bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of nerve growth factor in cerebrospinal fluid of congenital hydrocephalic and normal children
Authors: Mashayekhi F. , Salehi Z.
Published: July 2005

Cerebrospinal fluid (CSF) is secreted by the choroids plexuses and has the potential to act as a signaling pathway for physiological control as it has been demonstrated to contain molecules such as interleukins, leukoterins, neuropeptides, growth transforming factor‐beta (TGF‐β) and nerve growth factor (NGF), which are present at specific times during development. In this study, CSF from hydrocephalic and normal children were analysed using SDS‐PAGE followed by silver staining. In order to obtain semi‐quantitative estimates of the relative amounts of 26 kDa protein, an image analyzer was used to determine the intensities of the band in the respective lanes in silver‐stained gels. Quantification of the silver‐stained gels from repeated experiments showed that the amount of 26 kDa protein was clearly increases in the hydrocephalic CSF when compared with the normal CSF. A Western blot analysis using anti‐NGF antibody as a probe confirmed the presence of NGF. Using enzyme‐linked immunosorbent assay (ELISA), it was shown that the level of NGF in the hydrocephalic CSF is higher than in normal CSF. It is concluded that NGF is not only a constant component of human CSF but could also be significantly involved in the pathophysiology of hydrocephalus.
Induction of endogenous neural precursors in mouse models of spinal cord injury and disease
Authors: Azari M. F. , Profyris C. , Zang D. W. , Petratos S. , Cheema S. S.
Published: July 2005

Adult neural precursor cells (NPCs) in the mammalian central nervous system (CNS) have been demonstrated to be responsive to conditions of injury and disease. Here we investigated the response of NPCs in mouse models of spinal cord disease [motor neuron disease (MND)] with and without sciatic nerve axotomy, and spinal cord injury (SCI). We found that neither axotomy, nor MND alone brought about a response by Nestin‐positive NPCs. However, the combination of the two resulted in mobilization of NPCs in the spinal cord. We also found that there was an increase in the number of NPCs following SCI which was further enhanced by systemic administration of the neuregulatory cytokine, leukaemia inhibitory factor (LIF). NPCs were demonstrated to differentiate into astrocytes in axotomized MND mice. However, significant differentiation into the various neural cell phenotypes was not demonstrated at 1 or 2 weeks following SCI. These data suggest that factors inherent to injury mechanisms are required for induction of an NPC response in the mammalian spinal cord.
The long‐term safety and tolerability of high‐dose interferon β‐1a in relapsing–remitting multiple sclerosis: 4‐year data from the PRISMS study
Authors: Gold R. , Rieckmann P. , Chang P. , Abdalla J. ,   the PRISMS Study Group
Published: July 2005

In the prevention of relapses and disability by interferon subcutaneously in multiple sclerosis (PRISMS) study, 560 patients with relapsing–remitting multiple sclerosis were randomized to receive subcutaneous interferon (IFN) β‐1a, 22 or 44 μg three times weekly, or placebo, for 2 years. Patients receiving placebo were then re‐randomized to one of the two doses of IFN β‐1a for a further 2 years, whilst patients receiving active treatment continued their original treatment. Safety assessments were performed throughout the study. The most common adverse events for patients originally randomized to active treatment were injection‐site inflammation (72% of patients had at least one event), headache (71%) and influenza‐like symptoms (69%). These were generally mild in nature and most frequent during the first month of treatment. The 4‐year adverse event profiles for the two IFN β‐1a doses were comparable with those observed during the initial phase of the study and, for the most part, with each other. There was no association between IFN β‐1a and depression or suicide/attempted suicide. The most common laboratory abnormalities were asymptomatic lymphopenia and elevated serum liver transaminase levels. These were generally mild and resolved spontaneously. Therapy with subcutaneous IFN β‐1a three times weekly for up to 4 years was well tolerated without dose‐limiting safety concerns.
Induction of pro‐apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease and cultured neurons after amyloid‐β exposure
Authors: Dong‐Gyu Jo , Joo‐Yong Lee , Yeon‐Mi Hong , Sungmin Song , Inhee Mook‐Jung , Jae‐Young Koh , Yong‐Keun Jung
Published: July 2005

Calsenilin/DREAM/KChIP3 was identified as a calcium‐binding protein that interacts with presenilins, serves as a transcription repressor, and binds to the A‐type potassium channel. In this study, we hypothesized that calsenilin might be involved in the neurodegeneration of Alzheimer's disease and examined calsenilin expression in Alzheimer's disease. Calsenilin levels were elevated in the cortex region of Alzheimer's patient brains and in the neocortex and the hippocampus of Swedish mutant β‐amyloid precursor protein transgenic mice brains. Induction of calsenilin was also observed in the activated astroglia as well as in the neurons surrounding β‐amyloid (Aβ)‐ and Congo red‐positive plaques. Exposing cultured cortical and hippocampal neurons to Aβ42, an amyloid‐β peptide whose deposition in the brain is a characteristic of Alzheimer's disease, induced both calsenilin protein and mRNA expression, and cell death. Moreover, blocking the calsenilin expression protected the neuronal cells from Aβ toxicity. These findings suggest that chronic up‐regulation of calsenilin may be a risk factor for developing Alzheimer's disease, perhaps by facilitating calsenilin‐mediated neurodegeneration.
Mitogen‐activated protein kinase/extracellular signal‐regulated kinase attenuates 3‐hydroxykynurenine‐induced neuronal cell death
Authors: Lee Hyun Jung , Bach Jae‐Hyung , Chae Hee‐Sun , Lee Sang Hyung , Joo Wan Seok , Choi Se Hoon , Kim Kyung Yong , Lee Won Bok , Kim Sung Su
Published: July 2005

