bluuebunny/crossref_metadata_2025 huggingface dataset:
Participatory Conservation? Community‐based Natural Resource Management in Botswana
Authors: TWYMAN CHASCA
Published: July 2005

This paper examines the complexities of participatory conservation through a case study of the process of participation in a government funded community‐based natural resource management programme in Western Botswana. The paper argues that different stakeholders have very different views on the levels of participation taking place in particular projects. Furthermore local people find it difficult to voice their concerns about the environment and issues of sustainability given the power relations involved in this ‘participatory’process. The paper questions the accountability and motivation of the different stakeholders involved in participatory projects and suggests that implicit in the policy implementation process are mechanisms which constrain empowerment and dictate the forms of participatory conservation which can emerge. The paper concludes by reviewing the case study in the light of new policy developments in Botswana.
The Geography of Edible Insects in Sub‐Saharan Africa: a study of the Mopane Caterpillar
Authors: ILLGNER PETER , NEL ETIENNE
Published: July 2005

Entomophagy, the human consumption of insects, has not received significant attention in Western literature, despite the critical role which it plays as a protein supplement in many parts of the world. This paper explores the importance of entomophagy in Africa within the context of food security and indigenous technical knowledge. These issues are further investigated through a case study of the mopane caterpillar in Southern Africa. The findings clearly indicate the contribution which insects make to the diet of rural Africans.
Geomorphology of the eastern Badia basalt plateau, Jordan
Authors: ALLISON ROBERT J. , GROVE JAMES R. , HIGGITT DAVID L. , KIRK ALASTAIR J. , ROSSER NICHOLAS J. , WARBURTON JEFF
Published: July 2005

The eastern Badia of the Hashemite Kingdom of Jordan is a landscape developed predominantly on late Tertiary and Quaternary basalt lava flows, which vary in age between 8.9 million and 0.1 million years. Pyroclastic deposits are associated with remnant volcanic cones. There is limited, seasonal rainfall. Natural vegetation regenerates during cool, damp months. Slopes, which range from concave to convex forms and have varying relief, can be related to different basalts and the time since emplacement. Much of the ground surface is mantled with boulders. In many places the continuity of boulder cover produces a desert pavement. Clasts show differing degrees of burial or exhumation, depending on the surrounding topography. Water and sediment movement are important to landscape development. Much sediment is deposited in pans, which evolve at topographic lows. The pans, known locally as Qa, vary in form depending on drainage network development. Transitional forms, known as Marab, develop where wadis widen out and sediments are deposited along ephemeral channels. Groundwater is significant, with three aquifers beneath much of the eastern Badia. Recharge of the upper aquifer is predominantly on the footslopes of the Druze Mountains, with north to south flow. Groundwater extraction has resulted in the expansion of agriculture, with consequent changes in soil and water quality.
Soil fertility management strategies on the Jos Plateau: the need for integrating ‘empirical’ and ‘scientific’ knowledge in agricultural development
Authors: PASQUINI M W , ALEXANDER M J
Published: July 2005

Tin mining carried out on the Jos Plateau since the beginning of the last century has disturbed some 320 km2 of agricultural land. Formal attempts at reclamation of this land failed, but local farmers have developed a successful informal strategy for reclamation. This paper reports on a study undertaken to comprehend the farmers’‘informal’ approach to soil fertility management. Their soil fertility management practices centre on the use of a complex combination of traditional organic manures and ‘modern’ inorganic fertilizers that they have developed entirely on the basis of experimentation. A central focus of this paper is therefore the empirical knowledge base of the farmers and an assessment of any underlying scientific explanations for their strategies, including an analysis of their assertion that different brands of NPK fertilizers differ in their nutrient value. This discussion is followed by a consideration of the difficulties in accessing and understanding empirical knowledge. It is concluded that farmers’ knowledge and understanding of the values of different fertilizers and manures does have a scientific basis. It is argued that for further agricultural development to take place on the Jos Plateau, there must be synergy between farmers’ empirical knowledge (which has led to the development of successful and effective soil fertility management strategies, unlike the attempts of the local ‘scientific’ communities) and scientific knowledge (which can identify health and environmental hazards which may not be immediately visible to farmers).
Seismic and volcanic hazards in Peru: changing attitudes to disaster mitigation
Authors: DEGG MARTIN R , CHESTER DAVID K
Published: July 2005

Over the last 15 years there have been dramatic shifts in the consensus over how best to cope with natural hazards in economically developing regions such as South America. One very positive outcome of the United Nations sponsoredInternational Decade for Natural Disaster Reduction(IDNDR 1990–2000) has been that there is now greater interchange between the work of earth scientists examining the processes and mechanics of hazard occurrence and impact, and social scientists exploring the causes of human vulnerability to hazard – and thereby disaster. This paper traces the development of this new understanding with reference to earthquakes and volcanic eruptions in Peru, one of the most hazardous countries in South America. Particular focus is placed on the excellent progress currently being made by scientists in better understanding the physical dimensions of natural hazard exposure, and the ground‐breaking work by social scientists in promoting new approaches to understanding and mitigating human vulnerability to disaster. The paper concludes by emphasizing the need to build on this research to produce more inclusive, incultured and unified strategies of disaster mitigation at the local, national and international levels.
Annihilation of both place and sense of place: the experience of the Cheslatta T’En Canadian First Nation within the context of large‐scale environmental projects
Authors: WINDSOR J E , MCVEY J A
Published: July 2005

