bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemokine‐receptor expression on T cells in lung compartments of challenged asthmatic patients
Authors: Kallinich T. , Schmidt S. , Hamelmann E. , Fischer A. , Qin S. , Luttmann W. , Virchow J. C. , Kroczek R. A.
Published: January 2005

Background
The interaction of chemokines with their receptors strongly influences the migration of leucocytes.

Objective
In order to assess the contribution of these molecules to the local recruitment of T cells in bronchial asthma, we analysed the expression of 14 chemokine receptors on lung‐derived T cells.

Methods
Chemokine‐receptor expression by T cells derived from the peripheral blood, the bronchoalveolar lavage fluid and the bronchial mucosa was analysed by flow cytometry and immunohistochemistry. Expression profiles in healthy and mildly asthmatic individuals were compared, the latter prior and after segmental allergen provocation.

Results
Compared with peripheral blood, alveolar T cells expressed significantly more CCR2, CCR5, CCR6, CXCR3 and CCR4. However, no differences were observed between healthy controls and unchallenged asthmatics. In patients developing significant inflammatory responses following specific allergen challenge, a marked increase in the percentage of CCR4+ and CCR7+, and reduced numbers of CXCR3‐bearing alveolar T cells were detected. Following specific allergen challenge, chemokine‐receptor expression profiles of T cells from the alveolar space and the mucosa or the submucosa were similar, excluding a particular subcompartmentalization of the chemokine/chemokine‐receptor system.

Conclusion
The expression of certain chemokine receptors by lung T cells suggests a contribution to the physiological recruitment of T cells to the lungs, both in healthy controls and unchallenged mild asthmatics. However, strong allergen‐induced airway responses were associated with a specific chemokine‐receptor profile, suggesting the involvement of certain chemokine receptors in the pathogenesis of allergic bronchial inflammation.
Tissue‐selective mast cell reconstitution and differential lung gene expression in mast cell‐deficient KitW‐sh/KitW‐sh sash mice
Authors: Wolters P. J. , Clair J. Mallen‐St. , Lewis C. C. , Villalta S. A. , Baluk P. , Erle D. J. , Caughey G. H.
Published: January 2005

Background
Mast cell‐deficient KitW/KitW‐v mice are an important resource for studying mast cell functions in vivo. However, because they are compound heterozygotes in a mixed genetic background and are infertile, they cannot be crossed easily with other mice.

Objective
To overcome this limitation, we explored the use of KitW‐sh/KitW‐sh mice for studying mast cell biology in vivo.

Results
These mice are in a C57BL/6 background, are fertile and can be bred directly with other genetically modified mice. Ten‐week‐old KitW‐sh/KitW‐sh are profoundly mast cell‐deficient. No mast cells are detected in any major organ, including the lung. Gene microarrays detect differential expression of just seven of 16 463 genes in lungs of KitW‐sh/KitW‐sh mice compared with wild‐type mice, indicating that resting mast cells regulate expression of a small set of genes in the normal lung. Injecting 107 bone marrow‐derived mast cells (BMMC) into tail veins of KitW‐sh/KitW‐sh mice reconstitutes mast cell populations in lung, stomach, liver, inguinal lymph nodes, and spleen, but not in the tongue, trachea or skin. Injection of BMMC into ear dermis or peritoneum reconstitutes mast cells locally in these tissues. When splenectomized KitW‐sh/KitW‐sh mice are intravenously injected with BMMC, mast cells circulate longer and are found more often in the liver and inguinal lymph nodes, indicating that the spleen acts as a reservoir for mast cells following injection and limits migration to some tissues.

Conclusion
In summary, these findings show that mast cell‐deficient KitW‐sh/KitW‐sh mice possess unique attributes that favour their use for studying mast cell functions in vivo.
Allergic diseases and asthma in relation to serum immunoglobulins and salivary immunoglobulin A in pre‐school children: a follow‐up community‐based study
Authors: Lúðvíksson B. R. , Arason G. J. , Thorarensen O. , Árdal B. , Valdimarsson H.
Published: January 2005

Background
We have previously reported an association between low IgA and allergic manifestations in early childhood (0–2 years) and have now followed our cohort for an additional 2 years.

Objective
To evaluate in a longitudinal community‐based cohort study the association between maturation of Ig production and allergic manifestations in the first 4 years of life.

Methods
A cohort of 161 randomly selected children was followed from birth to the age of 42–48 months and evaluated at 18–23 months (EV1; n=179) and again at the age of 42–48 months (EV2; n=161). Diagnoses were made with the help of a clinical questionnaire, physical examination and skin prick tests (SPTs) to 10 common allergens. Serum immunoglobulins were measured at EV1 and EV2, and salivary IgA (sal‐IgA) at EV2.

Results
Serum IgA, IgE, IgG1, IgG2 and IgG4 increased from 2 to 4 years of age (P<0.001) and their levels showed close correlations (P0.01 for most comparisons). Children with one or more positive SPTs had lower serum IgA (P=0.004) and IgG4 (P=0.05) at EV2 than those who did not respond, and children who developed allergic rhinitis between EV1 and EV2 had low sal‐IgA (P=0.006) and IgG3 (P<0.05) at EV2. Atopic eczema was associated with low sal‐IgA at EV2, and children who developed eczema between EV1 and EV2 had significantly lower sal‐IgA than those who recovered after EV1 (P=0.02).

