bluuebunny/crossref_metadata_2025 huggingface dataset:
A population‐based study of severity of comorbidity among patients with non‐Hodgkin's lymphoma: prognostic impact independent of International Prognostic Index
Authors: Janssen‐Heijnen Maryska L.G. , van Spronsen Dick Johan , Lemmens Valery E.P.P. , Houterman Saskia , Verheij Kees D.G.W. , Coebergh Jan Willem W.
Published: July 2005

Over 60% of patients aged over 70 years, diagnosed with non‐Hodgkin's lymphoma (NHL) in the Netherlands have serious comorbidity. We studied the independent influence of comorbidity on choice of treatment, dose reductions, treatment‐related toxicity and prognosis, using data from a random sample of 381 patients from the population‐based Eindhoven Cancer Registry. About 45% of patients over 60 years of age with NHL had high impact comorbidity at the time of cancer diagnosis. The proportion of patients with aggressive NHL who received chemotherapy decreased from 85% in patients aged 40–60 years to 70% in those over 60 years. About 65% of systematically treated patients with aggressive NHL suffered from treatment‐related toxicity. Toxicity appeared to be more common among females and those with high‐intermediate or high International Prognostic Index (IPI) risk. Among patients with aggressive NHL, the chance of dying for those with high impact comorbidity was twice as high compared with those without comorbidity. This was independent of the IPI risk. Dose reductions are frequently unavoidable for patients with severe comorbidity, poor performance status or chemotherapy‐related toxicity. Whether the less frequent prescription of (full dose) chemotherapy for patients with advanced age and/or with comorbidity is justified remains a question for debate.
Reduced efficacy of clinical probability score and d‐dimer assay in elderly subjects suspected of having deep vein thrombosis
Authors: Schutgens Roger E. G. , Haas Fred J. L. M. , Biesma Douwe H.
Published: July 2005

The combined strategy of a pretest clinical probability (PCP) score and d‐dimer has shown to be of value in the diagnosis of deep vein thrombosis (DVT). As d‐dimer concentrations increase with age, the effect of age on the usefulness of this strategy was retrospectively investigated in outpatients suspected of having DVT. In all patients, participants of a prospective management trial, a PCP score and d‐dimer (Tina‐quant®) were performed. In a total of 812 patients, 317 (39%) had thrombosis. Patients were divided into quartiles according to their age. Sensitivity and negative predictive value of a low/moderate PCP score and a normal d‐dimer were 98–100% and did not differ between the different age quartiles. Specificity in the highest quartile was 17·4% compared with 49·2% in the youngest (P < 0·000001). The proportion of patients with a low/moderate PCP score and a normal d‐dimer decreased with age: 12% in the highest quartile (>73·8 years) versus 25% in younger patients (P = 0·00005). We therefore conclude that the combined strategy of a low/moderate PCP score with a normal d‐dimer test is safe for excluding DVT in all age groups, but is less useful in the elderly.
An elevated venous haemoglobin concentration cannot be used as a surrogate marker for absolute erythrocytosis: a study of patients with polycythaemia vera and apparent polycythaemia
Authors: Johansson Peter L. , Safai‐Kutti Soodabeh , Kutti Jack
Published: July 2005

The diagnosis of polycythaemia vera (PV) has been established upon sets of clinical criteria, which require the presence of absolute erythrocytosis (AE). The most recent clinical criteria for PV, published by the World Health Organization (WHO) in 2001, also required AE, and stated that the measured red cell mass (RCM) could be replaced by a surrogate marker for AE; a haemoglobin (Hb) value of >18·5 g/dl in males and >16·5 g/dl in females. The present study evaluated the potential of venous haematocrit (Hct) and Hb values as possible surrogate markers for AE in a series of 77 consecutive patients with PV and 66 patients with apparent polycythaemia (AP), in all of whom the RCM had been previously determined. In only 35% of the male PV patients would Hb values >18·5 g/dl indicate the presence of AE. Conversely, 14% of male AP patients would be misdiagnosed as having AE. A Hb > 16·5 g/dl would predict the presence of AE in 63% of the female PV patients, but 35% of female AP cases would be misdiagnosed as having AE. However, when the Hct was ≥0·60 an AE was always present, and this was true for both male and female subjects.
Molecular mechanisms of eosinophil activation in allergic diseases
Authors: Chihara J.
Published: July 2005

Eosinophils are major effector cells in allergic diseases. These cells possess a variety of membrane receptors that mediate their activation in the presence of pro‐inflammatory chemokines such as IL‐5, regulated on activation, normal T cell expressed and secreted, eotaxin, and intracellular adhesion molecule (ICAM)‐1. ICAM‐1 is also implicated in stimulating the production of reactive oxygen species and inducing degranulation of eosinophil granule proteins. Treatment with peroxisome proliferator‐activated receptor‐γ agonist inhibits IL‐5‐stimulated eosinophil survival and eotaxin‐directed eosinophil chemotaxis, suggesting that such agents could serve as a new therapeutic modality for the treatment of allergic diseases.
Eosinophils and rhinitis
Authors: Howarth P. H.
Published: July 2005

