Estimating the effect of continual disturbances on discrete-time population models

In this paper, methods for estimating the effect of continual (but bounded) disturbances on ecosystems modelled by difference equations are discussed. The approach adopted is to estimate the region of state space (called a reachable set) which can be reached by the disturbed system from an initial healthy state in a given time period. Liapunov stability methods for estimating these reachable sets are presented and applied to two specific population models.     

Sequential changes in lung metabolism, permeability, and edema after ANTU

Lung injury and pulmonary edema were induced in rats after intraperitoneal injection of 10 mg/kg alpha-naphthylthiourea (ANTU). The time course of development of lung injury was assessed by the clearance of 99mTc-diethylenetriamine pentaacetate (99mTcDTPA) from the lung into the blood, the pharmacokinetics of tritiated prostaglandin E2 [( 3H]PGE2) in the isolated perfused lung, and by increase in the weight ratio (wet-to-dry) of lung. Two hours after ANTU administration, the clearance of 99mTcDTPA was significantly faster than in untreated animals and implied an increase in permeability of the alveolar-capillary barrier. This change preceded the increase in wet-to-dry weight ratio of lung, which was not significant until 5 h after ANTU administration. The pharmacokinetics of [3H]PGE2 were significantly altered after ANTU and these changes persisted beyond the time when both lung weight ratio and 99mTcDTPA clearance had recovered to normal values. We conclude that both 99mTcDTPA clearance and PGE2 pharmacokinetics change in ANTU-induced lung injury but with different time courses. In the progressive phase of lung injury due to ANTU, the early change in clearance of 99mTcDTPA suggests that an increased permeation of the alveolar capillary barrier by this small molecule precedes pulmonary edema due to an increased colloid permeability of the barrier. Abnormal metabolism in the pulmonary microvasculature persists when the permeability defect and edema have recovered.     

Proposed follow up programme after curative resection for lower third oesophageal cancer

Cyclins are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation. Recent studies have also revealed more mechanisms through which cyclins can express their oncogenic potential. This review focuses on the aberrant expression of G1/S cyclins and especially cyclin D and cyclin E; the pathways through which they lead to tumour formation and their involvement in different types of cancer. These elements indicate the mechanisms that could act as targets for cancer therapy.     

Strategies to Improve Survival from Surgery for Heart Valve Implantation in Sheep

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by difficulties in restarting the heart, causing significant on-table mortality. Therefore, optimal cardioprotective management during heart valve implantation in sheep is essential. However, little is known about successful cardioprotective management techniques in sheep. This article reports our experience in the cardioprotective management of 20 female sheep that underwent surgical aortic valve replacement with a stented tissue-engineered heart valve prosthesis. During this series of experiments, we modified our cardioprotection protocol to improve survival. We emphasize the importance of total body hypothermia and external cooling of the heart. Furthermore, we recommend repeated cardioplegia administration at 20 min intervals during surgery, with the final dosage of cardioplegia given immediately before the de-clamping of the aorta. To reduce the number of defibrillator shocks during a state of ventricular fibrillation (VF), we have learned to restart the heart by reclamping the aorta, administering cardioplegia until cardiac arrest, and de-clamping the aorta thereafter. Despite these encouraging results, more research is needed to finalize a protocol for this procedure.

Sheep are a commonly used and well-validated model for cardiovascular research, particularly for heart valve research, as blood pressure, heart rate, cardiac output, and intracardiac pressures are similar between sheep and humans. Sheep are particularly useful for heart valve research because observable changes in implanted heart valve bioprostheses that would take several years to develop in humans are apparent after only a few months in sheep.^3,11 This feature allows the ovine model to provide relevant and important information about heart valve prostheses in a relatively short time span. The first preclinical step in developing novel heart valves is to test the valve in the pulmonary position in sheep. This surgical technique is relatively easy, as the procedure can be performed on a beating heart in a low-pressure circulation. However, aortic valve surgery is the most frequently performed valvular surgical intervention in human patients.¹² Thus, an important next step is to prove the clinical applicability of a new valve by testing the valve in-vivo in the aortic position in an animal model. In contrast to pulmonary valve replacement, aortic valve replacement must be performed on an arrested heart, which makes the surgical procedure significantly more complex. The sheep is a difficult model for aortic valve replacements due to its narrow annulus, short distance between the annulus and coronary ostia, a short ascending aorta, and difficulty in de-airing of the heart prior to suturing the aortotomy.¹⁹ Consequently, high on-table mortality rates, ranging from 9% to 33%, have been reported.^1,18,21,24 Furthermore, the incidence of mortality during the first 30 d after surgery, directly related to the surgical procedure, is often high, ranging from 17% to 50%.^1,2,16,18,21 Therefore, optimizing cardioprotective strategies during surgery would improve postoperative survival. However, little is known about protective strategies in sheep. In the current series of experiments, we implanted stented, tissue engineered, aortic heart valve prostheses in 20 adult domestic sheep and developed cardioprotective techniques to increase survival rates. In this observational study, we share our experience and insights regarding cardioprotective management to potentially improve the outcome of future surgeries that require an arrested heart in sheep.