Solid-organ transplantation in older adults: current status and future research.

An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas.

Lung transplantation in patients with prior cardiothoracic surgical procedures.

The full spectrum of prior cardiothoracic procedures in lung transplant candidates and the impact of prior procedures on outcomes after lung transplantation (LTx) remain unknown, though the impact is considered to be large. Patients transplanted at our institution from 2004 to 2009 were identified (n = 554) and divided into two groups: patients who had undergone cardiothoracic surgical (CTS) procedures prior to LTx (n = 238) and patients who had not (non-CTS: n = 316). Our primary endpoint was survival. Secondary endpoints included allograft function and the incidence of major complications including reexploration due to bleeding, prolonged ventilation, renal insufficiency and primary graft dysfunction. Long-term survival was not significantly different between the groups whereas postoperative bleeding, nerve injury, respiratory and renal complications were higher in the CTS group. Posttransplant peak FEV1 was lower in the CTS group (73.4% vs. 86.9%, p < 0.05). In multivariate analysis, performance of a chemical pleurodesis procedure and prolonged cardiopulmonary bypass were significantly associated with mortality (OR, 1.7; CI, 1.5-2.0; p < 0.005). Our results suggest that patients with LTx and prior CTS remain technically challenging and experience worse outcomes than patients without prior CTS. A surgical strategy to minimize cardiopulmonary bypass time is critical for these challenging LTx patients.

[Identification and grouping of pain patients according to claims data]. / Identifikation und Gruppierung von Schmerzpatienten anhand von Routinedaten einer Krankenkasse.

The ICD classification does not provide the opportunity to adequately identify pain patients. Therefore we developed an alternative method for the identification and classification of pain patients which is based on prescription and diagnoses data from the year 2006 of one nationwide sickness fund (DAK) and which is led by two main assumptions: 1. Beneficiaries without prescription of an analgetic drug but with a diagnosis pattern that is characteristic of patients who are treated with opioids are also likely to be pain patients. 2. Each combination of diagnosis groups can be traced back to one primary diagnosis out of a diagnosis group according to the patient classification system CCS (Clinical Classifications Software). The selection of this diagnosis group (CCS) allows for the allocation of the beneficiary to only one pain type. As a result we identified 65 combinations of CCS diagnosis groups--aggregated to nine "CCS pain types"--to which 77.1% of all patients with at least two opioid prescriptions can be allocated: 26.3% to pain due to arthrosis, 18.0% to pain due to intervertebral disc illnesses, 13.1% to other specific back pain, 6.7% to neuropathic pain, 4.5% to unspecific back pain, 4.2% to headache, 2.4% to pain after traumatic fractures, 1.3% to pain of multimorbid, high-maintenance patients, and 0.6% to cancer pain. Based on our method beneficiaries who have a high probability of suffering from moderate to strong pain can be identified and included in further claims data analyses of health care delivery and utilization pattern of pain-related disorders in Germany.

Hierarchical Bayesian scaling of soil properties across urban, agricultural, and desert ecosystems.

Ecologists increasingly use plot-scale data to inform research and policy related to regional and global environmental change. For soil chemistry research, scaling from the plot to the region is especially difficult due to high spatial variability at all scales. We used a hierarchical Bayesian model of plot-scale soil nutrient pools to predict storage of soil organic carbon (oC), inorganic carbon (iC), total nitrogen (N), and available phosphorus (avP) in a 7962-km2 area including the Phoenix, Arizona, USA, metropolitan area and its desert and agricultural surroundings. The Bayesian approach was compared to a traditional approach that multiplied mean values for urban mesic residential, urban xeric residential, nonresidential urban, agricultural, and desert areas by the aerial coverage of each land-use type. Both approaches suggest that oC, N, and avP are correlated with each other and are higher (in g/m2) in mesic residential and agricultural areas than in deserts or xeric residential areas. In addition to traditional biophysical variables, cultural variables related to impervious surface cover, tree cover, and turfgrass cover were significant in regression models predicting the regional distribution of soil properties. We estimate that 1140 Gg of oC have accumulated in human-dominated soils of this region, but a significant portion of this new C has a very short mean residence time in mesic yards and agricultural soils. For N, we estimate that 130 Gg have accumulated in soils, which explains a significant portion of "missing N" observed in the regional N budget. Predictions for iC differed between the approaches because the Bayesian approach predicted iC as a function of elevation while the traditional approach employed only land use. We suggest that Bayesian scaling enables models that are flexible enough to accommodate the diverse factors controlling soil chemistry in desert, urban, and agricultural ecosystems and, thus, may represent an important tool for ecological scaling that spans land-use types. Urban planners and city managers attempting to reduce C emissions and N pollution should consider ways that landscape choices and impervious surface cover affect city-wide soil C, N, and P storage.