3‐Hydroxykynurenine (3‐HK), an endogenous tryptophan metabolite, is known to have toxic effects in brain. However, the molecular mechanism of the toxicity has not been well identified. In this study, we investigated the involvement of MAPK/extracellular signal‐regulated kinase (ERK) in the 3‐HK‐induced neuronal cell damage. Our results showed that 3‐HK induced apoptotic neuronal cell death and ERK phosphorylation occurred during cell death. Inhibition of ERK activation using PD98059 considerably increased cell death. Furthermore, cell death was preceded by mitochondrial malfunction including collapse of mitochondrial membrane potential (ΔΨm) and cytochrome c release from mitochondria to the cytosol. Interestingly, inhibition of ERK dramatically increased mitochondrial malfunction, and enhanced caspase activation, resulting in enhanced neuronal cell death. Thus, our results show that ERK plays a protective role by maintaining mitochondrial function and regulating caspase activity under conditions of cellular stress.
AGENT BANK BEHAVIOR IN BANK LOAN SYNDICATIONS
Authors: Jones Jonathan D. , Lang William W. , Nigro Peter J.
Published: July 2005

Using Shared National Credit (SNC) Program data from 1995 to 2000, we extend previous empirical work on bank loan syndications. First, we examine recent trends in the volume and examiner‐based credit quality of loans syndicated through the banking system. Second, we estimate a panel regression model to explain changes in an agent bank's retained share of a syndicated loan in terms of information asymmetries, loan credit quality, capital constraints, and loan age and maturity. We find that these variables are significant determinants of the proportion of a SNC loan retained by an agent bank for its portfolio over time.
CAN STOCK MARKET LIBERALIZATION IN EMERGING ECONOMIES MITIGATE LEGAL SYSTEMS DEFICIENCIES?
Authors: Kim Wi Saeng , Lyn Esmeralda , Zychowicz Edward J.
Published: July 2005

We document positive valuation effects around the time of stock market liberalization. We find that the valuation effects are larger for countries with civil law traditions compared with countries with common law origins. Similarly, we find that countries with weaker shareholder protections exhibit greater market valuation increases compared with countries with stronger shareholder protections. The results reinforce the importance of country legal systems and of shareholder protections in determining the quality of corporate governance systems and financial market outcomes. The findings suggest that stock market liberalization may mitigate deficiencies in the existing institutional environments not supportive of effective corporate governance systems.
TRADING COSTS OF NON‐U.S. STOCKS ON THE NEW YORK STOCK EXCHANGE: THE EFFECT OF INSTITUTIONAL OWNERSHIP, ANALYST FOLLOWING, AND MARKET REGULATION
Authors: Jiang Christine X. , Kim Jang‐Chul
Published: July 2005

We investigate the differences in market microstructure between U.S. and non‐U.S. stocks cross‐listed on the New York Stock Exchange using a sample of 316 pairs of matched stocks. We find that non‐U.S. stocks have wider spreads and larger adverse‐selection costs than U.S. stocks even after controlling for macro‐level institutional differences. Regression analysis shows that spreads and adverse‐selection costs are negatively correlated with institutional ownership and analyst followings. Thus, the higher spreads and adverse‐selection costs for non‐U.S. stocks can be partly explained by the lower institutional ownership and analyst following of non‐U.S. stocks. In addition, we find that although the spreads and adverse‐selection costs for non‐U.S. stocks are significantly higher before the implementation of Regulation Fair Disclosure (FD), the differences become even greater after Regulation FD, suggesting that Regulation FD has improved the information environment for U.S. stocks.
Effects of Habitat Fragmentation on Effective Population Size in the Endangered Rio Grande Silvery Minnow
Authors: ALÒ DOMINIQUE , TURNER THOMAS F.
Published: July 2005

Abstract: We assessed spatial and temporal patterns of genetic diversity to evaluate effects of river fragmentation on remnant populations of the federally endangered Rio Grande silvery minnow (Hybognathus amarus). Analysis of microsatellite and mitochondrial DNA detected little spatial genetic structure over the current geographic range, consistent with high gene flow despite fragmentation by dams. Maximum‐likelihood analysis of temporal genetic data indicated, however, that present‐day effective population size (NeV) of the largest extant population of this species was 78 and the ratio of effective size to adult numbers (NeV/N) was ∼ 0.001 during the study period (1999 to 2001). Coalescent‐based analytical methods provided an estimate of historical (river fragmentation was completed in 1975) effective size (NeI ) that ranged between 105and 106. We propose that disparity between contemporary and historical estimates ofNeand low contemporaryNe/Nresult from recent changes in demography related to river fragmentation. Rio Grande silvery minnows produce pelagic eggs and larvae subject to downstream transport through diversion dams. This life‐history feature results in heavy losses of yearly reproductive effort to emigration and mortality, and extremely large variance in reproductive success among individuals and spawning localities. Interaction of pelagic early life history and river fragmentation has altered demographic and genetic dynamics of remnant populations and reducedNeto critically low values over ecological time.
Rare Species and Ecosystem Functioning
Authors: LYONS K. G. , BRIGHAM C. A. , TRAUT B.H. , SCHWARTZ M. W.
Published: July 2005

