bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term reversal of hypocholesterolaemia in patients with chronic hepatitis C is related to sustained viral response and viral genotype
Authors: FERNÁNDEZ‐RODRÍGUEZ C. M. , LÓPEZ‐SERRANO P. , ALONSO S. , GUTIÉRREZ M. L. , LLEDÓ J. L. , PÉREZ‐CALLE J. L. , TEMIÑO R. , CACHO G. , NEVADO M. , CASAS M. L. , GASALLA J. M. , BONET B. 
Published: July 2006

SummaryBackgroundGenotype‐3 of hepatitis C virus (HCV) has been associated with serum lipid changes (reversible with sustained viral response) and liver steatosis.AimTo characterize the relationships among hepatic steatosis, cholesterol and sustained viral response in these patients.MethodsPatients (n = 215) with chronic hepatitis C (157 with genotype‐1 of HCV) had age, body mass index, gender, alcohol intake, glycaemia, serum lipids, transaminases, grade and stage (METAVIR and Scheuer), degree of liver steatosis, sustained viral response, insulinaemia, leptinaemia, β‐hydroxybutyrate and glycerol measured, and were compared with 32 hepatitis B virus (HBV)‐infected subjects.ResultsGenotype‐3 of HCV patients had age‐adjusted hypocholesterolaemia and more frequent hepatic steatosis (P < 0.001). Steatosis was inversely correlated with serum cholesterol (P < 0.01) and directly with viral load (P < 0.03). In patients with genotype‐3 of HCV and sustained viral response, serum cholesterol increased from 138 (95% CI: 120–151) to 180 mg/dL (95% CI: 171–199) 12 months after treatment conclusion (P < 0.0001). By contrast, cholesterol values were unchanged in genotype‐3 of HCV non‐responders and in patients with genotype‐1 of HCV regardless of response. Rising cholesterol in sustained viral response did not parallel the changes in β‐hydroxybutyrate.ConclusionsBesides causing hepatic steatosis, genotype‐3 specifically decreases serum cholesterol. This interference with the metabolic lipid pathway is related to viral load, is reversed with sustained viral response, and seems unrelated to mitochondrial dysfunction.
Review article: management of hepatic disease following haematopoietic cell transplant
Authors: McDONALD G. B. 
Published: July 2006

SummaryHepatic diseases are common complications of haematopoietic cell transplant. The causes are multiple: myeloablative conditioning regimens may cause sinusoidal injury; acute and chronic graft‐versus‐host disease lead to damaged hepatocytes and small bile ducts; microcrystalline deposits in the gall bladder can cause biliary symptoms; drug‐induced liver injury is common; and the liver may be infected by viruses and fungi during the period of severe immune suppression that follows transplant.Pre‐transplant evaluation and prevention of liver injury are often more useful than treatment of deeply jaundiced patients in improving transplant outcomes.This review covers pre‐transplant evaluation, common hepatobiliary problems in the six months following transplant, and hepatic problems in long‐term survivors.
Meta‐analysis: intradermal vs. intramuscular vaccination against hepatitis B virus in patients with chronic kidney disease
Authors: FABRIZI F. , DIXIT V. , MAGNINI M. , ELLI A. , MARTIN P. 
Published: July 2006

SummaryBackgroundDialysis patients have suboptimal response towards hepatitis B virus (HBV) vaccine and intradermal hepatitis B virus vaccination has been used to improve the response rate; however, its efficacy remains unclear.DesignMeta‐analysis of controlled trials comparing intradermal vs. intramuscular vaccine against HBV among chronic kidney disease patients.IdentificationTwelve studies involving 640 unique patients were included if they had controlled design, intervention and control group patients received intradermal or intramuscular vaccine against HBV, respectively. Patients were followed for a minimum of 7 months after the first vaccine dose.Main outcome measuresThe odds ratio of failure to respond to HBV vaccine among patients who received vaccine by intradermal vs. intramuscular route was the end point of interest. It was calculated at completion of HBV vaccination and over follow‐up.ResultsPooling of study results demonstrated a decreased risk of failure to respond to HBV vaccine among patients who were vaccinated by intradermal vs. intramuscular route (pooled odds ratio at completion of vaccine protocol: 0.36; 95% CI: 0.21–0.62; test of study heterogeneity, P =0.089). This difference did not occur over follow‐up (6–60 months after completing vaccine schedule; pooled odds ratio: 1.1; 95% CI: 0.47–2.5).ConclusionsDialysis patients show higher seroprotection after intradermal than intramuscular vaccination schedules; this was not apparent over follow‐up. Further studies are warranted to assess if the higher seroprotection rates obtained by intradermal route translates into reduced incidence of de novo HBV virus among chronic kidney disease patients.
Relationship of glutathione S‐transferase genotypes with side‐effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus
Authors: Zhong Shilong , Huang Min , Yang Xiuyan , Liang Liuqin , Wang Yixi , Romkes Marjorie , Duan Wei , Chan Eli , Zhou Shu‐Feng 
Published: July 2006

AimsCyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S‐transferases (GSTs). However, data are lacking on the relationship between the short‐term side‐effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE.MethodsDNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)‐multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile→Val) was analyzed by a PCR‐restriction fragment length polymorphism (RFLP) assay.ResultsOur study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*‐105I/V (heterozygote) and GSTP1*‐105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high‐dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high‐dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short‐term side‐effects of pulsed high‐dose CTX therapy in SLE patients.ConclusionsThe GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short‐term side‐effects of pulsed high‐dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high‐dose CTX therapy in SLE patients.
Pharmacokinetics of ribavirin in patients with hepatitis C virus
Authors: Wade Janet R. , Snoeck Eric , Duff Frank , Lamb Matthew , Jorga Karin 
Published: July 2006

AimA population pharmacokinetic analysis was performed using plasma concentration data (n = 7025) from 380 patients to examine the relationship between ribavirin dose and its pharmacokinetics.MethodsRibavirin pharmacokinetics were described by a three‐compartment model with sequential zero‐order and a first‐order absorption processes. Interoccasion variability and food effects were included.ResultsLean body weight (range 41–91 kg) was the only covariate with a clinically significant influence on ribavirin pharmacokinetics, affecting clearance (15.3–23.9 l h−1) and the volume of the larger peripheral compartment.ConclusionThe model provided a good description of the available data, confirmed by accurate estimates of parameter values and low residual variability (17%).
Ultraviolet-A (UVA-1) radiation suppresses immunoglobulin production of activated B lymphocytesin vitro
Authors: Polderman M C A , Van Kooten C , Smit N P M , Kamerling S W A , Pavel S 
Published: July 2006

SummaryPrevious studies have shown that low-dose ultraviolet-A (UVA-1) total body irradiations were capable of improving disease activity in patients with systemic lupus erythematosus (SLE). We hypothesized that UVA-1-induced suppression of immunoglobulin production by activated B cells in the dermal capillaries could be (partly) responsible for this effect. Our experiments with donor skin demonstrated that approximately 40% of UVA-1 could penetrate through the epidermis. Irradiation of peripheral blood mononuclear cells (PBMCs) with 2 J/cm2 of UVA-1 resulted in 20% cell death. This toxic effect could be prevented totally by preincubation of the cell cultures with catalase. This indicates that the generation of hydrogen peroxide plays a role in UVA-1 cytotoxicity. T cells and B cells appeared to be less susceptible to UVA-1 cytotoxicity than monocytes. With the use of a CD40–CD40L B cell activation method we measured immunoglobulin production after various doses of UVA-1 irradiation (0–2 J/cm2). The doses of 2 J/cm2 caused a significant decrease of IgM, IgG, IgA and IgE production under the conditions of interleukin (IL)-10 or IL-4 (IgE) stimulation. Although UVA-1 can cause apoptosis of B lymphocytes, we show that relatively low doses of UVA-1 radiation also affect the function of these cells. Both effects may be responsible for the observed improvement of disease activity in SLE patients.
A potential role for interleukin-18 in inhibition of the development ofCryptosporidium parvum
Authors: McDonald V , Pollok R C G , Dhaliwal W , Naik S , Farthing M J G , Bajaj-Elliott M 
Published: July 2006

SummaryAccumulating evidence suggests that intestinal epithelial cells (IECs) constitutively express the immunoregulatory cytokine interleukin (IL)-18. IECs also serve as the host cell for the intracellular parasitic protozoan Cryptosporidium parvum. In the present study, C. parvum infection of a human enterocyte cell-line HCT-8 resulted in increased expression of IL-18 mRNA as measured by quantitative reverse transcription–polymerase chain reaction (RT-PCR). IL-18 protein was detected in control uninfected cells and following infection there was increased expression as measured by enzyme-linked immunosorbent assay (ELISA). Gene expression revealed the presence of the IL-18 receptor subunits not only in cell-lines but also in freshly isolated IECs, suggesting that IL-18-mediated signalling events may contribute to epithelial host defence during infection. Recombinant IL-18 inhibited intracellular development of the parasite in HCT-8 and HT-29 cells. Increased expression of bactericidal antibiotic peptides LL-37 and α-defensin 2 by IL-18 in HCT-8 and HT-29 cells may represent one mode of action by which this pluripotent cytokine aids in limiting the development of intracellular pathogens such as C. parvum in the gastrointestinal tract.
Emerging role of a phosphatonin in mineral homeostasis and its derangements
Authors: Bielesz B. 
Published: July 2006