Historical and current atmospheric deposition to the epilithic lichen Xanthoparmelia in Maricopa County, Arizona.

Spatial patterns of atmospheric deposition of trace elements to an epilithic lichen were assessed using a spatial grid of 28 field sites in 1998 throughout Maricopa County, Arizona, USA. In addition, samples of Xanthoparmelia spp. from Arizona State University lichen herbarium material (1975-1976) was utilized for a limited number of sites in order to explore temporal trends. The lichen material was cleaned, wet digested and analyzed by ICP-MS for a suite of elemental concentrations [antimony (Sb), cadmium (Cd), cerium (Ce), chromium (Cr), cobalt (Co), copper (Cu), dysprosium (Dy), europium (Eu), gadolinium (Gd), gold (Au), holmium (Ho), lead (Pb), lutetium (Lu), neodymium (Nd), nickel (Ni), palladium (Pd), platinum (Pt), praseodymium (Pr), samarium (Sm), scandium (Sc), silver (Ag), terbium (Tb), thulium (Tm), tin (Sn), uranium (U), ytterbium (Yb), yttrium (Y), and zinc (Zn)]. Cluster analysis and principal component analysis suggest three major factors, which, depending on regional aerosol fractionation, explain most of the variation in elemental signatures: (1) a group of widely distributed rare earth elements (2) a highly homogenous Co, Cr, Ni, and Sc component representing the influence of mafic rocks, and (3) anthropogenic emissions. Elemental concentrations in Maricopa County lichens were generally comparable to those reported for relatively unpolluted areas. Only highly urbanized regions, such as the greater Phoenix Metropolitan Area and the NW corner of the county, exhibited elevated concentrations for Zn, Cu, Pb, and Cd. Lead levels in lichens have fallen over the last 30 years by 71%, while Zn concentrations for some regions have increased by as much as 245%. From the spatial pattern of elemental deposition for Cd, Cu, Ni, Pr, Pb, and Cu, we infer that agriculture, mining, industrial activities, and traffic probably are the major air pollutant sources in Maricopa County.

Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator.

This study assessed the effects of raloxifene, a selective estrogen receptor modulator (SERM), on ovarian morphology and circulating hormone levels in rats. Female Fischer-344 rats (65/group) were given dietary raloxifene for 6 months at average daily doses of 0, 15, 75, and 365 mg/kg. Morphologic evaluation of ovaries was conducted on 25 rats/group at the end of the treatment period and from 20 rats per group after 1 and 3 months withdrawal from treatment. Plasma hormone analyses were conducted on 10 rats pergroup at the end of the treatment period and aftereach withdrawal period. Treatment with raloxifene for 6 months resulted in disruption of the hypothalamic-pituitary-ovarian axis, manifested by increased plasma concentrations of luteinizing hormone (LH) and estradiol-17beta (E2), and failure of ovulation, manifested by ovarian follicular prominence (retained anovulatory follicles), lack of corpora lutea (CL), and depressed plasma progesterone (P4). Many (56% to 80%) rats in all raloxifene treated groups had focal, minimal to slight hyperplasia of granulosa cells within individual retained follicles. A few treated rats in the mid- and high-dose groups (2 of 25 and 3 of 25, respectively) had more extensive focal proliferation of granulosa cells. These foci were approximately 3 to 6 mm in overall size and were characterized by moderate papillary proliferation of large granulosa cells associated with cystic spaces, often with hemorrhage. In 4 of the 5 rats with this focal cystic granulosa cell hyperplasia, the remainder of the involved ovary and the contralateral ovary were atrophic. After 1 or 3 months of drug withdrawal, most previously treated rats examined had morphologic evidence of ovarian cyclic changes. including developing follicles, various stages of CL, and normal plasma levels of LH, E2, and P4. Continued lack of cyclic changes was limited to 4 of 20 rats from the low-dose group after 1 month of recovery and to 1 low dose rat after 3 months. Intrafollicular granulosa cell hyperplasia was not seen in rats in the reversibility phase. Areas of prior focal cystic granulosa cell hyperplasia were represented by focal sclerosis that included hemorrhage and/or hemosiderin. The foci of sclerosis were associated with cystic spaces after 1 month and were solid after 3 months. A granulosa cell tumor, approximately 12-13 mm diameter, was present in a high-dose rat in the 3-month reversibility group. This tumor effaced 1 ovary and was characterized by proliferative granulosa cells, usually in papillary formations and cords within cystic spaces. This rat had atrophy of the uninvolved ovary, excessive plasma levels of E2 and prolactin, and high P4 levels considering the absence of CL. The results of this study indicate that ovarian granulosa cells in rats are susceptible to proliferative changes when stimulated chronically with excessive trophic hormones. Most of these proliferative changes were reversible upon cessation of the hormonal stimulation. However, the proliferative lesion in one treated rat progressed to apparent autonomous (neoplastic) growth.