The water resources of Canada are today, and have always been, of major importance to the welfare of Canadians. Throughout most of Canada's history, these resources have been viewed within a supply–management framework and, frequently, exploited through the construction of ‘megaprojects’, often with little or no concern for issues such as environmental harm and social and community disruption. As in many parts of the world, those most affected by such large‐scale water resource developments have been aboriginals (in Canada, ‘First Nations’ peoples). Although the issues of environmental, social and economic damage to First Nations as a result of water megaprojects have been investigated, little has been written about the impact of such projects – especially dam construction – on the loss of sense of place of deracinated peoples. This paper investigates one example of such loss of sense of place, that of the Cheslatta T’En forcibly removed from their ancestral lands in the 1950s so as to allow for the construction of a private hydroelectric dam by the Aluminum Company of Canada (Alcan).
Agribusiness and farmers in Mexico: the importance of contractual relations
Authors: ECHÁNOVE FLAVIA , STEFFEN CRISTINA
Published: July 2005

In recent decades contract farming as a mechanism that integrates and subordinates agricultural production to export oriented agribusiness has expanded in Third World countries. In Mexico contract farming dominates the production of horticultural crops for processing and export. It is also used for barley and to grow some varieties of wheat for Cargill. The contract farming labour agreement represents an institution that links local and global processes where agribusiness is the key actor that integrates local farmers to national and world markets. The purpose of this paper is to analyse the implications of contract farming for productive relations by examining its impact upon farmers and firms. The study found that despite the disadvantages of contract farming for growers, and the disproportional risks born by producers, they enter into contract farming labour agreements because they lack alternatives for financing, technical assistance and access to markets. The experience of contract farming in Mexico and several Third World countries shows that its growth is related to the implementation of neo‐liberal policies that are accompanied by the withdrawal of state support and regulation of agricultural production. In this context, contract farming represents a livelihood strategy for many Mexican growers.
A Matter of Classes: Stratifying Health Care Populations to Produce Better Estimates of Inpatient Costs
Authors: Rein David B.
Published: July 2005

Objective. To stratify traditional risk‐adjustment models by health severity classes in a way that is empirically based, is accessible to policy makers, and improves predictions of inpatient costs.

Data Sources. Secondary data created from the administrative claims from all 829,356 children aged 21 years and under enrolled in Georgia Medicaid in 1999.

Study Design. A finite mixture model was used to assign child Medicaid patients to health severity classes. These class assignments were then used to stratify both portions of a traditional two‐part risk‐adjustment model predicting inpatient Medicaid expenditures. Traditional model results were compared with the stratified model using actuarial statistics.

Principal Findings. The finite mixture model identified four classes of children: a majority healthy class and three illness classes with increasing levels of severity. Stratifying the traditional two‐part risk‐adjustment model by health severity classes improved its R2 from 0.17 to 0.25. The majority of additional predictive power resulted from stratifying the second part of the two‐part model. Further, the preference for the stratified model was unaffected by months of patient enrollment time.

Conclusions.

Stratifying health care populations based on measures of health severity is a powerful method to achieve more accurate cost predictions. Insurers who ignore the predictive advances of sample stratification in setting risk‐adjusted premiums may create strong financial incentives for adverse selection. Finite mixture models provide an empirically based, replicable methodology for stratification that should be accessible to most health care financial managers.
Nursing Home Spending Patterns in the 1990s: The Role of Nursing Home Competition and Excess Demand
Authors: Mukamel Dana B. , Spector William D. , Bajorska Alina
Published: July 2005

Objective. To examine nursing home expenditures on clinical, hotel, and administrative activities during the 1990s and to determine the association between nursing home competition and excess demand on expenditures.

Data Sources/Study Setting. Secondary data sources for 1991, 1996, and 1999 for 500 free‐standing nursing homes in New York State.

Study Design. A retrospective statistical analysis of nursing homes' expenditures. The dependent variables were clinical, hotel, and administrative costs in each year. Independent variables included outputs (inpatient and outpatient), wages, ownership, New York City location, and measures of competition and excess demand.

Data Collection/Extraction Method. Variables were constructed from annual financial reports submitted by the nursing homes, the Patient Review Instrument and Medicare enrollment data.

Principal Findings. Clinical and administrative costs have increased over the decade, while hotel expenditures have declined. Increased competition was associated with higher clinical and administrative costs while excess demand was associated with lower clinical and hotel expenditures.

Conclusions. Nursing home expenditures are sensitive to competition and excess demand conditions. Policies that influence competition in nursing home markets are therefore likely to have an impact on expenditures as well.
Patients' Preferences for Technical versus Interpersonal Quality When Selecting a Primary Care Physician
Authors: Fung Constance H. , Elliott Marc N. , Hays Ron D. , Kahn Katherine L. , Kanouse David E. , McGlynn Elizabeth A. , Spranca Mark D. , Shekelle Paul G.
Published: July 2005

Objective. To assess patients' use of and preferences for information about technical and interpersonal quality when using simulated, computerized health care report cards to select a primary care provider (PCP).

