Prednisone-Free Maintenance Immunosuppression—A 5-Year Experience

Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (+/-SD) at 1 year was 1.6 +/- 0.6; at 5 years, 1.7 +/- 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good.     

Kathepsin D bei Ovarialtumoren

Zusammenfassung In der vorgestellten Arbeit wurden insgesant 15 Ovarialtumoren auf ihren Kathepsin D-Gehalt untersucht. Sowohl bei den benignen Ver?nderungen wie auch bei den malignen konnte diese Protease nachgewiesen werden. Bei den malignen Tumoren fand sich keinerlei Korrelation des Kathapsin D zur Exprimierung des Markers Ca 125 und zum ?strogenrezeptorbesatz.     

Search for coloured objects in natural surroundings by people with abnormal colour vision

Background: People with abnormal colour vision often report difficulty seeing coloured berries and flowers in foliage, which suggests they will have a diminished capacity for visual search when target objects are marked out by colour. There is very little experimental evidence of the effect of abnormal colour vision on visual search and none relating to search for objects in natural foliage. Method: We showed 79 subjects with abnormal colour vision (seven protanopes, 10 deuteranopes, 16 protanomals and 46 deuteranomals) and 20 subjects with normal colour vision photographs of natural scenes and asked them to locate clumps of red berries, to trace the length of a red string on grass and to name the season depicted in a photograph taken in the Autumn and the same scene photographed in the Summer. Colour vision was assessed using the Ishihara, the Medmont C100, the Farnsworth D15, the Richmond HRR and the Nagel anomaloscope. Results: All the subjects with abnormal colour vision located fewer clumps of red berries than those with normal colour vision. The subjects who failed the Farnsworth D15 performed significantly worse than those who passed but the distribution of scores in the two groups overlaps. The majority of subjects with abnormal colour vision could not trace the full length of the string: only 38 per cent of anomalous trichromats who passed the Farnsworth D15 test and three per cent of those who failed it were able to trace the full length of the string. Fifty‐five per cent of those classed as having a mild deficiency by the HRR test could trace the whole string. Most dichromats were unable to identify the Autumn season and those who did may have been assisted by guessing. Most (94 per cent) of those who passed the Farnsworth D15 test and all those classified as having a ‘mild’ deficiency by the HRR test could identify the season. Conclusions: All people with abnormal colour vision, even those with a very mild deficiency, have some degree of impairment of their ability to see coloured objects in natural surroundings. A pass at the Farnsworth D15 test or a ‘mild’ classification with the Richmond HRR test identifies those likely to have the least problems with visual search and identification tasks. The results have practical implications for the selection of personnel in occupations that involve visual search in natural terrain.     

Hong Kong nurses' health-related behaviours: implications for nurses' role in health promotion

The health-related behaviours of a random sample (n=92) of Hong Kong nurses were assessed by a questionnaire written either in English or in English and Chinese. Hong Kong nurse reported negligible smoking or a alcohol use, low levels of breast self-examination, cervical screening behaviour and regular exercising, seat belt use and driving within the speed limit. The sample reported high levels of making efforts to avoid foods high in cholesterol, eating foods high in fibre and eating fruit daily. Dental hygiene was reported to be high. Just over half the sample reported sleeping 7–8 hours each night and eating breakfast daily. Most nurse reported maintaining their body weight at a healthy level and eating snacks between meals. The English language version of the questionnaire produced a slightly better response rate than the bilingual questionnaires. The results are discussed with reference to previous studies of females' health-related behaviours in Hong Kong and elsewhere. The implications for Hong Kong nurses' role in health promotion is discussed.     

Epinephrine reduces the sedative side effects of epidural sufentanil for labour analgesia

PURPOSE: The use of opioids in labour analgesia has primarily been as an adjuvant to local anesthetics. For early labour, satisfactory analgesia with epidural sufentanil alone is possible. This study evaluates the impact of epinephrine on sedative side effects and analgesia related to the latter technique. METHODS: After Institutional Review Board approval and informed consent this prospective, randomized, double-blind study evaluated 43 nulliparous subjects requesting epidural analgesia. The study site, a tertiary care obstetric unit, accommodates 3500-4500 deliveries annually. Group selection was randomized and blinded by selection of a sealed envelope containing a number which corresponded to a premixed labelled syringe of saline or epinephrine (100 microg/mL). An epidural catheter was placed in a standardized fashion. All subjects received 40 microg of sufentanil and 0.5 mL from the premixed syringe, diluted to 10 mL with NaCl. A blinded observer collected data on maternal sedation, lightheadedness, hemodynamics, oxygenation, and fetal heart rate over a one-hour period following sufentanil injection. RESULTS: The addition of epinephrine significantly (P <0.05) reduced the incidence of sedation and lightheadedness after epidural sufentanil at all data collection points, except two. Analgesic duration was also significantly prolonged by this addition (120 +/- 56 vs 84 +/- 32 min). Maternal satisfaction was high regardless of solution. CONCLUSION: Forty micrograms of epidural sufentanil produces satisfactory analgesia in early labour. The addition of epinephrine improves the side effect profile of this technique while prolonging the duration of analgesia. Epidural sufentanil requires attention to maternal monitoring of oxygenation as maternal desaturation occurred in both groups.     