Allergic rhinitis (AR) is typified by the nasal mucosal and luminal recruitment of eosinophils. These changes are evident in both seasonal and perennial disease, although the magnitude of these cellular changes is often greater with the more transient intense stimulation associated with seasonal allergen exposure than with the chronic persistent stimulation linked to perennial disease. Measures of eosinophil activation markers in nasal lavage such as eosinophil cationic protein and eosinophil protein X parallel the eosinophilic cellular changes and have been used serially to monitor allergic inflammation in association with intranasal allergen challenge and in therapeutic intervention studies. In both naturally occurring disease and laboratory allergen challenge, there is considerable inter‐subject variability in the magnitude of eosinophil airway recruitment and activation. Studies evaluating the mechanisms involved in nasal eosinophil recruitment identify systemic involvement of bone marrow stimulation and tissue recruitment of circulating progenitor cells. Interleukin‐5 (IL‐5) is a key cytokine involved in this process, acting on both marrow and circulating progenitors, with chemokines such as stromal cell derived factor‐1, RANTES (regulated on activation, normal T cell expressed and secreted) and eotaxin potentially being involved in tissue uptake and localization within the nasal airways. Inflammatory mediators such as leukotrienes acting through the cys‐LT1 receptor, in conjunction with IL‐5, and prostaglandin D2 acting through eosinophil‐expressed DP and CRTH2 cell surface receptors also contribute in animal models of allergic inflammation. The function of nasal eosinophils in AR can be debated. Genetic and nasal challenge models, with chemokines that promote eosinophil influx, support the relevance of eosinophils to symptom expression in rhinitis while the timing of the eosinophil recruitment following intranasal allergen challenge, the relationship between eosinophils and plasma protein exudation as well as the appreciation that clinical disease expression can arise in the apparent absence of nasal eosinophilia favour a restorative function for this cell. In the absence of specific eosinophil‐targeted intervention in rhinitis, it is not possible to conclusively apportion the relative involvement of eosinophils in these inductive and restorative processes but it has to be appreciated that the close association between eosinophils and clinical disease expression in rhinitis is not necessarily causal.
Analysis of Th1, Th2, Tc1 and Tc2 cells in patients with allergic rhinitis
Authors: Ohta N. , Sakurai S. , Yoshitake H. , Aoyagi M.
Published: July 2005

Allergic rhinitis (AR) is an IgE‐mediated inflammatory disease of the nasal mucous membranes, characterized by paroxysms of sneezing, itching of the nose, eyes, palate, pharynx, and conjunctivae, nasal stuffiness with partial or total obstruction of airflow and mucous secretion often accompanied by post‐nasal drainage. A T helper (Th)1/Th2 cytokine imbalance with a predominance of Th2 cytokines has been suggested of pathogenic importance in AR. To evaluate the role of Th1/Th2 cytokines in AR, the subsets of Th1, Th2, T cytotoxic type 1 (Tc1) and Tc2 cells from patients with AR were examined by intracellular cytokine flow cytometry. The population of Tc1 cells (52.3±23.6%) in AR was significantly increased compared with that in control (35.4±14.6%, P<0.05). Th1, Th2 and Tc2 cells in AR were not significantly increased vs. control. However, the ratio of Th1/Th2 was significantly decreased and the ratio of Tc1/Tc2 was significantly higher in patients with AR compared with healthy individuals (P<0.05 and P<0.01, respectively). These results indicate that the predominance of Th2 and Tc1 cells might contribute to the pathogenetic mechanism in AR.
Extension tectonics in the Afar Triangle
Authors: Waltham Tony
Published: July 2005

On the Red Sea coast of Africa, the triangular wedge of land named after its Afar people has been created by excess basalt production at a triple junction of divergent plate boundaries. Its harsh desert terrain is a remote wilderness that receives few visitors, yet is a spectacular suite of extension tectonics dominated by sinking grabens, salt basins below sea level, active faults and effusive volcanoes.
Using smart card technology to monitor the eating habits of children in a school cafeteria: 2. The nutrient contents of all meals chosen by a group of 8‐ to 11‐year‐old boys over 78 days
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 abilities of the newly created smart card system to track the nutrient contents of foods chosen over several months by individual diners in a school cafeteria.

Methods  From the food choice and composition of food data sets, an Access database was created encompassing 30 diners (aged 8–11 years), 78 days and eight nutrients. Data were available for a total of 1909 meals.

Results  Based upon population mean values the cohort were clearly choosing meals containing higher than the recommended maximum amounts for sugar and lower than the recommended minimum amounts of fibre, iron and vitamin A. Protein and vitamin C contents of meals chosen were well above minimum requirements. Over the 1909 meals, nutrient requirements were met 41% of the time.

Conclusions  The system created was very effective at continually monitoring food choices of individual diners over limitless time. The data generated raised questions on the common practice of presenting nutrient intakes as population mean values calculated over a few days. The impact of heavily fortified foods on such studies in general is discussed.
Using smart card technology to monitor the eating habits of children in a school cafeteria: 3. The nutritional significance of beverage and dessert choices
Authors: Lambert N. , Plumb J. , Looise B. , Johnson I. T. , Harvey I. , Wheeler C. , Robinson M. , Rolfe P.
Published: July 2005

Objective  The consumption patterns of beverages and desserts features highly in the current debate surrounding children's nutrition. The aim of this study was to continuously monitor the choice of beverages and desserts made by nearly 1000 children in a school cafeteria.