Data Sources/Study Setting. Primary data collected from 304 adult consumers living in Los Angeles County in January and February 2003.

Study Design/Data Collection. We constructed computerized report cards for seven pairs of hypothetical individual PCPs (two internal validity check pairs included). Participants selected the physician that they preferred. A questionnaire collected demographic information and assessed participant attitudes towards different sources of report card information. The relationship between patient characteristics and number of times the participant selected the physician who excelled in technical quality are estimated using an ordered logit model.

Principal Findings. Ninety percent of the sample selected the dominant physician for both validity checks, indicating a level of attention to task comparable with prior studies. When presented with pairs of physicians who varied in technical and interpersonal quality, two‐thirds of the sample (95 percent CI: 62, 72 percent) chose the physician who was higher in technical quality at least three out of five times (one‐sample binomial test of proportion). Age, gender, and ethnicity were not significant predictors of choosing the physician who was higher in technical quality.

Conclusions. These participants showed a strong preference for physicians of high technical quality when forced to make tradeoffs, but a substantial proportion of the sample preferred physicians of high interpersonal quality. Individual physician report cards should contain ample information in both domains to be most useful to patients.
Assessing the Implementation of the Chronic Care Model in Quality Improvement Collaboratives
Authors: Pearson Marjorie L. , Wu Shinyi , Schaefer Judith , Bonomi Amy E. , Shortell Stephen M. , Mendel Peter J. , Marsteller Jill A. , Louis Thomas A. , Rosen Mayde , Keeler Emmett B.
Published: July 2005

Objective. To measure organizations' implementation of Chronic Care Model (CCM) interventions for chronic care quality improvement (QI).

Data Sources/Study Setting. Monthly reports submitted by 42 organizations participating in three QI collaboratives to improve care for congestive heart failure, diabetes, depression, and asthma, and telephone interviews with key informants in the organizations.

Study Design. We qualitatively analyzed the implementation activities of intervention organizations as part of a larger effectiveness evaluation of yearlong collaboratives. Key study variables included measures of implementation intensity (quantity and depth of implementation activities) as well as fidelity to the CCM.

Data Collection/Extraction Methods. We developed a CCM‐based scheme to code sites' intervention activities and criteria to rate their depth or likelihood of impact.

Principal Findings. The sites averaged more than 30 different change efforts each to implement the CCM. The depth ratings for these changes, however, were more modest, ranging from 17 percent to 76 percent of the highest rating possible. The participating organizations significantly differed in the intensity of their implementation efforts (p<.001 in both quantity and depth ratings). Fidelity to the CCM was high.

Conclusions. Collaborative participants were able, with some important variation, to implement large numbers of diverse QI change strategies, with high CCM fidelity and modest depth of implementation. QI collaboratives are a useful method to foster change in real world settings.
Dynamic Effects among Patients' Treatment Needs, Beliefs, and Utilization: A Prospective Study of Adolescents in Drug Treatment
Authors: Schell Terry L. , Orlando Maria , Morral Andrew R.
Published: July 2005

Objective. To document the prospective, reciprocal relationships among substance use problems, utilization of drug treatment, and predisposing beliefs thought to increase treatment utilization.

Data Source. Persistent Effects of Treatment Study‐Adolescent (PETS‐A), conducted by the Center on Substance Abuse Treatment. This was a longitudinal study of youths originally participating in one of two CSAT studies; one sample included 476 youths receiving residential drug treatment, and the other included 519 youths receiving outpatient treatment.

Study Design. This study uses five waves of data collected over a 12‐month period to examine the temporal relationships among four variables: treatment dose, substance use problems, drug resistance self‐efficacy, and perceived need for treatment (PNT). Data from this longitudinal study were analyzed using cross‐lagged panel models, and structural equation modeling techniques were used to estimate the prospective, reciprocal relationships among these four variables in each of the two samples, while controlling for several covariates.

Principal Findings. Both PNT and low drug resistance self‐efficacy led to higher levels of subsequent treatment. However, low self‐efficacy presaged increases in drug problems while PNT predicted decreases.

Conclusions. Understanding the role of psychological variables in the utilization of health services is complicated for psychological disorders because beliefs that affect treatment can also influence the disorder itself. Efforts to keep adolescents in drug treatment should focus on convincing youth that treatment can help them with their problems, rather than convincing them that they cannot resist drugs on their own. While both messages increase treatment utilization, the latter belief undermines the effects of treatment.
The Quality of the Quality Indicator of Pain Derived from the Minimum Data Set
Authors: Wu Ning , Miller Susan C. , Lapane Kate , Roy Jason , Mor Vincent
Published: July 2005

Objective. To examine facility variation in data quality of the level of pain documented in the minimum data set (MDS) as a function of level of hospice enrollment in nursing homes (NHs).

Data Source. Clinical assessments on 3,469 nonhospice residents from 178 NHs were merged with On‐line Survey Certification and Reporting data of 2000, Medicare Claims data of 2000 and the MDS of 2000–2002.