AbstractBackground  The study of a distinct group of renal phosphate wasting disorders with bone disease which comprise X‐linked hypophosphatemic rickets (XLH), autosomal dominant hypophosphatemic rickets (ADHR) and tumour‐induced osteomalacia (TIO) gave rise to the identification of different hormone‐like peptides, also known as phosphatonins. These factors are responsible for the major disease features that characterize XLH, ADHR and TIO. Recent reports on one of these phosphatonins, fibroblast growth factor‐23 (FGF‐23), point to a general role of this factor in mineral ion metabolism.Objectives  The main focus regards recent evidence implicating FGF‐23 in normal and disordered mineral homeostasis with special emphasis on chronic kidney disease. The interactions of FGF‐23 with phosphate, parathyroid hormone and vitamin D are discussed in detail.Summary  The FGF‐23 has been shown to increase urinary phosphate excretion, inhibit bone mineralization and suppress 1,25‐dihydroxy vitamin D3[1,25(OH)2D3], the main characteristics that XLH, ADHR and TIO have in common. Apart from its role in these phosphate wasting disorders serum FGF‐23 is elevated in hypoparathyroidism and humoral hypercalcaemia of malignancy and responds to altered dietary phosphate and calcium supply in healthy subjects. The FGF‐23 is also variably elevated in chronic kidney disease and associated secondary hyperparathyroidism where it correlates positively with serum phosphate and parathyroid hormone and negatively with 1,25(OH)2D3. Such relationships, along with data from experimental studies, raise the question of whether FGF‐23 contributes to the pathophysiology of chronic kidney disease.
Development of renal bone disease
Authors: Ferreira A. 
Published: July 2006

AbstractRenal osteodystrophy (ROD) develops as the early stages of chronic renal failure (CRF) and covers a spectrum of bone changes observed in the uraemic patient, which extend from high remodelling bone disease (frequently known as osteitis fibrosa) to low turnover, or adynamic disease. Between these two extremes there are also cases of bone mineralization compromised in variable degrees, as is the case of ‘mixed bone disease’ and osteomalacia. The dynamic process of bone remodelling is compromised in CRF, and a positive or negative bone balance can be observed in uraemic patients.In addition to the classic modulators of bone remodelling, like parathyroid hormone, calcitriol and calcitonin, other factors were recently identified as significant modulators of osteoblast and osteoclast activation in uraemic patients. In fact, different cytokines and growth factors, acting at an autocrine or paracrine level, seem to play a relevant role in the bone and mineral changes observed in uraemia.Recently, observations have been made of the development of more sensitive and specific techniques to assay different biochemical markers of bone turnover and mineral metabolism. Analogously, new contributions of conventional bone histology, bone immunocytochemistry and molecular biology, which enabled the understanding of some etiopathogenic mechanisms of ROD, were observed.
Diagnosis of renal osteodystrophy
Authors: Schwarz C. , Sulzbacher I. , Oberbauer R. 
Published: July 2006

AbstractThe idiom renal osteodystrophy (ROD) represents a heterogeneous pattern of bone disturbances caused by chronic renal insufficiency and concomitant diseases. For the clinical decision of therapy it is most important to differentiate between high and low or adynamic turnover ROD because the therapeutically consequences of these two ends of the ROD spectrum are fundamentally different.Bone histology remains the gold standard for the exact classification of ROD. Serological markers of bone metabolism are not suited for the accurate nomenclature of ROD but are useful for the sequential follow up of ROD after a clear diagnosis has been made. Similarly, radiological diagnosis of ROD using dual energy X‐ray absorptiometry (DEXA) or quantitative computer tomography scan (q‐CT) is inaccurate and thus more suited for the routine follow up of established disease.Besides mineralization, bone strength and the rate of fractures are strongly determined by the architecture of the bone matrix. This information, however, is also only available on bone biopsy sections and cannot be estimated by non‐invasive diagnostic methods.In summary, bone biopsy should be used more liberally for correct classification of bone disease. The sequential follow up and guidance of therapy success can be performed by non‐invasive procedures such as biochemical bone marker determination in blood. X‐ray imaging and densitometry is suitable only for sequential evaluation of osteoporosis.
Expression of CD8α identifies a distinct subset of effector memory CD4+ T lymphocytes
Authors: Macchia Iole , Gauduin Marie‐Claire , Kaur Amitinder , Johnson R. Paul 
Published: July 2006