Conclusion
Allergic manifestations in predisposed children may be influenced by the rate of maturation of immunological components that counteract sensitization or inhibit effector mechanisms of allergy.
Allergen skin weal/radioallergosorbent test relationship in childhood populations that differ in histamine skin reactivity: a multi‐national survey
Authors: Ronchetti R. , Villa M. P. , Rennerova Z. , Haluszka J. , Dawi E. B. , Felice G. D. , Al‐Bousafy A. , Zakrzewski J. , Barletta B. , Barreto M.
Published: January 2005

Background
Histamine skin reactivity (HSR, the dimension of the skin weal elicited by histamine 10 mg/mL) is a variable that differs in children from different European countries and increases over time in the same place (Italy).

Objective
In this epidemiologic study, we investigated to what extent differences in HSR influence the relationship between positive allergen skin prick tests (ASPTs) and serum‐specific IgE concentrations.

Methods
Between October 2001 and February 2002, 591 unselected 9–10‐year‐old schoolchildren drawn from five small towns in central Poland (Starachowice), central Italy (Ronciglione, Guardea) and Libya (Al‐Azyzia, near the Mediterranean sea and Samno, 900 km south of the coast) were analysed for histamine, common ASPT and for serum total and specific IgE.

Results
HSR differed markedly in children from the three countries (Libya>Italy>Poland) whereas serum total IgE concentrations remained the same. The prevalence of children with measurable serum specific IgE (0.35 kU) or with a positive ASPT for five common allergens was high in Italy, lower in Poland and far lower in Libya. A 3‐mm ASPT weal corresponded to a serum‐specific IgE concentration that was two to threefold higher in children with low HSR compared with children with high HSR (P=0.008).

Conclusion
These findings suggest that HSR – a variable that differs in schoolchildren populations from the three countries studied – independently influences the results of ASPT and its influence should be considered when ASPT are assessed in international studies. The HSR differences found in the populations reported here probably reflect a complex, dynamic, environmental interaction that should be monitored in the different parts of the world.
Fel d 1‐derived T cell peptide therapy induces recruitment of CD4+CD25+; CD4+ interferon‐γ+ T helper type 1 cells to sites of allergen‐induced late‐phase skin reactions in cat‐allergic subjects
Authors: Alexander C. , Ying S. , B. Kay A. , Larché M.
Published: January 2005

Background
Specific immunotherapy with whole allergen extracts is associated with local accumulation of IFN‐γ+ and CD25+ cells indicating recruitment of activated T‐helper type 1 (Th1) and/or T regulatory cells. We have studied allergen‐induced, late‐phase skin biopsies before and after T cell peptide therapy for evidence of alterations in the pattern of local recruitment of Th1, T‐helper type 2 (Th2) and T regulatory cells.

Objective
To evaluate the effect of T cell peptide therapy on the allergen‐induced cutaneous late‐phase reaction.

Methods
Increasing doses of synthetic Fel d 1‐derived peptides were administered (by intradermal injection) to eight cat‐allergic asthmatics at 14‐day intervals. Twenty‐four‐hour skin biopsies were taken from whole cat allergen‐ and diluent‐injected sites, before and after treatment and studied by immunohistochemistry and in situ hybridization.

Results
Fel‐d 1 peptides decreased airway hyper‐responsiveness (P=0.02) and inhibited the late‐phase cutaneous reaction (LPCR) to whole cat allergen (P=0.03). This was associated with significant increases (post‐ vs. pre‐treatment) in the number of cutaneous CD4+/IFN‐γ+ (P=0.03) and CD4+/CD25+ cells (P=0.04), but not in CD4+/IL‐10+ or CD4+/CTLA‐4+ cells.

Conclusions
Treatment with allergen‐derived T cell peptides results in allergen‐dependent recruitment to the skin of Th1, rather than T regulatory cells, to cutaneous late‐phase reaction sites.
Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood
Authors: Shaheen S. O. , Newson R. B. , Henderson A. J. , Headley J. E. , Stratton F. D. , Jones R. W. , Strachan D. P. ,   the ALSPAC Study Team
Published: January 2005

Background
We recently found that paracetamol (acetaminophen) use in late pregnancy was associated with an increased risk of early wheezing in the offspring.

Objective
To see whether use of paracetamol in late pregnancy is associated with an increased risk of asthma, wheezing and other atopic outcomes in the child at school age.

Methods
In the population‐based Avon Longitudinal Study of Parents and Children, we measured associations of paracetamol and aspirin use in late pregnancy (20–32 weeks) with asthma, hayfever, eczema (n=8511) and wheezing (8381) in the offspring at 69–81 months, and with atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n=6527) and blood total IgE (n=5148) at 7 years. We used logistic and linear regression to analyse binary outcomes and log‐transformed IgE, respectively, controlling for potential confounders.

Results
Use of paracetamol, but not aspirin, in late pregnancy was positively associated with asthma (odds ratios (ORs), comparing children whose mothers took paracetamol ‘sometimes’ and ‘most days/daily’ with those whose mothers never took it, 1.22 (95% confidence interval (CI): 1.06–1.41) and 1.62 (95% CI: 0.86–3.04), respectively; P trend=0.0037), wheezing (ORs 1.20 (95% CI: 1.02–1.40) and 1.86 (95% CI: 0.98–3.55), respectively; P trend=0.011), and total IgE (geometric mean ratios 1.14 (95% CI: 1.03–1.26) and 1.52 (95% CI: 0.98–2.38), respectively; P trend=0.0034), but not hayfever, eczema or skin test positivity. The proportion of asthma attributable to paracetamol use in late pregnancy, assuming a causal relation, was 7%.

