bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional signatures of protective antiviral T‐cell immunity in human virus infections
Authors: Harari Alexandre , Dutoit Valérie , Cellerai Cristina , Bart Pierre‐Alexandre , Du Pasquier Renaud A. , Pantaleo Giuseppe
Published: June 2006

Summary:  The most common human viruses have different abilities to establish persistent chronic infection. Virus‐specific T‐cell responses are critical in the control of virus replication and in the prevention of disease in chronic infection. A large number of phenotypic markers and a series of functions have been used to characterize virus‐specific CD4+ and CD8+ T‐cell responses, and these studies have shown great phenotypic and functional heterogeneity of the T‐cell responses against different viruses. The heterogeneity of the T‐cell response has been proposed to be specific to each virus. However, over the past 2 years, several studies have provided evidence that the phenotypic and functional heterogeneity of CD4+ and CD8+ T‐cell responses is predominantly regulated by the levels of antigen load. The levels of antigen load modulate the phenotypic and functional patterns of the T‐cell response within the same virus infection. Furthermore, the functional characterization of virus‐specific CD4+ and CD8+ T‐cell responses has identified signatures of protective antiviral immunity. Polyfunctional, i.e. interleukin‐2 and interferon‐γ (IFN‐γ) secretion and proliferation, and not monofunctional, i.e. IFN‐γ secretion, CD4+ and CD8+ T‐cell responses represent correlates of protective antiviral immunity in chronic virus infections.
Making sense of inflammation, epigenetics, and memory CD8+ T‐cell differentiation in the context of infection
Authors: Pearce Erika L. , Shen Hao
Published: June 2006

Summary:  Recent findings suggest a new paradigm that early inflammatory cytokines promote the effector T‐cell response while inhibiting the development of CD8+ T‐cell memory. Although this opposing effect may appear paradoxical at first, it makes biological sense in the context of an infection, by ensuring a maximal effector response that will clear the pathogen. Once infection is controlled, the withdrawal of inflammatory cytokines allows the differentiation of effectors into long‐lived memory cells that provide protective immunity against re‐infection. Memory T cells differ from naïve T cells in their responsiveness to stimulation, which leads to the rapid expression of effector functions. The molecular basis for enhanced functionality of memory T cells remains largely unknown. Recent results indicate that certain epigenetic changes are imprinted in memory T cells that play an important role in keeping them poised to respond immediately upon antigen re‐encounter. These epigenetic modifications occur as naïve T cells become activated and are influenced by factors that regulate memory formation. Thus, epigenetic changes are an integral component of memory T‐cell differentiation, while inflammation plays an unexpected regulatory role in the process. These advances in our understanding of T‐cell memory will undoubtedly help design unconventional vaccine strategies for inducing large populations of long‐lived and functional memory CD8+ T cells.
The role of alcohol and drugs in homicides in England and Wales
Authors: Shaw Jenny , Hunt Isabelle M. , Flynn Sandra , Amos Tim , Meehan Janet , Robinson Jo , Bickley Harriet , Parsons Rebecca , McCann Kerry , Burns James , Kapur Nav , Appleby Louis
Published: June 2006

Background  The annual number of homicide convictions in England and Wales is increasing. Previous studies have highlighted the aetiological role of alcohol and drugs in homicide.

Aims  To examine rates of alcohol and drug misuse and dependence in people convicted of homicide; the role of alcohol and drugs in the offence; the social and clinical characteristics of alcohol‐ and drug‐related homicides; and the social and clinical characteristics of patients with dual diagnosis who commit homicide.

Methods  A national clinical survey based on a 3‐year (1996–9) consecutive sample of people convicted of homicide in England and Wales. Information on rates of alcohol and drug misuse/dependence, the role of alcohol and drugs in the offence and social and clinical characteristics of perpetrators were collected from psychiatric reports prepared for the court in homicide convictions. Detailed clinical information was gathered from questionnaires completed by mental health teams for those in contact with mental health services.

Results  Of the 1594 homicide perpetrators, more than one‐third (42%) occurred in people with a history of alcohol misuse or dependence and 40% in people with a history of drug misuse or dependence. Alcohol or drug misuse played a contributory role in two‐fifths of homicides. Alcohol played a major role in 52 (6%) and a minor role in 364 (39%) homicides. Drugs played a major role in six (1%) and a minor role in 138 (14%) homicides. Forty‐two homicides (17%) were committed by patients with severe mental illness and substance misuse. Alcohol‐ and drug‐related homicides were generally associated with male perpetrators who had a history of violence, personality disorders, mental health service contact and with stranger victims.

Conclusions  Substance misuse contributes to the majority of homicides in England and Wales. A public health approach to homicide would highlight alcohol and drugs before severe mental illness.
Review article: intestinal failure
Authors: LAL S. , TEUBNER A. , SHAFFER J. L.
Published: June 2006

Intestinal failure is a specific disease entity resulting from intestinal resection or disease‐associated malabsorption and characterized by the inability to maintain protein‐energy, fluid, electrolyte or micronutrient balance. We performed a MEDLINE search (1966–2006) to identify relevant articles, using keywords intestinal failure, parenteral or enteral nutrition, intestinal fistula and short bowel syndrome.