Abstract:  The role of diversity in the maintenance of ecosystems has been studied widely in the past decade. By correlating richness and diversity with basic ecosystem processes, these investigations lend support to the hypothesis that species diversity significantly influences ecosystem functioning and, in turn, provide support for the conservation of biodiversity. Nonetheless, the majority of these investigations demonstrate that conservation of a relatively small number of generally dominant species is sufficient to maintain most processes. Indeed, there is remarkably little evidence to support the contention that less common species, those likely of highest conservation concern, are important in the maintenance of ecosystem functioning. Here we summarize studies, most employing alternative methodological strategies, wherein less common and rare species are demonstrated to make significant contributions to ecosystem functioning. Evidence exists among studies of keystone species, aggregate effects of less common species, and species turnover. Our findings suggest that (1) less common species can make significant ecosystem contributions; (2) further investigation into the effects of rare and less common species on ecosystem maintenance is sorely needed; (3) further investigation should embrace a variety of approaches; and (4) until further research is conducted a prudent conservation approach is warranted wherein the contribution of less common species to ecosystem functioning is assumed.
Use of Traditional Ecological Knowledge in Marine Conservation
Authors: DREW JOSHUA A.
Published: July 2005

Abstract:  Traditional ecological knowledge (TEK) represents multiple bodies of knowledge accumulated through many generations of close interactions between people and the natural world. TEK and its application via customary ecological management plans can be useful in modern conservation programs. I disaggregate the term TEK into its constituent parts and show several ways in which TEK can strengthen research designs by increasing locality‐specific knowledge, including environmental linkages occurring in those localities. Examples of the uses of TEK in conservation include folk taxonomy in systematics in Micronesia, species knowledge for conservation in Kiribati, and fishers' knowledge of ecological interactions for reserve design in Belize. When conservationists recognize the utility of TEK, they can engage in an equitable exchange of knowledge and foster shared responsibility with indigenous people. These types of exchanges can also provide an opportunity for indigenous people to develop a scientific infrastructure.
Effect of Propagule Size and Landscape Structure on Morphological Differentiation and Asymmetry in Experimentally Introduced Roesel's Bush‐Crickets
Authors: BERGGREN ÅSA
Published: July 2005

Abstract: Conservation efforts involving introductions, reintroductions, and translocations of populations have an inherent and inescapable problem of small initial populations. Small founding populations are likely to have a small proportion of the genetic variability carried by the original population. This may manifest phenotypically through changes in individual morphology, such as decreased body size, increased degree of fluctuating asymmetry, or changing susceptibility to environmental stressors. I investigated the effects of population and landscape variables on the morphology and fluctuating asymmetry in individual bush‐crickets by examining 584 individual Roesel's bush‐crickets (Metrioptera roeseli) from 29 established populations from different propagule sizes that were introduced in areas previously unoccupied by the species. The introduction sites were in landscapes similar to where the species occurs naturally, but sites differed in connectivity and amount of surrounding suitable habitat. Individuals were caught up to 9 years after the initial introduction, and five different morphological traits were measured. All introduced individuals originated from the same population and individuals from this source population were also collected for comparison in the analyses. Male body weight and female body length were positively affected by initial population size and degree of connectivity of the introduction patch. Isolation also affected fluctuating asymmetry in male tibias, with a higher degree of asymmetry in males that came from more isolated populations. In a relatively short time period, I was able to detect the effect of isolation and small population sizes on morphology and asymmetry. Small propagule sizes and habitat isolation are both likely to have resulted in decreased genetic diversity, the latter by reducing population sizes through decreased survival. These results show the importance of both large propagule sizes and good connectivity of habitats when introducing populations. The differences between the sexes in response to the variables examined also indicate that studies on morphology and fluctuating asymmetry need to consider males and females separately to avoid inaccurate generalizations of the state of the population.
Conservation Prioritization Based on Distribution of Land Snails in Hungary
Authors: SÓLYMOS PÉTER , FEHÉR ZOLTÁN
Published: July 2005

Abstract: The preservation of biodiversity requires high‐quality data and efficient methods for prioritizing species and sites for conservation. We examined the distribution data of 121 Hungarian land snail species in a 10 × 10 km resolution grid system. The spatial consistency of the data set varied significantly among regions, so we excluded cells with <5 species. Thus we used data from 512 out of 1052 grid cells. We prioritized Hungarian land snail species based on an additive scoring index ranging from 2 to 10 in which higher scores indicate rarer species. The index included global range size, local frequency, and a correction factor because of the biased frequency estimate or special importance of some species. We analyzed the relationship between protection status and rarity scores for each species. There were 15 unprotected species of land snails out of 30 considered rare, according to the quartile definition of rarity, and 16 protected species fell out of the score range of rare species. Four of these protected species are threatened by other than their restricted ranges (e.g., habitat loss and overexploitation). We prioritized areas by simple‐ranking and complementary‐areas methods based on species richness (SR), sum of rarity scores (RS), 25% rarest species richness (SQ), and a multiple‐criteria index (SSQ = SR ×[SQ + 1]). In the area‐selection procedures the indices based on the quartile definition of rarity (SQ and SSQ) were slightly more efficient in representing species than species richness and sum of rarity scores. We also made regional comparisons, identified hotspots at the national scale, and investigated the overlap between hotspots and existing reserve areas. The distribution of species richness and rarity among the main geographical regions of Hungary revealed differences between lowland and highland areas. Most of the hotspots were located in the mountain areas and isolated hotspots were identified in lowland areas. All species of Hungarian land snails occurred within current protected areas, but selected hotspots did not overlap with current protected areas in all cases. The location of protected areas in Hungary is adequate to preserve land snails, although we recommend that unprotected hotspots be considered for protection.
The Capacity of the National Wildlife Refuge System to Conserve Threatened and Endangered Animal Species in the United States
Authors: CZECH BRIAN
Published: July 2005