Conclusion: Paracetamol exposure in late gestation may cause asthma, wheezing and elevated IgE in children of school age.
Living with a stoma: a review of the literature
Authors: Brown Hannah , Randle Jacqueline
Published: January 2005

Aims and objectives.  This systematic review looks at the psychological and social impact of stoma surgery on peoples’ lives.

Background.  The formation of a stoma can have a negative effect on a person's quality of life and affect lifestyle in a number of ways.

Methods.  The review examines nursing literature from 1990 to date and focuses on how stoma patients’ lives are affected by the presence of a stoma. It informs nursing practice so nurses are better able to help individuals improve, maintain or recover their health following ostomy surgery.

Results.  The findings of the review indicate that stoma surgery can impact on individuals’ lives in many different ways.

Relevance to clinical practice.  Knowledge of the problems stoma patients can experience can help nurses plan care in an individualized way. Recommendations for nursing practice and future research are made.
Experimental evidence for the effects of additional water, nutrients and physical disturbance on invasive plants in low fertility Hawkesbury Sandstone soils, Sydney, Australia
Authors: LEISHMAN MICHELLE R. , THOMSON VIVIEN P.
Published: January 2005

The environmental conditions of a site are thought to influence its invasibility by exotic plants. We tested the effects of physical disturbance, water and nutrient addition on growth and survival of a total of 28 plant species from urban bushland remnants on low fertility Hawkesbury Sandstone soils in Sydney, Australia. Species were classified as native (to Australia, including the local community) or exotic (from outside Australia) and as non‐invasive or invasive.

In a glasshouse experiment the treatments were control (natural soil), added water, added nutrients and added water and nutrients. We found significant differences in response of the plant types to additional nutrients but not to water. Under additional nutrients, exotic invasive species had better survival than all other plant types. There were strong biomass responses to added nutrients for all plant types except native non‐invasives. In contrast, the survival and growth of all plant types were similar under control and additional water treatments.

In a field experiment the factors were site (high and low nutrient soils) and physical disturbance but survival differed between plant types only in relation to site. Exotic species had much better survival than native species at the high nutrient site only. Exotic invasive species had the strongest biomass responses to the high nutrient site while native and exotic non‐invasive species showed relatively smaller growth responses.

Differences between invasive and non‐invasive plants were not consistent between exotic and native species. Exotic invasives had greater survival than exotic non‐invasives under high nutrient conditions in both experiments, and only exotic invasives showed consistently strong biomass responses to nutrient addition. For native species, there were no differences between invasives and non‐invasives in survival in high nutrient conditions in the glasshouse or field; however, only invasive species showed a positive growth response to high nutrient conditions.

This study provides clear evidence that the success of exotic invasive species in this low fertility vegetation community is facilitated by the addition of nutrients. It would appear that on relatively infertile (particularly phosphorus‐limited) sites, invasive species cannot take advantage of additional resources provided by physical disturbance or water addition due to overwhelming nutrient‐limitation. We suggest that a combination of the environmental conditions (nutrient‐enrichment) and invading species having traits that allow high survival and faster growth in response to nutrients, may allow successful invasion in Hawkesbury Sandstone communities.
Linking physiological traits to impacts on community structure and function: the role of root hemiparasitic Orobanchaceae (ex‐Scrophulariaceae)
Authors: PHOENIX G. K. , PRESS M. C.
Published: January 2005

The hemiparasitic Orobanchaceae (ex‐Scrophulariaceae) are characterized by a distinctive suite of ecophysiological traits. These traits have important impacts on host plants and non‐host plants, and influence interactions with other trophic levels. Ultimately, they can affect community structure and functioning. Here, we review these physiological traits and discuss their ecological consequences.

The root hemiparasitic Orobanchaceae form a convenient subset of the parasitic angiosperms for study because: they are the most numerous and most widely distributed group of parasitic angiosperms; their physiological characteristics have been well studied; they are important in both agricultural and (semi)natural communities; and they are tractable as experimental organisms.

Key traits include: high transpiration rates; competition with the host for nutrients and haustorial metabolism of host‐derived solutes; uptake of host‐derived secondary metabolites; dual autotrophic and heterotrophic carbon nutrition; distinct carbohydrate biochemistry; high nutrient concentrations in green leaf tissue and leaf litter; and small (often hairless and non‐mycorrhizal) roots.

Impacts on the host are detrimental, which can alter competitive balances between hosts and non‐hosts and thus result in community change. Further impacts may result from effects on the abiotic environment, including soil water status, nutrient cycling and leaf/canopy temperatures.

However, for non‐host species and for organisms that interact with these (e.g. herbivores and pollinators) or for those that benefit from changes in the abiotic environment, the parasites may have an overall positive effect, suggesting that at the community level, hemiparasites may also be considered as mutualists.