Causes of intestinal failure are varied, with self‐limiting or ‘Type 1’ intestinal failure occurring relatively commonly following abdominal surgery, necessitating short‐term fluid or nutritional support. The rarer, ‘Type 2’ intestinal failure, is associated with septic, metabolic and complex nutritional complications, usually following surgical resection in patients with Crohn's or mesenteric vascular disease. A multidisciplinary approach to the management of patients with Type 2 intestinal failure is crucial: resolution of sepsis is required before adequate nutritional repletion can be achieved, and it is important to optimize nutritional status, not only through enteral or parenteral supplementation, but also by addressing complications of short bowel syndrome, before considering definitive surgical reconstruction.

A structured approach to the management of Type 2 intestinal failure should reduce the likelihood of these complex patients developing ‘Type 3’ intestinal failure, which is characterized by the need for long‐term parenteral nutrition.
Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response
Authors: TRAPERO‐MARUGÁN M. , GARCÍA‐BUEY L. , MUÑOZ C. , QUINTANA N. E. , MORENO‐MONTEAGUDO J. A. , BORQUE M. J. , FERNÁNDEZ M. J. , SALVANÉS F. R. , MEDINA J. , MORENO‐OTERO R.
Published: June 2006

Background

An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection.

Aim

To analyse the Th1/Th2 cytokine profile in peripheral blood CD4+ and CD8+ T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon‐α2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR).

Methods

Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG‐IFNα2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non‐responders. Sixteen healthy controls were analysed. The production of IL‐4, IFNγ and TNFα by CD4+ and CD8+ T cells was measured using flow cytometry, both in resting and phorbol‐ester‐stimulated cells.

Results

First three months of treatment: the synthesis of TNFα by phorbol‐ester‐stimulated‐CD4+ T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNγ by stimulated‐CD4+ and CD8+ T cells (P < 0.05). At the end of follow‐up, a higher intracellular expression of IFNγ by CD4+ T cells was associated with a SVR.

Conclusions

A Th1‐type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNγ and TNFα.
Review article: recent advances in the management of bleeding gastric varices
Authors: TRIPATHI D. , FERGUSON J. W. , THERAPONDOS G. , PLEVRIS J. N. , HAYES P. C.
Published: June 2006

Gastric variceal bleeding can be challenging to the clinician. Tissue adhesives can control acute bleeding in over 80%, with rebleeding rates of 20–30%, and should be first‐line therapy where available. Endoscopic ultrasound can assist in better eradication of varices. The potential risks of damage to equipment and embolic phenomena can be minimized with careful attention to technique.

Variceal band ligation is an alternative to tissue adhesives for the management of acute bleeding, but not for secondary prevention due to a higher rate of rebleeding. Endoscopic therapy with human thrombin appears promising, with initial haemostasis rates typically over 90%. The lack of controlled studies for thrombin prevents universal recommendation outside of clinical trials.

Balloon occluded retrograde transvenous obliteration is a recent technique for patients with gastrorenal shunts, although its use is limited to clinical trials. Transjugular intrahepatic portosystemic stent shunt is an option for refractory bleeding and secondary prophylaxis, with uncontrolled studies demonstrating initial haemostasis obtained in over 90%, and rebleeding rates of 15–30%.

Non‐cardioselective β‐blockers are an alternative to transjugular intrahepatic portosystemic stent shunt for secondary prophylaxis, although the evidence is limited.

Shunt surgery should be considered in well‐compensated patients. Splenectomy or embolization is an option in patients with segmental portal hypertension.
Clay‐sized organo‐mineral complexes in a cultivation chronosequence: revisiting the concept of the ‘primary organo‐mineral complex’
Authors: Chenu C. , Plante A. F.
Published: June 2006

Primary organo‐mineral complexes are defined as organic matter (OM) bound to primary mineral particles, isolated after complete dispersion of soil. Organic matter present in < 2 μm particle‐size fractions of soils has slow turnover times and it is assumed to be stabilized mainly by interaction with minerals. We aimed to quantify how much of the organic matter in < 2 μm particle‐size fractions was free versus bound to minerals and to describe the nature of the association. Furthermore, we hypothesized that this bound organic matter was more resistant to biodegradation than free organic particles. We tested this by using a cultivation chronosequence on temperate silty soils and quantified free and clay‐bound organic matter using density fractionation coupled with elemental analyses, as well as transmission electron microscopy (TEM) coupled with image analyses. Both methods showed that free organic matter was a minor fraction and that it was more depleted by cultivation than clay‐bound organic matter. We deduced that clay‐bound organic matter was more resistant to biodegradation. TEM showed that the distribution of organic matter in clay‐sized fractions was patchy and that many of the so‐called < 2 μm ‘particles’ were in fact nanometre‐ to micrometre‐sized microaggregates in which OM was encrusted by minerals or coated minerals. We conclude that true primary organo‐mineral complexes do not correspond to reality and must be regarded as conceptual entities. We suggest that the very small microaggregates, which were evidenced here, are major sites of OM stabilization, both by adsorption and by entrapment of organic matter.
A distinct Toll‐like receptor repertoire in human tonsillar B cells, directly activated by Pam3CSK4, R‐837 and CpG‐2006 stimulation
Authors: Månsson Anne , Adner Mikael , Höckerfelt Ulf , Cardell Lars‐Olaf
Published: June 2006