Methods  A newly developed smart card system was used to monitor the food choices of diners (7–16‐year‐old boys) in a school cafeteria over 89 days. A wide variety of beverages and desserts were on offer daily.

Results  Despite coming from an affluent, well‐educated demographic group, the boys’ choices of beverages and desserts mirrored those of children in general. Buns and cookies were over 10 times more popular than fresh fruits and yogurts. Sugary soft‐drinks were over 20 times more popular than fresh fruit drinks and milk combined. Appropriate choices could, over a month, reduce intake of added sugar by over 800 g and fat by over 200 g.

Conclusion  The smart card system was very effective at monitoring total product choices for nearly 1000 diners. In agreement with a recent national school meal survey, where choice is extensive, children show a preference for products high in fat and/or sugar. The consequences of these preferences are discussed.
Estimation of total body water from foot‐to‐foot bioelectrical impedance analysis in patients with cancer cachexia – agreement between three prediction methods and deuterium oxide dilution
Authors: Bauer J. , Capra S. , Davies P. S. W.
Published: July 2005

Introduction  Bioelectrical impedance analysis (BIA) is a useful bedside measure to estimate total body water (TBW). The aim of this study was to determine the agreement between three equations for the prediction of TBW using BIA against the criterion method, deuterium oxide dilution, in patients with cancer cachexia.

Methods  Eighteen measurements of TBW using foot‐to‐foot BIA in seven outpatients with cancer cachexia (five male and two female, age 56.4 ± 6.7 years) at an Australian hospital. Three prediction formulae were used to estimate TBW – TBWca‐radiotherapy developed in patients with cancer undergoing radiotherapy, TBWca‐underweight and TBWca‐normal weight developed in underweight and normal weight patients with cachexia. TBW was measured using the deuterium oxide dilution technique as the gold standard.

Results  Mean measured TBW was 39.5 ± 6.0 L. There was no significant difference in measured TBW and estimates from prediction equations TBWca‐underweight and TBWca‐radiotherapy. There was a significant difference in measured TBW and TBWca‐normal weight. All prediction equations overestimated TBW in comparison with measured TBW. The smallest bias was observed with TBWca‐underweight (0.38 L). The limits of agreement are wide (>7.4 L) for each of the prediction equations compared with measured TBW.

Conclusions  At a group level, TBWca‐underweight is the best predictor of measured TBW in patients with cancer cachexia. For an individual however, the limits of agreement are wide for all prediction equations and are unsuitable for use. Practitioners need to be aware of the limitations of using TBW prediction equations for individuals.
Integration and individuality in healthy eating: meanings, values, and approaches of childless, dual earner couples
Authors: Ristovski‐Slijepcevic S. , Chapman G. E.
Published: July 2005

Introduction and objectives  Although considered to be an important component of food choice, perceptions and practices regarding healthy eating vary between people and change over the life‐course. The purpose of this paper is to examine integration and individuality in healthy eating meanings, values, and approaches of individuals in childless, dual earner couples.

Materials and methods  Fourteen participants (from seven couples) were recruited using notices and snowball sampling. Food journals and individual interviews were used to explore the nature of and negotiations between partners’ healthy eating values and approaches. Data were analysed through iterative procedures that included coding, thematic analysis and memo writing.

Results  Participants presented individual healthy eating values and approaches based on their own experiences with food over time. Cohabitation resulted in a continuum of healthy eating negotiation outcomes, including congruent values and approaches, congruent values but divergent approaches, and divergent values and approaches. In combination with other salient factors, cohabitation provides an opportunity for improving healthy eating approaches.

Discussion  Cohabitation has the potential to lead to positive changes in healthy eating approaches. Practitioners need to tailor messages for clients’ specific needs and encourage change in the direction of the partner with the healthier eating approach.
Immune modulating nutrition support for a patient with severe toxic epidermal necrolysis
Authors: Windle E. M.
Published: July 2005

Toxic epidermal necrolysis (TEN) is a rare but serious condition with a high mortality rate, whose clinical features resemble major thermal injury. Nutritional substrates which can affect the immune response have been shown to benefit burned and critically ill patients but there is a lack of data in the TEN literature. A case study is presented of a 63‐year‐old female admitted to our burn unit with extensive skin and mucosal involvement. Immune modulating artificial nutrition support was given initially via the parenteral route and then the nasogastric route. Maintenance of the patient's nutritional status and clinical outcome suggest that there may be a role for this type of intervention in TEN.
Performance of a mixed Lagrange time delay estimation autoregressive (MLTDEAR) model for single‐image signal‐ to‐noise ratio estimation in scanning electron microscopy
Authors: SIM K. S. , CHUAH H. T. , ZHENG C.
Published: July 2005