It is clear that through their distinctive suite of physiological traits hemiparasitic Orobanchaceae, have considerable impacts on community structure and function, can have both competitive and positive interactions with other plants, and can impact on other trophic levels. Many community level effects of parasitic plants can be considered analogous to those of other parasites, predators or herbivores.
Abiotic constraints at the upper boundaries of two Rumex species on a freshwater flooding gradient
Authors: LENSSEN J. P. M. , DE KROON H.
Published: January 2005

Competition is widely thought to be responsible for constraining species limits at the favourable ends of freshwater flooding gradients. However, field studies testing this idea rarely consider the role of competition beyond a species’ field distribution limits.

To test whether species distributions are, instead, constrained by physiological limits, and only narrowed by biotic interactions, we measured the effect of competition on survival and fecundity of Rumex crispus and Rumex palustris within and above their distribution range along an elevation gradient in a river floodplain.

Flooding reduced the fitness of both species at the lowest elevations. A decline in fitness was also noticed at the two highest elevations in control as well as in removal plots, although standing crop measurements indicated that conditions here were the most favourable.

Both leaf herbivore damage and likeliness of drought increased with elevation. Because herbivore damage only reinforced prevailing abiotic influences, drought appeared to be the strongest constraint at higher positions.

Competition merely narrowed both species’ physiological ranges by displacing them downwards from their optimum and maximum elevation. The displacement was strongest for the weak competitor Rumex palustris.

Our study provides experimental field evidence for earlier suggestions that both ends of a species niche can be defined in hydrological terms. It thus indicates that spatial variability in water availability may segregate species niches and thereby promote species richness in plant communities.
Plant zonation in low‐latitude salt marshes: disentangling the roles of flooding, salinity and competition
Authors: PENNINGS STEVEN C. , GRANT MARY‐BESTOR , BERTNESS MARK D.
Published: January 2005

We investigated the factors producing zonation patterns of the dominant plants in south‐eastern USA salt marshes where Juncus roemerianus dominates the high marsh, and Spartina alterniflora the middle and low marsh.

Juncus did not occur naturally in the Spartina zone and performed poorly when transplanted there, irrespective of whether neighbours were present or removed, indicating that its lower limit was set by physical stress.

In contrast, although Spartina occurred naturally at low densities in the Juncus zone, it performed well if transplanted there only if neighbours were removed, indicating that its upper limit was set by competition.

Parallel laboratory and field manipulations of flooding, salinity and competition indicated that the lower limit of Juncus was mediated by both flooding and salinity, but not by competition.

The general mechanisms producing zonation patterns of vegetation in coastal salt marshes may be universal, as suggested by previous studies, but the importance of particular factors is likely to vary geographically. In particular, salinity stress probably plays a much more important role in mediating plant zonation patterns at lower latitudes.

Our results suggest that the nature of ecological interactions is likely to vary geographically because of variation in the physical environment, and this variation must be taken into account in order to successfully generalize the results of field studies across geographical scales.
Why the need to reduce medical errors is not obvious
Authors: Buetow Stephen
Published: January 2005

According to Leape & Berwick (2000) the need to reduce medical errors is ‘obvious and the mandate is clear’. My article questions this assertion. I go beyond the unknown incidence of medical errors in a general medical population to suggest that the meaning of medical errors is itself equivocal. I contest the assumption that the ‘wrongness’ of medical errors is always problematic, arguing instead for a distinction between desirable errors and undesirable errors. This distinction takes into account the consequences of errors, and why they may occur. Reasons include the inappropriateness of two cultural contexts – evidence‐based medicine and continuous quality improvement – within which patient safety standards can be constructed and hence, medical errors can be defined.
Hand‐held miniaturized cardiac ultrasound instruments for rapid and effective bedside diagnosis and patient screening
Authors: Scholten Christine , Rosenhek Raphael , Binder Thomas , Zehetgruber Manfred , Maurer Gerald , Baumgartner Helmut
Published: January 2005

Rationale, aims and objectives  Technological progress in recent years has made it possible that ultrasound industry can now offer affordable, portable and battery‐operated ultrasound systems the size of a laptop computer. The purpose of this study was to compare these hand‐carried ultrasound instruments with standard echocardiography in order to investigate the facility of a rapid bedside diagnosis in patients with suspected or known cardiovascular disease.

Methods  Fifty consecutive patients were studied with miniaturized ultrasound equipment (SonoHeart TM®) and a conventional scanner (Acuson Sequoia®) in a blinded manner. All studies were performed by three board‐certified cardiologists skilled and experienced in echocardiographic practice. Investigators were not aware of any previous medical reports.

Results  With the new system, adequate images could be obtained in all patients. Left ventricular and left atrial diameters measured with the hand‐held system correlated well with those obtained with conventional scanning: r = 0.87, mean difference 3.12 ± 2.7 mm and r = 0.84, mean difference 2.8 + 2.4 mm, respectively. The presence of left ventricular dysfunction, regional wall motion abnormalities, relevant valvular regurgitation (moderate or more) or valve stenosis was correctly diagnosed in all patients. However, there was a tendency towards underestimating the extent of wall motion abnormalities particularly in patients difficult to image. Discrepancies also frequently occurred in patients with trivial or mild regurgitation, where false‐positive and false‐negative findings were described.

Conclusion  Currently available hand‐held echocardiography systems can facilitate rapid bedside diagnosis and patient screening. However, this recent development in echocardiography also raises a number of questions and its actual impact on general clinical practice still remains to be evaluated.
Patient expectations in placebo‐controlled randomized clinical trials
Authors: Stone David A. , Kerr Catherine E. , Jacobson Eric , Conboy ScD Lisa A. , Kaptchuk Ted J.
Published: January 2005

Objective  To explore participants’ experience in placebo‐controlled randomized clinical trials (RCTs) specifically in relationship to their expectations.