Abstract:  The U.S. Fish and Wildlife Service manages the 38‐million‐ha National Wildlife Refuge System, which is devoted primarily to wildlife conservation. I examined the capacity of the refuge system to conserve federally listed threatened and endangered animal species. Population viability data for a random sample of these species were analyzed and extrapolated. Three levels of population viability were distinguished: outbreeding, demographic, and evolutionary. One hundred eighty‐six of the 514 federally listed animal species reside in whole or in part on the refuge system. Of these 186 species, approximately 81, 101, and 107 are supported by the system at evolutionary, demographic, and outbreeding viability levels, respectively. These figures correspond to 16%, 19%, and 21% of the 514 federally listed animal species, respectively. Various federal policies and programs facilitate the expansion of the refuge system, but other federal policies and programs facilitate economic growth, which tends to require the conversion of habitats faster than it provides for habitat conservation. Therefore the long‐run effectiveness, extent, and endurance of the refuge system will depend largely on macroeconomic policy context.
A Blueprint for the Oceans: Implications of Two National Commission Reports for Conservation Practitioners
Authors: GRANEK ELISE F. , BRUMBAUGH DANIEL R. , HEPPELL SCOTT A. , HEPPELL SELINA S. , SECORD DAVID
Published: July 2005

Abstract: In the first comprehensive reviews since 1969, two high‐level reports on the status of U.S. marine ecosystems and resources have been released: that of the nongovernmental Pew Oceans Commission in 2003 and that of the congressionally mandatedU.S. Commission on Ocean Policy in 2004. Although the two commissions differed in the breadth and depth of their mandates, their findings on the state of our oceans and need for new management approaches are similar, and their major recommendations for science, governance, management and conservation, and education echo and reinforce each other. The history behind the two commissions and the structure and objectives of each remind us of the crucial roles conservation practitioners and scientists must play in the implementation of report recommendations. The reports suggest priorities for conservation practitioners to improve science, management, conservation, governance, and education to better manage and protect ocean resources and ecosystems. To redirect activities affecting the state of global marine resources, integrated research; education and outreach by terrestrial, aquatic, and marine conservation practitioners; and a clear definition of their roles in the implementation of recommendations is essential. Marine ecosystems provide a test case of society's ability to manage complexity in human and natural systems in an integrated manner, with extensive opportunities for participation by conservation practitioners from all disciplines.
The Effects of Competition on Variation in the Quality and Cost of Medical Care
Authors: Kessler Daniel P. , Geppert Jeffrey J.
Published: July 2005

We estimate the effects of hospital competition on the level of and the variation in quality of care and hospital expenditures for elderly Medicare beneficiaries with heart attack. We compare competition's effects on more‐severely ill patients, whom we assume value quality more highly, to the effects on less‐severely ill, low‐valuation patients. We find that low‐valuation patients in competitive markets receive less intensive treatment than in uncompetitive markets, but have statistically similar health outcomes. In contrast, high‐valuation patients in competitive markets receive more intensive treatment than in uncompetitive markets, and have significantly better health outcomes. Because this competition‐induced increase in variation in expenditures is, on net, expenditure‐decreasing and outcome‐beneficial, we conclude that it is welfare‐enhancing. These findings are inconsistent with conventional models of vertical differentiation, although they can be accommodated by more recent models.
How to Regulate Heterogeneous Hospitals?
Authors: Dormont Brigitte , Milcent Carine
Published: July 2005

In many areas of health care financing, there is controversy over the sources of cost variability and about the respective roles of inefficiency versus legitimate heterogeneity. This paper proposes a payment system that creates incentives to increase hospital efficiency when hospitals are heterogeneous, without reducing the quality of care. We consider an extension of Shleifer's yardstick competition model and apply an econometric approach to identify and evaluate observable and unobservable sources of cost heterogeneity. Moral hazard can be seen as the result of two components: long‐term moral hazard (hospital management can be permanently inefficient) and transitory moral hazard. The latter is linked to the manager's transitory cost‐reducing effort. For instance, he or she can be more or less rigorous each year when bargaining prices for supplies delivered to the hospital by outside firms. The use of a three‐dimensional nested database makes it possible to identify transitory moral hazard and to estimate its effect on hospital cost variability. Econometric estimates are performed on a sample of 7,314 stays for acute myocardial infarction observed in 36 French public hospitals over the period 1994–1997. We obtain two alternative payment systems. The first takes all unobservable hospital heterogeneity into account, provided that it is time invariant, whereas the second ignores unobservable heterogeneity. Simulations show that substantial budget savings—at least 20%—can be expected from the implementation of such payment rules. The first method of payment has the great advantage of reimbursing high‐quality care. It leads to substantial potential savings because it provides incentives to reduce costs linked to transitory moral hazard, whose influence on cost variability is far from negligible. This payment rule could be extended to other areas of health care financing, such as Adjusted Average Per Capita Cost to calculate Medicare Managed Care reimbursements in the United States.
The Effect of Prescription Drug Advertising on Doctor Visits
Authors: Iizuka Toshiaki , Jin Ginger Zhe
Published: July 2005