Study Design. Using the same assessment protocol, NH staff and study nurses independently assessed 3,469 nonhospice residents. Study nurses' assessments being gold standard, we quantified and compared quality of NH staff's pain rating across NHs with high, medium, or low hospice use. Multilevel models were built to assess the effect of NH hospice use levels on the occurrence of false positive (FP) and false negative (FN) errors in NH‐rated “severe pain.”

Principal Findings. Of 178 NHs, 25 had medium and 41 high hospice use. NHs with higher hospice use had lower sensitivities. In multilevel analysis, we found a significant facility‐level variation in the probability of FP and FN errors in facility‐rated “severe pain.” Resident characteristics only explained 4 and 0 percent of the facility variation in FP and FN, respectively; characteristics and locations (state) of NHs further explained 53 and 52 percent of the variance. After controlling for resident and NH characteristics, staff in NHs with medium or high hospice use were less likely to have FP or FN errors in their MDS documentation of pain than were staff in NHs with low or no hospice use.

Conclusions. The examination of data quality of pooled MDS data from multiple NHs is insufficient. Multilevel analysis is needed to elucidate sources of heterogeneity in the quality of MDS data across NHs. Facility characteristics, e.g., hospice use or NH location, are systematically associated with overrated/underrated pain and may bias pain quality indicator (QI) comparisons. To ensure the integrity of QI comparison in the NH setting, the government may need to institute regular audits of MDS data quality.
An Educational Intervention to Enhance Nurse Leaders' Perceptions of Patient Safety Culture
Authors: Ginsburg Liane , Norton Peter G. , Casebeer Ann , Lewis Steven
Published: July 2005

Objective. To design a training intervention and then test its effect on nurse leaders' perceptions of patient safety culture.

Study Setting. Three hundred and fifty‐six nurses in clinical leadership roles (nurse managers and educators/CNSs) in two Canadian multi‐site teaching hospitals (study and control).

Study Design. A prospective evaluation of a patient safety training intervention using a quasi‐experimental untreated control group design with pretest and posttest. Nurses in clinical leadership roles in the study group were invited to participate in two patient safety workshops over a 6‐month period. Individuals in the study and control groups completed surveys measuring patient safety culture and leadership for improvement prior to training and 4 months following the second workshop.

Extraction Methods. Individual nurse clinical leaders were the unit of analysis. Exploratory factor analysis of the safety culture items was conducted; repeated‐measures analysis of variance and paired t‐tests were used to evaluate the effect of the training intervention on perceived safety culture (three factors). Hierarchical regression analyses looked at the influence of demographics, leadership for improvement, and the training intervention on nurse leaders' perceptions of safety culture.

Principal Findings. A statistically significant improvement in one of three safety culture measures was shown for the study group (p<.001) and a significant decline was seen on one of the safety culture measures for the control group (p<.05). Leadership support for improvement was found to explain significant amounts of variance in all three patient safety culture measures; workshop attendance explained significant amounts of variance in one of the three safety culture measures. The total R2 for the three full hierarchical regression models ranged from 0.338 and 0.554.

Conclusions. Sensitively delivered training initiatives for nurse leaders can help to foster a safety culture. Organizational leadership support for improvement is, however, also critical for fostering a culture of safety. Together, training interventions and leadership support may have the most significant impact on patient safety culture.
More May Be Better: Evidence of a Negative Relationship between Physician Supply and Hospitalization for Ambulatory Care Sensitive Conditions
Authors: Laditka James N. , Laditka Sarah B. , Probst Janice C.
Published: July 2005

Objective. To conduct an empirical test of the relationship between physician supply and hospitalization for ambulatory care sensitive conditions (ACSH).

Data Sources/Study Setting. A data set of county ACSH rates compiled by the Safety Net Monitoring Initiative of the Agency for Healthcare Research and Quality (AHRQ). The analytical data set consists of 642 urban counties and 306 rural counties. We supplemented the AHRQ data with data from the Area Resource File and the Environmental Protection Agency.

Study Design. Ordinary least squares regression estimated ACSH predictors. Physician supply, the independent variable of interest in this analysis, was measured as a continuous variable (MDs/100,000). Urban and rural areas were modeled separately. Separate models were estimated for ages 0–17, 18–39, and 40–64.

Data Extraction Methods. Data were limited to 20 states having more than 50 percent of counties with nonmissing data.

Principal Findings. In the urban models for ages 0–17, standardized estimates indicate that, among the measured covariates in our model, physician supply has the largest negative adjusted relationship with ACSH (p<.0001). For ages 18–39 and 40–64, physician supply has the second largest negative adjusted relationship with ACSH (p<.0001, both age groups). Physician supply was not associated with ACSH in rural areas.

Conclusions. Physician supply is positively associated with the overall performance of the primary health care system in a large sample of urban counties of the United States.
The Impact of an Innovative Reform to the South Carolina Dental Medicaid System
Authors: Nietert Paul J. , Bradford W. David , Kaste Linda M.
Published: July 2005

Objective. To evaluate the effectiveness of an innovative reform in 2000 to the Dental Medicaid program in South Carolina.

Data Sources/Study Setting. South Carolina Medicaid enrollment data and dental services utilization data from 1998, 1999, and 2000.

