Pharmacodynamics of combined estrogen–progestin oral contraceptives: 4. Effects on uterine and cervical epithelia

ABSTRACT

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.

Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 μg), medium- (30 μg), low- (20 μg), ultralow- (15 μg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.

Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.

Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.

In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.     

Living donor liver transplantation.

Initially living donor liver transplantation (LDLT) was almost exclusively performed in infants and children. Adult LDLT programmes were initiated several years later. In the west this programme was introduced in view of a critical shortage of deceased donors and a constant increase in waiting list mortality. At present, this procedure is accepted as a therapeutic option for patients with end-stage liver disease to make up for the shortage of donor organs from dead patients. In Asia, however, LDLT has become the predominant means of liver transplantation as donor organs from the diseased cannot be used for religious and ethical reasons. Although there have been significant improvements in surgical techniques and consequently in recipient outcome over recent years, the LDLT procedure is still associated with donor morbidity and even mortality. The overall reported donor mortality was 0.2% and donor morbidity ranged between 0% and 100%. Biliary complications and infections were the most commonly reported donor complications. Therefore, a thorough medical as well as psychological evaluation of the donor and recipient are necessary prior to this procedure. To date, LDLT comprises less than 5% of adult liver transplantations in Europe and in the United States. Recipient and graft survival are almost identical to those seen with liver transplantations from deceased donors (DD). Biliary and vascular complications are more often seen in the LDLT setting. So far, no studies have focussed on the impact of LDLT on waiting list mortality. There is international consensus that this procedure should be restricted to centres with large experience in deceased donor liver transplantations as well as in hepatobiliary surgery. Ethical issues, optimal utility and application of adult LDLT and optimal recipient and donor characteristics have yet to be defined.     

Transesophageal echocardiography-guided cardioversion of atrial fibrillation. Selection of a low-risk group for immediate cardioversion.

INTRODUCTION: In patients (pts) with atrial fibrillation (AF) of more than 48 hours' duration, electrical cardioversion (ECV) should only be performed after 3 weeks of effective anticoagulation. Transesophageal echocardiography (TEE) allows earlier ECV; however, despite exclusion of thrombi in the atrium and left atrial appendage (LAA), cases of thromboembolism related to ECV have been documented in AF. To define a low-risk group for cardioversion without previous anticoagulation, pts were selected for immediate ECV if no thrombi or dynamic spontaneous echo contrast (auto-contrast) were found after TEE and if LAA velocity was more than 0.25 m/sec. METHODS AND RESULTS: We performed TEE in 31 consecutive pts referred for ECV for AF of more than 48 hours' duration and without previous anticoagulation. After TEE the pts eligible for immediate ECV began anticoagulation with low molecular weight heparin (enoxaparin), subcutaneously in therapeutic doses, together with warfarin immediately before cardioversion. Enoxaparin was continued until an INR of over 2 was reached. Based on the TEE findings, the pts were divided in 2 groups: immediate ECV, group A, 20 pts with a mean age of 62 +/- 13 years, 6 female; and conventional therapy with warfarin before ECV, group B, 11 pts, mean age of 67 +/- 10 years (p < 0.05), 2 female. None of the pts in either group had mitral stenosis or previous episodes of thromboembolism. The mean transverse diameter of the left atrium in the 31 pts was 47 +/- 4.5 mm, without statistically significant differences between the 2 groups. Of the 11 pts in group B, 3 had a thrombus in the LAA, 6 dynamic spontaneous echo contrast and the remainder LAA velocities of less than 0.25 m/sec. ECV was achieved in all the pts, with no complications. Oral anticoagulation was maintained for at least a month. At one month, sinus rhythm was maintained in 75% of group A and 45% of group B (p < 0.01). CONCLUSION: In pts with AF of more than 48 hours' duration and no previous history of thromboembolism, the use of our exclusion criteria during TEE enabled stratification of a low-risk population for immediate ECV, which was accomplished effectively and safely in 2/3 of the pts. This strategy is associated with early symptomatic improvement, and may contribute to maintenance of sinus rhythm after one month, which was significantly better than in the pts who had prolonged therapy with warfarin before ECV, despite the differences found in age and left ventricular function.     

Convergent nipple-areolar complexes corrected by inferior curved pedicle technique

We report a case of mammaplasty followed by a marked convergence of the nipple-areolar complex and describe the surgical repair by means of an inferior dermal-fat curved flap. The curve of the inferior pedicle permits one to raise the nipple to its normal position with ease and exceptional viability, even if a breast reduction procedure is associated.     

Dermonecrotic and lethal components of Loxosceles gaucho spider venom.

Loxosceles gaucho spider venom causes a typical dermonecrotic lesion in bitten patients and rarely causes lethal systemic effects. Gel filtration on Sephadex G 100 of L. gaucho spider venom resulted in three fractions: fraction A, containing the higher mol. wt components (approximately 35,000); fraction B, containing lower mol. wt components (approximately 15,000); and fraction C, containing very low mol. wt components (probably small peptides). The dermonecrotic and lethal activities were detected exclusively in fraction A. The venom and fraction A produced large dermonecrotic lesions in rabbits with necrosis spreading by gravity to the skin of the lateral body wall. Analysis by SDS-PAGE showed that the proteins contained in fraction A are approximately 35,000 and 33,000 mol. wt. Immunoblotting analysis showed that the proteins responsible for the dermonecrotic and lethal activity are very immunogenic and the first to be detected by antibodies during the course of immunization.