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.     

Abnormal biochemical and cellular parameters in the blood of patients with Raynauds phenomenon

Finger blood flow is decreased in Raynauds Phenomenon (RP). This may be due not only to vasospasm, but also to blood abnormalities. 40 patients with Raynauds Disease (RD), 28 with suspected RP (SS) and 42 with secondary Raynauds syndrome (RS) were enrolled and compared to 50 controls. Results from base-line samples show that those with RP have abnormal haemostasis and rheology whereas those with mild Raynauds, RD do not. Blood sampled after cold challenge in 15 RS patients and 15 controls show that both groups exhibit platelet activation after emersion. The degree of activation however was much more marked in the RS patients. We have shown that abnormalities of haemostasis and rheology are found in patients likely to have endothelial damage (RS). These changes are probably a consequence rather than a cause of the disease. After cold challenge the results become more abnormal and correlate with severity of disease.     

Effects of autologous mesothelial cell seeding on prostacyclin production within Dacron arterial prostheses

Canine abdominal aortas have been replaced with Dacron arterial prostheses to assess the effects of mesothelial cell seeding on graft prostacyclin and thromboxane A2 release. At both 2 weeks and 6 weeks after surgery, three seeded and two unseeded control grafts were examined for prostacyclin release. In addition, thromboxane release was assessed in one seeded and one unseeded graft. Sections of aorta and graft were removed and incubated in PBS containing either 10 microM calcium ionophore A23187 or 20 microM arachidonic acid. The incubation mixture was sub-sampled at 5 min intervals over a 20 min period to assess the progressive release of prostacyclin and thromboxane A2 using a radioimmunoassay for 6-keto-prostaglandin F1 alpha and thromboxane B2 respectively. In seeded grafts, 6-keto-prostaglandin F1 alpha release averaged 15 per cent compared with aorta at 2 weeks and 45 per cent compared with aorta at 6 weeks. By contrast, release from unseeded grafts was undetectable at 2 weeks; however, by 6 weeks there was some release amounting to 15 per cent compared with aorta. There was a statistically significant increase in the release of 6-keto-prostaglandin F1 alpha from mesothelial cell seeded grafts at 6 weeks compared with unseeded grafts (P less than 0.01). Thromboxane release from the graft sections was variable and unrelated to whether the grafts had been seeded or not. These preliminary results, showing that grafts seeded with autologous peritoneal mesothelial cells release more prostacyclin than unseeded grafts, further highlight the role of the mesothelial cell as an alternative to the endothelial cell for improving the patency of arterial Dacron prostheses in the early postoperative days.     

The value of a domiciliary nurse as part of a hospital diabetes service — Report on a 12 month study

SINCE 1976 the standard inpatient and outpatient service for diabetic patients at the Mater Hospital has been supplemented by a day centre facility incorporating education and management. We feel that the service could be improved further by the availability of a specialist nurse who would visit patients at their homes. A pilot study was carried out over a twelve month period and this paper details the benefits of such a service.     

Multimodal, Multidimensional Models of Mouse Brain

Summary:  Naturally occurring mutants and genetically manipulated strains of mice are widely used to model a variety of human diseases. Atlases are an invaluable aid in understanding the impact of such manipulations by providing a standard for comparison and to facilitate the integration of anatomic, genetic, and physiologic observations from multiple subjects and experiments. We have developed digital atlases of the C57BL/6J mouse brain (adult and neonate) as comprehensive frameworks for storing and accessing the myriad types of information about the mouse brain. Along with raw and annotated images, these contain database management systems and a set of tools for comparing information from different techniques and different animals. Each atlas establishes a canonical representation of the mouse brain and provides the tools for the manipulation and analysis of new data. We describe both these atlases and discuss how they may be put to use in organizing and analyzing data from mouse models of epilepsy.