Study Design. The study was observational and retrospective in nature. Quarterly data were used in general linear regression models to examine time trends in the percent of Medicaid enrollees ages 21 and younger who received dental services. Trends in the total number of dental procedures provided per Medicaid enrollee were also analyzed, with sub‐analyses performed on the four most frequent categories of procedures.

Data Collection/Extraction Methods. Data were provided by the state's Quality Improvement Organization.

Principal Findings. From 1998 to 1999, there was a downward trend in the number and percent of Medicaid enrollees ages 21 and younger receiving dental services and in the total number of services provided. This trend was dramatically reversed in 2000.

Conclusions. The January 2000 dental Medicaid reform in South Carolina had marked impact on Medicaid enrollees' access to dental services.
Physician Visits, Hospitalizations, and Socioeconomic Status: Ambulatory Care Sensitive Conditions in a Canadian Setting
Authors: Roos Leslie L. , Walld Randy , Uhanova Julia , Bond Ruth
Published: July 2005

Objective.To determine whether rates of physician visits for ambulatory care sensitive (ACS) conditions are lower for people of low‐socioeconomic status than of high‐socioeconomic status in an urban population with universal health care coverage.

Data Sources/Study Setting.Physician claims and hospital discharge abstracts from fiscal years 1998 to 2001 for urban residents of Manitoba, Canada. The 1996 Canadian Census public use database provided neighborhood household income information. The study included all continuously enrolled urban residents in the Manitoba Health Services Insurance Plan.

Study Design.Twelve ACS conditions definable using 3‐digit ICD‐9‐CM codes permitted cross‐sectional and longitudinal comparison of ambulatory visits and hospitalizations. Neighborhood household income data provided a measure of socioeconomic status.

Data Collection/Extraction Methods.Files were extracted from administrative data housed at the Manitoba Centre for Health Policy.

Principal Findings.All conditions showed a socioeconomic gradient with residents of the lowest income neighborhoods having both more visits and more hospitalizations than their counterparts in higher income areas. Six of nine conditions with a sufficientNshowed individuals living in the lowest income neighborhoods to have significantly more ambulatory visits before hospitalization for an ACS condition than did those in the most affluent neighborhoods. Many conditions showed a gradient in rate of hospitalization even after controlling for the number of ambulatory care visits.

Conclusions.In the Canadian universal health care plan, the poor have reasonable access to ambulatory care for ACS conditions. Ambulatory care may be more effective in preventing hospitalizations among relatively affluent individuals than among the less well off.
Increasing Health Insurance Costs and the Decline in Insurance Coverage
Authors: Chernew Michael , Cutler David M. , Keenan Patricia Seliger
Published: July 2005

Objective. To determine the impact of rising health insurance premiums on coverage rates.

Data Sources & Study Setting. Our analysis is based on two cohorts of nonelderly Americans residing in 64 large metropolitan statistical areas (MSAs) surveyed in the Current Population Survey in 1989–1991 and 1998–2000. Measures of premiums are based on data from the Health Insurance Association of America and the Kaiser Family Foundation/Health Research and Educational Trust Survey of Employer‐Sponsored Health Benefits.

Study Design. Probit regression and instrumental variable techniques are used to estimate the association between rising local health insurance costs and the falling propensity for individuals to have any health insurance coverage, controlling for a rich array of economic, demographic, and policy covariates.

Principal Findings. More than half of the decline in coverage rates experienced over the 1990s is attributable to the increase in health insurance premiums (2.0 percentage points of the 3.1 percentage point decline). Medicaid expansions led to a 1 percentage point increase in coverage. Changes in economic and demographic factors had little net effect. The number of people uninsured could increase by 1.9–6.3 million in the decade ending 2010 if real, per capita medical costs increase at a rate of 1–3 percentage points, holding all else constant.

Conclusions. Initiatives aimed at reducing the number of uninsured must confront the growing pressure on coverage rates generated by rising costs.
Somatostatin inhibits pro‐inflammatory cytokine secretion from rat hepatic stellate cells
Authors: Lang Alon , Sakhnini Emad , Fidder Herma H. , Maor Yaakov , Bar‐Meir Simon , Chowers Yehuda
Published: July 2005

Abstract: Background/aims: Activated hepatic stellate cells (HSCs) have been implicated in hepatic fibrosis. Somatostatin (SOM) has an immunomodulatory role. The aim of this study was to assess the secretion of pro‐inflammatory cytokines by HSCs and to determine the effect of SOM on the secretion of these mediators.

Methods:
Activated rat HSCs were evaluated for their secretion of IL‐1β, IL‐8, and TNF‐α using ELISA. RNA protection assay was used to determine cytokine mRNA levels. The expression of chemokine and cytokine mRNA and the secretion of these mediators were assessed following incubation with SOM or octreotide.

Results: HSCs spontaneously secreted IL‐1β, IL‐8, and TNF‐α. This secretion was augmented following stimulation by IL‐1β and TNF‐α. SOM inhibited the spontaneous and TNF‐α‐induced secretion of IL‐1β, IL‐8, and TNF‐α and suppressed the expression of IL‐1β and TNF‐α mRNA. Octreotide suppressed the secretion of IL‐1β and IL‐8.