Toll‐like receptors (TLRs) recognize specific pathogen‐associated molecular patterns (PAMPs), which subsequently trigger innate immunity. Recent data also suggest a role for TLRs in the direct activation of adaptive immune cells. In the present study, the expression and function of TLR1–TLR10 were characterized in purified human tonsillar B cells, focusing on differences among CD19+ CD38– CD27– (naïve B cells), CD19+ IgD– CD27–[germinal centre (GC) B cells] and CD19+ CD38– CD27+ (memory B cells) cells. The study was also designed to compare the TLR expression in B cells obtained from infected and hyperplastic tonsils that served as controls. The results demonstrated a distinct repertoire of TLRs, in which TLR1, TLR2, TLR7, TLR9 and TLR10 predominated. No differences were found among naïve, GC and memory B cells. Tonsillar infection did not substantially alter the TLR expression profile in ex vivo‐isolated B‐cell subsets. Purified CD19+ B cells stimulated with Pam3CSK4, R‐837 and CpG oligodeoxynucleotide (ODN) 2006, via TLR1/TLR2, TLR7 and TLR9, respectively, showed an induction of interleukin‐6 secretion and an up‐regulated expression of human leucocyte antigen (HLA)‐DR. Collectively, the present study demonstrates that B cells exhibit constitutively high levels of specific TLRs, which are not developmentally regulated during the B‐cell differentiation process. Ongoing microbial infections, such as chronic tonsillitis, do not appear to affect the TLR profile in B cells. Furthermore, the distinct expression of TLRs allows B cells to respond directly to the cognate PAMPs. This further emphasizes the role of TLRs in directly activating adaptive immune cells.
Vitamin D and fractures in people with intellectual disability
Authors: Vanlint S. , Nugent M.
Published: June 2006

Background  People with intellectual disability (ID) are thought to be at an increased risk of fractures. The extent of this increase in risk has been incompletely documented in the literature, and the underlying reasons remain to be elucidated.

Methods  The aims of our study were to document the vitamin D status and fracture incidence in an intellectually disabled population, to test for associations between vitamin D status and possible risk factors for reduced vitamin D levels, and to determine the efficacy of oral vitamin D supplementation in restoring appropriate vitamin D levels in those found to be vitamin D insufficient. A 5‐year retrospective audit of fractures in 337 individuals with ID receiving health care at a residential facility was performed. Data analysed included age, gender, mobility, dietary status, incident fractures, medications and 25‐hydroxyvitamin D levels. Vitamin D insufficient individuals received oral vitamin D supplementation, and had repeat testing to assess treatment efficacy.

Results  In total, 57% of individuals tested were found to be vitamin D insufficient. Vitamin D insufficiency was strongly correlated with reduced mobility (P < 0.001) and difficulty with consuming solids (P < 0.001). However, the correlation between vitamin D levels and fractures was not significant (P = 0.3). Oral vitamin D supplementation using cholecalciferol (vitamin D3) 100 000 IU every 4 months was effective in correcting vitamin D insufficiency. Sixty‐eight fractures occurred over the study period in 52 individuals, a rate of 1 fracture every 23.8 person years. A total of 55% of these fractures involved the extremities. Fractures were more common in men than in women. Peripheral fractures (hand, foot, wrist, ankle) accounted for 54% of all fractures, and were particularly prevalent in the most mobile individuals.

Conclusions  Fractures and vitamin D insufficiency are relatively common in people with ID. This study did not find a significant association between vitamin D insufficiency and fractures in the study population. Oral vitamin D supplementation is effective in restoring normal vitamin D levels, and should be considered routinely for those at the highest risk.
A case–control study of risk factors for hepatitis C infection in patients with unexplained routes of infection*
Authors: Karmochkine M. , Carrat F. , Dos Santos O. , Cacoub P. , Raguin G. ,   the GERMIVIC Study Group
Published: June 2006

Summary.  Twenty to 40% of hepatitis C virus (HCV)‐infected patients do not have a recognized parenteral risk factor suggesting that still‐unidentified modes of transmission exist. In order to investigate potential routes of HCV transmission for patients with no recognized parenteral risk factor, we conducted a multicentre case–control study. A total of 450 HCV‐seropositive patients with no history of transfusion or intravenous drug use and 757 controls were recruited from the general population and matched for sex, age, geographical residence and number of chronic diseases. All subjects answered an interviewer‐administered questionnaire on potential risk factors for HCV. Eighty per cent of cases had chronic hepatitis or cirrhosis. Respective percentages of genotypes 1, 2, 3, 4 and 5 were 65, 14, 11, 5 and 4. Among the 66 items considered, multivariate analysis identified 15 independent risk factors for HCV infection: nosocomial [admission to medical (odds ratio, OR = 2.1) or surgical ward (OR = 1.7), digestive endoscopy (OR = 1.9), abortion (OR = 1.7)], outpatient treatments [cutaneous ulcer and wound care (OR = 10.1), diathermy (OR = 3.0), gamma globulin (OR = 1.7), intravenous (OR = 1.7) or intramuscular (OR = 1.4) injections, varicose vein sclerotherapy (OR = 1.6), acupuncture (OR = 1.5)] and lifestyle‐associated [intranasal cocaine use (OR = 4.5), practice of contact sports (OR = 2.3), beauty treatments (OR = 2.0), professional pedicure/manicure (OR = 1.7)]. These factors could explain 73% of community‐acquired hepatitis C. In conclusion, for patients with unexplained routes of HCV infection, our data incriminate previously unidentified risk factors (abortions, some dermatological procedures, outpatient injections, contact sports, beauty treatments, professional pedicure/manicure) and confirm those already recognized (hospitalization, digestive endoscopy, acupuncture and intranasal cocaine use).
A library of Lick Observatory Image Dissector Scanner indices for binary stellar populations
Authors: Zhang Fenghui , Li Lifang
Published: June 2006