A novel technique based on the statistical autoregressive (AR) model has recently been developed as a solution to estimate the signal‐to‐noise ratio (SNR) in scanning electron microscope (SEM) images. In another research study, the authors also developed an algorithm by cascading the AR model with the Lagrange time delay (LTD) estimator. This technique is named the mixed Lagrange time delay estimation autoregressive (MLTDEAR) model. In this paper, the fundamental performance limits for the problem of single‐image SNR estimation as derived from the Cramer–Rao inequality is presented. We compared the experimental performances of several existing methods – the simple method, the first‐order linear interpolator, the AR‐based estimator as well as the MLTDEAR method – with respect to this performance bound. In a few test cases involving different images, the efficiency of the MLTDEAR single‐image estimation technique proved to be significantly better than that of the other three methods. Study of the effect of different SEM setting conditions that affect the autocorrelation function curve is also discussed.
Calcification of senile cataractous lens determined by Fourier transform infrared (FTIR) and Raman microspectroscopies
Authors: CHEN K.‐H. , CHENG W.‐T. , LI M.‐J. , YANG D.‐M. , LIN S.‐Y.
Published: July 2005

A calcified plaque on the surface of a senile cataractous lens (CL) isolated from a 79‐year‐old male patient was identified and its chemical composition quantified using Fourier transform infrared (FTIR) and confocal Raman microspectroscopies. The noncalcified area of the same CL and hydroxyapatite (HA) were selected as a control. Several unique absorption bands, at 960, 1034 and 1090 cm−1 assigned to the ν1 and ν3 stretching modes of phosphate and at 875 cm−1 attributed to carbonate, were clearly displayed in the infrared (IR) spectra of calcified plaque and HA. A peak at 961 cm−1 due to the ν1 stretching mode of phosphate was also evidenced in the Raman spectra of calcified plaque and HA. The calcified plaque formed within the lens protein was found to mainly consist of a mature HA, in which type‐A carbonate apatites (11.4%), type‐B carbonate apatites (55.6%) and liable surface carbonate ions (33.0%) were presented. A higher content of the liable carbonate implies that the calcification or mineralization in this calcified lens was incomplete and still in progress. Moreover, calcification seems not to influence the secondary structure of lens protein because both IR and Raman spectra for the lens protein in the noncalcified area and calcified plaque were similar. The result suggests that both microscopic FTIR and Raman spectroscopies were easy to perform and capable of determination of the chemical composition of a calcified CL.
Serum elastase and antithrombin‐3 in patients with acute graft‐vs.‐host disease after bone marrow transplantation
Authors: Toda Akinari , Takatsuka Hiroyuki , Nakajima Tosiyuki , Nomura Kaori , Wakae Takeshi , Itoi Hisayuki , Okada Masaya , Misawa Mahito , Hara Hiroshi
Published: July 2005

Abstract:  The mechanism by which inflammatory cytokines are involved in acute graft‐vs.‐host disease (GVHD) after hematopoietic stem cell transplantation has only been studied recently. We focused on the changes of serum elastase and antithrombin‐3 (AT‐3) from before pre‐treatment until the leukocyte recovery period after transplantation. We examined the correlation between these two parameters and the grade of acute GVHD, as well as the mechanism of onset. We measured the serum elastase and AT‐3 levels before pre‐treatment and during the leukocyte recovery period in 49 consecutive patients receiving bone marrow transplantation. The severity of acute GVHD was divided into five grades (0–4). No significant differences of pre‐transplantation elastase levels were observed among the GVHD grades, but the elastase level during the leukocyte recovery period showed a significant correlation with the grade of GVHD (p < 0.01). A significant inverse correlation was also observed (p < 0.05) between the pre‐transplantation level of AT‐3 and the grade of GVHD, as well as a significant correlation at the time of leukocyte recovery (p < 0.0001). Furthermore, a significant correlation (p < 0.0001) was observed between the elastase and AT‐3 levels during the leukocyte recovery period. These results suggest that elastase levels during the leukocyte recovery period are related to the grade of acute GVHD and the mechanism appears to include vascular endothelial injury mediated via AT‐3.
Patient and graft outcomes following liver transplantation for sarcoidosis
Authors: Lipson Evan J , Fiel Maria Isabel , Florman Sander S , Korenblat Kevin M
Published: July 2005

Abstract:  End‐stage liver disease as a consequence of hepatic sarcoidosis is a rare indication for liver transplantation. Consequently, there is a paucity of information on the pre‐transplant findings and post‐operative course of individuals transplanted for hepatic sarcoidosis. The purpose of this study was to evaluate our experience with liver transplantation for sarcoidosis. Cases were identified by review of the Mount Sinai Hospital liver transplant database. For each case, two control patients with other causes of liver failure matched for age, gender and date of transplant were selected for comparison. Hepatic sarcoidosis was the indication for liver transplantation in only seven of 2117 (0.3%) adult transplants performed from September 1988 to June 2004. The diagnosis of sarcoidosis was established by findings of extensive, non‐caseating granulomas in pre‐transplant liver biopsy specimens or in the native liver explant. Extrahepatic disease was limited to pulmonary involvement in four patients. Sarcoid cases were statistically more likely to have diabetes mellitus (100% vs. 21%, p = 0.001) and less likely to have antibodies to hepatitis C (0% vs. 50%, p = 0.047). Rates of acute cellular rejection were 57% in cases and 36% in controls (p = 0.397). Hepatic granulomas were identified in one patient at 5.6 yr of follow‐up. Among cases, the 1‐yr graft and patient survival rates were 100% and 5‐yr graft and patient survival rates were 86%. The 1‐ and 5‐yr graft and patient survival rates were comparable with those of patients transplanted for other indications.
Reproducibility of the Banff classification in subclinical kidney transplant rejection
Authors: Veronese Francisco Veríssimo , Manfro Roberto Ceratti , Roman Fernando Roberto , Edelweiss Maria Isabel , Rush David N , Dancea Sylvia , Goldberg Julio , Gonçalves Luiz Felipe
Published: July 2005