Proliferative lesions of ovarian granulosa cells and reversible hormonal changes induced in rats by a selective estrogen receptor modulator.

This study assessed the effects of raloxifene. a selective estrogen receptor modulator (SERM), on ovarian morphology and circulating hormone levels in rats. Female Fischer-344 rats (65/group) were given dietary raloxifene for 6 months at average daily doses of 0, 15, 75, and 365 mg/kg. Morphologic evaluation of ovaries was conducted on 25 rats/group at the end of the treatment period and from 20 rats per group after 1 and 3 months withdrawal from treatment. Plasma hormone analyses were conducted on 10 rats per group at the end of the treatment period and after each withdrawal period. Treatment with raloxifene for 6 months resulted in disruption of the hypothalamic-pituitary-ovarian axis, manifested by increased plasma concentrations of luteinizing hormone (LH) and estradiol-17beta (E2), and failure of ovulation, manifested by ovarian follicular prominence (retained anovulatory follicles), lack of corpora lutea (CL), and depressed plasma progesterone (P4). Many (56% to 80%) rats in all raloxifene treated groups had focal, minimal to slight hyperplasia of granulosa cells within individual retained follicles. A few treated rats in the mid- and high-dose groups (2 of 25 and 3 of 25, respectively) had more extensive focal proliferation of granulosa cells. These foci were approximately 3 to 6 mm in overall size and were characterized by moderate papillary proliferation of large granulosa cells associated with cystic spaces, often with hemorrhage. In 4 of the 5 rats with this focal cystic granulosa cell hyperplasia, the remainder of the involved ovary and the contralateral ovary were atrophic. After 1 or 3 months of drug withdrawal, most previously treated rats examined had morphologic evidence of ovarian cyclic changes, including developing follicles, various stages of CL, and normal plasma levels of LH, E2, and P4. Continued lack of cyclic changes was limited to 4 of 20 rats from the low-dose group after 1 month of recovery and to 1 low dose rat after 3 months. Intrafollicular granulosa cell hyperplasia was not seen in rats in the reversibility phase. Areas of prior focal cystic granulosa cell hyperplasia were represented by focal sclerosis that included hemorrhage and/or hemosiderin. The foci of sclerosis were associated with cystic spaces after 1 month and were solid after 3 months. A granulosa cell tumor, approximately 12-13 mm diameter, was present in a high-dose rat in the 3-month reversibility group. This tumor effaced 1 ovary and was characterized by proliferative granulosa cells, usually in papillary formations and cords within cystic spaces. This rat had atrophy of the uninvolved ovary, excessive plasma levels of E2 and prolactin, and high P4 levels considering the absence of CL. The results of this study indicate that ovarian granulosa cells in rats are susceptible to proliferative changes when stimulated chronically with excessive trophic hormones. Most of these proliferative changes were reversible upon cessation of the hormonal stimulation. However, the proliferative lesion in one treated rat progressed to apparent autonomous (neoplastic) growth.

Post-fire recolonization of dominant epiphytic lichen species on Quercus hypoleucoides (Fagaceae).

Following a forest fire (27 500 ha) in 1994, post-fire recolonization of Quercus hypoeleucoides by epiphytic lichens was documented as changes in lichen cover, number of small thalli, specific factors that affected reestablishment of lichens, and modes of dispersal. Three sites in the Chiricahua Mountains (Arizona, USA) were chosen according to the severity of fire damage-unburned, moderately burned, and severely burned. From 1994 through 1997, the amount of dead lichen cover significantly increased at the moderately burned site. For the same time period, the amount of live lichen cover significantly increased at the severely burned site. Numbers of new thalli increased significantly at the severely burned site each year but only in the last year (1996-1997) for the moderately burned site. Bark texture and proximity to trees with lichens were among the most important physical factors for recolonization. The most important means of dispersal for Flavopunctelia praesignis was fragmentation. For Punctelia hypoleucites, the primary means of dispersal was spores. Increases in live lichen cover and numbers of new thalli occur faster in severely burned areas probably due to the loss of lichens on tree trunks, which provides space and a lack of competition.

CRNA awareness and experience with perioperative DNR orders.