Conclusions: These observations indicate that SOM exerts an inhibitory immunomodulatory effect on HSCs.
Effects of sildenafil citrate on hepatic function and regeneration in normal and alcohol‐fed rats
Authors: Ji Hong , Shen Hong , Uhanova Julia , Zhang Manna , Minuk Gerald Y. , Gong Yuewen
Published: July 2005

Abstract: Sildenafil citrate is a potent inhibitor of specific phosphodiesterase‐5, which mediates metabolism of intracellular second message – cGMP. Sildenafil citrate has been widely used for erectile dysfunction in men. Moreover, it is known that men with liver diseases have higher rate of erectile dysfunction. Furthermore, it has been demonstrated that nitric oxide plays an important role in liver function and regeneration. The present study evaluates effects of sildenafil citrate on hepatic function and regeneration in normal and alcohol‐fed rats. In normal rats sildenafil citrate has a trend to improve hepatic function after partial hepatectomy (PHx). Moreover, sildenafil citrate significantly reduces hepatic regenerative activity at the concentration of 5 mg/kg body weight. However, sildenafil had no effects on hepatic function and regeneration of alcohol‐fed rats. In general, sildenafil citrate did not induce significant changes in hepatic function and regenerative activity after PHx in normal and alcohol‐fed rats, except at concentration of 5 mg/kg sildenafil citrate significantly inhibit hepatic regeneration in normal rats.
Diffuse expression of heparan sulfate proteoglycan and connective tissue growth factor in fibrous septa with many mast cells relate to unresolving hepatic fibrosis of congenital hepatic fibrosis
Authors: Ozaki Satoru , Sato Yasunori , Yasoshima Mitsue , Harada Kenichi , Nakanuma Yasuni
Published: July 2005

Abstract: Background and Aims: Congenital hepatic fibrosis (CHF) is characterized by dense portal/septal fibrosis and bile duct proliferation and tortuosity. In this study, the roles and significance of fibrosis‐related cells and molecules in the process of progressive and unresolving fibrosis of CHF were examined in comparison with other fibrotic liver diseases.

Methods: Seven CHF livers were examined, and a total of 74 control livers (chronic viral hepatitis (CVH), alcoholic fibrosis/cirrhosis (F/C), extrahepatic biliary obstruction and livers showing non‐specific reactive changes) were used as controls. All of these livers were wedge biopsied or surgically resected ones, and were formalin fixed and paraffin embedded. In addition to histologic observations, expression of heparan sulfate proteoglycan (HSPG), connective tissue growth factor (CTGF), mast cell‐specific tryptase, α‐smooth muscle actin for activated hepatic stellate cells (HSC) or myofibroblasts (MF) were immunohistochemically surveyed. HSPG and CTGF at mRNA were also examined by in situ hybridization.

Results: Portal/septal fibrosis of CHF were mature collagenous and elastic fiber poor, when compared with controls. HSPG and CTGF were diffusely abundant in fibrous portal tracts/septa in CHF, while they were more or less accentuated at periportal areas in alcoholic F/C and CVH. In CHF, the number of interface and portal/septal MF was increased from mild‐to‐moderate degree, while their increase was moderate to marked in alcoholic F/C and CVH, particularly F3/F4. While activated HSC were frequent in alcoholic F/C and CVH and they were continuous with interface MF, activated HSC in CHF were scanty. Instead, mast cells were increased in portal/septal fibrosis of CHF. Portal mononuclear cells and endothelial cells were positive for HSPG mRNA, and mononuclear cells for CTGF mRNA, and such cells were accentuated around proliferated bile ducts and ductules in CHF.

Conclusions: Abundant CTGF retained diffusely in HSPG in the fibrous portal tracts/septa may be responsible for non‐resolving hepatic fibrosis in CHF, and many mast cells and portal MF not related to HSC may causally relate to such characteristic finding in CHF.
Coordinated expression of cyclin D1 and LEF‐1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma
Authors: Schmitt‐Graeff Annette , Ertelt‐Heitzmann Viktoria , Allgaier Hans‐Peter , Olschewski Manfred , Nitschke Roland , Haxelmans Sabine , Koelble Konrad , Behrens Jürgen , Blum Hubert Erich
Published: July 2005

Abstract: Background: While the Wnt pathway has been widely implicated in hepatocarcinogenesis, the role of cyclin D1 as a direct downstream target gene of β‐catenin‐lymphoid enhancer factor‐1 (LEF‐1)/T‐cell factor (TCF) signaling is controversely discussed.

Methods: By immunohistochemical analyses we studied the subcellular localization of LEF‐1/TCF and cyclin D1 in 162 hepatocellular carcinoma (HCC). Single‐ and double‐label imaging by brightfield and confocal laser scanning microscopy was quantitated and correlated with β‐catenin, the Ki67+ proliferation fraction (PF), tumor size, grade, the Okuda stage and patient survival.

Results: The frequency of nuclear cyclin D1 expression was 28% and closely correlated with LEF‐1/TCF (P<0.0001) and the Ki67+ PF (P=0.03). Nuclear LEF‐1/TCF expression was observed in 52% of all cases, but was also present in 42% of cyclin D1− cases. Nuclear β‐catenin was identified in 37% of all HCCs and correlated with LEF‐1/TCF (P=0.04). The expression of cyclin D1, LEF‐1/TCF or β‐catenin did not correlate with other clinico‐pathological data.