Abstract:  The Banff classification for kidney allograft pathology has proved to be reproducible, but its inter and intraobserver agreement can vary substantially among centres. The aim of this study was to evaluate Banff reproducibility of surveillance renal allograft biopsies among renal pathologists from different transplant centres. This study included 32 renal transplant patients with stable graft function. Biopsies were performed 2 and 12 months post‐transplant. Histology was interpreted according to the Banff schema by three renal pathologists, and inter and intraobserver agreement were measured. The best reproducibility was obtained for the presence or absence of acute rejection (AR), with kappa values ranging from moderate (κ = 0.47; p = 0.006) to good (κ = 0.72; p = 0.0001). However, the agreement for ‘suspicious for AR’ category was poor between all observers. For scoring and grading interstitial inflammation and intimal arteritis the agreement were poor and moderate, respectively. Reproducibility for the presence or absence of chronic allograft nephropathy (CAN) was heterogeneous, ranging from poor (κ = 0.13; p = NS) to moderate (κ = 0.56; p = 0.007). Scoring chronic changes such as fibrous intimal thickening gave a reasonable interobserver agreement. Intraobserver reproducibility was good for presence or absence of AR, but was poor for the diagnosis of CAN. In conclusion, histologic analysis of stable renal allografts based on Banff criteria showed a good agreement for the diagnosis of AR and a reasonable kappa for CAN, but reproducibility for scoring and grading showed a substantial interobserver variation.
Fatal varicella zoster virus encephalitis in two patients following allogeneic hematopoietic stem cell transplantation
Authors: Hackanson Björn , Zeiser Robert , Bley Thorsten A , Pantazis Georgios , Huzly Daniela , Bertz Hartmut , Finke Jürgen
Published: July 2005

Abstract:  Background:  Reduced cellular immunocompetence following allogeneic hematopoietic stem cell transplantation (aHSCT) increases susceptibility to viral infections. Varicella zoster virus (VZV) reactivation in this setting most commonly manifests as dermatomal herpes zoster but in some cases life‐threatening VZV encephalitis occurs.

Study design/results:  We describe the cases of two patients who presented with shingles 3 and 18 months, respectively, after HLA‐matched peripheral blood stem cell transplantation (PBSCT). Unfortunately, in the further clinical course both patients developed fatal VZV encephalitis, despite initial high‐dose intravenous therapy with acyclovir and in one case with additional VZV‐immunoglobulin.

Conclusion:  These two cases suggest that rapid intervention with systemic treatment is warranted and raise the question whether initial combination therapy with intravenous acyclovir and foscarnet, VZV vaccination or long‐term low‐dose acyclovir are needed to improve treatment and clinical outcome in immunocompromised patients, having undergone allogeneic HSCT.
Clinical outcome after cyclosporine dose reduction based on C2 levels in long‐term liver transplant patients
Authors: Tha‐In Thanyalak , Hesselink Dennis A , Tilanus Hugo W , Elshove Lara , Wilschut Anneloes L , Hansen Bettina E , van Gelder Teun , Metselaar Herold J
Published: July 2005

Abstract:  Background:  Recent studies suggest that cyclosporine dose adjustment based on C2 levels results in improvement of renal function. This study investigates the effect on renal function after dose reduction based on the C2 levels in long‐term liver transplant patients.

Methods:  In 60 patients (>1 yr after transplantation), C2 levels were assessed (target 600 ng/mL ± 20%). Dose reduction was performed when C2 >720 ng/mL. Serum creatinine concentrations were measured and creatinine clearance was calculated.

Results:  Twenty‐three patients (38%) had C2 values >720 ng/mL. After dose reduction, mean cyclosporine dose decreased by 25% (p < 0.01). Mean C2 value decreased by 42% (p < 0.01). Serum creatinine concentrations remained stable. After dose reduction two patients experienced recurrence of PBC, in one patient AIH recurred and rejection was diagnosed in one patient.

Conclusion:  Cyclosporine C2 concentrations above 720 ng/mL are common in long‐term liver transplant patients. Dose reduction of 25% did not improve kidney function and was accompanied by immune activation.
Randomized calcineurin inhibitor cross over study to measure the pharmacokinetics of co‐administered enteric‐coated mycophenolate sodium
Authors: Kaplan Bruce , Meier‐Kriesche Herwig‐Ulf , Minnick Paula , Bastien Marie‐Claude , Sechaud Romain , Yeh Ching‐Ming , Balez Sebastien , Picard Franck , Schmouder Robert
Published: July 2005