Despite 2 decades of experience with do-not-resuscitate (DNR) orders, some controversy regarding their use still remains. By using a mailed questionnaire to a randomized sample of 500 active members of the American Association of Nurse Anesthetists, the present study explored the awareness, experiences, and opinions of nurse anesthetists regarding DNR orders for patients undergoing surgery. The purpose of the study was to evaluate the need for further education and discussion in this area. Of the 228 (45.6%) respondents, more than half had DNR policies at their facility, while the remainder reported no policy or were unsure whether a policy existed. Of those having policies, 67.2% indicated a policy of routine DNR suspension, approximately 20% had a policy of reevaluation, and the remainder were unsure of the type of policy. However, when asked what type of policy respondents thought was most appropriate, 54.2% favored a policy of reviewing the DNR order, with 95% advocating patient involvement in the reevaluation. Moreover, almost 90% of responding CRNAs indicated they would discuss DNR status with the patient before surgery. When a patient with a DNR order subsequently had an intraoperative cardiac event, 13% initiated resuscitation. Responding to a hypothetical question involving a patient with a DNR order, 42% to 48% of respondents indicated they would initiate resuscitative measures in such a situation depending on the cause of arrest.

An investigation of the current literature on the effectiveness of patient-controlled analgesia methods.

The purpose of this investigation was to determine, through current research in the literature, if a background basal infusion should routinely be used to improve the efficacy of traditional-demand patient-controlled analgesia (PCA) and would the safety of the PCA technique be maintained with the addition of a continuous infusion. Of the nine studies investigating PCA with and without continuous infusion, six found no improvement in pain control with the addition of a continuous infusion. The patients receiving continuous infusion did not make fewer demands than the control group, nor did they report lower pain scores. The addition of a continuous background infusion to PCA diminishes the inherent safety of the PCA modality of pain management. Many studies reported an increased incidence of side effects with the addition of a continuous infusion. This modality of PCA should be reserved for use in patients in whom traditional-demand PCA does not satisfy analgesic requirements.

Helicobacter sp. strain Mainz isolated from an AIDS patient with septic arthritis: case report and nonradioactive analysis of 16S rRNA sequence.

A campylobacter-like organism was isolated from an effusion of the left knee joint of an AIDS patient 2 weeks after bacteremia with a morphologically identical organism. Amplified genomic 16S rRNA sequences were analyzed by a nonradioactive blotting technique. The closest match was found with Helicobacter fenelliae (97.7% homology). Sequence data and phenotype suggest that the isolate may represent a so far unrecognized species of the genus Helicobacter.

Developmental toxicology studies of vancomycin hydrochloride administered intravenously to rats and rabbits.

Pregnant CD rats were given vancomycin intravenously in doses of 0, 40, 120, or 200 mg/kg on Gestation Days (GD) 6-15; pregnant New Zealand white rabbits were given 0, 40, 80, or 120 mg/kg intravenously on GD 6-18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated in the 120- and 200-mg/kg treatment groups by cortical tubular nephrosis. Maternal body weight gain and food consumption and fetal viability, weight, and morphology were not adversely affected by vancomycin. Maternal and developmental no observed adverse effect levels (NOAELs) in the rat were 40 and 200 mg/kg, respectively. In rabbits, maternal toxicity was indicated by cortical tubular nephrosis in the 80- and 120-mg/kg treatment groups; a single death and depression of body weight gain and food consumption occurred in the 120-mg/kg treatment group. Developmental toxicity was indicated by depression of fetal weight in the 120-mg/kg treatment group; fetal viability and morphology were not adversely affected by vancomycin. Maternal and developmental NOAELs in the rabbit were 40 and 80 mg/kg, respectively. Based on these data, vancomycin did not exhibit selective toxicity toward the developing rat or rabbit conceptus.

Use of vancomycin hydrochloride for treatment of Clostridium difficile enteritis in Syrian hamsters.

