Variceal hemorrhage and cystic fibrosis: outcomes and implications for liver transplantation.

Autopsy and imaging studies show that liver involvement is common in cystic fibrosis. However, complications of chronic liver disease including portal hypertension and variceal bleeding are infrequently encountered, and the degree to which variceal hemorrhage affects prognosis in cystic fibrosis is unclear. This uncertainty has lead to debate as to whether liver transplantation is indicated in these patients. We describe a case series of 18 patients and compare their survival with a control group of cystic fibrosis patients without liver disease. The median age at first bleed was 20.0 years (range 9.7-30.9). The median survival after first bleed was 8.4 years, compared to 13.0 years in the control group (P = 0.15). A total of 14 patients have died, 9 from respiratory disease with no discernable contribution from their liver disease. Liver disease contributed to 4 deaths. Only 1 patient suffered a fatal hemorrhage, which may have been either variceal or bronchial in origin. Long-term survival is a frequent occurrence in patients with cystic fibrosis who suffer variceal hemorrhage, and age at death is comparable to the general cystic fibrosis population. In conclusion, this suggests that liver transplantation is not indicated in these patients without additional features of liver decompensation.     

RBE and w(R) values of Auger emitters and low-range beta emitters with particular reference to tritium.

An apparent disparity exists between RBE (relative biological effectiveness) values for low-range beta and Auger emitters, and the current value for their radiation weighting factor (w(R)). This paper presents evidence that the current w(R) value of unity for these nuclides is inconsistent with most RBE evidence and should be increased by a factor of two to three. It recommends that the ICRP should clearly state that the most appropriate RBE value for these nuclides, and not the w(R) value, should be used in specific dose calculations, retrospective dose estimations and epidemiological studies. The ICRP should also publish guidance as to the methods and data sources that could be used for these RBE values.     

Stress-Related Changes in β-Endorphin Processing: The Limitations of Slaughterhouse Material

In the sheep, unlike many other species, a significant proportion (>25%) of immunoreactive β-endorphin in the anterior pituitary is post-translationally modified to opioid-inactive, α-N-acetylated forms. In a study to determine the precise molecular nature of α-N-acetylated β-endorphin immunoreactivity, we noted a striking difference in high-performance liquid chromatography profiles of anterior pituitary extracts between sheep killed on the farm, and age-, sex- and strain-matched slaughterhouse animals. These altered patterns of a-N-acetylated β-endorphin processing were reproduced in farm animals by chronic (≤ 4 days) treatment with the synthetic glucocorticoid dexamethasone; in contrast dexamethasone had no effect on a-N-acetylated β-endorphin processing in hypothalamo-pituitary disconnected sheep. These data suggest that (1) the change in processing is a stress response, mediated by prolonged glucocorticoid exposure, (2) this effect is central, rather than a direct effect on the pituitary, and (3) the relative abundance of various peptide sequences in slaughterhouse-derived material may not reflect their abundance under more physiological conditions.     

A mathematical model of volatile release in mouth from the dispersion of gelled emulsion particles.

This paper presents a mathematical model of in-mouth volatile release from gelled emulsion particles dispersed in a continuous aqueous phase. Data based on APCI MS-Breath analysis is presented to demonstrate the effect of particle size, oil content and oil-water partition coefficients. It is shown that in-mouth release of aroma from the dispersion of gelled emulsion particles follows a two-component kinetic equation with fast and slow components. Both the fast and slow rate constants depend on the particle size, oil content and oil water partition coefficient of the aroma. The relative amount of aroma contributing to the fast and slow components also depends on the size of the particles. In order to understand this unexpected behaviour, an analytical model was developed that considers the interplay between the mass transfer of flavour across the interface of the particles and that across the air-liquid interface. Analytical expressions for the two rate constants and the relative ratio of aroma contributing to the fast component have been derived. From this model, three regimes of in-mouth release of aroma from the dispersion of gelled emulsion particles were identified including, the emulsion regime, the transition regime and the gel particle regime. In the emulsion regime, changes in the size of gelled emulsion particles had negligible impact on the overall release. In the transition regime, the release was controlled by the interaction of flavour transfer from the particles with that across the air-water interface. In the gel particle regime, aroma release at long times was governed by the particles and that at short times was governed by the air-water interface, and the two processes were fully decoupled. A simple relationship was derived for the critical size above which the release of aroma from the dispersion of gelled emulsion particles is affected by the size of the particles.     