Abstract:  Enteric‐coated mycophenolate sodium (EC‐MPS) (myfortic®) is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA‐related upper gastrointestinal adverse events by delaying the release of MPA until the small intestine. A randomized, calcineurin inhibitor crossover, steady‐state pharmacokinetic study in stable renal transplant patients receiving EC‐MPS demonstrated increased MPA exposure of 19% higher, MPA Cmax,ss 19% lower and MPA Cmin,ss approximately twofold higher with tacrolimus, than cyclosporine microemulsion. No study drug‐related adverse events were recorded, but mean blood glucose concentration was higher in patients receiving tacrolimus (p = 0.031). The dose changes in relation to MPA exposure in patients is dependent on the clinical situation and may not always be warranted. These observations should be taken into consideration when switching from one calcineurin inhibitor to another, but the final dosage should be based on both this pharmacokinetic data and the clinical situation.
Extraskeletal myxoid chondrosarcoma: Updated clinicopathological and molecular genetic characteristics
Authors: Hisaoka Masanori , Hashimoto Hiroshi
Published: July 2005

Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft‐tissue sarcoma characterized by distinctive morphological and cytogenetical features. As its name implies, EMC was believed to represent a variant of soft‐tissue chondrosarcoma owing to its histological resemblance to chondroblastic tissue in the early stages of cartilage development or chondroid tumors such as skeletal chondrosarcoma. However, the chondroid nature has been a subject of controversy, and its line of differentiation remains to be determined. Consequently, the tumor is provisionally classified into a group of tumors of uncertain differentiation in the revised World Health Organization classification of tumors of soft tissue and bone. Moreover, immunohistochemical and ultrastructural features of neural or neuroendocrine differentiation have been recently reported in a subset of EMC, providing a new insight into their histogenetic nature. Chromosomal rearrangements involving 9q22, such as t(9;22)(q22;q12), and resultant NR4A3 fusion genes are tumor‐type specific or pathognomotic for this entity and are assumed to play an important role in the development of EMC. Although the biological mechanisms and functions are largely unknown, the NR4A3‐related pathway is considered a potential molecular target for future therapeutic intervention. Because of its protracted but resilient nature, a tenacious and long‐term follow up is necessary for any patient.
Aberrant expression of pyloric gland‐type mucin in mucin‐producing bile duct carcinomas: A clear difference between the core peptide and the carbohydrate moiety
Authors: Goto Masamichi , Shibahara Hiroaki , Tamada Shugo , Hamada Tomofumi , Oda Koji , Nagino Masato , Nagasaka Tetsuro , Imai Kohzoh , Nimura Yuji , Yonezawa Suguru
Published: July 2005

The authors have recently defined the clinopathological entity of a mucin‐producing bile duct tumor (MPBT), and divided MPBT into two distinct subtypes: ‘columnar‐type’ and ‘cuboidal‐type’ MPBT. Mucin core protein 6 (MUC6), which is present in normal pyloric glands, had higher expression levels in cuboidal‐type tumors than in columnar‐type tumors. In the pyloric glands, a carbohydrate antigen detected by monoclonal antibody HIK1083 (CA/HIK1083) is also expressed. In order to evaluate the coexpression pattern of MUC6 and CA/HIK1083 in MPBT, expression profiles were evaluated in 38 surgically excised mucin‐producing bile duct carcinomas (MPBC; cuboidal‐type, n = 15; columnar‐type, n = 23), using immunohistochemistry. The staining rate was graded as follows: –, <5% of neoplastic cells stained; +, 5% to <20%; + +, 20% to <50%; + + +, ≥50%. In cuboidal‐type MPBC, MUC6 was positive in all cases (+ + +, 13/15; + +, 1/15; +, 1/15), whereas CA/HIK1083 was negative in all cases (–, 15/15; P < 0.0001). In columnar‐type MPBC, MUC6 was positive in 65% of cases (+ + +, 6/23; + +, 8/23; +, 1/23; –, 8/23), and CA/HIK1083 was positive in 52% (+ +, 3/23; +, 9/23; –, 11/23; not significant). Our results clearly demonstrate that cuboidal‐type MPBC have an aberrant pyloric glandular phenotype, that is, MUC6+/CA/HIK1083–. This unique profile may be related to different outcomes of patients with MPBC.
Concordant loss of fragile gene expression early in breast cancer development
Authors: Guler Gulnur , Uner Aysegul , Guler Nilufer , Han Shuang‐Yin , Iliopoulos Dimitrios , McCue Peter , Huebner Kay
Published: July 2005

The FHIT and WWOX genes encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. Reduced Fhit and Wwox expression has been reported in approximately two‐thirds of invasive breast tumors. Expression of these fragile gene products, as well as ErbB2 and p53, were evaluated immunohistochemically in 44 pure and 31 adjacent‐to‐invasive ductal carcinoma in‐situ (DCIS) cases. Reduced Fhit and Wwox expression were observed in (i) 70% and 68% of pure DCIS; (ii) 52% and 55% of DCIS adjacent‐to‐invasive tumor cases; and (iii) 20% and 50% of adjacent normal tissue in pure DCIS cases. Reduced Wwox expression in adjacent normal tissue was observed in 30% of cases in the DCIS adjacent‐to‐invasive group. Reduced Fhit and Wwox expression was observed in 61% of adjoining invasive tumors. In all normal, pure DCIS, and DCIS adjacent‐to‐invasive lesions, Fhit and Wwox expression was positively associated (P = 0.034, P = 0.042, P = 0.004, respectively) and in the invasive component there was a positive trend toward association (P = 0.075). Fhit and Wwox were more frequently reduced in high‐grade lesions in the DCIS adjacent‐to‐invasive (P = 0.025, P = 0.004, respectively). In the pure DCIS group, there was a statistically significant negative association between Fhit and ErbB2 expression in DCIS (P = 0.035). In summary, reduced Fhit and Wwox expression in in‐situ breast cancer was associated, which may contribute to the high‐grade DCIS–invasive tumor pathway.
KIT expression in normal and neoplastic renal tissues: Immunohistochemical and molecular genetic analysis
Authors: Kato Noriko , Honma Keiichi , Hojo Hiroshi , Sasou Shun‐ichi , Matsuzaki Osamu , Motoyama Teiichi
Published: July 2005

