bluuebunny/crossref_metadata_2025 huggingface dataset:
The course of ADAMTS‐13 activity and inhibitor titre in the treatment of thrombotic thrombocytopenic purpura with plasma exchange and vincristine
Authors: Böhm Martina , Betz Christoph , Miesbach Wolfgang , Krause Manuela , von Auer Charis , Geiger Helmut , Scharrer Inge
Published: July 2005

The therapeutic efficacy of plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) is attributed to the restoration in ADAMTS‐13 (a disintegrin and metalloproteinase with thrombospondin motif‐13) activity by substitution of the enzyme and removal of ADAMTS‐13‐neutralizing autoantibodies. We explored this rationale by analysing ADAMTS‐13 activity and corresponding inhibitor levels during PE‐treatment in 27 episodes from 23 adults with TTP. All patients with an initial episode of TTP (n = 14) and nine of 11 patients with a relapse showed severe ADAMTS‐13 deficiency. ADAMTS‐13 inhibitors were detected in 81% of these patients. Twenty‐one patients responded to PE‐therapy and two patients died. For patients with severe ADAMTS‐13 deficiency, 15 patients (71%) showed a PE‐induced recovery in ADAMTS‐13 activity and six patients (29%) had persistent severe ADAMTS‐13 deficiency despite clinical response. Three patients with recurrent TTP demonstrated a permanent increase in inhibitor titre during therapy. Six patients (43%) with an initial episode of TTP displayed a transient increase in inhibitor titre during PE‐therapy, which was associated with deterioration in clinical and haematological symptoms of TTP. Treatment with vincristine induced an immediate increase in platelet count and ADAMTS‐13 activity in seven of eight patients. We conclude that ADAMTS‐13 activity and inhibitor levels, as measured using current methodology, do not solely determine the clinical course of TTP.
Long‐term outcomes of previously untreated myeloma patients: responses to induction chemotherapy and high‐dose melphalan incorporated within a risk stratification model can help to direct the use of novel treatments
Authors: Alvares Caroline L. , Davies Faith E. , Horton Clive , Patel Gita , Powles Ray , Sirohi Bhawna , Zuha Roslin , Gatt Alex , Saso Radovan , Treleaven Jennifer G. , Dearden Claire E. , Potter Michael N. , Ethell Mark E. , Morgan Gareth J.
Published: July 2005

Induction chemotherapy followed by high‐dose melphalan (HDM) is the standard treatment for fitter patients with myeloma. The place of bortezomib and the thalidomide analogues within this treatment paradigm is yet to be established. We sought to identify patients who may benefit from the introduction of novel agents during their initial management. An intention‐to‐treat analysis was performed on 383 patients with newly diagnosed myeloma eligible for HDM to determine whether the extent of response to induction therapy and HDM correlated with long‐term survival. Early response [complete response (CR) and partial response (PR)] to induction therapy was predictive of overall survival (OS) [median OS, 7·47 years for responders (CR and PR) versus 4·89 years for non‐responders; P = 0·035]. The attainment of CR at 3 months post‐HDM correlated with a prolonged progression‐free survival (PFS) (median PFS, 7·4 years in CR group versus 5·3 years in non‐CR group; P = 0·023). This data suggests that, at every stage of treatment, the aim should be to achieve CR. Patients with suboptimal responses could be offered alternative therapy. We propose a multiparametric risk‐adapted model that includes response to induction chemotherapy and HDM, for identifying patients who may benefit from novel approaches to treatment.
Aiming towards effective preventive medicine against Japanese cedar pollinosis: epidemiology, patient investigation and integrated research including genotype analyses
Authors: Terada N. , Kobayashi T. , Suzuki T. , Yamazaki K. , Izuhara K. , Konno A.
Published: July 2005

Environmental rather than genetic factors appear to play the major role in the recent increased prevalence of Japanese cedar pollinosis in Japan. However, investigating the genes that determine IgE levels and analysing gene polymorphisms may assist in finding new methods of treatment and establishing preventive medicine against this disease. Among a total of 219 asymptomatic individuals who were anti‐Japanese cedar pollen IgE antibody positive as determined by radioallergosorbent test (RAST), only a handful subsequently developed symptoms of Japanese cedar pollinosis or secondary onset of Japanese cedar pollinosis over 5–14 years of follow‐up. Among those who subsequently developed secondary onset of disease, >50% were found to have high initial RAST scores, suggesting that the incidence of Japanese cedar pollinosis is correlated with RAST score. Hence, it may be prudent to advise asymptomatic individuals with high RAST scores to avoid exposure to Japanese cedar pollen so as to delay onset of the disease. Analysis of sequence variants of the FcɛRIβ gene revealed that patients with nasal allergy exhibit a single‐nucleotide polymorphism in which the amino acid at 237 of the intracellular domain changes from glutamine to glycine more frequently than individuals without nasal allergy. Furthermore, Il homo polymorphism of the IL‐4Rα gene is associated with higher serum nonspecific IgE and Japanese cedar pollen‐specific IgE levels than are seen in individuals showing Il,Val hetero and Val homo expression types. When the age of pollinosis onset was compared among these three genotypes, it was found to be significantly lower among Il homo type than the other two expression types, suggesting that Il homo type individuals seem characteristically pre‐disposed to early onset of pollinosis. Studies comparing eosinophil‐associated gene polymorphism in healthy and pollinosis phenotypes have revealed several relationships among the various genotypes and specific disease parameters and suggest that Eotaxin G (123G/A) and IL5 (–703C/T) genotypes can affect the timing of symptom onset after sensitization as well as nasal mucosal hyper‐responsiveness.
Role of T cells in allergic rhinitis
Authors: Horiguchi S. , Okamoto Y.
Published: July 2005