Conclusions: A large proportion of HCCs does not appear to be linked to a deregulation of cyclin D1. However, the coordinated expression of cyclin D1 and LEF‐1/TCF in some cases suggests the role of cyclin D1 as a Wnt target gene in a subset of HCCs.
Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation – a pilot study
Authors: Choi Jong Young , Bae Si Hyun , Yoon Seung Kew , Cho Se Hyun , Yang Jin Mo , Han Joon Yeol , Ahn Byung Min , Chung Kyu Won , Sun Hee Sik , Kim Dong Goo
Published: July 2005

Abstract: Purpose: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute‐on‐chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT).

Patients and methods: Between January and December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia (>20 mg/dl) and hepatic encephalopathy grade ≥2) were studied. MARS was used in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF patients who received LDLT before clinical use of MARS were used as historical controls.

Results: Because of a shortage of donors, only five out of 10 patients considered for LDLT could receive transplants. Three patients were treated with MARS for 8 h the day before receiving LDLT, and all three survived. The remaining two patients who received transplants, and who were not pretreated with MARS, died from sepsis and multi‐organ failure within 2 weeks. Four of the patients who did not receive transplants because of donor shortage died despite 1 or 3 MARS treatments, however bilirubin levels and grade of encephalopathy were significantly reduced in these patients.

Conclusions: Results of this small pilot study suggest that MARS, by reducing the severity of jaundice and encephalopathy, might be effective as a bridging option in AoCLF patients awaiting LDLT.
Treatment of experimental hepatic fibrosis by combinational delivery of urokinase‐type plasminogen activator and hepatocyte growth factor genes
Authors: Lin Yong , Xie Wei‐Fen , Chen Yue‐Xiang , Zhang Xin , Zeng Xin , Qiang Hui , Chen Wei‐Zhong , Yang Xiu‐Jiang , Han Ze‐Guang , Zhang Zhong‐Bing
Published: July 2005

Purpose: To investigate the effect of combinational delivery of urokinase‐type plasminogen activator (uPA) and hepatocyte growth factor (HGF) genes on hepatic fibrosis.

Methods: Replication‐deficient adenoviral vectors expressing either human HGF (AdHGF) or uPA (AduPA) were generated. HGF gene was transferred into primary cultured hepatocytes and uPA gene to hepatic stellate cell (HSC) to investigate the effect on the biological character of cells. Combinational adenoviruses were infused into hepatic fibrosis rats. Serum markers as well as histological and immunohistochemical examination were carried out to test the reversal of hepatic fibrosis.

Results: Transfection of exogenous HGF gene induced expression of c‐met/HGF receptor and stimulated hepatocyte proliferation. uPA gene delivered into HSC decreased the amount of collagen types I and III accompanied with the increased expression of matrix metalloproteinase‐2. In vivo, the area of extracellular matrix in the fibrotic liver decreased to 72% in AdHGF‐treated rats (P<0.01), 64% in the AduPA‐treated group (P<0.01), and 51% in bi‐genes transfection (P<0.01), compared with that of the controls. Moreover, immunohistochemical staining of collagen types I and III revealed that combinational genes delivery exerted more effect on reversal of hepatic fibrosis than mono‐gene transfection.

Conclusions: Our study indicated that simultaneous delivery of two antifibrotic genes could confer synergistic effect on hepatic fibrosis.
p53 mutations in human cholangiocarcinoma: a review
Authors: Khan Shahid A. , Thomas Howard C. , Toledano Mireille B. , Cox I. Jane , Taylor‐Robinson Simon D.
Published: July 2005

Abstract: The reported mortality from intrahepatic bile duct tumours is increasing markedly in industrialised countries, for reasons that remain unknown. Inactivation of the tumour suppressor gene p53, is the commonest genetic abnormality in human cancer and has been implicated in the genesis of cholangiocarcinoma in various immunohistochemical and molecular epidemiological investigations, including gene sequencing studies. The structure and function of p53 and its role in linking cancer to specific carcinogens by way of mutational signatures is reviewed. The findings of previous p53 studies and their relevance in human cholangiocarcinoma are summarised.
Non‐interferon‐based therapy: an option for amelioration of necro‐inflammation in hepatitis C patients who cannot afford interferon therapy
Authors: El‐Zayadi Abdel‐Rahman , Attia Mohy , Badran Hanaa M. , El‐Tawil Ahmed , Zalata Khaled , Barakat Eman , Selim Osaima , El‐Nakeeb Adham , Saied Ahmed
Published: July 2005

Objectives: Interferon (IFN) therapy is not affordable by the majority of Egyptian patients. Our aim was to tailor an effective and inexpensive regimen that ameliorates hepatic necro‐inflammatory activity among chronic hepatitis C (CHC) patients.