SummaryCirculating CD4+ CD8+ T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4+ CD8+ T cells in rhesus macaques. Two distinct populations of CD4+ CD8+ T cells were identified: the dominant one was CD4hi CD8lo and expressed the CD8αα homodimer, while the minor population was CD4lo CD8hi and expressed the CD8αβ heterodimer. The majority of CD4hi CD8αlo T cells exhibited an activated effector/memory phenotype (CCR5lo CD7– CD28– HLA‐DR+) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus‐specific T cells was enriched five‐fold in CD4hi CD8αlo T cells compared to single‐positive CD4+ T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)‐specific T cells. Cross‐sectional studies of SIV‐infected animals demonstrated that the frequency of CD4hi CD8αlo T cells was lower in wild‐type SIV‐infected animals compared to uninfected controls, although prospective studies of SIV‐infected animals demonstrated depletion of CD4hi CD8αlo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4+ T cells expressing CD8α represent an effector/memory subset of CD4+ T cells and that this cell population can be depleted during the course of SIV infection.
Base‐pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq
Authors: Kawamoto Hiroshi , Koide Yukari , Morita Teppei , Aiba Hiroji 
Published: July 2006

SummarySgrS is an Hfq‐binding small antisense RNA that is induced upon phosphosugar stress. It forms a ribonucleoprotein complex with RNase E through Hfq to mediate silencing of the target ptsG mRNA encoding the membrane component of the glucose‐specific phosphoenolpyruvate phosphotransferase system. Although SgrS is believed to act on ptsG mRNA through base pairing between complementary regions, this was not previously tested experimentally. We addressed the question of whether SgrS indeed forms an RNA–RNA duplex with ptsG mRNA to exert its regulatory function. Specific single nucleotide substitutions around the Shine–Dalgarno (SD) sequence of ptsG completely eliminated SgrS action while compensatory mutations in SgrS restored it. A systematic mutational analysis of both ptsG and SgrS RNAs revealed that six base pairs around SD sequence of ptsG are particularly important for SgrS action. We also showed in vitro that SgrS forms a stable duplex with the ptsG mRNA, and that Hfq markedly facilitates the rate of duplex formation.
Large scale evaluation of WHO's ultrasonographic staging system of schistosomal periportal fibrosis in Ethiopia
Authors: Berhe Nega , Geitung Jonn T. , Medhin Girmay , Gundersen Svein G. 
Published: July 2006

SummaryObjectives  To evaluate the recent WHO's ultrasonographic diagnostic staging system of schistosomal periportal thickening/fibrosis and to assess intra/inter‐observer variation associated with its use.Methods  Local standard of portal branch wall thickness (PBWT) for height was established using 150 healthy subjects. Intra and inter‐observer variation in image pattern identification and PBWT measurements were assessed in 94 and 35 subjects, respectively, with differing stages of periportal thickening fibrosis. WHO's diagnostic criteria were evaluated in 2451 community members (1277 males, 1174 females; mean age 18.8 years) with an overall Schistosoma mansoni prevalence estimate of 65.9%.Results  There were no significant inter/intra‐observer variations in image pattern identification and PBWT measurements. Based on Ethiopian PBWT‐for‐height standard, 128/2451 (5.2%) had insipient, 46/2451 (1.9%) had possible/probable and 112/2451 (4.6%) had definite/advanced periportal thickening/fibrosis. Comparable figures were obtained using the Senegalese PBWT‐for‐height standard and there was good agreement between Ethiopian and Senegalese healthy control‐based diagnostic criteria in classifying the 286 subjects into stages of periportal thickening/fibrosis (κ = 0.87, P < 0.001).Conclusions  With further improvement, the WHO's ultrasonographic diagnostic criteria can be used in health institutions and community surveys. Image pattern based assessment is simple and more reproducible than PBWT based assessment of periportal thickening/fibrosis. The latter is, however, more useful in clarifying the status of an individual with doubtful image pattern, and in monitoring post‐treatment outcome of periportal thickening/fibrosis. Considering the comparability of PBWT‐for‐height standards, setting one international standard of PBWT‐for‐height is more practical than developing local standards for each endemic area.
Who needs ‘pukka1anthropologists'? A study of the perceptions of the use of anthropology in tropical public health research
Authors: Napolitano Dora A. , Jones Caroline O. H. 
Published: July 2006

SummaryOver the past 50 years, there have been considerable changes both in how medical anthropologists view their relationship to topical public health and in how tropical public health professionals view the role of anthropologists. In particular, in recent decades critical currents have emerged from an anthropology of medicine, calling for an examination of biomedicine and its conceptualisation of public health. There are parallel debates in public health about a narrow disease‐focused or broader socio‐cultural approach to improving population health. Based on a review of the literature and a qualitative study of the views of public health professionals and anthropologists working in tropical public health, the data presented in this paper suggest that public health professionals remain unaware of many of the contributions anthropology could make to tropical public health theory and practice. However, the objectives of a critical social science are not dissimilar to those of the broader concept of public health. We suggest that there are grounds for optimism. For those of us concerned not just with disease but also with inequities in health, the challenge is to work towards a critical tropical public health which draws as much from social science as from biomedicine, in theory and practice.