A characteristic feature of allergic rhinitis (AR) is the production of allergen‐specific IgE antibodies. It is widely accepted that the induction of antigen‐specific type 2 CD4+ helper cells (Th2) is a key event in this disease. Allergen‐specific T cell–B cell interaction is indispensable for the induction of human IgE synthesis. Th2 cells also cause influx and activation of eosinophils, mast cells and basophils. Th2 cytokine‐inducing cells play a major role in AR; this is known as the ‘Th2 paradigm’. In this review, we examine the Th1/Th2 cell dysregulation of AR and discuss new treatment approaches to improve this dysregulation.
Roles of protein tyrosine kinase Syk in nasal polyps
Authors: Yamada T. , Takahashi N. , Sunaga H. , Narita N. , Yamamoto H. , Fujieda S.
Published: July 2005

The non‐receptor protein tyrosine kinase Syk is widely expressed and plays an important role in intracellular signal transduction in haematopoietic cells including B cells, mast cells, eosinophils, platelets, macrophages, neutrophils and T cells. We found that Syk is expressed in human nasal polyp tissue‐derived fibroblasts and plays a critical role in chemokine production and activation of c‐Jun N‐terminal kinase 1 stimulated with lipopolysaccharide or IL‐1. In mast cells, cross‐linking FcɛRI via IgE bound to multivalent antigen induces tyrosine phosphorylation of immunoreceptor tyrosine‐based activation motifs, and binds and modifies the activity of Syk, thereby initiating downstream signalling. In eosinophils, Syk is essential for activating the antiapoptotic pathway and generating reactive oxygen intermediates in response to Fcγ receptor engagement. In nasal polyps, Syk inhibition might influence the levels and function of specific IgE to Staphylococcus aureus enterotoxins that are thought to drive local eosinophilic inflammation therein. The regulation of Syk expression may prove to be a useful strategy in the treatment of airway diseases.
Distinct role for nasal fibroblasts in initiation of the eosinophilic inflammatory response
Authors: Nonaka M. , Pawankar R. , Fukumoto A. , Ogihara N. , Sakanushi A. , Yagi T.
Published: July 2005

Background
It is now generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play essential roles in the pathogenesis of nasal polyposis, a disorder characterized by chronic eosinophilic inflammation and varying degrees of structural abnormalities. The mechanisms that cause the predominance of eosinophil infiltration in nasal polyposis have yet to be clarified; however, there is growing evidence that fibroblasts could be major sources of chemotactic factors for eosinophils. As the first point of contact for incoming potentially injurious agents such as microorganisms and their breakdown products including lipopolysaccharide (LPS), the nasal mucosa is exposed to many environmental pathogens.

Objective
We investigated whether airway fibroblasts produce the CC chemokines regulated upon activation, normal T cell expressed and secreted (RANTES) and eotaxin when stimulated with LPS and/or Th2 cytokines such as IL‐4 and examined whether there is any heterogeneity among fibroblasts from different airway tissue sites with regard to CC chemokine expressions.

Methods
Fibroblast cell lines were established from human airway biopsy tissues. The expression of chemokine mRNA and amount of chemokines in supernatants were measured.

Results
LPS stimulated the synthesis of RANTES in nasal fibroblasts but not in pharyngeal, tracheal, bronchial and lung fibroblasts. Combined stimulation with LPS and IL‐4 synergistically induced the production of eotaxin in nasal fibroblasts but not in lung fibroblasts.

Conclusions
These results indicate distinct contributions of nasal fibroblasts to eosinophilic inflammation in the airway.
The strange case of the Dudley Bug
Authors: Worton Graham
Published: July 2005

Or, how the ‘Dudley Bug’ escapes from a town Museum in the English Midlands and tries to find its way back on to Dudley's Coat of Arms…
Using smart card technology to monitor the eating habits of children in a school cafeteria: 1. Developing and validating the methodology
Authors: Lambert N. , Plumb J. , Looise B. , Johnson I. T. , Harvey I. , Wheeler C. , Robinson M. , Rolfe P.
Published: July 2005

Objective  The aim of the study was to test the feasibility of using smart card technology to track the eating behaviours of nearly a thousand children in a school cafeteria.

Methods  Within a large boys’ school a smart card based system was developed that was capable of providing a full electronic audit of all the individual transactions that occurred within the cafeteria. This dataset was interfaced to an electronic version of the McCance and Widdowson composition of foods dataset. The accuracy of the smart card generated data and the influence of portion size and wastage were determined empirically during two 5‐day trials.

Results  The smart card system created succeeded in generating precise data on the food choices made by hundreds of children over an indefinite time period. The data was expanded to include a full nutrient analysis of all the foods chosen. The accuracy of this information was only constrained by the limitations facing all food composition research, e.g. variations in recipes, portion sizes, cooking practices, etc. Although technically possible to introduce wastage correction factors into the software, thereby providing information upon foods consumed, this was not seen as universally practical.