As part of an 18-month carcinogenicity study, 680 Syrian hamsters (Mesocricetus auratus) received daily gavage doses of fenazaquin, an experimental miticide. Mortality associated with severe enteritis was noticed beginning when the hamsters were 4 months old and ranged from one to five deaths per month until the hamsters were about 10 months old, when 41 deaths occurred in a 1-month period. Ante- and postmortem findings were consistent with those reported for antibiotic-induced enteritis in hamsters. Clostridium difficile was isolated from 12 of the 13 samples of cecal contents analyzed. Toxin assays of C. difficile isolates collected from 11 affected animals were positive for both cyto- and enterotoxins. Daily oral administration of vancomycin hydrochloride at a dose of 20 mg/kg was initiated when the hamsters were about 10 months old. Deaths due to C. difficile enteritis were significantly decreased within 2 weeks, and treatment was continued for 3 months. A trial withdrawal period for a subset of 64 hamsters (approximately 16% of the total population) was initiated to evaluate survival after discontinuation of the antibiotic treatment. Clostridium difficile enteritis recurred within 2 weeks and caused 19 deaths during the next month; therefore, these hamsters were returned to daily vancomycin treatment for the remainder of the study. With the exception of severe gaseous distention of the ceca, which caused death in 17 (< 4% of the total population) of the affected hamsters, vancomycin treatment did not cause any major adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of spontaneous neoplastic and nonneoplastic lesions in Charles River CD-1 mice varies with breeding origin.

Three separate control lifetime studies were conducted with untreated Crl:CD-1 (ICR)BR mice using a total of 400 mice/sex maintained to 21 mo of age. Similar husbandry practices and environmental conditions were used for all 3 studies. It was noted after study initiation that the Charles River breeding facility of origin was different for each study. The aggregate range of survival and incidence of neoplasms for the combined studies was similar to that previously reported. However, these 3 groups of mice had prominent variation in survival and in the incidence of pulmonary adenomas and systemic amyloidosis in males and females, and in the incidence of hepatocellular neoplasms in males. The present studies indicate that consistent procurement of test animals is an additional variable to be considered in the establishment of a valid database within a test facility when using an outbred mouse.

Carcinogenicity studies of fluoxetine hydrochloride in rats and mice.

The antidepressant drug fluoxetine HCl was tested for carcinogenicity in three well designed and controlled studies in Fischer rats and C57BL/6 x C3H F1 mice. The compound was administered to the animals for 24 months at dietary doses of approximately 0, 0.5, 2.0, or 10.0 mg/kg body weight in rats and 1.0, 5.0, or 10.0 mg/kg in mice. The highest dose tested was a maximum tolerated dose for both species as evidenced by clinical signs (rats and mice) and some mortality (mice) referable to central nervous system pharmacological effects, decreased weight gain (rats), and histopathological changes of phospholipidosis (rats) and hepatic fatty change (mice). There was no evidence of an increased incidence of any type of unusual or commonly occurring spontaneous neoplasm in either rats or mice. There were statistically significant decreases in a few commonly occurring neoplasms. The data reported herein provide convincing evidence that fluoxetine is neither a complete carcinogen nor a tumor promoter.

Dose-response relationships for SO2 fumigations in the lichens Evernia prunastri (L.) Ach. and Ramalina fraxinea (L.) Ach.

Sulphur dioxide fumigation of the lichens Evernia prunastri (L.) Ach and Ramalina fraxinea (L.) Ach, whose thallus water content was held at 100-120%, throughout each experiment, resulted in changes in net photosynthesis, dark respiration and chlorophyll content in relation to both concentration and duration of exposure. Net photosynthesis was the most sensitive response variable. Significant reduction in chlorophyll content was found when no recovery in net photosynthesis occurred after two weeks. A reduction in dark respiration was only found at high SO2 concentrations. Evernia prunastri was affected by lower concentrations and shorter exposure times than Ramalina fraxinea and the data for both species showed dose-response relationships.

Comparative toxicity of oral cephalosporin antibiotics in the rabbit and in a rabbit kidney cell line (LLC-RK(1)).

The nephrotoxic potential of four oral cephalosporin antibiotics, cephalexin, cefaclor, LY195885 and LY171217, was determined in rabbits given single oral doses of 250-500 mg/kg body weight. Histopathological changes, blood chemistry, and ex vivo renal slice function were evaluated 48 hr after dosing. Additionally, the viability of rabbit renal cells in culture (LLC-RK(1)) was evaluated by nigrosin dye exclusion after 48 hr exposure to each antibiotic at concentrations of 0.5-2.0 mg/ml. Only LY171217 was significantly nephrotoxic in vivo. Prominent lesions were observed at 500 mg/kg body weight and were accompanied by marked increases in blood urea nitrogen and serum creatinine, and decreases in ex vivo renal slice gluconeogenesis and p-aminohippurate and tetraethylammonium uptake. In vitro toxicity to renal cells correlated well with the in vivo results yielding TC(50) values (TC(50) = concentration producing 50% lethality) > 1.0 mg/ml for cephalexin, LY195885 and cefaclor. LY171217, on the other hand, was significantly toxic in vitro (TC(50) = < 0.5). These results suggest that renal cells in culture may provide a useful method for examining the nephrotoxic potential of oral cephalosporins before in vivo studies.