Background  Aspects of being in RCTs, such as informed consent, perception of benefit and understanding of randomization, have been examined. In contrast, little is known concerning the formation of patient expectations before and during trials.

Methods  Qualitative methods using in‐depth interviews with a semi‐structured interview guide of nine patients from four different RCTs. Data analysis was conducted using a codebook format arranging participant responses under broad analytical headings. The interviewer used a semi‐structured interview guide to direct the conversation from one broad topic to the next within the context of the ongoing conversation. A checklist of topics encouraged participants to describe their experiences in RCTs. Narratives concerning expectation, blinding and placebo  were compared  to  identify  common  themes.

Results  Patient anticipatory processes were influenced and modified both before and during the trial from multiple inputs. Such factors as past experiences in RCTs, past experiences of ineffective treatment, stress of being off regular medications, fear of being a ‘placebo responder’, input of non‐study doctors or other health professionals, the experience of other participants, measurements of health parameters made during the trial and the presence or absence of side‐effects all   affected   patient   expectation.

Conclusion  Expectations in RCTs are not fixed and instead may be viewed as continuously shaped by multiple inputs that include experience and information received both before and during the trial. Variability in placebo response observed in previous studies may be related to the fluid nature of expectations. Trying to control and equalize expectations in RCTs may be more difficult than previously assumed.
Keeping Capital Flowing: The Role of the IMF*
Authors: Bordo Michael D. , Mody Ashoka , Oomes Nienke
Published: January 2005

In this paper, we examine the role of the International Monetary Fund (IMF) in maintaining the access of emerging market economies to international capital markets. We find evidence that both macroeconomic aggregates and capital flows improve following the adoption of an IMF programme, although they may initially deteriorate somewhat. Consistent with theoretical predictions and earlier empirical findings, we find that IMF programmes are most successful in improving capital flows to countries with bad, but not very bad, fundamentals. In such countries, IMF programmes are also associated with improvements in the fundamentals themselves.
The need of mycophenolic acid monitoring in long‐term renal transplants
Authors: David‐Neto Elias , Pereira Lilian M , Kakehashi Erica , Sumita Nairo M , Mendes Maria E , Castro Maria CR , Romano Paschoalina , Mattos Renata M , Batista Vania RM , Nahas William C , Ianhez Luiz E
Published: January 2005

Abstract:  Background:  There is little information regarding the 12‐h mycophenolic acid (MPA) pharmacokinetics (PK), a way to monitor the drug and the need of frequent monitoring, in stable patients.

Methods:  A cohort of 35 adults, under long‐term mycophenolate mofetil (MMF) therapy plus cyclosporin A (n = 12), TACimus (n = 12) or MMF only (n = 11); all with prednisone had a 12‐h MPA‐PK performed to ascertain the percentage of them within a defined therapeutic window. In 13 other patients, two PK studies undergone 1 wk apart were performed to evaluate the need for frequent measurements.

Results:  Fourteen (40%) patients were within the defined therapeutic window (36–60 μg h/mL). Nine patients (26%) were overexposed while 12 (34%) were underexposed. A Cmax≥10 μg/mL was seen in 20 (57%) of the patients. These percentages were equally distributed between the treatment groups both for AUC0−12 and Cmax. The equations using C0, C2 or both predict exposure, although the use of C2 seems to be more adequate in clinical practice. There were no differences in MPA exposure in patients with a repeated PK evaluated 1 wk later.

Conclusion:  The use of MMF without monitoring MPA blood levels may cause over‐/underexposure to the drug in stable recipients. However, in patients under MMF for more than 1 yr, MPA levels are stable and there is no need for frequent measurements.
Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab
Authors: Alausa Morufu , Almagro Urias , Siddiqi Nauman , Zuiderweg Ron , Medipalli Radhika , Hariharan Sundaram
Published: January 2005

Abstract:  Acute rejection is an expected event after transplantation and has been associated with poor long‐term kidney transplant outcome. The presence of B cells in the kidney graft with acute rejection is thought to be an omnious sign, as it has been associated with poor graft outcome. There is no definitive treatment for acute rejection with B cells in the graft. Rituximab, a humanized monoclonal antibody against CD20, has been used in the treatment of B cell lymphoma. We present the case of a 49‐yr‐old Caucasian male with early acute kidney allograft rejection that was refractory to high doses of steroids and rabbit anti‐thymocyte globulin (thymoglobulin). Repeat renal biopsy revealed T cell and B cells in the kidney graft and responded to the combination of rituximab and muromonab (a mouse monoclonal antibody to CD3 receptor). Over 9 months post‐transplant, the patient remains rejection free with a serum creatinine of 1.7 mg/dL.
Incidence of serum creatine kinase elevation and its relation to medications used after heart transplantation
Authors: Hsu Ron‐Bin , Chen Robert J , Wang Shoei‐Shen , Chu Shu‐Hsun
Published: January 2005

Abstract:  Background:  Rhabdomyolysis after heart transplantation is well described as a drug‐related phenomenon. The incidence of serum creatine kinase (CK) elevation after heart transplantation is not formally reported in previous clinical studies. This study sought to find the incidence of asymptomatic serum CK elevation after heart transplantation and assess its relation to medications that are commonly used after transplantation.