Using evolutionary population synthesis, we present 13 refined absorption-line indices defined by the Lick Observatory Image Dissector Scanner (Lick/IDS) system for an extensive set of instantaneous-burst binary stellar populations (BSPs) at high resolution (∼0.3 Å), and 38 indices at intermediate resolution (3 Å). The ages of the populations are at an interval of 1 Gyr in the range 1–15 Gyr, and the metallicities are in the range 0.004–0.03. These indices are obtained by two methods: (i) using the empirical fitting functions (FFs method); (ii) measured directly from the synthetic spectra (DC method). Together with our previous paper, a data base of Lick/IDS spectral absorption-line indices for BSPs at high and intermediate resolutions is provided. This set of indices includes 21 indices of Worthey et al., four Balmer indices defined by Worthey & Ottaviani, and 13 indices with the new passband definitions of Trager et al. The full set of synthetic indices and the integrated pseudo-continuum are listed in the Appendices, which are only available online at https://doi.org/10.1111/j.1365-2966.2006.10557.x or from our website (http://www.ast9.com/), or on request from the first author. Moreover, the full set of the integrated spectral energy distributions can be obtained from our website.

We compare the synthetic Lick/IDS indices obtained by the FFs method and those by the DC method for BSPs with various metallicities, and find that the discrepancies are significant: Ca4455 (index 6), Fe4668 (8), Mgb (13), Fe5709 (17), NaD (19), TiO1 (20) and TiO2 (21, except for Z= 0.02) in the W94 system, Ca4455T (6T), C24668T (8T), NaDT (19T), TiOT1 (20T) and TiOT2 (21T, except for Z= 0.02) in the T98 system obtained by the DC method are less (bluer) than the corresponding ones obtained by the FFs method for all metallicities. Ca4227 (index 3), Fe5782 (18), Ca4227T (3T) and Fe5782T (18T) are greater at Z= 0.03 and become bluer at Z= 0.004; the Fe5709T (17T) index is less at Z= 0.03 and becomes redder at Z= 0.004 than the corresponding ones obtained by the FFs method.
Deposition and derivation of clastic carbonates on a Mesozoic continental margin, Othris, Greece
Authors: PRICE ILFRYN
Published: June 2006

The Othris Mountains of eastern Greece contain a calcareous continental margin/ocean basin sequence exposed in a stack of Cretaceous thrust sheets. Upper Triassic to Lower Cretaceous shelf, submarine fan and basinal successions overlie shallow marine units of Lower Triassic and Permian age. In off‐shelf sequences the older sediments are separated from the younger by a horizon of alkaline ‘early‐rifting’ basalts. Ophiolites overthrust the marginal sequence. Pre‐rifting sediments are represented by a varied suite of limestones and clastics resting on metamorphic basement and include distinctive, green lithic arenites. In the thrust sheet immediately over the para‐autochthonous shelf sequence, pre‐rifting sediments are separated from the rift basalts by an intermittent horizon of calcareous sandstones and conglomerates reworked from uplifted basement and older sediments. Textural and petrographic immaturity suggests that these are probably deposits derived from fault scarps, produced in an early phase of rifting. Above the basalts in the same sheet is a suite of calciclastic sediment‐gravity‐flow deposits, apparently sedimented on a submarine fan. Progressive downslope modification of calcirudites suggests deposition from evolving, high concentration flows. Massive calcarenite facies (? grain flows) are unusually abundant; a possible reflection of a shallow palaeo‐shelf break since provenance and palaeocurrent evidence proves the clastic carbonates to have been derived from a calcareous shelf. In addition to limestone lithoclasts the calcirudites, but not the massive calcarenites, contain fragments of pre‐rifting lithologies including the distinctive arenites. Since the shelf sequence in Othris is totally nondetrital these clasts imply derivation of coarse sediment from an off‐shelf position; probably the walls of a submarine canyon. This may have occurred either by direct erosion of wall rock, or by reworking of material from an older clastic sequence. In the latter case the inferred fault‐scarp deposits are a likely source.
Evaluating reserves for species richness and representation in northern California
Authors: Dunk Jeffrey R. , Zielinski William J. , Welsh Hartwell H.
Published: June 2006