Conclusion  The study demonstrated the power of smart card technology for monitoring food/nutrient choice over limitless time in environments such as school cafeterias. The strengths, limitations and applications of such technology are discussed.
Can we use mid upper arm anthropometry to detect malnutrition in medical inpatients? A validation study
Authors: Burden S. T. , Stoppard E. , Shaffer J. , Makin A. , Todd C.
Published: July 2005

Background and aims  Mid upper arm anthropometry (MUAA) is often used as a measure of nutritional status to detect changes in body composition. The aim of this study was to investigate the reliability and validity of MUAA including mid arm circumference (MAC) and triceps skin fold thickness (TSFT) to determine the usefulness in clinical practice.

Method  We measured MUAA in 158 consecutive admissions along with subjective global assessment (SGA) and body mass index (BMI). Inter‐ and intra‐rater reliability was evaluated in an additional 50 patients.

Results  The sensitivity and specificity of MUAA <5th percentile was compared with SGA and BMI. MAC and TSFT had a low sensitivity and a high specificity with low positive predictive values when compared with criterion values which were BMI ≤18 and SGA‐C. The intra‐class correlation coefficient for inter‐ and intra‐rater reliability for MAC were 0.98 (95% CI 0.96–0.98) and 0.99 (95% CI 0.98–0.99) respectively and for TSFT were 0.97 (95% CI 0.91–0.97) and 0.98 (95% CI 0.95–0.98) respectively.

Conclusion  MUAA <5th percentile had a high specificity but low sensitivity when compared with indicators of malnutrition. Although MUAA could be reliably measured, it has poor validity and is thus unlikely to be a good predictor of clinical outcome. Percentiles based on healthy populations do not generalize well to the individuals seen in clinical practice.
Does the provision of cooled filtered water in secondary school cafeterias increase water drinking and decrease the purchase of soft drinks?
Authors: Loughridge J. L. , Barratt J.
Published: July 2005

Background  Secondary school students often do not drink sufficient quantities of water during the school day to prevent dehydration, promote learning and good health. The study aimed to measure the effect of health promotion and the free provision of cooled filtered water on the consumption of water and soft drinks. It also aimed to explore students’ views of drinking water provision.

Methods  A study was conducted with three secondary schools in North Tyneside. Over a 3 month period one school was given cooled filtered water and active promotion (W + P), another had water only (W). The control school (C) took part in post‐intervention focus group work.

Results  The average volume of water drunk by students, in school ‘W + P’ was greater (P = 0.05) than that drunk in school ‘W’ and control school ‘C’. The volume of soft drinks purchased by students in all three schools before and during the intervention remained static. Focus group data revealed that students viewed their existing water provision as poor and wanted sufficient supplies of cooled filtered water in school.

Conclusions  This pilot study indicates that active promotion of water drinking increased consumption of water by secondary school students. Further developments of the project are suggested.
A new stereological principle for test lines in three‐dimensional space
Authors: CRUZ‐ORIVE L. M.
Published: July 2005

A new principle is presented to generate isotropic uniform random (IUR) test lines hitting a geometric structure in three‐dimensional space (3D). The principle therefore concerns the estimation of surface area, volume, membrane thickness, etc., of arbitrary structures with piecewise smooth boundary. The principle states that a point‐sampled test line on an isotropic plane through a fixed point in 3D is effectively an invariant test line in 3D. Particular attention is devoted to the stereology of particles, where an alternative to the surfactor method is obtained to estimate surface area. An interesting case arises when the particle is convex. The methods are illustrated with synthetic examples.
Electron and ion imaging of gland cells using the FIB/SEM system
Authors: DROBNE D. , MILANI M. , ZRIMEC A. , LEŠER V. , BERDEN ZRIMEC M.
Published: July 2005

The FIB/SEM system was satisfactorily used for scanning ion (SIM) and scanning electron microscopy (SEM) of gland epithelial cells of a terrestrial isopod Porcellio scaber (Isopoda, Crustacea). The interior of cells was exposed by site‐specific in situ focused ion beam (FIB) milling. Scanning ion (SI) imaging was an adequate substitution for scanning electron (SE) imaging when charging rendered SE imaging impossible. No significant differences in resolution between the SI and SE images were observed. The contrast on both the SI and SE images is a topographic. The consequences of SI imaging are, among others, introduction of Ga+ ions on/into the samples and destruction of the imaged surface. These two characteristics of SI imaging can be used advantageously. Introduction of Ga+ ions onto the specimen neutralizes the charge effect in the subsequent SE imaging. In addition, the destructive nature of SI imaging can be used as a tool for the gradual removal of the exposed layer of the imaged surface, uncovering the structures lying beneath. Alternative SEM and SIM in combination with site‐specific in situ FIB sample sectioning made it possible to image the submicrometre structures of gland epithelium cells with reproducibility, repeatability and in the same range of magnifications as in transmission electron microscopy (TEM). At the present state of technology, ultrastructural elements imaged by the FIB/SEM system cannot be directly identified by comparison with TEM images.
A new aquatic beetle family, Meruidae, from Venezuela (Coleoptera: Adephaga)
Authors: Spangler Paul J. , Steiner Warren E.
Published: July 2005