Methods:  Data were collected in outpatient basis between August 2002 and August 2003. Patients with acute rejection, infection or muscle pain were excluded. All patients were followed monthly at a special clinic. Physical examinations and routine blood tests including serum CK were performed monthly. We evaluated the results of 106 asymptomatic patients and 765 serial data to determine the incidence of serum CK elevation after transplantation. Logistic regression was used to identify its risk factors.

Results:  The incidence of serum CK elevation in asymptomatic heart transplant recipients was 16.2%. Risk factors of its elevation were diabetes mellitus and use of medications including cyclosporine, drugs for hypertriglyceridemia, antihypertensives, and prednisolone. Among the antihypertensives commonly used, angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium antagonists were associated with a higher incidence of serum CK elevation, but beta‐blockers protected patients from serum CK elevation.

Conclusion:  The incidence of serum CK elevation in asymptomatic heart transplant recipients was not low. Serum CK measurements should be part of the routine follow‐up in transplant recipients, especially when patients had diabetes mellitus. Medications commonly used after heart transplantation significantly affected the incidence of serum CK elevation.
Induction therapy with either anti‐CD25 monoclonal antibodies or rabbit antithymocyte globulins in liver transplantation for hepatitis C
Authors: Kamar Nassim , Borde Jean‐Sébastien , Sandres‐Saune Karine , Suc Bertrand , Barange Karl , Cointault Olivier , Lavayssière Laurence , Durand Dominique , Izopet Jacques , Rostaing Lionel
Published: January 2005

Abstract:  Background:  Hepatitis C virus (HCV)‐related end‐stage liver disease (ESLD) is the leading cause for orthotopic liver transplantation (OLT). The aim of our sequential study was to assess the safety and efficacy of induction therapy using either rabbit antithymocyte globulins (RATG) or anti‐CD25 monoclonal antibodies.

Methods:  From January 2000 to January 2003, 31 patients underwent OLT for HCV‐related ESLD, and survived more than 1 month post‐transplantation. Up to July 2001, induction relied on RATG (Thymoglobulins®; Sangstat, Lyon, France) which was given for a median of 5 d, i.e. a total dose of 406 ± 45 mg (n = 16; group I). Thereafter, induction was based on either basiliximab or dacluzimab (n = 15; group II). Steroids and tacrolimus (from day 1 onwards) were given as maintenance therapy. The primary end‐points were at 6 months post‐transplantation.

Results:  Patient and graft survivals were excellent and similar in both groups. The acute rejection rate was 37.5% in group I and 20% in group II (p = ns). The rates of serious bacterial and fungal infections as well as cytomegalovirus infections were similar in both groups. Even if the overall pattern of post‐transplant liver enzymes did not differ between the two groups, the rate of HCV recurrence tended to be higher in group II (80%) compared with group I (56.25%; p = ns) patients. Both induction therapies were clinically and biologically well tolerated.

Conclusion:  RATG induction therapy is as efficient and as safe as induction with anti‐CD25 monoclonal antibodies.
Living donors’ experiences 1 wk after donating a kidney
Authors: Andersen Marit Helen , Mathisen Lars , Øyen Ole , Wahl Astrid Klopstad , Hanestad Berit Rokne , Fosse Erik
Published: January 2005

Abstract:  In Norway living kidney donors account for approximately 40% of all renal transplants. There is a shortage of information about how living kidney donors experience the donation process during the initial recovery from surgery. The aim of this study was to explore physical and psychosocial issues related to the experiences of living kidney donors 1 wk after open donor nephrectomy. A total of 12 living kidney donors participated in the study. Data were collected by individual in‐depth interviews and analysed using empirical phenomenological method. Being a living kidney donor is a complex experience. The informants expressed strong feelings of responsibility and obligation concerning the recipients and had a positive attitude towards the donation. On the other hand, the donors experienced it strange to be a fit individual and go through a major operation. Several of the donors reported that it was painful to go through donor surgery and regarded the recovery period as troublesome. Some donors also reported the double role of being both a patient and a relative to be a stressful experience. This study reveals the importance of being aware of the complex situation of living kidney donors. Health professionals need to understand the nature of the donation process and the donors’ needs. It is essential to focus on physical, mental and interpersonal factors when counselling potential living kidney donors.
Objective measures of health‐related quality of life over 24 months post‐liver transplantation
Authors: Krasnoff Joanne B. , Vintro Andrea Q. , Ascher Nancy L. , Bass Nathan M. , Dodd Marylin J. , Painter Patricia L.
Published: January 2005