The Klamath‐Siskiyou forests of northern California and southern Oregon are recognized as an area of globally outstanding biological distinctiveness. When evaluated at a national or global level, this region is often, necessarily, considered to be uniformly diverse. Due to large variation in biotic and abiotic variables throughout this region, however, it is unlikely that biological diversity is uniformly distributed. Furthermore, land management decisions nearly always occur at spatial scales smaller than this entire region. Therefore, we used field data from a random sampling design to map the distribution of local and regional richness of terrestrial molluscs and salamanders within northern California's portion of the Klamath‐Siskiyou region. We also evaluated the protection afforded by reserves established for varying reasons (e.g. for inspiration and recreation for people vs. species conservation) to hotspots of species richness and species representation of these taxa. No existing reserves were created with these taxa in mind, yet it was assumed that reserves established largely around considerations for the northern spotted owl (Strix occidentalis caurina) would afford adequate protection for many lesser‐known species. Species of terrestrial molluscs and salamanders share two general features: (1) they have extremely low vagility, and (2) they are often associated with moist, cool microclimates. Existing reserves disproportionately included areas of hotspots of species richness for both taxa, when hotspots included the richestc. 25% of the area, whereas non‐reserved lands contained greater than expected areas with lower species richness. However, when a more strict definition of hotspot was used (i.e. the richestc.10% of areas), local hotspots for both taxa were not disproportionately found in reserves. Reserves set aside largely for human aesthetics and recreation and those set aside for biodiversity both contributed to the protection of areas with high (greatest 25%) species richness. Existing biodiversity reserves represented 68% of mollusc species and 73% of salamander species, corresponding to the 99th and 93rd percentiles, respectively, of species representation achieved by simulating a random distribution of the same total area of reservation. Cumulatively, however, reserves set aside for inspiration and biodiversity represented 83% of mollusc species and 91% of salamander species. The existing reserves provide conservation value for terrestrial molluscs and salamanders. This reserve network, however, should not be considered optimal for either taxa.
The impact of donor cocaine use on the outcome of adult liver transplantation
Authors: Komokata Teruo , Nishida Seigo , Ganz Susan , Levi David M. , Fukumori Tatuya , Tzakis Andreas G.
Published: June 2006

Abstract:  Backgrounds:  To investigate the feasibility of adult liver transplantation from donors with cocaine use.

Methods:  Of 807 adult liver transplantations performed between 1994 and 2000, 72 donors (8.9%) were current cocaine users. Donor characteristics and post‐transplantation outcomes were retrospectively compared between the 72 cocaine and 126 control group selected from the remaining 735 donors, matched for age and having no history of drug use.

Results:  Marijuana, opiates and amphetamines were drugs of abuse often present with cocaine. Except for a high incidence of acute alcohol use in the cocaine donors, donor characteristics were comparable. The cocaine group had a significantly higher graft loss within three months of transplant (18.1% vs. 7.9%, p<0.05), and had a trend toward lower graft survival (76% vs. 86% at one yr).

Conclusions:  Potential adverse effect of cocaine and substances concurrently involved on donor liver was suggested. To clarify the distinct acceptance criteria of cocaine users for liver donation, prospective study is warranted.
Renal function in renal or liver transplant recipients after conversion from a calcineurin inhibitor to sirolimus
Authors: Bäckman L. , Varberg Reisæter A. , Wramner L. , Ericzon B.‐G. , Salmela K. , Brattström C.
Published: June 2006

Abstract:  Two Six‐month pilot studies were conducted in renal (n=17) or liver (n=15) transplant recipients to evaluate renal function after conversion from calcineurin inhibitor (CI)‐ to sirolimus (SRL)‐based immunosuppression. After an SRL loading dose, doses were individualized to achieve whole blood trough levels of 10–22 ng/mL. Overall, serum creatinine did not change from baseline to six months post‐conversion but an improvement from 219.9 to 201.4 μmol/L at three months was noted in renal transplant recipients (p<0.05). Another finding was a numerical increase in the mean glomerular filtration rate (GFR) from 26.8 to 33.2 mL/min/1.73 m2 at six months among liver transplant recipients (NS). All patients survived and all grafts were functioning at the end of the study. In conclusion, renal function remained stable, with a tendency towards improvement, after abrupt conversion from CI‐ to SRL‐based therapy in renal or liver transplant recipients with moderate renal insufficiency.
Commercial cadaveric renal transplant: an ethical rather than medical issue
Authors: Sun Chiao‐Yin , Lee Chin‐Chan , Chang Chiz‐Tzung , Hung Cheng‐Chih , Wu Mai‐Szu
Published: June 2006

Abstract: Donor organ shortage is a universal problem. The organ source has been extended to controversial death‐penalty outlaws in certain countries. It was claimed that commercial transplant had a worse short‐term clinical outcome. The aim of this study is to investigate the long‐term outcome of patients receiving commercial cadaveric renal transplant. Seventy‐five renal transplant recipients receiving long‐term follow‐up were included. Thirty‐one patients received overseas commercial cadaveric transplant. Forty‐four patients had legal domestic transplant in Taiwan. The age of the patients receiving the commercial cadaveric transplant was significantly older than those with legal domestic transplant (commerical vs. legal: 46.1±11.4 vs. 35.6±9.0 yr old, p<0.001). The renal function estimated by creatinine and 1/creatinine up to eight yr showed no significant difference between the two groups. The graft survivals of the two groups were not different. The mortality rate between the two groups was comparable in 10 yr (91.1% in domestic and 88.9% in overseas). There was no significant difference inde novoviral hepatitis, cytomegalovirus infection, and acute rejection. The clinical outcome of overseas commercial cadaveric transplant was not different from the domestic legal transplant. To stop the unethical procedure, ethnicity and humanity are the major concerns.
Predictors of employment after liver transplantation
Authors: Sahota Amandeep , Zaghla Hassan , Adkins Rodney , Ramji Alnoor , Lewis Susan , Moser Jennifer , Sher Linda S. , Fong Tse‐Ling
Published: June 2006