Renal chromophobe cell carcinomas (ChCC) and oncocytomas express KIT. This character seems to reflect their common histogenesis from distal nephrons. In the normal kidney, however, the expression and localization of KIT are unclear. KIT expression in angiomyolipoma and congenital mesoblastic nephroma (CMN), is still controversial. c‐kit mutations are reportedly rare in ChCC, but there is little information in other renal neoplasms, and no reported data on mutations of platelet‐derived growth factor receptor (PDGFR). In order to address these issues the authors examined five ChCC, five oncocytomas, seven papillary cell carcinomas, two collecting duct carcinomas, 12 angiomyolipomas, and three CMN, as well as 10 normal renal tissues. In the normal kidney KIT was specifically expressed in the distal nephrons. Nine of 12 (75%) angiomyolipomas contained scattered KIT‐positive cells, whereas all three CMN were completely negative for KIT. The presence of KIT‐positive cells in angiomyolipomas was likely to correspond to that of melanocytic marker‐positive cells, which mainly showed epithelioid morphology. Polymerase chain reaction‐single‐strand conformation polymorphism showed no evidence of mutations of c‐kit or PDGFR in any of the tumors examined.
Regular expression of osteopontin in granular cell tumor: Distinctive feature among Schwannian cell tumors
Authors: Hoshi Nobuo , Sugino Takashi , Suzuki Toshimitsu
Published: July 2005

For further characterization of S‐100 protein‐positive granular cell tumor (GCT), the expression of osteopontin (OPN) in the tumor cells was compared with other types of Schwannian cell tumors. Twenty GCT, three amputation neuromas, 12 neurilemmomas (NM) and three malignant peripheral nerve sheath tumors (MPNST) were used. In addition, two granular cell epulides were employed because of histological similarity to that of GCT. Immunohistochemistry by anti‐OPN‐monoclonal antibody revealed OPN‐immunoreactivity in tumor cells of all GCT and stromal macrophages in neurilemmomas and one MPNST, but neither in amputation neuromas nor in granular cell epulides. All nine GCT studied by in situ hybridization (ISH) and all three GCT analyzed by reverse transcription–polymerase chain reaction (RT‐PCR) were positive for OPN mRNA. In contrast, seven NM and three amputation neuromas were negative for OPN mRNA by either ISH or RT‐PCR, while macrophages infiltrated in these tumors had OPN mRNA consistently. Double immunostaining for OPN and CD68, a lysosome‐associated glycoprotein, showed their colocalization in tumor cells of GCT, suggesting a possible degradation of OPN by lysosomes. In conclusion, GCT among Schwannian cell tumors consistently express OPN, but its biological significance requires further investigation.
Human papillomavirus genotyping by oligonucleotide microarray and p16INK4A expression in uterine cervical intraepithelial neoplasm and in invasive carcinoma in Korean women
Authors: Lin Zhen‐Hua , Shen Xiong‐Hu , Jin Zhe , Kim Youngsik , Lee Eungseok , Kim Hankyeom , Kim Insun
Published: July 2005

For evaluating the diagnostic significance of p16INK4A over‐expression in the uterine cervical intraepithelial neoplasm and in invasive carcinoma, human papillomavirus (HPV) was detected and genotyped by oligonucleotide microarray in archival tissues of 117 cervical specimens, including 47 invasive squamous cell carcinomas (SCC), 30 cases of cervical intraepithelial neoplasia (CIN), 20 adenocarcinomas, and 20 cases of non‐neoplastic cervix. The expression of p16INK4A protein was immunohistochemically studied in these cases and in five HPV‐positive and one HPV‐negative cervical cancer cell lines. HPV was detected in 50% of CIN, 61.7% of SCC, and 45.5% of adenocarcinomas. p16INK4A expression was seen in all 20 cases of adenocarcinoma, 78.7% (37/47) of SCC, and 96.7% (29/30) of CIN, but not in any cases of the non‐neoplastic cervix. There was no difference in p16INK4A expression between the HPV‐positive and HPV‐negative cervical lesions. All HPV‐positive and ‐negative cervical cancer cell lines expressed p16INK4A protein. In conclusion, the presence of p16INK4A expression in cervical squamous and glandular epithelium indicates the existence of dysplasia or malignancy in the uterine cervix, regardless of HPV infection.
Primary bone carcinosarcoma: Chondrosarcoma and squamous cell carcinoma with keratin pearl formation
Authors: Shiraishi Junichi , Mukai Makio , Yabe Hiroo , Shibata Rie , Yamada Taketo , Miura Keiko , Anazawa Ukei , Morioka Hideo , Sakamoto Michiie
Published: July 2005