The dramatic increase of direct‐to‐consumer advertising (DTCA) of prescription drugs created intensive debates on its effects on patient and doctor behaviors. Combining 1994–2000 DTCA data with the 1995–2000 National Ambulatory Medical Care Surveys, we examine the effect of DTCA on doctor visits. Consistent with the proponents' claim, we find that higher DTCA expenditures are associated with increased doctor visits, especially after the Food and Drug Administration clarified DTCA rules in August 1997. After 1997, every $28 increase in DTCA leads to one drug visit within 12 months. We also find that the market‐expanding effect is similar across demographic groups.
Spillover Effects of Restrictive Drug Formularies on Physician Prescribing Behavior: Evidence from Medicaid
Authors: Wang Y. Richard , Pauly Mark V.
Published: July 2005

Restrictive drug formularies may influence physician prescribing behavior for other patients with more generous drug benefit, so‐called “spillover effects.” We focus on Protonix, a proton pump inhibitor, introduced at a discount price, and study subsequent physician prescribing decision for open‐formulary Medicaid patients. Using two national databases on physician prescribing patterns and health plan drug formularies, we find consistent evidence of significant, positive spillover effects from 1‐PPI and 2‐PPI formularies that include Protonix onto Medicaid, with a larger effect from the most restrictive, 1‐PPI formularies. Physicians who prescribe a higher proportion of Protonix to their non‐Medicaid patients because of restrictive formularies, also prescribe a higher proportion of Protonix to their Medicaid patients with an open formulary. Each 10% increase in Protonix's predicted non‐Medicaid share results in an 8% increase in its share of Medicaid prescriptions (p < 0.001). Similar spillover effects seem to exist for older PPI products as well. A restrictive drug formulary therefore influences physician prescribing behavior for other patients not directly subject to its restrictions.
The Prevalence and Correlates of Major and Minor Depression in Older Medical Inpatients
Authors: McCusker Jane , Cole Martin , Dufouil Carole , Dendukuri Nandini , Latimer Eric , Windholz Sylvia , Elie Michel
Published: July 2005

Objectives: To describe the prevalence of and characteristics associated with major and minor depression in older medical inpatients and to compare associated characteristics by sex and history of depression.

Design: Cross‐sectional study of two patient samples, with and without a screening diagnosis of major or minor depression.

Setting: The medical services of two acute care hospitals.

Participants: Medical admissions of people aged 65 and older with at most mild cognitive impairment (N=380).

Measurements: Diagnoses of major and minor depression (Diagnostic Interview Schedule), cognitive impairment (Mini‐Mental State Examination), premorbid disability, sociodemographic variables (including social networks and support), comorbidity, severity of illness, history of depression.

Results: The prevalence of major depression differed by hospital, ranging from 14.2% (95% confidence interval (CI)=11.7–17.1) in Hospital A to 44.5% (95% CI=33.1–56.4) in Hospital B. The prevalence of minor depression was similar in the two hospitals, ranging from 9.4% (95% CI=7.4–11.9) in Hospital A to 7.9% (95% CI=2.9–16.3) in Hospital B. After adjustment for hospital, the same characteristics (history of depression, premorbid disability, cognitive impairment, perceived adequacy of support, and visits from friends) were associated with major and minor depression, although most of these associations tended to be weaker for minor depression. Most of these factors were also associated with depression in multivariate analyses. The most important characteristics in women were premorbid disability, history of depression, and adequacy of emotional support; in men they were history of depression, cognitive impairment, and adequacy of emotional support. A cerebrovascular or other cardiovascular diagnosis did not explain the association between depression and cognitive impairment.

Conclusion: Major and minor depression occur frequently in older medical inpatients and are associated with similar patient characteristics. A history of depression and the patient's sex should be considered in the identification and interpretation of these associated factors.
Conceptions of Dementia in a Multiethnic Sample of Family Caregivers
Authors: Hinton Ladson , Franz Carol E. , Yeo Gwen , Levkoff Sue E.
Published: July 2005