Local tissue properties in bone healing: Influence of size and stability of the osteotomy gap

To characterize the site-specific mechanical and histological properties in fracture repair and to relate these properties to the initial mechanical situation, an experimental fracture model was used in the metatarsus of 42 sheep. the mechanical situation of a transverse osteotomy was described by three gap sizes (1,2, or 6 mm) and two amounts of strain (7 or 31 %). An external fixator that allowed a defined axial movement provided control of these settings. Nine weeks following surgery, the healing area was dissected and tensile and compressive properties were measured in subregions of the fracture gap and the periosteal callus. The central, sagittal section was used for quantitative histology. We found the quality of the tissue along the osteotomy line to be most important for regaining mechanical stability. Increasing the size of osteotomy gaps resulted in poorer mechanical and histological qualities, and the repair process was less complete. Interfragmentary strain did not significantly influence the repair process. The smaller strain levels had already stimulated the secondary repair process, and this stimulatory effect could not be further enhanced by increasing the amount of strain. Our finding that large gaps between bone segments were not as well healed as were smaller gaps suggests that it is advantageous to avoid large gaps in fracture treatment.     

Individual differences in adult human sleep and wakefulness: Leitmotif for a research agenda

This paper reviews the literature on interindividual variability in human sleep parameters, sleepiness, responses to sleep deprivation, and manifestations of sleep disorders. Variability among individuals in sleep/wake biology and behavior is pervasive. The magnitude of such individual differences is often considerable and comparable to the effect sizes of many experimental and clinical interventions. Evidence is accumulating that certain aspects of sleep/wake-related variability--such as sleep duration, daytime sleepiness, and vulnerability to the effects of sleep loss--involve trait characteristics in healthy populations and among sleep-disordered patients. Establishing the trait-specific nature of variability in sleep/wake parameters is a prerequisite for elucidating the corresponding neurophysiologic and/or genetic mechanisms. At present, it remains largely unknown what underlies or predicts sleep/wake-related traits, what relationships these traits may have to each other, and what functional significance may be associated with specific traits. Scientific studies addressing these issues are warranted, as understanding the basis of trait variability may yield new insights into sleep/wake regulation and sleep pathology. Understanding individual differences in sleep and wakefulness may also have provocative but important implications for health economics and clinical care, as well as for safety, productivity, and general well-being. This paper gives suggestions for a research agenda focusing on individual differences in sleep research and sleep medicine.     

Altered splenic B cell subset development in mice lacking phosphoinositide 3-kinase p85alpha

The signaling enzyme phosphoinositide 3-kinase (PI3K) is activated following B cell receptor (BCR) engagement and by many other receptors on B lymphocytes. Mice lacking p85alpha, the predominant PI3K regulatory isoform, exhibit defects in B cell development and activation that are grossly similar to those found in mice lacking Bruton's tyrosine kinase (Btk) and other critical signaling molecules. However, a detailed analysis of splenic B cell subsets in p85alpha-deficient mice has not been reported. Here we show that these mice are deficient in four major B cell subsets: transitional-1, transitional-2, follicular and marginal zone. These defects are distinct from those observed in Xid mice that express a mutant Btk unable to interact with PI3K lipid products. Moreover, mice with both genetic lesions exhibit even greater impairment in B cell development. Finally, we show that transgenic expression of the anti-apoptotic protein Bcl-2 in p85alpha-deficient mice restores the transitional B cell subsets but not the marginal zone subset, and produces a follicular population with an aberrant phenotype. These findings establish a role for PI3K-p85alpha in differentiation of both follicular and marginal zone B cells, and suggest that these functions are required not solely for the propagation of anti-apoptotic signals.     

Survival and Implantation of Escherichia coli in the Intestinal Tract

Preliminary experiments established that a 0.5-ml inoculum that is introduced directly into the stomach of mice was cleared rapidly into the small intestine. Bicarbonate buffer, but not skim milk, protected such an inoculum from stomach acid until at least 90% of it had entered the small intestine. Passage and survival of various Escherichia coli strains through the mouse gut were tested by introducing a buffered bacterial inoculum directly into the stomach, together with the following two intestinal tracers: Cr(51)Cl(3) and spores of a thermophilic Bacillus sp. Quantitative recovery of excreted bacteria was accomplished by collecting the feces overnight in a refrigerated cage pan. The data show that wild-type E. coli strains and E. coli K-12 are excreted rapidly (98 to 100% within 18 h) in the feces without overall multiplication or death. E. coli varkappa1776 and DP50supF, i.e., strains certified for recombinant DNA experiments underwent rapid death in vivo, such that their excretion in the feces was reduced to approximately 1.1 and 4.7% of the inoculum, respectively. The acidity of the stomach had little bactericidal effect on the E. coli K-12 strain tested, but significantly reduced the survival of more acidsensitive bacteria (Vibrio cholerae) under these conditions. Long-term implantation of E. coli strains into continuous-flow cultures of mouse cecal flora or into conventional mice was difficult to accomplish. In contrast, when the E. coli strain was first inoculated into sterile continuous-flow cultures or into germfree mice, which were subsequently associated with conventional mouse cecal flora, the E. coli strains persisted in a large proportion of the animals at levels resembling E. coli populations in conventional mice. Metabolic adaptation contributed only partially to the success of an E. coli inoculum that was introduced first. A mathematical model is described which explains this phenomenon on the basis of competition for adhesion sites in which an advantage accrues to the bacterium which occupies those sites first. The mathematical model predicts that two or more bacterial strains that compete in the gut for the same limiting nutrient can coexist, if the metabolically less efficient strains have specific adhesion sites available. The specific rate constant of E. coli growth in monoassociated gnotobiotic mice was 2.0 h(-1), whereas the excretion rate in conventional animals was -0.23 h(-1). Consequently, limitation of growth must be regarded as the primary mechanism controlling bacterial populations in the large intestine. The beginnings of a general hypothesis of the ecology of the large intestine are proposed, in which the effects of the competitive metabolic interactions described earlier are modified by the effects of bacterial association with the intestinal wall.