Tamoxifen Therapy for Breast Cancer and Endometrial Pathology

Background

Tamoxifen, used as adjuvant therapy for carcinoma breast in postmenopausal women to prevent relapse has estrogenic effect on the endometrium.

Methods

104 patients on tamoxifen for more than six months were subjected to a clinical examination and transvaginal sonography. Patients with endometrial thickness > 8 mm were further evaluated by hysteroscopy and endometrial biopsy.

Results

35(34%) patients were symptomatic. The average endometrial thickness was 11.2 mm which correlated with duration of tamoxifen use. 27(48%) patients had abnormal hysteroscopic findings. 35 (63%) of endometrial biopsies revealed abnormal endometrium. One case of endometrial carcinoma was diagnosed. The results were statistically analysed. There is a significant association between symptomatic status and endometrial thickness and duration of tamoxifen use.

Conclusion

All patients on long term tamoxifen should be annually screened for endometrial pathology.Key Words: Tamoxifen, Endometrium, Transvaginal sonography     

Placement of Umbilical Artery Catheters High vs. Low

Placement of umbilical artery catheters was retrospectively reviewed in 181 newborns to evaluate random placement of catheter tip in the "high" position between T₇ and T₉ in the thoracic aorta of 127 infants and in the "low" position below 4 in the abdominal aorta of 54 infants. Group differences in gestational age, asphyxia, hypotension, respiratory disease, duration of catheterization, or infusate type were not significant. Cyanosis or blanching in the low extremities occurred in 67% of the "low" group and 21% of the "high" group ( P < .001). Hematuria occurred in 39% of the "low" group and 21% of the "high" group ( P < .05). High placement appears to have fewer complications. Prompt intervention by neonatal nurse practitioners can help reverse complications that occur during umbilical artery catheterizations.     

Early ultrastructural changes in RU-486-exposed decidua

An antiprogesterone (RU-486) was administered to women undergoing voluntary interruption of pregnancy. Five patients received 100 mg 12 h before surgical interruption, 5 others received 100 mg twice, 24 and 12 h before interruption, respectively, and another 5 received no drug at all and served as controls. Placentas and deciduae were examined morphologically with the light microscope and by electron microscopy. No specific lesions were detected in placental tissue. With conventional histology, the deciduae showed various degrees of interstitial edema and necrosis, changes which did not enable a distinction between treated cases and controls, although stromal disintegration tended to be more marked in RU-486-treated patients. At the ultrastructural level, the endothelium of decidual capillaries showed striking hyperplasia of the endoplasmic reticulum. Morphometric evaluation showed a statistically significant difference between RU-486-treated patients (2 X 100 mg) and controls. A possible link between these morphological changes and the induction of prostaglandin synthesis by the antiprogesterone is suggested. However, the full significance of the observed lesions remains uncertain and does not allow definite conclusions concerning the abortifacient effect of RU-486.     

Apoptosis protease activator protein-1 expression is dispensable for response of human melanoma cells to distinct proapoptotic agents

Loss of expression of the apoptosis protease activator protein-1 (APAF-1) in human melanoma is thought to promote resistance to programmed cell death by preventing caspase-9 activation. However, the role of the APAF-1-dependent pathway in apoptosis activated by cellular stress and/or DNA damage has been recently questioned. We investigated APAF-1 expression in a large panel of human melanomas and assessed cellular response to several proapoptotic agents in tumors expressing or lacking APAF-1 protein. In two melanomas with wild-type p53 but with differential expression of APAF-1, treatment with camptothecin, celecoxib, or an nitric oxide synthase inhibitor (1400W) significantly modulated expression of 36 of 96 genes in an apoptosis-specific cDNA macroarray, but APAF-1 mRNA levels were not induced (in APAF-1(-) cells) nor up-regulated (in APAF-1(+) cells), a finding confirmed at the protein level. Treatment with cisplatin, camptothecin, etoposide, betulinic acid, celecoxib, 1400W, and staurosporine promoted enzymatic activity not only of caspases -2, -8, and -3 but also of caspase-9 in both APAF-1(+) and APAF-1(-) tumor cells. Moreover, drug-induced caspase-9 enzymatic activity could be not only partially but significantly reduced by caspase-2, -3, and -8 -specific inhibitors in both APAF-1(+) and APAF-1(-) tumor cells. In response to 1 to 100 micromol/L of cisplatin, camptothecin, or celecoxib, APAF-1(+) melanomas (n = 12) did not show significantly increased levels of apoptosis compared with APAF-1(-) tumors (n = 7), with the exception of enhanced apoptosis in response to a very high dose (100 micromol/L) of etoposide. These results suggest that the response of human melanoma cells to different proapoptotic agents may be independent of their APAF-1 phenotype.     

Long-term use of oral contraceptive therapy in women with the prothrombin 20210 G-A polymorphism without thrombotic complications: a study of 13 women (12 heterozygotes and 1 homozygote)

Thirteen female patients with the prothrombin 20210 G-A abnormality (twelve heterozygotes and one homozygote) were selected out of 551 patients admitted to our Department of Medicine or to our Outpatient Hemostasis Units between January 1999 and October 2000. The selection was based on the fact that all patients had taken or were still taking oral contraceptives (OC) for a period of 3 years or longer than 3 years. None of these patents as gathered from history, physical examination, private physician records and our records has shown any DVT during or immediately after OC intake. Physical and compression ultrasonography examinations at the time of study were all negative. The average length of oral contraceptives therapy (OCT) was 10 years (range 3-23). The average age of patients at the time of oral contraception was 30 years. The 13 women had also 17 pregnancies without any venous thrombosis. The observations casts several doubt about the prothrombotic effect of this polymorphism. Since DVT has been shown to occur occasionally even in normal women, it is likely that the same may occur in women with this polymorphism regardless of the existence or not of any pathogenetic relationship between the two phenomena. Occasional reports suggesting a link between this polymorphism and oral contraception-related venous thrombosis should be carefully evaluated in order to avoid premature and incorrect conclusions.