Heart rate and blood pressure variability as markers of sensory blockade with labour epidural analgesia

PURPOSE: To evaluate the correlation between the progression of somatosensory blockade and changes in autonomic outflow following the onset of labour epidural analgesia. METHODS: Twelve labouring parturients consented to participate in the study. Baseline electrocardiogram, blood pressure (BP) and respiratory rate were recorded for ten minutes. The epidural consisted of 0.125% bupivacaine with 50 microg of fentanyl (total volume 20 mL). Measurements were repeated for ten minutes after initiation of the block. The level of sensory block was measured bilaterally with loss of sensation to ice at two-minute intervals. Wavelet transform was used to obtain heart rate (HR) and BP variability every two minutes following the loading dose of epidural medication. High frequency power of HR variability was used to assess changes in parasympathetic activity. The total power of BP variability was used to assess changes in sympathetic activity. A nonparametric repeated measures ANOVA was used for the variability data, and a Spearman rank correlation test was used to evaluate the relationship between the sensory block and HR and BP variability. RESULTS: The sensory block progressed to T9 at ten minutes post-epidural and was the mirror image of the decrease in total power of BP variability. High frequency power of HR variability increased to a plateau at six minutes post-epidural. A significant correlation was found between the increase in sensory block and the observed decrease in BP variability (r = -1.000, P = 0.0028). CONCLUSION: In this study of labouring parturients, BP variability correlated with the progression of both sympathetic and somatosensory block following epidural anesthesia, while HR variability was shown to be a surrogate marker of increased parasympathetic activity.     

Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone.

Paget's disease is a focal condition of bone. To study changes in cells within pagetic lesions, we cultured osteoblasts and stromal cells from 22 patients and compared gene expression in these cells to cells from healthy bone. We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions. INTRODUCTION: Paget's disease is a focal condition of bone of unknown cause. Although it is regarded as primarily an osteoclast disorder, the tight coupling of the activity of osteoclasts and osteoblasts suggests that the osteoblast could play a key role in its pathogenesis. The aim of the study was to identify possible changes in pagetic osteoblasts and stromal cells that might contribute to the development of pagetic lesions. MATERIALS AND METHODS: Candidate genes were identified based on known bone cell regulators, supplemented with microarray analysis. Gene expression was determined by real-time PCR in primary cultures of osteoblasts and bone marrow stromal cells from pagetic patients and control subjects. Concentrations of secreted proteins were determined by ELISA. RESULTS: Dickkopf1 mRNA and protein levels were increased in both pagetic osteoblast and stromal cell cultures, and interleukin (IL)-1 and IL-6 were overexpressed in pagetic osteoblasts. These changes parallel recent findings in myeloma bone disease, which shares some clinical similarities with Paget's disease. Alkaline phosphatase was overexpressed, and bone sialoprotein and osteocalcin were underexpressed in pagetic osteoblasts, consistent with their circulating levels in pagetic patients. It is hypothesized that overexpression of Dickkopf1, IL-1, and IL-6 would result in stimulation of osteoclast proliferation and inhibition of osteoblast growth, leading to the development of the characteristic lytic bone lesions. By stimulating osteoblast differentiation, Dickkopf1 and IL-6 may also promote mineralization, leading to the conversion of lytic lesions to sclerotic. CONCLUSIONS: These findings suggest that dysregulated gene expression in pagetic osteoblasts could cause the changes in bone cell number and function characteristic of Paget's disease.     

Chronobiological characteristics of postoperative pain: Diurnal variation of both static and dynamic pain and effects of analgesic therapy

BACKGROUND: Previous postoperative investigations report morning peaks in analgesic administration. However, few studies have examined diurnal variation of both pain and analgesic consumption and little is known about dynamic pain in this context. METHODS: The diurnal pattern of postoperative pain is described using pain intensity and analgesic consumption data from a recently published hysterectomy trial. RESULTS: In the presence of patient-controlled analgesia with morphine, pain at 8 a.m. was significantly higher (P<0.05) than at noon, 4 p.m. or 8 p.m. on postoperative day one (for rest pain and pain evoked by sitting, forced expiration and cough) and on postoperative day two (for pain evoked by forced expiration and cough only). This temporal pattern was observed both with and without the co-administration of non-opioid analgesics (gabapentin and/or rofecoxib). Morphine use during the four hours preceding 8 a.m. on either postoperative day was not significantly lower than any of the other corresponding time intervals. CONCLUSIONS: Based on data from our post-hysterectomy analgesic clinical trial, static and dynamic pain in the morning appears to be more intense than pain later in the day. This pattern was observed in the presence of substantial nocturnal morphine use. Based on these and other previous observations, specifically designed investigations are needed to better characterize the clinical, neurohormonal and neurophysiological features of postoperative circadian pain variation - including pain during sleeping hours. If the above observations are replicated, future study of nocturnal sustained-release opioids as well as time-shifting the administration of non-opioid co-analgesic drugs to the very early morning may be warranted.     

Adult Liver Transplant Candidate Attitudes Toward Graft Sharing Are Not Obstacles to Split Liver Transplantation

Split liver transplantation (SLT) benefits society by increasing the total number of transplants that can be performed, but it is yet unknown if a decreased post-transplant survival (in comparison to whole liver transplantation) would make participation in SLT less appealing to adult liver transplant candidates. A 20-item questionnaire was administered to 50 adult candidates to assess attitudes toward SLT and organ sharing. The overall attitudes of 60% of participants were classified as utilitarian (maximizing benefit to greatest number of candidates), while 26% were classified as self-preserving (maximizing individual benefit) and 14% were undecided. Ninety percent of participants would be willing to share even if expected survival was less than that of whole liver transplantation, and 69% felt that pediatric candidates should have priority over adult candidates. In conclusion, attitudes toward graft sharing and the possibility of compromised survival benefit are not barriers to SLT for most adult liver transplant candidates.