Understanding variability in conceptions of dementia in multiethnic populations is important to improve care and guide research. The objectives of this study were to describe caregiver conceptions of dementia using a previously developed typology and to examine the correlates of conceptions of dementia in a multiethnic sample. This is a cross‐sectional study conducted in Boston and the San Francisco Bay area. Participants were a convenience sample of 92 family dementia caregivers from four ethnic/racial groups: African‐American, Anglo European‐American, Asian‐American, and Latino. In‐depth, qualitative interviews explored the caregivers' ideas about the nature and cause of dementia (i.e., explanatory models). Explanatory models of caregivers were categorized as biomedical, folk, or mixed (folk/biomedical). Quantitative analyses examined the association between ethnicity and other caregiver characteristics, and explanatory model type. Overall, 54% of caregivers, including 41% of Anglo European Americans, held explanatory models that combined folk and biomedical elements (i.e., mixed models). For example, many families attributed Alzheimer's disease and related dementias to psychosocial stress or normal aging. Ethnicity, lower education, and sex were associated with explanatory model type in bivariate analyses. In multiple logistic regression analysis, minority caregivers (P<.02) and those with less formal education (P<.02) were more likely to hold mixed or folk models of dementia. Although minority and nonminority caregivers often incorporated folk models into their understanding of dementia, this was more common in minority caregivers and those with less formal education. Further research on cross‐ethnic differences in a larger, more‐representative sample is needed.
Ethnic Variation in Site of Death of Older Adults Dually Eligible for Medicaid and Medicare
Authors: Enguidanos Susan , Yip Judy , Wilber Kathleen
Published: July 2005

This is a retrospective study using secondary data to investigate variation in site of death by ethnicity and to determine how hospice enrollment affects site of death. Data for this study were obtained between 1996 and 2000 from linked Medi‐Cal and Medicare claims from 18 California counties participating in a state legislated effort to improve chronic care services in California. Subjects examined in this study included 38,519 decedents aged 65 and older who died between 1997 and 2000 and were dually eligible the entire year immediately before death. Demographic variables were site of death, cause of death, hospice use, and care setting in the year before death. Results revealed that blacks and Latinos were significantly more likely than whites to die at home, although being black or Asian was negatively associated with hospice use. This variation did not change when hospice use was controlled. Thus, although minorities were more likely to die at home, they were less likely to receive hospice care. Because patients dying at home without hospice care report higher rates of pain than those who have hospice care, physicians must work to ensure that minority patients understand all end‐of‐life care options, including hospice, and how these care options can be delivered in a culturally competent manner.
Serum Erythropoietin and Aging: A Longitudinal Analysis
Authors: Ershler William B. , Sheng Shan , McKelvey Julie , Artz Andrew S. , Denduluri Neelima , Tecson Josephine , Taub Dennis D. , Brant Larry J. , Ferrucci Luigi , Longo Dan L.
Published: July 2005

Objectives: To determine the changes in serum erythropoietin with age in patients with and without anemia and to assess the importance of certain comorbidities on changes in erythropoietin level and the development of anemia.

Design: Clinical history, hematological parameters, and serum erythropoietin levels were examined at 1‐ to 2‐year intervals for 8 to 30 years.

Setting: Baltimore Longitudinal Study on Aging (BLSA), National Institute on Aging.

Participants: One hundred forty‐three BLSA participants.

Measurements: Complete blood count and serum chemistries were performed at the time of each visit, and archived serum samples were used for erythropoietin level.

Results: Although all subjects were healthy and without anemia at the time of initial evaluation, some developed chronic illness—most notably hypertension and diabetes mellitus. Erythropoietin levels rose significantly for the group as a whole, and the slope of the rise was found to be greater for those who did not have associated diabetes mellitus or hypertension. During the subsequent years, subjects who developed anemia but did not have hypertension or diabetes mellitus had the greatest slope in erythropoietin rise over time, whereas those with hypertension or diabetes mellitus and anemia had the lowest erythropoietin slope.

Conclusion: The increase in serum erythropoietin with aging may be compensation for subclinical blood loss, increased red blood cell turnover, or increased erythropoietin resistance of red cell precursors. It is suspected that, with very advanced age, or in those with compromised renal function (e.g., diabetes mellitus or hypertension), the compensatory mechanism becomes inadequate and anemia results.
The Cost Effect of Newer Medication Adoption in an Older Medicaid Cohort
Authors: Shireman Theresa I. , Rigler Sally K. , Jachna Carolyn M. , Griebling Tomas L. , Eng Marty L.
Published: July 2005

Objectives: State Medicaid programs struggle with rapidly increasing expenditures for pharmaceuticals, and Medicare will likely face the same challenge. This article demonstrates how the adoption of newer drugs across diverse therapeutic classes contributed to one state's Medicaid expenditures over a 3‐year period.

Design: Retrospective analysis of administrative claims data.

Setting: Older Kansas Medicaid community dwellers and institutionalized beneficiaries.

Participants: A 15% random sample (N = 6,256) of recipients aged 60 and older.

Measurements: Prescription medication use was tracked for three sequential 1‐year periods for eight therapeutic classes accounting for the greatest Medicaid drug expenditures, categorizing individual medications as newer or older agents based on generic availability and other clinical distinctions. Outcome measures were utilization per person‐year, price per prescription, market share as percentage of prescriptions, and market share as percentage of expenditures for prescriptions within each class.

Results: Use increased for all classes, driven by the adoption of newer agents. Mean prescription prices rose in nearly all classes primarily because of the higher prices of the newer agents. Newer drugs accounted for more than 50% of prescriptions in four of eight classes and constituted a disproportionately greater share of expenditures than their prescription share among several classes: antidepressants (>95%), antipsychotics (>92%), antiulcer agents (>63%), antiinflammatory drugs (>60%), and opiates (>45%).