Abstract: Employment after orthotopic liver transplantation (OLT) indicates recipients’ physical/psychosocial adjustment. Our aim was to determine clinical, socioeconomic and health‐related quality of life parameters influencing employment after OLT. Questionnaire on demographics, medical conditions, alcohol and drug use before/after OLT, and a validated 12‐Item Short Form Health Survey (SF‐12) were mailed to 126 adult OLT patients. Stepwise logistic regression was conducted to identify best predictors of post‐OLT employment. Among non‐retirees, 49% were employed after OLT. The predictors of employment were: employment status, income, disability status before OLT and Model of End Stage Liver Disease score. These variables had prediction rate of 82%. Individuals working during the five yr prior to OLT were likely to return to work (p < 0.0001), particularly those who held a job for >6 months prior to OLT (p < 0.0001), income >$80 000 before OLT compared with <$30 000 (p = 0.036). Patients receiving Social Security Insurance (SSI) payment for ≥6 months prior to OLT, were less likely to work (p = 0.0005). Severity/duration of liver dysfunction prior to OLT did not correlate with employment. Sense of physical health was poorer in those employed after OLT than in unemployed (p = 0.0003). Socioeconomic factors were the most important predictors of post‐OLT employment.
Comparative outcomes of reduced intensity and myeloablative allogeneic hematopoietic stem cell transplantation in patients under 50 with hematologic malignancies
Authors: Kim Inho , Yoon Sung Soo , Lee Kyung‐Hun , Keam Bhumsuk , Kim Tae Min , Kim Jin‐Soo , Kim Hoon‐Gu , Oh Myoung‐Don , Han Kyou‐Sup , Park Myoung Hee , Park Seonyang , Kim Byoung Kook
Published: June 2006

Abstract:  We have conducted a direct comparison of the outcomes of reduced intensity and myeloablative conditioning in younger adults with hematological malignancies <50 yr. One hundred and five patients received transplants from human leukocyte antigen (HLA)‐matched donors, via either reduced intensity (n = 35) or myeloablative conditioning (n = 70). The median ages of the reduced intensity and myeloablative groups were 36 and 33 yr (p = 0.014). Neutrophil engraftment (i.e. time to absolute neutrophil count >0.5 × 109/L) occurred more rapidly in the reduced intensity group (median: 10 d; range: 0–21 d) than in the myeloablative group (median: 18 d; range: 11–38 d; p < 0.0001). The incidence of grades 2–4 acute graft‐vs.‐host disease were similar between the reduced intensity and myeloablative groups, at 17% vs. 24% respectively (p = 0.40). The cumulative incidence of day 100 non‐relapse mortality was 18% in the reduced intensity group, and 21% in the myeloablative group (p = 0.88). The overall two‐yr survival rates were 43% in the reduced intensity group, and 35% in the myeloablative group (p = 0.72). In conclusion, reduced intensity transplantation yielded outcomes comparable with those of myeloablative transplantation in patients under 50 with hematological malignancies.
Impact of venous drainage on regeneration of the anterior segment of right living‐related liver grafts
Authors: Mizuno Shugo , Iida Taku , Yagi Shintaro , Usui Masanobu , Sakurai Hiroyuki , Isaji Shuji , Uemoto Shinji
Published: June 2006

Abstract:  The effect of additional venous reconstruction on morphologic and functional regeneration of the anterior segment of right‐lobe liver grafts was compared among three groups according to graft type: right liver graft without the middle hepatic vein (MHV) or MHV tributaries (n = 7), with MHV tributaries (n = 25) and with the MHV (n = 10). Whole graft volume (GV) and anterior segment volume (ASV) were estimated from CT scans and post‐operative laboratory data and daily ascitic fluid volume were examined. Peak GV in each group was reached two or three wk after surgery. The ASV/GV ratios of the grafts with the MHV or MHV tributaries were higher than those of grafts without additional venous reconstruction. However, the asparate aminotransferase and ascitic fluid volume values in the group that received grafts with MHV tributaries were higher than in the group that received grafts with the MHV in the same period. Although rapid enlargement of the anterior segment of right‐lobe grafts with MHV tributaries occurred in the early post‐operative period, complete functional liver regeneration may not occur even after additional tributary reconstruction. These results suggest that the selection of right‐lobe grafts with the MHV is more beneficial for recipients, as long as donor safety is protected and that as many MHV tributaries as possible should be reconstructed in right‐lobe grafts without MHV.
Subcutaneous administration of hepatitis B immune globulin in combination with lamivudine following orthotopic liver transplantation: effective prophylaxis against recurrence
Authors: Powell James J. , Apiratpracha Wichian , Partovi Nilufar , Erb Siegfried R. , Scudamore Charles H. , Steinbrecher Urs P. , Buczkowski Andrezj K. , Chung Stephen W. , Yoshida Eric M.
Published: June 2006

Abstract: Prophylaxis against recurrent hepatitis B virus (HBV) infection with hepatitis B immune globulin (HBIG), in combination with antiviral agents such as lamivudine, has allowed transplantation for this condition to become feasible and accepted. Current protocols allow for HBIG administration either intravenously or intramuscularly. To date, there has been no reported experience with the subcutaneous route of post‐transplant HBIG delivery. We report our experience of a 60‐yr‐old man for whom liver transplantation was performed for chronic HBV. HBIG was administered intramuscularly during the anhepatic phase of surgery. The finding of a portal vein thrombosis requiring repeated thrombectomy necessitated chronic anticoagulation. Post‐operatively, HBIG was administered subcutaneously, in four separate injections, for a daily dose of 2170 IU along with continued lamivudine dosing. Hepatitis B surface antibody (anti‐HBs) titres reached a serum concentration of >500 IU/L by seven d post‐transplant and approximately 1000 IU/L by nine d post‐transplant. Five months post‐transplant, with continued combination of subcutaneous HBIG and lamivudine, there has been no recurrent HBV infection and anti‐HBs titres have been at target levels. Our experience suggests that subcutaneous delivery of HBIG may be a feasible consideration when intramuscular/intravenous dosing is not possible.
Creatinine‐based formulae for the estimation of glomerular filtration rate in heart transplant recipients
Authors: Delanaye Pierre , Nellessen Eric , Grosch Stéphanie , Depas Gisèle , Cavalier Etienne , Defraigne Jean‐Olivier , Chapelle Jean‐Paul , Krzesinski Jean‐Marie , Lancellotti Patrizzio
Published: June 2006