Abstract: Many studies have reported improved health‐related quality of life (HRQoL) from pre‐ to immediate post‐orthotopic liver transplantation (OLT). However, few studies have evaluated longitudinal changes over the first 2 yr post‐OLT and none have simultaneously examined objective measures of health‐related fitness. A total of 50 OLT recipients (32 males,18 females; 51.4 ± 11.8 yr) completed testing at 2, 6, 12, and 24 months post‐OLT. Testing included assessment of exercise capacity (peakVO2), quadriceps muscle strength, body composition, physical activity participation, and self‐reported functioning (SF‐36). Repeated measures of analysis of variance (ANOVA) withpost hoccontrasts was performed to determine differences over time and a second ANOVA assessed differences over time between genders. All patients increased peakVO2, quadriceps muscle strength, and percent body fat (p < 0.0001) from 2 to 24 months. Men and women differed in their changes of peakVO2and percent body fat (p < 0.05). At 24 months, only 50% of the patients reported participating in regular physical activity. All SF‐36 physical measures except general health, improved from 2 to 24 months (p < 0.0001). Measures of health‐related fitness and QoL improve over the first 2 yr post‐OLT with the greatest gains occurring in the first 6 months and all measures remain lower than recommended for cardiovascular and overall health. A randomized clinical trial of lifestyle modifications such as diet and exercise intervention is warranted to determine the impact of such modifications on HRQoL and fitness post‐OLT.
Lobular damage caused by cellular and humoral immunity in liver allograft rejection
Authors: Sawada Tokihiko , Shimizu Akira , Kubota Keiichi , Fuchinoue Shohei , Teraoka Satoshi
Published: January 2005

Abstract:  Backgrounds:  Diagnosis of acute liver allograft rejection (ALAR) is usually performed by the estimation of changes in portal areas. In this study, changes in the hepatic lobules were investigated retrospectively by immunohistochemistry, and compared with changes in the portal areas. Humoral immunity in ALAR was also studied by C4d‐staining.

Materials and methods:  In total, 35 biopsy specimens from 20 patients who had undergone living‐related liver transplantation were included. Specimens had been graded as mild, moderate‐to‐severe acute rejection based on the Banff Schema. Changes in hepatic lobules were investigated by hematoxylin‐eosin (H & E) staining, an immunohistochemical study using anti‐CD3 (T cells), anti‐GMP‐17 (cytotoxic cells), anti‐CD68 (macrophages) and C4d, and the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP‐biotin nick end‐labeling (TUNEL) method.

Results:  Changes in hepatic lobules consisted of the infiltration of mononuclear cells, swelling and necrosis of hepatocytes, and hemorrhages. The degree of these changes increased with the severity of ALAR. Immunohistochemical analysis revealed that infiltrating cells included CD3+ T cells, GMP‐17+ cytotoxic cells and CD68+ macrophages. The number of infiltrating cells increased with the severity of the ALAR. The TUNEL assay demonstrated apoptotic cells in ALAR and the number of apoptotic cells increased with the severity of the ALAR. In moderate‐to‐severe rejection, C4d depositions were observed in the hepatic sinusoids as well as the portal veins and hepatic arteries.

Conclusions:  Changes in the hepatic lobules were observed in ALAR and the severity increased with the severity of ALAR. Apoptosis was involved in the mechanism of cell death and humoral immunity plays a role in the mechanism of ALAR.
Acitretin and skin cancer in kidney transplanted patients. Clinical and histological evaluation and immunohistochemical analysis of lymphocytes, natural killer cells and Langerhans’ cells in sun exposed and sun protected skin
Authors: Carneiro Renata V , Sotto Mírian N , Azevedo Luiz S , Ianhez Luiz E. , Rivitti Evandro A
Published: January 2005

Abstract:  Background:  Renal transplanted recipients have an increased incidence of actinic keratosis and skin cancer.

Methods:  In order to examine the chemoprophylatic effects of low‐dose acitretin on keratosis and skin cancer development we submitted 13 renal transplanted patients who presented actinic keratosis to acitretin therapy (20 mg/d) for 12 months. The patients were assessed at monthly intervals during the first 6 months and every 2 months until the 12th month for new skin lesions and for acitretin toxicity. Normal skin biopsies of sun exposed and sun protected areas were taken for histopathological examination and submitted to immunohistochemistry technique to demonstrate CD4+ and CD8+ T lymphocytes, natural killer (NK) cells and Langerhans’ cells which were counted and compared before, after 6 and 12 months of the treatment.

Results:  There was an improvement of actinic keratosis in all patients. Only one patient developed new skin cancer. Side‐effects were well tolerated and no significant biochemical effects were observed. There were no differences in the microscopic aspects of the skin and in the number of CD4+ and CD8+ T lymphocytes and NK cells. There was a significant increase in the number of epidermal Langerhans’ cells after 12 months of acitretin therapy.

Conclusions:  The data obtained permit us to conclude that low dose acitretin therapy is safe, well tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients. The increase in epidermal Langerhans’ cells observed may be an expression of the immunomodulatory effect of acitretin.
Economic evaluation of everolimus vs. azathioprine at one year after de novo heart transplantation
Authors: Radeva Jasmina I. , Reed Shelby D. , Kaló Zoltán , Kauf Teresa L. , Cantu Edward , Cretin Nathalie , Schulman Kevin A.
Published: January 2005

Abstract:  Background:  Everolimus decreases acute rejection and cardiac allograft vasculopathy after heart transplantation. We compared within‐trial costs and resource use over 1 yr of follow‐up in de novo heart transplant patients randomized to everolimus 1.5 mg/d (n = 209), everolimus 3.0 mg/d (n = 211), or azathioprine (n = 214).

Patients and methods:  Resource use data were collected prospectively for 634 patients from 14 countries. We used the nonparametric bootstrap method to test for differences in mean costs and to estimate confidence intervals for cost‐effectiveness ratios.