Conclusion: Newer drug products for a variety of treatment indications consume a majority of pharmaceutical expenditures through widespread adoption and higher prices. Although these agents may offer some therapeutic advantages, further research is needed to determine in what circumstances, and for which patients, the advantages of new pharmaceuticals outweigh their higher costs.
Procalcitonin and Infection in Elderly Patients
Authors: Stucker Fabien , Herrmann François , Graf Jean‐Daniel , Michel Jean‐Pierre , Krause Karl Heinz , Gavazzi Gaëtan
Published: July 2005

Objectives: To compare the usefulness of procalcitonin (PCT) in detecting infection in elderly patients with that of other clinical and biological markers.

Design: Prospective observational study to compare PCT levels in infected and uninfected patients.

Setting: Geriatric teaching hospital in Switzerland.

Participants: Two hundred eighteen elderly patients aged 75 and older admitted to an acute geriatric care unit.

Measurements: Demographic characteristics, comorbidities, Charlson index, general signs (respiratory rate, temperature, pulse rate, confusion, falls, shivering), presence of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, functional score (Functional Independence Measurement (FIM)) biological parameters (PCT, C‐reactive protein (CRP), leukocytes, albumin), and definite diagnosis at admission were collected prospectively for each patient.

Results: Long‐term corticotherapy, chronic immune diseases, fever of 38°C or higher, white blood cell count, pulse rate, FIM, SIRS, sepsis, CRP of 3 mg/mL or higher, and PCT of 0.5 ng/mL or higher were associated with an infection at admission. In multivariate analysis, only sepsis and CRP of 3 mg/mL or higher were still associated with an infection; PCT levels do not show any significant association in the multivariate analysis. In addition, when PCT had good specificity (94%), it had low sensitivity (24%). False‐negative PCT was related to lower severity of infection (lower inflammatory reaction and lower acute renal failure) than true‐positive PCT. This finding may also be related to aging per se.

Conclusion: PCT may be useful to identify severely ill elderly patients admitted to an acute geriatric ward but not to discriminate patients with infection from those without.
Effect of temporin A modifications on its cytotoxicity and antimicrobial activity
Authors: MÄNTYLÄ T. , SIROLA H. , KANSANEN E. , KORJAMO T. , LANKINEN H. , LAPPALAINEN K. , VÄLIMAA A. L. , HARVIMA I. , NÄRVÄNEN A.
Published: July 2005

Temporin A (TA), a short α‐helical antimicrobial peptide isolated from the skin of the frog Rana temporaria, is effective against a broad spectrum of Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant Enterococcus faecium strains. TA interacts directly with the cell membrane of the microorganism and it has been reported to be non‐toxic to erythrocytes at concentrations that are antimicrobial. Less is known about the effects on the viability and growth of nucleated eukaryotic cells. In this study we have tested antibacterial and growth‐inhibitory properties of TA, its dimeric analogue (TAd), and all‐L (TAL L512) and all‐D (TAD L512) enantiomeric derivatives of modified TA towards S. aureus and cultured human keratinocytes, respectively. All molecules were antibacterial at concentrations from 1.5 μM to 10 μM. In keratinocyte cultures, TAD L512, as well as TAd, showed cytotoxicity. The original TA and TAL L512 did not affect the viability of the cells at their bacteriolytic concentrations. The growth of keratinocytes in low‐ and high‐calcium media was only slightly inhibited by temporins at concentrations which were antibacterial to S. aureus. This suggests that original TA and its modification, TAL L512, are promising molecules against multiresistant bacterial infections.
Pulmonary adenocarcinoma with micropapillary component: an immunohistochemical study
Authors: KURODA N. , HAMAUZU T. , TOI M. , YAMAOKA K. , MIYAZAKI E. , HIROI M. , NAKATA H. , TAGUCHI H. , ENZAN H.
Published: July 2005

Micropapillary carcinoma has been described in various organs, including the breast, urinary bladder, ovary and lung. We here present a case of pulmonary micropapillary carcinoma in a 72‐year‐old Japanese man who died of respiratory failure and septic shock, following which autopsy was performed. A mass measuring 2.5×2.5×2.5 cm was observed in the left lower lobe of the lung. The tumor showed moderately differentiated papillary adenocarcinoma with a focal micropapillary component. Carcinomatous lymphangiosis was also observed in the left lung and metastatic lesions were observed in the bilateral lung, liver, vertebra, muscle layer of the urinary bladder, right adrenal gland, spleen and lymph nodes. The micropapillary component was predominant at some metastatic sites. Immunohistochemically, both the adenocarcinoma and micropapillary components were positive for cytokeratin (CK) 7, CK19, TTF (thyroid transcription factor)‐1, carcinoembryonic antigen (CEA) and surfactant apoprotein A (SP‐A), and negative for CK20, estrogen receptor, progesterone receptor, uroplakin III, and CA125. The invasive area of the conventional adenocarcinoma component contained a large number of myofibroblasts, whereas the stroma of the micropapillary component contained a small number of myofibroblasts. However, no myofibroblasts were observed in the stroma of the central core of the non‐invasive micropapillary carcinoma. Several lymphatic invasions by neoplastic cells were identified in the peripheral area of the micropapillary component using D2–40 antibody. The immunohistochemical profile may be helpful in determining the primary location of the neoplasm containing micropapillary features. Myofibroblasts are present in the stroma of the invasive neoplastic nests in the micropapillary component as well as the conventional adenocarcinoma component, and D2–40 monoclonal antibody may be useful for evaluating the lymphatic invasion of pulmonary micropapillary carcinoma.
Atraumatic rupture of the spleen associated with hemophagocytic syndrome and isolated splenic peliosis
Authors: ETZION YORAM , BENHARROCH DANIEL , SAIDEL MARCELLO , RIESENBERG KLARIS , GILAD JACOB , SCHLAEFFER FRANCISC
Published: July 2005