Abstract. An unknown beetle collected in the Territorio Federal Amazonas, Venezuela, and designated as belonging to a new family, is described (asMeru phyllisaegen.n.,sp.n.) and illustrated by line drawings and scanning electron micrographs. The new family, Meruidae, is diagnosed and assigned to the suborder Adephaga with a discussion of some characters and likely phylogenetic affinities. With a body length of 0.85–0.9 mm,M. phyllisaeis the smallest known member of aquatic Adephaga. Based on the observed skeletal and behavioural characters to date, the taxon appears to represent the sister clade to the remaining families of Dytiscoidea, but also has features suggesting a close relationship among Noteridae and/or Haliplidae. A description and photographs of the habitat are included, with a list of other associated water beetle taxa. Some observations on the behaviour of captive beetles are given. The minute ‘comb‐clawed cascade beetles’ are known only from the type locality, El Tobogán, where streams flow among exposed areas of bedrock in the geologically ancient Guyana Shield region.
Flavohaemoglobin HmpX from Erwinia chrysanthemi confers nitrosative stress tolerance and affects the plant hypersensitive reaction by intercepting nitric oxide produced by the host
Authors: Boccara Martine , Mills Catherine E. , Zeier Jürgen , Anzi Chiara , Lamb Chris , Poole Robert K. , Delledonne Massimo
Published: July 2005

Host cells respond to infection by generating nitric oxide (NO) as a cytotoxic weapon to facilitate killing of invading microbes. Bacterial flavohaemoglobins are well‐known scavengers of NO and play a crucial role in protecting animal pathogens from nitrosative stress during infection. Erwinia chrysanthemi, which causes macerating diseases in a wide variety of plants, possesses a flavohaemoglobin (HmpX) whose function in plant pathogens has remained unclear. Here we show that HmpX consumes NO and prevents inhibition by NO of cell respiration, indicating a role in protection from nitrosative stress. Furthermore, infection of Saintpaulia ionantha plants with an HmpX‐deficient mutant of E. chrysanthemi revealed that the lack of NO scavenging activity causes the accumulation of unusually high levels of NO in host tissue and triggers hypersensitive cell death. Introduction of the wild‐type hmpX gene in an incompatible strain of Pseudomonas syringae had a dramatic effect on the hypersensitive cell death in soya bean cell suspensions, and markedly reduced the development of macroscopic symptoms in Arabidopsis thaliana plants. These observations indicate that HmpX not only protects against nitrosative stress but also attenuates host hypersensitive reaction during infection by intercepting NO produced by the plant for the execution of the hypersensitive cell death programme.
Strengths and weaknesses of museum and national survey data sets for predicting regional species richness: comparative and combined approaches
Authors: Guralnick Robert , Van Cleve Jeremy
Published: July 2005

We compiled three independent data sets of bird species occurrences in northeastern Colorado to test how predicted species richness compared to a combined analysis using all the data. The first data set was a georeferenced regional museum data set from two major repositories — the Denver Museum of Nature, and the Science and University of Colorado Museum. The two national survey data sets were the Breeding Bird Survey (summer), and the Great Backyard Bird Count (winter). Resulting analyses show that the museum data sets give richness estimates closest to the combined data set while exhibiting a skewed abundance distribution, whereas survey data sets do not accurately estimate overall richness even though they contain far more records. The combined data set allows the strengths of one data set to augment weaknesses in others. It is likely some museum data sets display skewed abundance distributions due to collectors’ potentially self‐selecting under‐represented species over common ones.
Case of emphysematous pyelonephritis in a renal allograft
Authors: Fujita Shiro , Watanabe Jota , Reed Alan I , Hemming Alan W , Solis Diego , Netzel Tisha C , Banull Katherine , Schain Denise C , Howard Richard J
Published: July 2005

Abstract:  Emphysematous pyelonephritis is a rare, but serious complication after renal transplantation. This is a case report of a 49‐yr‐old female who had a renal transplant for diabetic nephropathy. She presented to ER with about 1 wk history of right lower abdominal pain and fever 15 months after the transplant. She had gross hematuria and mental status changes just prior to presentation. A computed tomography (CT) scan of the abdomen showed extensive retroperitoneal and extraperitoneal air dissecting from the transplanted kidney in the right lower quadrant to the level of the mediastinum. There was air in the urinary bladder. These findings were highly suggestive of extensive emphysematous pyelonephritis. The patient was taken to the operating room emergently and underwent a transplant nephrectomy. Blood culture and urine culture were subsequently positive for Salmonella (serogroup O 6, 8 or C2). Initial blood culture also yielded Enterobacter cloacae. The patient was treated with imipenem, cefepime, flagyl, and diflucan empirically: this was later changed to complete a 6‐wk course of ciprofloxacin upon discharge. Her hospital course was complicated by a urinary leak; she was discharged to home on day 21. This is the 12th reported case of emphysematous pyelonephritis occurred in a renal transplant recipient.
Significance of subclinical rejection in early renal allograft biopsies for chronic allograft dysfunction
Authors: Miyagi Moriatsu , Ishikawa Yukio , Mizuiri Sonoo , Aikawa Atsushi , Ohara Takehiro , Hasegawa Akira
Published: July 2005