Results:  Everolimus patients had lower incidence of efficacy failure compared with azathioprine patients (41.6%, everolimus 1.5 mg; 32.2%, everolimus 3.0 mg; 52.8%, azathioprine). Compared with patients receiving azathioprine, everolimus patients spent more days in the hospital [36.3 d for everolimus 1.5 mg/d (p = 0.21); 38.4 d for everolimus 3.0 mg/d (p = 0.01); 32.2 d for azathioprine]. Mean total costs, excluding the study medications, were not significantly different among treatment groups ($72 065 for everolimus 1.5 mg; $72 631 for everolimus 3.0 mg; $70 815 for azathioprine).

Conclusions:  Over 1 yr of follow‐up after heart transplantation, everolimus did not significantly increase treatment costs, excluding the costs of the study medications, while reducing efficacy failure. Longer follow‐up and the cost of everolimus are required to fully evaluate the cost‐effectiveness of everolimus vs. azathioprine in post‐transplant maintenance.
An open‐label, pilot study evaluating the safety and efficacy of converting from calcineurin inhibitors to sirolimus in established renal allograft recipients with moderate renal insufficiency
Authors: Ram Peddi V , Jensik Stephen , Pescovitz Mark , Pirsch John , Adler Scott H , Richard Thistlethwaite J , Vincenti Flavio , Cohen David J
Published: January 2005

Abstract:  This pilot study was designed to evaluate the safety and efficacy of converting from a calcineurin inhibitor (CI) to a sirolimus (SRL)‐based regimen in established renal transplant recipients with moderate renal insufficiency. Sixty renal transplant recipients on CI‐based immuno‐suppression with a serum creatinine (SCr) between 159 and 265 μM (1.8 and 3.0 mg/dL) and a glomerular filtration rate (GFR) between 30 and 70 mL/min were enrolled. SRL dosing was dependent upon concomitant immunosuppressive therapy. The mean patient age was 45 yr and the mean time from transplant to study enrollment was 60.8 months (range: 7–198). The median SCr was 168 μM (1.9 mg/dL) and the median GFR was 51 mL/min. Twelve months after conversion the patient and graft survival rates were 96.7% and 95%, respectively. The incidence of biopsy‐proven acute rejection was 3.3% (two cases reported, Banff grades IA and IB). The median SCr and median creatinine clearance were 168 μM (1.9 mg/dL) and 53 mL/min, respectively. Hyperlipidemia, diarrhea, peripheral edema, rash, and anemia were the most commonly reported adverse events. Patients with moderate renal insufficiency can be converted from CI to SRL‐based therapy and maintain renal function over a 1‐yr period.
Price Equilibria in Pure Strategies for Homogeneous Oligopoly
Authors: Allen Beth , Thisse Jacques‐François
Published: January 2005

For a homogeneous product oligopoly market, possibilities for pure strategy Nash equilibria in prices are studied. Consumers, who each nonstrategically purchase one unit up to a common reservation price, are hypothesized to be more concerned with large price differences (and therefore buy from the cheapest firm) than slightly different prices. For the duopoly case, existence, uniqueness, and characterization results are provided. Linear examples are given with 2 and n firms.
EconometricAnalysisofCollusiveBehaviorin aSoft‐DrinkMarket
Authors: Gasmi F. , Laffont J.J. , Vuong Q.
Published: January 2005

This paper proposes an empirical methodology for studying various (implicit or explicit) collusive behaviors on two strategic variables, which are price and advertising, in a differentiated market dominated by a duopoly. In addition to Nash or Stackelberg behaviors, we consider collusion on both variables, collusion on one variable and competition on the other, etc. Using data on the Coca‐Cola and Pepsi‐Cola markets from 1968 to 1986, full information maximum likelihood estimation of cost and demand functions are obtained allowing for various collusive behaviors. The collusive hypothesis is not rejected, and the best form of collusive behavior is selected via nonnested testing procedures. Using the best model, Lerner indices are computed for both duopolists to provide summary measures of market power. Finally, our approach is contrasted with the conjectural variation approach and is shown to give superior results.
Collusionby Asymmetrically Informed Firms
Authors: Kihlstrom Richard , Vives Xavier
Published: January 2005

We analyze the implementation problem faced by firms when trying to collude in the face of asymmetric information about costs. Assuming that transfer payments are possible, we examine the incentive compatibility and individual rationality constraints that must be satisfied by any cartel agreement. Two scenarios are considered. Firms may or may not withdraw from the agreement after each firm's costs become known. If no withdrawal is possible, we find that the monopoly rule is implementable when weak types of individual rationality constraints are required. This contrasts with some results in the literature. If withdrawal is possible, we find a potential conflict between different forms of individual rationality constraints, in particular, between interim and ex post constraints. This conflict disappears in industries with a large number of firms.
REGULATION BY DUOPOLY
Authors: Auriol Emmanuelle , Laffont Jean‐Jacques
Published: January 2005

This paper analyzes, within the framework of the new regulatory economics that emphasizes asymmetries of information, the optimal structure of an industry. The duplication of fixed costs incurred in a duopoly structure may be socially justified in a static model by three effects: the sampling effect, the yardstick competition effect, and the increasing marginal cost effect.

We show that in general, asymmetric information favors duopoly when the market structure is decided before firms discovers their cost characteristics (a common situation in dual sourcing for procurement), and favors monopoly when the market structure is decided after firms discover their cost characteristics (the case of split‐award auctions).