Atraumatic rupture of the spleen is an uncommon condition that may be associated with various etiologies. The hemophagocytic syndrome (HS) and isolated splenic peliosis are two rare conditions, each of which has previously been described in association with splenic rupture. We describe a unique case of atraumatic splenic rupture in which concurrent HS and splenic peliosis were diagnosed following splenectomy. Given that both these rare conditions have probably caused the splenic rupture, a possible association between these entities is discussed.
Glomerular structural changes in pregnant, diabetic, and pregnant‐diabetic rats
Authors: RASCH RUTH , LAUSZUS FINN , THOMSEN JESPER SKOVHUS , FLYVBJERG ALLAN
Published: July 2005

Kidneys enlarge both during pregnancy and in diabetes. The enlargement and morphology of glomeruli was studied during pregnancy and in diabetes in order to examine possible similarities, differences, and interactions in the growth in these conditions. Morphometric investigations were performed on glomeruli in pregnant rats, in rats with 2 weeks' diabetes, and in pregnant‐diabetic rats. Kidneys were enlarged 22% in the midterm pregnant rats compared with controls, 74% in diabetic rats, and a further 21% in pregnant‐diabetic rats. Glomerular volume was enlarged by 26% during midterm pregnancy in normal animals. Diabetes induced an enlargement in glomerular volume of 58% and a further 18% in midterm diabetic animals due to pregnancy. Within the glomerulus, pregnancy in normal animals induced minor non‐significant changes. Diabetes induced significant increase in several parameters: mesangial volume and cell volume, capillary and glomerular basement membrane volume, capillary wall surface area, foot process width, filtration slit length, and nuclear number. Pregnancy in diabetic animals induced no significant additional changes. In conclusion, kidney enlargement in pregnancy shows very few glomerular changes in either normal or diabetic animals. Enlargement of glomeruli in diabetes involves hypertrophy and hyperplasia concurrent with several morphological changes within the glomerulus.
Porcine humoral immune responses to multiple injections of murine monoclonal antibodies
Authors: LOHSE LOUISE , NIELSEN JENS , KAMSTRUP SØREN , OLEKSIEWICZ MARTIN B. , ERIKSEN LIS
Published: July 2005

In humans and cattle, multiple injections of murine monoclonal antibodies (m‐mAbs) induce anti‐mouse antibody responses. The objectives of the present study were to investigate whether a similar response could be seen when pigs were subjected to m‐mAb therapy, and to study the kinetics of such a response. In two separate animal experiments, long‐term treatment was performed with m‐mAbs at low‐dose levels and therapeutic levels, respectively. Two specific m‐mAbs that recognized cognate antigen in the pigs (CD4 and CD8 surface antigens on T‐lymphocytes) and two irrelevant control m‐mAbs having no cognate antigen in the pigs were used. Enzyme‐linked immunosorbent assays (ELISA) were used to quantitate the circulating m‐mAbs, as well as the induced pig anti‐mouse antibodies (PAMA), in serum samples from m‐mAb‐treated pigs. As expected, we generally saw vigorous PAMA responses within 10 days after the start of m‐mAb treatment with the specific m‐mAbs. However, the different mAbs showed striking differences in the kinetics and levels of PAMA responses, differences that might be ascribed to the m‐mAb formulation and epitope specificity. In conclusion, treatment of pigs with m‐mAbs against T‐cell surface antigens induced rapid PAMA responses. This may influence and possibly decrease the effect of the m‐mAb treatment by narrowing the time period where m‐mAbs can efficiently be used for cell depletion.
TASTE PERCEPTIONS AND DIETARY INTAKES OF SMOKELESS TOBACCO USERS AND NONTOBACCO USERS†
Authors: SCHUELLER RHONDA A. , ALBRECHT JULIE A. , YOUNG LINDA
Published: July 2005

Smokeless tobacco and nontobacco users differed for certain concentrations of perceived intensities of the four solutions – significantly for sweet (P ≤ 0.008) and salty (P = 0.001). Sensitivity to salty (P = 0.02) and bitter (P = 0.11) solutions decreased with increasing hours of exposure to smokeless tobacco. Smokeless tobacco and nontobacco users rated fruits and vegetables for preference and the four taste senses differently, with a decreasing trend for sweet tastes in smokeless tobacco users with increasing hours of exposure to smokeless tobacco. Smokeless tobacco users consumed more total fat (P = 0.06) and fat per 1000 kcal (P = 0.13) than nontobacco users. Higher intakes of total fat (P = 0.005), total fat per 1000 kcal (P = 0.18), total sodium (P = 0.03) and total Vitamin E (P = 0.06) were found with increasing hours of exposure to smokeless tobacco. Although fruit and vegetable intakes did not differ between smokeless tobacco and nontobacco users, both groups should increase their consumption of fruits and vegetables.