Abstract:  To determine the significance of early subclinical rejection of renal allografts, we reviewed 127 biopsy specimens obtained soon after transplantation. Histological finding was categorized according to a modification of the Banff scheme as: acute rejection (AR), borderline changes (BL); non‐specific inflammatory changes, (NI) and no rejection (NR). Subclinical rejection was defined as AR, BL or NI. Patients with BL or NI were divided into two groups; one was treated with high‐dose methylprednisolone (MP), the other remained untreated. Freedom from chronic allograft dysfunction (defined as non‐doubling of serum creatinine 5 yr after transplantation) was significantly more frequent in the NR group (89%) than in the BL (70%) and AR (64%) groups. At 1 yr after transplantation, mean serum creatinine had increased significantly only in the untreated group (p < 0.05), and re‐biopsy showed that interstitial fibrosis had developed to a significantly greater extent in the untreated group than in the treated group (p < 0.01). Subclinical rejection in the early protocol biopsies correlated closely with subsequent allograft dysfunction. High‐dose MP treatment for early subclinical rejection may be effective in suppressing the development of interstitial fibrosis at 1 yr after transplantation.
Endothelin‐1 plasma levels and hypertension in cyclosporine‐treated renal transplant patients
Authors: Cauduro Rafael L , Costa Cesar , Lhulier Francisco , Garcia Règis G , Cabral Renan D , Gonçalves Luiz FS , Manfro Roberto C
Published: July 2005

Abstract:  Experimental models suggest that endothelin‐1 (ET‐1) has a significant role in the pathogenesis of cyclosporin A (CyA)‐induced hypertension. However, its serum levels evaluated in different studies, including patients who received solid organ transplants, exhibited controversial results. Our study population consisted of 43 renal transplant patients: 33 were taking CyA as a component of their immunosuppressive regimen (CyA group) and 10 that were not taking CyA (control group). Baseline laboratory data, blood pressure and ET‐1 levels were taken at baseline and 3 and 4 h after the ingestion of CyA. In the control group samples were collected in the corresponding periods of time. Blood pressure was significantly higher in the CyA group (mean blood pressure: 101.2 ± 9.5 vs. 91.1 ± 10.7 mmHg; p < 0.001), who also presented higher serum creatinine (1.2 ± 0.28 vs. 0.97 ± 0.13 mg/dL; p < 0.001) and ET‐1 levels. In the CyA group an ET‐1 peak was evident by the third hour after CyA ingestion that showed its maximum concentration after 1–2 h; the control group exhibited significantly lower levels of ET‐1 (p = 0.044). ET‐1 levels compared between patients with and without hypertension showed a non‐statistically significant difference (1.54 ± 0.76 vs. 1.27 ± 0.62 ng/mL; p = 0.27, respectively). In conclusion, in the present study chronic CyA ingestion was associated with higher blood pressure and plasma ET‐1 levels.
Emergent autotransplantation of a renal allograft
Authors: Casingal Vincent P , Asolati Massimo , Hunter David , Gruessner Rainer WG
Published: July 2005

Abstract:  Renal autotransplantation is an acceptable treatment for a variety of renal pathology. Indications for autotransplantation include renal artery diseases, loin pain hematuria syndrome, repair of ureteral pathology, ex vivo tumor resection, and repair of traumatic injury. Long‐term results confirm that autotransplantation is a safe and effective procedure. Renal allograft autotransplantation has also been described for repair of vascular disease, and relocation of an allograft. We describe the first case, to our knowledge of an emergent autotransplant of a renal allograft. The patient had undergone a simultaneous kidney–pancreas transplant 7 yr prior. During attempted stenting of a common iliac artery occlusion, the stent migrated, thus jeopardizing the renal allograft. The patient was taken emergently to the operating room for open repair. This included autotransplantation of the entire kidney. The patient recovered to baseline renal function. This article reviews the indications for renal autotransplantation and autotransplantation of a renal allograft. A case of emergent autotransplant of a renal allograft is described.
Efficacy and cardiovascular safety of daclizumab, mycophenolate mofetil, tacrolimus, and early steroid withdrawal in renal transplant recipients: a multicenter, prospective, pilot trial
Authors: Abramowicz Daniel , Vanrenterghem Yves , Squifflet Jean‐Paul , Kuypers Dirk , Mourad Michel , Meurisse Michel , Wissing Martin
Published: July 2005

Abstract:  This single‐arm, open‐label, pilot study was designed to assess the efficacy and cardiovascular safety profile of daclizumab, a humanized monoclonal interleukin (IL)‐2Rα antibody, in combination with mycophenolate mofetil (MMF), tacrolimus, and early corticosteroid withdrawal in renal transplant recipients. Seventy‐nine renal allograft recipients were treated with daclizumab (1 mg/kg; five doses starting on the day before transplant and then every two weeks), MMF (1 g b.i.d.), tacrolimus (0.2 mg/kg/d), and low‐dose prednisolone, which was withdrawn at day 150 after transplant. The rate of acute rejection was determined at 12 months. Lipid profile, oral glucose tolerance, and adverse events were monitored. Of the 76 patients eligible for analysis, eight (10.5%) developed biopsy‐proven acute rejection (BPAR). Ten (13.2%) experienced clinical and/or BPAR. Corticosteroids were withdrawn completely in 91% of patients at 12 months. Graft and patient survival were 97.5% and 98.7% respectively. Mean total cholesterol and triglycerides were significantly lower at 12 months post‐transplant than at baseline (201 ± 47.5 vs. 190.8 ± 43.6 mg/dL, p = 0.005 and 196.2 ± 133.2 vs. 144.5 ± 76.8 mg/dL, p < 0.001, respectively). Mean hemoglobin A1c levels did not differ between baseline (5.54%) and 12 months (5.48%). New‐onset post‐transplant diabetes mellitus occurred in 6.6% of the non‐diabetic transplanted patients. The proportion of patients with abnormal oral glucose tolerance test (OGTT) was 47% at 3 months and 39% at 12 months (p = NS). Daclizumab induction in combination with MMF, tacrolimus, and low‐dose (followed by withdrawal) prednisolone appears to be effective and safe in patients receiving renal allografts. The regimen appears to be associated with a favorable cardiovascular profile.
Living‐related liver transplantation for Wilson's disease
Authors: Tamura Sumihito , Sugawara Yasuhiko , Kishi Yoji , Akamatsu Nobuhisa , Kaneko Junichi , Makuuchi Masatoshi
Published: July 2005

