Effect of pulsed estrogen therapy on hemostatic markers in comparison with oral estrogen regimen in postmenopausal women

BACKGROUND/AIMS: Hormone replacement therapy (HRT) is associated with an increased risk of thromboembolism dependent on the type of HRT; therefore, we compared therapy effects of intranasal with oral estrogens on coagulation and fibrinolysis markers in postmenopausal women. METHODS: A randomized study in which 29 healthy hysterectomized women received intranasal 17beta-estradiol or oral estrogens for 3 months. RESULTS: There were no significant differences in the baseline characteristics between groups. Those women receiving intranasal estradiol showed a mild increment in plasminogen activator inhibitor-1 (PAI-I) (from 6.8 +/- 3.5 to 9.6 +/- 3.9 U/ml, p < 0.01); however, fibrinogen, factor VII-tissue factor complex (VIIa-rTF), antithrombin III (ATIII), protein C (PC) activity, protein S (PS) activity, plasminogen (PLG), and tissue-type plasminogen activator antigen (t-PA) were unchanged. In contrast, oral unopposed estrogens elevated t-PA (from 4.9 +/- 2.9 to 9.6 +/- 5.1 ng/ml, p < 0.01) in parallel with a decrement in PAI-I (from 5.2 +/- 4.0 to 2.7 +/- 1.7 U/ml, p < 0.05) and VIIa-rTF (from 201.2 +/- 181.0 to 140.6 +/- 108.7 mU/ml, p < 0.05). Fibrinogen, ATIII, PC, PS, and PLG were unchanged. CONCLUSIONS: Nasal 17beta-estradiol had no effect on the coagulation markers, except a moderate increment in PAI-1. In contrast, oral estrogens elicited a decrement in both VIIa-rTF and PAI-1; however, those changes did not surpass normal limits.     

Shoulder dystocia at noninstrumental vaginal delivery

This study examines the relationship between episiotomy and the occurrence of shoulder dystocia among noninstrumental vaginal deliveries. Analysis of data from a retrospective database was used to study noninstrumental vaginal deliveries in New Jersey during the years 1996 to 2001. The episiotomy group and nonepisiotomy group were analyzed separately using univariate and multivariate analysis. Among 358,664 deliveries, rate of shoulder dystocia was 1.0% (n = 3596). Thirty-five percent of deliveries were assisted by episiotomy. Rate of dystocia was 1.42% with the use of episiotomy, and 0.81% when episiotomy was not used. This increased rate with episiotomy was noted across all of the racial groups, all birthweight categories, and all of the risk factor subgroups analyzed. There was a gradual decrease in the use of episiotomy from 37.30 to 26.03% without a corresponding increase in the rate of dystocia. Among noninstrumental deliveries, the rate of shoulder dystocia is higher in the episiotomy group. Decrease in the use of episiotomy has not resulted in an increase in the occurrence of dystocia.     

Bioluminescence imaging correlates with tumor progression in an orthotopic mouse model of lung cancer

Background and ObjectivesTo determine whether bioluminescence imaging of human lung cancer cells growing in an orthotopic murine model provides a sensitive tool for monitoring tumor progression in athymic nude mice.MethodsHuman lung cancer (A549) cells were stably transfected with the firefly luciferase gene and inoculated into the right lung of athymic nude mice. Seven days after inoculation tumor growth was evaluated using the Kodak in-vivo Imaging System FX and continued to be monitored on a weekly basis.ResultsIn duplicate experiments, human lung cancer tumors formed in 90% of animal’s injected orthotopically. The mean intensity of the bioluminescence signal emitted from the lung cancer cells increased logarithmically during the course of study. Mice with positive bioluminescence signaling had confirmed tumors by microscopic histological analysis. Bioluminescence activity had a strong correlation with the tumor volume as determined histologically.ConclusionsBioluminescence intensity directly correlates with tumor volume and therefore offers a reliable approach for detecting and monitoring the growth of human lung cancer cells in orthotopic murine models.     