Abstract: Chronic renal failure (CRF) is a common complication in heart transplant patients. Serum creatinine has clear limitations for the detection and estimation of glomerular filtration rate (GFR). Various creatinine‐based formulae are classically used for GFR estimation, but little scientific evidence exists for such use in a heart transplant population. GFR was measured using the plasmatic clearance of the glomerular tracer51Cr‐EDTA in 27 heart transplant patients with two measures for 22 of the patients. Forty‐nine measures were thus available for analysis. The precision and accuracy (Bland and Altman analysis) of the Cockcroft, simplified Modified Diet in Renal Diseases (MDRD) and new Mayo Clinic formulae were compared. The mean GFR of the population was 39 ± 15 mL/min/1.73 m2. All formulae were well correlated with the GFR. With the Bland and Altman analysis, the accuracy of the MDRD formula appeared higher than that of the Cockcroft or the Mayo Clinic formulae (bias of +12 mL/min/1.73 m2, vs. +19.9 mL/min/1.73 m2, and +22.1 mL/min/1.73 m2, respectively). The difference between the estimated and measured GFR was higher than 20 mL/min/1.73 m2in 51% and 55% cases when using the Cockcroft and the Mayo Clinic formulae respectively, whereas the difference was only noted in 14% cases when the MDRD was used. Among creatinine‐based formulae, the MDRD appears the most precise and accurate for estimating the GFR in heart transplant patients. However, when the GFR must be measured with high accuracy, we recommend the use of a reference method like inulin or51Cr‐EDTA plasma clearance techniques.
Successful reuse of liver grafts after death of the first recipient
Authors: Castellote José , Lladó Laura , Xiol Xavier , Julià David , Ballester Raquel , Ramos Emilio , Fabregat Joan , Rafecas Antoni
Published: June 2006

Abstract:  Brain death secondary to cerebrovascular disease is a possible early complication of orthotopic liver transplantation. If liver graft continues to function normally, the reuse of liver for another patient may be considered. We report three cases of successful reuse of liver grafts after death of the first recipient. In our experience, liver graft can be reused in the first weeks after a previous transplantation provided that liver function is good, in the absence of systemic uncontrolled infection, graft rejection and after gross graft examination at laparotomy.
Survey of endoscopic ultrasonographic practice and training in the Asia‐Pacific region
Authors: Ho Khek Yu
Published: June 2006

Background:  Little is known about the current status of endoscopic ultrasonography (EUS) training in the Asia–Pacific region. The aim of the present study was to assess EUS practice and training in the Asia–Pacific region and seek to identify areas where the development of EUS expertise could be further enhanced.

Methods:  A direct mail survey was sent out to 87 practising endosonographers in various parts of the Asia–Pacific region outside of Japan. They were asked to report on their prior training, utilization of EUS, and EUS training in their country.

Results:  The respondents (n = 71) were mostly young (median age 40 years), male (97%), practising in academia (36.6%) or public hospitals (50.7%) and fairly experienced (median 5 years) in EUS practices; they had performed a median of 500 procedures in their career. Among them, 49.3% were self‐taught. Only 22.5% and 21.1% had undergone formal overseas fellowship lasting ≥6 months, and local gastrointestinal fellowships of various durations, respectively. Fifty‐six percent were currently involved in EUS teaching. Most (90%) thought that a formal EUS training fellowship is necessary for acquiring acceptable competence and there should be a minimum number (median 100) of supervised procedures performed and minimum amount of time (median 6 months) spent on training.

Conclusions:  Although EUS practitioners in the Asia–Pacific region were not behind their European or US counterparts in hands‐on experience, the lack of formal EUS training programs and opportunities remains an area of concern. For the region to increase EUS utilization, the current shortage of training opportunities needs to be addressed.
Candida albicans aggravates duodenal ulcer perforation induced by administration of cysteamine in rats
Authors: Nakamura Tetsuya , Yoshida Masashi , Ishikawa Hideki , Kameyama Kaori , Wakabayashi Go , Otani Yoshihide , Shimazu Motohide , Tanabe Minoru , Kawachi Shigeyuki , Kumai Koichiro , Kubota Tetsuro , Saikawa Yoshiro , Sano Katsuko , Kitajima Masaki
Published: June 2006

Background:  Candida sp are frequently isolated from the ascitic fluid of patients with perforated ulcers. The present study was performed to examine whether Candida infection may be involved in the process of ulcer perforation.

Methods:  Male Wistar rats were divided into a saline group (n = 15) and a Candida group (n = 17). Cysteamine‐HCl (Sigma; 31 mg/100 g) was administered thrice on day 1 to both groups of animals. Candida albicans at a density of 108 in 0.5 mL of saline was administered 1 h before, and 12 h and 24 h after the first administration of cysteamine in the Candida group.