Abstract:  Liver transplantation with liver grafts from deceased donors is the treatment of choice for patients suffering from Wilson's disease (WD) with end‐stage liver disease. There are few reports, however, on the use of liver grafts from living‐related donors for WD. Five (two pediatric and three adult recipients) underwent living‐related liver transplantation (LRLT) for WD at the University of Tokyo. Two patients presented with fulminant hepatic failure with hemolysis, and the other three presented with decompensating cirrhosis, one with an overlapping neurologic WD. All recipients had a low serum ceruloplasmin level (median: 18 mg/dL), high urinary copper level (mean: 1119 μg/d), and presented with Kayser–Fleischer rings before transplantation. Although one patient died from early graft thrombosis unrelated to WD, the other four patients have shown an excellent long‐term prognosis. Following successful transplantation, there was a significant reduction in urinary copper excretion (median: 64 μg/d) in all patients. The neurologic symptoms of WD in one patient, however, worsened after 2 months and gradually subsided, but not completely, over the 2‐yr follow‐up. For advanced liver failure in WD, we consider LRLT a valuable life‐saving option. The improvement of neurologic symptoms, however, requires further evaluation.
Causes of early acute graft failure after liver transplantation: analysis of a 17‐year single‐centre experience
Authors: Varotti Giovanni , Grazi Gian Luca , Vetrone Gaetano , Ercolani Giorgio , Cescon Matteo , Gaudio Massimo Del , Ravaioli Matteo , Cavallari Antonino , Pinna Antonio
Published: July 2005

Abstract:  Despite satisfactory overall results reported, early post‐operative period after liver transplantation (LT) still represents a critical time with persistently high rate of graft loss. We retrospectively reviewed our experience of 17 yr in LT, analysing the impact on grafts and patient survivals of the acute complications affecting the graft in the early period following LT. To evaluate the changes that occurred over the years in case of early acute graft failure (EAGF), the study population was divided into three equal groups of 223 patients corresponding to three different periods. Ninety (13.5%) experienced an EAGF. Causes of EAGF were hepatic artery thrombosis (HAT) in 32 cases (4.8%), primary graft non‐function in 29 cases (4.3%), caval stenosis in 19 (2.8%), early irreversible acute rejection in 6 (0.9%) and portal vein thrombosis in 4 (0.6%). The use of elderly donors and the introduction of the piggyback technique proved to be associated with a higher incidence of HAT and caval stenosis, respectively. Female recipients of male donors were independently associated with Primary graft non‐function. Of 90 patients with EAGF, 20 (22.2%) died within the first month after LT, 34 (37.8%) underwent retransplantation (ReLT) and 36 (40%) received conservative treatment. Conservative treatments increased from 3.6% in the first group to 47.0 and 66.8% in the second and third one (p = 0.000). One‐year graft and patient survival of patients with EAGF significantly improved over the three eras analysed. The incidence of EAGF remains consistent. Nevertheless, a better understanding of the clinical situations and changes in treatment strategies have led to significant improvements in terms of graft and patient survival rates, now close to the survival rate of EAGF‐free patients.
High incidence of recurrence and hematologic events following liver transplantation for Budd–Chiari syndrome
Authors: Cruz Elizabeth , Ascher Nancy L , Roberts John P , Bass Nathan M , Yao Francis Y
Published: July 2005

Abstract:  Background:  Most cases of Budd–Chiari syndrome (BCS) in Western countries are related to underlying hematologic diseases with inherent thrombogenic propensity. We evaluated the long‐term outcome, risks for recurrent disease, and other hematologic complications following orthotopic liver transplantation (OLT) for BCS.

Methods:  Clinical data from 11 consecutive patients with BCS who underwent OLT were retrospectively reviewed. Four patients had a prior transjugular intrahepatic portosystemic shunt and one had a surgical shunt procedure. All patients were started on intravenous heparin within the first 24 h following OLT. All except one patient who had protein C deficiency were maintained on long‐term oral anticoagulation.

Results:  The Kaplan–Meier survival rates at 1, 5 and 10 yr were 81, 65 and 65%, respectively. Three patients developed BCS recurrence, including two who died as a consequence of rapid graft failure within days after OLT. Three patients developed other thrombotic events, including splenic vein thrombosis associated with gastric variceal hemorrhage requiring splenectomy, portal vein thrombosis and pulmonary embolism. Four patients experienced severe bleeding complications within 7 d after OLT requiring exploratory laparotomy. One patient died after transformation of polycythemia vera to acute myelogenous leukemia at 2.1 yr after OLT.

