group I were also obese. Patients in group III were older than PCO patients and needed more gonadotropins to reach an ovarian response which resulted in a reduced number of oocytes retrieved. Fertilization was also impaired in group I, in which no pregnancy was recorded. Conclusions: This study shows that there is a particular subgroup of PCO patients with lower fertilization rates and embryos unable to implant. These patients are obese and nonhyperandrogenic and show derangements of insulin secretion.     

FISH Preimplantation Diagnosis of Chromosome Aneuploidy in Recurrent Pregnancy Wastage

Purpose: Our purpose was to detect aneuploidy for chromosomes 13, 16,18, 21, 22, X, and Y in preimplantation embryos from patients with a history of unexplained recurrent miscarriage. Methods: Three patients with a history of unexplained recurrent spontaneous abortion were included in this study. Embryos were biopsied at the eight-cell stage, individually fixed on slides, and processed for fluorescent in situ hybridization (FISH). A multiple FISH protocol for seven chromosomes pairs (13, 16, 18, 21, 22, X, and Y) has been developed. Results: A total of 39 embryos was studied with the multiple FISH protocol developed. Successful analysis of the biopsied embryos was achieved within the time limits usually allowed in a preimplantation diagnosis program. Analysis of the blastomeres showed that 17 embryos were chromosomally normal for the probes used, 16 embryos were aneuploid, and in 6 embryos no informative results were obtained. Conclusions: In the patients studied, a large proportion of embryos (41%) exhibited chromosomal abnormalities for the probes used. Preimplantation diagnosis to screen for chromosome abnormalities could be a feasible approach to improve the possibility of successful pregnancy in these couples.     

Study of daunorubicin cardiotoxicity prevention with pyridoxal isonicotinoyl hydrazone in rabbits.

Risk of cardiotoxicity is the most serious drawback of the clinical usefulness of anthracycline antineoplastic antibiotics, which however, remain among the most powerful and widely employed anticancer drugs. In this study we have used daunorubicin-induced cardiomyopathy in rabbits as a model to investigate possible cardioprotective effects of pyridoxal isonicotinoyl hydrazone (PIH)-a principal representative of a novel group of aroylhydrazone iron chelators. Three groups of animals were used: a control group (n=11; i.v. saline), daunorubicin-treated animals (n=11; 3mg/kg, i.v.), and animals pretreated with PIH (n=9, 25 mg/kg, i.p.) 60 min before daunorubicin administration. All substances were administered once weekly for 10 weeks. Repeated administration of daunorubicin caused premature death in four animals and induced conspicuous histopathological changes in the myocardium, progressive and significant impairment of systolic heart function (a decrease in left ventricular dP/dt(max), ejection fraction, an increase in the pre-ejection period/left ventricular ejection time index), and a gradual increase in cardiac troponin T plasma concentrations. On the contrary, all the PIH-treated animals have survived all daunorubicin applications. Furthermore, in this group, the daunorubicin-induced cardiac changes were in most functional, biochemical as well as morphological parameters less pronounced than in the group receiving daunorubicin alone. Hence, PIH and other aroylhydrazones merit further investigation as potentially protective agents against anthracycline-induced cardiotoxicity.     

The usefulness of ovarian volume, antral follicle count and age as predictors of menopausal status.

OBJECTIVE: To compare the accuracy of ovarian volume, antral follicle count and age in predicting menopausal status in healthy women. METHODS: The cross-sectional study was set in the Gynecology Division at the Leonor Mendes de Barros Maternity Hospital, S?o Paulo, Brazil. The subjects of this study were premenopausal (n = 121) and postmenopausal (n = 71) healthy women aged between 40 and 55 years. They were submitted to a medical interview and transvaginal ultrasound examination. The ovarian volume (cm3), antral follicle count and chronological age were recorded in both groups and the accuracies of these parameters in predicting menopausal status were compared. RESULTS: Premenopausal women presented larger ovaries than postmenopausal women (p < 0.01). Premenopausal women had a higher number of antral follicles than postmenopausal women (p < 0.01). The receiver operating characteristic curves showed that ovarian volume, age and antral follicle count had similar sensitivities and specificities in predicting menopausal status. The best cut-off points were observed when ovarian volume was <4 cm3, age was > or =48 years and antral follicle count was < or = two follicles. CONCLUSIONS: Ovarian volume, antral follicle count and chronological age are all individually predictive of menopausal status, with similar accuracies.     

Needlescopic thoracic sympathectomy: treatment for palmar hyperhidrosis

BACKGROUND: Open thoracic sympathectomy has been the established option for patients with essential hyperhidrosis. Recently, video-assisted endoscopic sympathectomy has provided a simple, safe, reliable, and cost-effective alternative to the earlier technique. With advances in instrumentation, performing the procedure through 2-mm and 3-mm needlescopic ports is now possible. The authors evaluate the effectiveness of so-called needlescopic thoracic sympathectomy for the treatment of primary hyperhidrosis. METHODS: Thirty five consecutive patients with a mean age of 24 years, including 23 men and 12 women, underwent bilateral needlescopic thoracic sympathectomies at the National University Hospital of Singapore. RESULTS: The mean operative duration was 56 minutes, and the mean hospital stay was 1.2 days. In no patient did Horner's syndrome or significant pneumothorax develop. The rate of success, defined as completely dry hands, was 97%. Two patients had unilateral recurrences that responded well to repeat needlescopic sympathectomies. We performed a total of 72 sympathectomies. CONCLUSIONS: Our study demonstrates that the use of miniature port access sites produces excellent medical and cosmetic results and is associated with a short hospital stay and low risk of complications.