Methods: One hundred and seventy naïve CHC patients with elevated alanine aminotransferase (ALT) (>1.5‐fold) and detectable hepatitis C virus (HCV)‐RNA by polymerase chain reaction, who cannot afford IFN‐based therapy were randomly allocated either to non‐interferon‐based therapy (N‐IFN‐BT) (group I) or silymarin therapy (group II). Group I comprised 87 patients (biopsy proved chronic hepatitis in 62 patients) who were administered a daily combination of ribavirin (600–800 mg) plus amantadine (200 mg) and ursodeoxycholic acid (UDCA) (500 mg) for 24 weeks. Group II comprised 83 patients who were administered Silymarin 450 mg/day for 24 weeks.

Results: Statistical evaluation was conducted on 82 patients from group I and 72 from group II because of the withdrawal of five and 11 patients from Groups I and II, respectively. Age, sex, social status and biochemical parameters were comparable in both groups. Normalization of ALT at the end of treatment was achieved in 58.5% and 15.3% (P<0.001), whereas end of treatment virologic response (ETVR) was achieved in 2.4% and 0% of Groups I and II, respectively. Twenty‐four weeks after cessation of therapy, sustained biochemical response (SBR) was achieved in 28% and 2.8% (P<0.001), while sustained virologic response (SVR) was maintained in 2.4% and 0% of the patients in Groups I and II, respectively. In Group I, histopathological examination revealed a decreased activity index by an average score of 1.5 points among 38/62 of the rebiopsied patients.

Conclusion: Twenty‐four weeks N‐IFN‐BT achieved a fourfold‐higher ETBR and a tenfold‐higher SBR compared with silymarin therapy, which reflects an improvement of necroinflammatory activity as proven by repeat histopathology.
Hepatic gene expression in patients with obesity‐related non‐alcoholic steatohepatitis
Authors: Younossi Zobair M. , Gorreta Francesco , Ong Janus P. , Schlauch Karen , Del Giacco Luca , Elariny Hazem , Van Meter Amy , Younoszai Abraham , Goodman Zachary , Baranova Anna , Christensen Alan , Grant Geraldine , Chandhoke Vikas
Published: July 2005

Abstract: Background: Non‐alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic syndromes that includes non‐alcoholic steatohepatitis (NASH) that has potential for progression. The pathogenesis of NASH is poorly characterized.

Aim: This study was designed to identify differences in hepatic gene expression in patients with NASH and to relate such differences to their clinical characteristics.

Design: Consecutive patients undergoing bariatric surgery were prospectively recruited. Extensive clinical data and two liver biopsy specimens were obtained at the time of enrollment. A single hepatopathologist reviewed and classified the liver biopsies. Patients with excessive alcohol use and other causes of liver disease were excluded. A group of 29 NASH patients, 12 with steatosis alone, seven obese controls and six non‐obese controls were selected for further investigation. Customized cDNA microarrays containing 5220 relevant genes were designed specifically for this study. Microarray experiments were run in triplicate for each sample and a selected group of genes were confirmed using real‐time PCR.

Outcome Measure: Differential hepatic gene expressions in patients with NASH as compared with controls.

Results: Thirty‐four genes with significant differential expression were identified in patients with NASH when compared with non‐obese controls. Moreover, 19 of these genes showed no significant expression differences in obese vs. non‐obese controls, suggesting a stronger association of these genes to NASH.

Conclusions: Several differentially expressed genes in patients with NASH are related to lipid metabolism and extracellular matrix remodeling. Additionally, genes related to liver regeneration, apoptosis, and the detoxification process were differentially expressed. These findings may help clarify the molecular pathogenesis of NASH and identify potential targets for therapeutic intervention.
Early treatment response predicts the need for liver transplantation in autoimmune hepatitis
Authors: Tan Patrick , Marotta Paul , Ghent Cameron , Adams Paul
Published: July 2005

Abstract: Background: The need for immunosuppression in autoimmune hepatitis is established. Previous studies have investigated short‐term outcomes in patients who respond to treatment. This study assesses long‐term prognosis of patients who fail to respond to standard immunosuppression.

Methods: 163 charts were reviewed, composed of 108 non‐transplant patients and 55 patients who required liver transplantation (LT). Clinical endpoints were based on aminotransaminases: Early treatment response (ER) was a 50% improvement at 6 months of therapy, Complete remission (CR) was an improvement to <2X normal, Relapse was worsening to >3X normal, Incomplete response (IR) was some response but no CR in 3 years, and No response (NR) was no improvement after 3 years.

Results: 85% of non‐LT and 25% of LT patients achieved ER, 91% of non‐LT and 26% of LT patients achieved CR. 41% of non‐LT patients relapsed on maintenance treatment, and 41% of non‐LT patients relapsed when withdrawn from treatment. 9% of non‐LT and 58% of LT patients had IR. 16% in LT group showed NR, while all non‐LT patients showed some response. All paired comparisons were statistically different (P<0.05). Multiple regression analysis revealed that lack of ER predicts need for LT (P=0.0005). 87% of patients who achieved ER did not require LT, whereas 16% of patients who failed ER showed NR and all required LT. Odds ratio of a patient who failed ER proceeding to LT, compared to a patient who achieved ER, was 16.8 (7.5 to 37.7, 95% CI).

Conclusion: Patients who fail to show a 50% improvement in transaminases at 6 months of standard immunosuppression should be considered for alternate treatment modalities or be referred earlier for LT.