Conclusion:  We observed a high incidence of recurrent BCS and complications related to the underlying hematologic disorder or anticoagulation after OLT for BCS. The present series also included the first two cases of rapid recurrence of BCS and graft failure within days after OLT.
Thymoglobulin induction protects liver allografts from ischemia/reperfusion injury
Authors: Bogetti Diego , Sankary Howard N , Jarzembowski Tomasz M , Manzelli Antonio , Knight Peter S , Thielke James , Chejfec Gregorio , Cotler Scott , Oberholzer Jose , Testa Giuliano , Benedetti Enrico
Published: July 2005

Abstract:  Background:  Interventions that minimize hepatic ischemia/reperfusion injury (IRI) can expand the donor organ pool. Thymoglobulin (TG) induction therapy has been shown to ameliorate delayed graft function and possibly decrease IRI in cadaver renal transplants recipients. This controlled randomized trial was designated to assess the ability of TG to protect against IRI in liver transplant recipients.

Patients and methods:  Twenty‐two cadaveric liver transplant recipients were randomized to receive either TG (1.5 mg/kg/dose) during the anhepatic period and QOD ×2 doses or no TG. No differences in recipients’ demographics were present and donor characteristics were similar in terms of age, cause of death, and cold ischemia time. Maintenance immunosupression consisted of Tacrolimus (or Cyclosporine) and steroids for both groups. Donor biopsies were obtained during organ procurement, cold storage and 1 h after re‐vascularization. Post‐operative liver function tests were monitored. Early graft function, length of stay, patient and graft survival rates, incidence of primary non‐function and rate of rejection were assessed. Results: Patient and graft survival at 3 months was 100%. There was no incidence of primary graft non‐function and no need for re‐transplantation. The incidence of acute rejection was similar between the two groups. Patients in the TG group had significant decreases in alanine aminotransferase test at day 1 compared to the control group (p = 0.02). There were also near significant decreases of total bilirubin at day 5 and shorter length of hospitalization. Liver biopsy (at procurement, when cold, and post‐reperfusion) of TG group demonstrated a trend for increased central ballooning.

Conclusion:  The TG allowed for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function. Further studies on the degree of apoptosis in the liver biopsy post‐reperfusion are underway.
Memory functions in prednisone‐treated kidney transplant patients
Authors: Bermond Bob , Surachno Sugianto , Lok Anja , Ten Berge Ineke JM , Plasmans Barbara , Kox Cornelis , Schuller Esther , Schellekens Peter TA , Hamel Ronald
Published: July 2005

Abstract:  The literature indicates that high daily doses of gluco‐corticosteroids have a degenerating effect upon the hippocampus and thus result in reduced declarative memory capacities. In order to prevent rejection, renal transplant recipients are treated with moderate daily doses of gluco‐corticosteroids and, if necessary, with high pulse‐doses during a few days. The question, therefore, arises as to whether or not such standard treatments result in memory impairments. For this reason, declarative memory capacities were measured, by means of a Dutch version of Rey's 15 Words Test, in a group of 52 renal transplant recipients. Results clearly indicated severe reductions in declarative memory capacities in these patients.
Evaluation of MR‐angiography for pre‐operative assessment of living kidney donors
Authors: Prosst Ruediger L , Fernández Emilio Domínguez , Neff Wolfgang , Braun Claude , Neufang Thomas , Post Stefan
Published: July 2005

Abstract:  Introduction:  Pre‐operative magnetic resonance tomography (MR) and MR‐angiography (MRA) have rendered favorable results for the assessment of renal anatomy preceding living‐related kidney transplantation. However, limited value of MRA in the detection of accessory renal vasculature is reported.

Methods:  We compared the results of pre‐operative contrast‐medium‐enhanced MRA of the last 30 consecutively performed nephrectomies in living kidney donors with the intraoperative findings of vascular, parenchymal, and ureteral anatomy.

Results:  Pre‐operative MRA diagnosed a solitary renal artery in 24 cases (80%) and a normal venous, ureteral and parenchymal anatomy in all cases. Intraoperatively, the surgeon confirmed the normal pre‐operative MRA findings of ureter and parenchyma. Yet, in 6 out of 30 patients (20%) vascular architecture differed from the pre‐operative imaging: four of them, who had a radiologically regular anatomy, were found to have accessory vessels upon surgical preparation. In the fifth patient, MRA revealed an accessory lower polar artery, which was confirmed during surgery. An undiagnosed third arterial vessel, located behind the renal vein, led to an aortic bleeding. In the sixth case, the adrenal gland artery was misinterpreted as an accessory superior polar artery of the kidney in MRA. Additionally, a radiologically undetected inferior polar artery was dissected during nephrectomy and led to partial hypoperfusion of the graft. Subsequent retrospective reevaluation of the MRA by experienced radiologists was unable to identify the intraoperative anatomical discrepancies. Hence, sensitivity of MRA was 60% (6 out of 10 cases) for accessory renal vessel detection and 80% (24 out of 30 cases) for overall sensitivity in determining renal vessel number.

Discussion:  MRA is a reliable method for the non‐invasive investigation of living kidney donors and provides valuable information required by the surgeon. But, as the technique misses small diameter vessels, it cannot be recommended as sole diagnostic tool in unclear cases.
Increased risk of post‐transplant diabetes mellitus despite early steroid discontinuation in Hispanic kidney transplant recipients
Authors: Walczak Debra A , Calvert Denise , Jarzembowski Tomasz M , Testa Giuliano , Sankary Howard N , Thielke James , Oberholzer José , Benedetti Enrico
Published: July 2005