Results:  Perforated duodenal ulcers were observed in 94.1% of the rats in the Candida group, but only 26.7% of the rats in the saline group (P < 0.01). The area of the duodenal ulcers in the Candida group was 40.89 ± 33.07 mm2, whereas that in the saline group was 16.53 ± 20.4 mm2 (P < 0.05). The mortality rate was significantly higher in the Candida group than in the saline group. In the Candida group, colonization by C. albicans was recognized at the ulcer base, surrounded by marked granulocytic infiltration. The number of eosinophils infiltrating the ulcer base was also significantly greater in the Candida group than in the saline group. Immunohistochemical analysis revealed the expression of secretory aspartyl protease (SAP) in the region of the ulcer showing colonization by C. albicans in the Candida group.

Conclusion:  Candida albicans aggravates duodenal ulcer perforation in the experimental model of cysteamine‐induced duodenal ulcer perforation. The present findings suggest that SAP and host–parasite relationships, including granulocyte‐dependent mechanisms, may be involved in the aggravation of ulcer perforation by C. albicans.
Long‐term results with azathioprine therapy in patients with corticosteroid‐dependent Crohn’s disease: Open‐label prospective study
Authors: Chebli Julio Maria Fonseca , Gaburri Pedro Duarte , De Souza Aécio Flávio Meirelles , Pinto André Luiz Tavares , Chebli Liliana Andrade , Felga Guilherme Eduardo Gonçalves , Forn Cecília Ganini , Pimentel Carolina Frade Magalhães Girardin
Published: June 2006

Background:  A substantial number of patients with Crohn’s disease (CD) become dependent on steroids after induction therapy. Treatment with azathioprine (AZA) may be beneficial in such patients. The present open‐label study evaluated the long‐term safety and efficacy of AZA in steroid‐dependent CD patients.

Methods:  Adult patients with steroid‐dependent CD were enrolled for AZA therapy over a 7‐year period. The average dose of AZA was 2.0–3.0 mg/kg per day, adjusted according to clinical response and occurrence of adverse effects. Steroid therapy was tapered off according to a predefined schedule. Long‐term outcome and adverse reactions were evaluated.

Results:  Sixty‐nine patients were prospectively included. Steroid‐free remission was achieved in 68–81% of patients, partial response in 14.5–27.3% and failure to respond to AZA in 4–15.9% over the initial 48 months. However, the rate of wean from steroid therapy decreased to 53–60% while the rate of failure increased from 6.7% to 17.6% after this period. A breakthrough of symptoms during continuous AZA therapy was common, particularly after 48 months on AZA. The mean leukocyte count at the end of 12 months of therapy was significantly lower in patients who achieved complete response on AZA than in the non‐responders (5197 ± 1250 cells/mm3 vs 8340 ± 1310 cells/mm3, respectively; P < 0.01). Azathioprine was relatively well‐tolerated and the incidence of serious adverse effects was small.

Conclusions:  Azathioprine was relatively safe and moderately effective for long‐term maintenance of steroid‐free clinical remission in corticosteroid‐dependent CD patients. Patients were more successfully weaned from prednisone treatment, and clinical remission was more often maintained during the first 48 months of AZA therapy. A significant decrease in the white blood cell count at the end of 12 months on AZA was the single factor associated with weaning from steroid dependence.
Role of clinical presentation in diagnosing reflux‐related non‐cardiac chest pain
Authors: Mousavi Shahrokh , Tosi Jahfar , Eskandarian Rahime , Zahmatkesh Mehrdad
Published: June 2006

Introduction:  Non‐cardiac chest pain (NCCP) presents as a frequent diagnostic challenge, with patients tending to use a disproportionate level of health‐care resources. Gastroesophageal reflux disease (GERD) is the most frequent cause of NCCP. Thus the typical symptoms of reflux, such as heartburn and regurgitation, when present as predominant symptoms are quite specific for diagnosing GERD but in patients with NCCP the clinical diagnosis of reflux is difficult, and invasive methods or the omeprazole test are required for its detection. The aim of the present study was to evaluate the role of clinical presentation when diagnosing GERD among patients with NCCP.

Methods:  Patients with NCCP underwent upper endoscopy, Bernstein and omeprazole tests. The patients were divided into two groups based on GER‐ or non‐GER‐related chest pain, and clinical presentation was compared between these two groups. Gastroesophageal reflux disease was considered positive when at least two methods were positive.

Results:  From 78 NCCP patients (41 male; mean age 50.4 ± 2.3 years), the chest pain was related to GERD in 35 patients (44.8%). The two groups were the same based on sex and age. The chest pain severity, site, radiation and relation to food, exercise, and sleep were equal in the two groups, except for two symptoms: pain that was relieved by antacid (P < 0.031) and presence of classical reflux symptoms (P < 0.009), seen in the GERD patients. With regard to recent patient history, heartburn and regurgitation symptoms were seen more frequently in GERD patients (P < 0.036 and P < 0.002, respectively).

Discussion:  Clinical presentation is important in diagnosing GERD in NCCP. Although the chest pain is the same in reflux‐ and non‐reflux‐related NCCP, the symptoms of heartburn or regurgitation in the present or recent patient history are diagnostic for GERD‐related chest pain.