Plasma matrix metalloproteinases and postmenopausal breast cancer risk: a nested case–control study in the Multiethnic Cohort study

The survival of malignant breast cells depends upon the remodeling of the extracellular matrix, including complex interactions with matrix metalloproteinases (MMPs). It has been hypothesized that circulating MMPs may serve as early indicators of breast cancer development in hospital-based case–control studies. A nested case–control study of the association of pre-diagnostic plasma levels of MMPs with the subsequent risk of postmenopausal breast cancer was conducted within the Multiethnic Cohort. During the follow-up period, 713 women with incident invasive breast cancer were identified and individually (1:1) matched to controls. Four types of MMPs (1, 2, 3, and 7) were analyzed by microsphere immunofluorescence assay. Mean plasma levels of MMPs did not differ significantly between cases and controls; nor were there differences in breast cancer risk by MMP level. No difference in the risk of breast cancer by plasma level of the MMPs was found within strata of age, or ethnicity, although MMP-1 levels were positively associated with breast cancer risk in obese women and women by hormone replacement medications (P values for interaction <0.05). Few significant differences in risk by levels of the MMPs were found by any of the clinical variables. Circulating MMPs were not associated with postmenopausal breast cancer risk.     

Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (review)

The most common therapeutic approach for many cancers is chemotherapy. However, many patients relapse after treatment due to the development of chemoresistance. Recently, targeted therapies represent novel approaches to destroy cancer cells. The PI3K/PTEN/AKT pathway is a key signaling pathway involved in the regulation of cell growth. Dysregulated signaling of this pathway may be associated with activating mutations of PI3K-related genes. Analyses of these mutations reveal that they increase the PI3K signal, stimulate downstream Akt signaling, promote growth factor-independent growth and increase cell invasion and metastasis. In this review, we summarize the PI3K/PTEN/AKT pathway genetic alterations in cancer and their potential clinical applications.     

The inhibitory effect of MI paste, fluoride and a combination of both on the progression of artificial caries-like lesions in enamel

This in-vitro study evaluated the inhibition of demineralization in enamel sections produced by MI paste, fluoride and a combination of both, compared to artificial saliva and NaF 5000 ppm in a caries progression pH-cycling model. Twenty-one teeth were demineralized to create subsurface enamel lesions (approximately 200 microns in depth). The teeth were sectioned and characterized using polarized-light-microscopy (PLM). A single section from each lesion was assigned to a treatment group: Artificial saliva, NaF 5000 ppm (Prevident, Colgate), MI paste (Recaldent, GC America Inc), NaF 1100 ppm (Crest, Procter & Gamble) and NaF 1100 ppm plus MI paste. The sections were covered with varnish except for an exposed window on the external surface of the lesion and placed in a six-day pH-cycling model with two daily treatment applications of two minutes each. The sections were characterized by PLM, and the lesion areas were measured using a digital image analysis system. Based on a paired-sample t-test, significant differences (p < .05) in percentage of change in lesion size were found between the high fluoride group and all the other groups. No significant difference was found between the artificial saliva and MI paste group, neither was there any significant difference between the NaF 1100 ppm, the combined application group or the MI paste group alone. In conclusion, the higher concentration of NaF (5000 ppm) reduced lesion progression to the greatest extent. The MI paste group did not show any effect on the inhibition of lesion progression. Further studies on the preventive effect and longer treatment applications are recommended.     

Performance of the rebound,noncontact and Goldmann applanation tonometers in routine clinical practice

Purpose: To compare rebound tonometry (RBT) and noncontact tonometry (NCT) using Goldmann applanation tonometry (GAT) as reference. Methods: The study sample was comprised of 108 eyes of 108 subjects consecutively examined at a general ophthalmology clinic. The order of use of the three tonometers was randomized at the study outset. The difference between the methods was plotted against the mean to compare the tonometers. The hypothesis of zero bias was examined by a paired t‐test and 95% limits of agreement (LoA) were also calculated. Differences with respect to GAT were assessed according to the international standard for ocular tonometers (ISO 8612). Results: Mean intraocular pressures (IOPs ± SD) obtained using the three instruments were GAT 17.5 ± 3.8 mmHg; RBT 18.5 ± 5.5 mmHg and NCT 17.4 ± 5.6 mmHg. The 95% LoA were from ?7.9 to +7.7 mmHg for NCT–GAT and from ?6.8 mmHg to +8.7 mmHg for RBT–GAT. A difference with respect to GAT under ±1 mmHg was observed in 11.1% of the eyes measured by NCT and 18.5% of eyes measured by RBT. According to the IOP ranges established by the ISO 8612, differences from GAT measurements greater than ±5 mmHg were always above the accepted level of 5%. Correlations between IOP and central corneal thickness (CCT) were significant for all three tonometers. Conclusions: The rebound and noncontact tonometer behaved similarly when used to measure IOP taking GAT measurements as the reference standard. Neither tonometer fulfilled ISO 8612 requirements. Both were similarly influenced by CCT.