Abstract:  Early steroid discontinuation (ESD) has been associated with a lower incidence of post‐transplant diabetes mellitus (PTDM). We retrospectively reviewed the incidence of PTDM in relation to racial groups in kidney transplant recipients treated with ESD. Between January 2002 and September 2003, 125 consecutive primary adult kidney transplants were performed. Group A (n = 91) had steroids discontinued on postoperative day 6 and maintenance immunosuppression of Tacrolimus and mycophenolate mofetil. Group B (n = 34), received the same immunosuppression but was maintained on steroids indefinitely. Induction consisted of thymoglobulin in African–Americans; all others received Simulect. At 1 yr, patient/graft survival, serum creatinine and rate of acute rejection were similar in both groups. The incidence of PTDM was significantly lower in group A (7%) compared with group B (26%, p = 0.0209). The incidence of PTDM in group A was limited to Hispanic patients with a family history of diabetes mellitus. African–Americans and Caucasians in group A did not experience PTDM (p = 0.005 compared with African–American in group B). Our steroid free protocol nearly eliminated the incidence of PTDM in African–Americans and Caucasians, but was still associated with significant rate of PTDM in Hispanic recipients. Alternative immunosuppression may benefit this population.
Influence of cumulative number of marginal donor criteria on primary organ dysfunction in liver recipients
Authors: Pokorny H , Langer F , Herkner H , Schernberger R , Plöchl W , Soliman T , Steininger R , Muehlbacher F
Published: July 2005

Abstract:  Background:  The aim of this cohort study was to assess the cumulative effect of marginal donor criteria on initial graft function and patient survival after liver transplantation.

Methods:  We included 734 consecutive patients who underwent orthotopic liver transplantation at the Vienna General Hospital between January 1993 and December 2003. We employed the local registry of the Department of Transplant Surgery, where variables of all patients are routinely and prospectively recorded. Primary outcome was initial graft function, secondary outcome was patient survival.

Results:  Cumulative number of marginal donor criteria was significantly and linearly associated with an increased rate of primary dysfunction (PDF; p = 0.005). In patients with more than three cumulative marginal donor criteria the rate of PDF was 36%. Patient survival was not influenced by the cumulative number of donor criteria (log‐rank test, p = 0.81). Independent marginal donor criteria to predict PDF were cold ischemia time >10 h [odds ratio (OR) 0.56; 95% CI 0.32–0.98] and donor peak serum sodium >155 mEq/L (OR 0.44; 95% CI 0.26–0.77), as assessed in a multivariate regression model.

Conclusions:  The use of marginal liver donors with more than three marginal donor criteria shows deleterious effects on initial graft function. Noteworthy, patient survival was not associated with marginal donor criteria, which may be explained by early and successful retransplantation of liver recipients with primary non‐function.
Up‐regulation of cyclooxygenase‐2 during acute human renal allograft rejection
Authors: Rangel Érika B , Moura Luiz A , Franco Marcello F , Pacheco‐Silva Álvaro
Published: July 2005

Abstract:  Background:  Cyclooxygenases‐1 and ‐2 (COX‐1 and COX‐2) are important in renal physiology and in many abnormal states. However, there is poor information about them during renal allograft rejection. The purpose of this study was to analyze cyclooxygenases expression in renal tissue allograft during acute rejection.

Methods:  COX‐1 and COX‐2 transcripts and proteins were analyzed by semi‐quantitative RT‐PCR and immunohistochemistry in samples from human renal allografts obtained from nephrectomy because of irreversible acute rejection.

Results:  In samples with acute rejection, we detected higher expression of COX‐2 mRNA in comparison with COX‐1 (p < 0.001) being COX‐2 expression not different from COX‐1 in samples from renal allografts without acute rejection. COX‐1 and COX‐2 localization was in accordance with data described in literature, however COX‐2 protein was higher in interstitial cells in the group with rejection than in the group without rejection (p = 0.04). In addition, in samples with acute rejection COX‐2 immunoreactivity was more prominent in podocytes (p < 0.001), in proximal tubules (p < 0.001), in collecting duct cells (p = 0.003) and in interstitial cells (p < 0.001) when compared with COX‐1.

Conclusions:  Our data show that there is an increased production of COX‐2 during acute renal rejection.
Pulmonary complications of cystic echinococcosis in children in Uruguay
Authors: Sakamoto Tsukasa , Gutierrez Carmen
Published: July 2005

Cystic echinococcal lesions surgically removed from 99 patients aged 1–15 years in Uruguay were histopathologically studied. The lesions were collected from the lungs, liver, peritoneum, omentum, pleura, ovary, appendix and perinephrium. All intact cysts were well‐developed and unilocular. Pulmonary and hepatic fertile cysts in which protoscoleces were produced were in 75% and 47%, respectively, of all patients. Fertile cysts having many protoscoleces were in the lungs of a 1‐year‐old infant. Sixteen ruptured pulmonary cysts were found in the lungs of 13 patients and four ruptured hepatic cysts were found in the liver of three patients. Pulmonary complications were seen in patients having pulmonary echinococcal cysts. In lung tissue surrounding echinococcal cysts, pulmonary complications included chronic congestion, hemorrhage, bronchopneumonia, as well as interstitial pneumonia that included histological changes caused by bronchiolitis, organizing pneumonia and obstructive pneumonia. Liver tissue adjacent to echinococcal cysts showed atrophy of hepatic cells, proliferation of interstices, small focal hemorrhages, and infiltration of mononuclear cells. The present study shows that a close relationship exists between pulmonary echinococcosis and pneumonia. The term ‘echinococcal pneumonia’ is proposed for pneumonia accompanying pulmonary echinococcosis.