Malignant bone tumors with epithelial differentiation are extremely rare. Only one case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma has ever been reported. Reported herein is a case of primary malignant bone tumor with distinct squamous cell carcinoma and chondrosarcoma, so‐called carcinosarcoma of bone, arising in the femur of a 53‐year‐old man. The tumor was located within the femur and was diagnosed by curettage as a well‐differentiated chondrosarcoma. No primary tumor was detected in any other organ. Within a few months the tumor had rapidly grown toward the soft tissue, and hemipelvectomy was performed. Examination of the surgical specimen revealed that the tumor was mainly composed of undifferentiated spindle sarcoma cells with scattered foci of chondrosarcoma and of squamous cell carcinoma with keratin pearl formation. The patient died approximately 6 months postoperatively. At autopsy multiple metastases were detected in the heart, both lungs, muscles, and lymph nodes. Interestingly, the chondrosarcoma and squamous cell carcinoma components were observed in several metastatic foci. The tumors in both the previously reported case and the present case contained components of chondrosarcoma and squamous cell carcinoma with keratin pearl formation, and this combination of histological features may be a unique characteristic of carcinosarcoma of bone.
Malignant myoepithelioma (myoepithelial carcinoma) of soft tissue
Authors: Harada Oi , Ota Hiroyoshi , Nakayama Jun
Published: July 2005

Malignant myoepithelioma of soft tissue is extremely rare. Presented herein is a case arising in a 17‐year‐old man. The tumor was initially noticed as a painless deep soft‐tissue mass in the right forearm when the patient was aged 3 years. Thereafter, it grew without remarkable symptoms, such as pain or tenderness, until his visit to the hospital because of swelling of his forearm when he was 17 years old. An excisional biopsy specimen disclosed an invasive tumor exhibiting a lobular architecture. The tumor cells were arranged in a reticular and/or trabecular fashion with a myxoid background, and nuclear atypia was evident. Mitoses and tumor necrosis were also observed. Immunohistochemically, S‐100 protein and epithelial markers were diffusely positive. Faint intercellular junctions and basal laminae were identified by electronmicroscopy. On the basis of these findings, the tumor was diagnosed as a malignant myoepithelioma of soft tissue. Six months later, multiple lung metastases were observed, and an open biopsy revealed a neoplasm displaying the same histological feature as the previously biopsied specimens. The patient died of his disease 18 months after the lung biopsy. Malignant myoepithelioma shoud be kept in mind in diagnosis of deep soft‐tissue tumors with epithelioid features.
Intracerebral schwannoma clinically and radiologically mimicking meningioma
Authors: Takei Hidehiro , Schmiege Lorenz , Buckleair Linda , Goodman J. Clay , Powell Suzanne Z.
Published: July 2005

A case of intracerebral schwannoma (ICS) occurring in a 33‐year‐old woman is presented. The patient's history of headache, numbness, tingling and the recent development of weakness of the right upper extremity with right facial droop began during pregnancy. Magnetic resonance imaging (MRI) showed a 4 × 2 × 2 cm heterogeneous, gadolinium‐enhanced mass at the left frontoparietal junction, with peritumoral edema and a dural‐based attachment. During her pregnancy, the mass increased in size. The surgically resected specimen consisted of lobulated, somewhat gelatinous soft tissue. Microscopically, the tumor demonstrated classic biphasic Antoni type A and B patterns, admixed with degenerative changes. Immunohistochemically, the neoplastic cells were positive for S‐100 protein (diffuse and strong), CD34 (primarily in Antoni B areas), glial fibrillary acidic protein (GFAP; weak and diffuse) and calretinin (mainly in Antoni A areas), while none was positive for CD31, estrogen and progesterone receptors, bcl‐2, or epithelial membrane antigen (EMA). Ultrastructurally, basal laminae and Luse bodies were identified. The differential diagnosis includes fibrous meningioma, solitary fibrous tumor, and ICS. Twenty‐seven cases of ICS were reviewed in which the histological diagnosis was confirmed immunohistochemically or ultrastructually, and the cases were summarized (including the present case). A combined use of immunostains (S‐100 protein, EMA, CD34, and maybe calretinin) is of great help in distinguishing ICS from its histological mimickers.
Autopsy case of microscopic polyangiitis with crescentic glomerulonephritis and necrotizing pancreatitis
Authors: Iwasa Satoshi , Katoh Ryohei
Published: July 2005

Herein is reported the case of an 84‐year‐old woman who initially manifested rapidly progressive glomerulonephritis following a urinary tract infection. Laboratory findings showed a high titer of myeloperoxidase‐antineutrophil cytoplasmic antibody (MPO‐ANCA). Treatment with high‐dose i.v. steroids resulted in clinical recovery and an undetectable MPO‐ANCA titer. Two months later the patient was readmitted in a state of severe shock. Laboratory examination showed the deterioration of renal function, leukocytosis, and coagulation abnormalities consistent with disseminated intravascular coagulation (DIC). The patient died 12 days later. The post‐mortem examination revealed necrotizing pancreatitis due to acute‐stage vasculitis typified by fibrinoid necrosis of the arterioles and venules, and crescentic glomerulonephritis with healed‐stage vasculitis. In the lungs, capillaritis with diffuse alveolar hemorrhage was not evident, but arteriolitis and phlebitis were occasionally seen. This case represents an unusual complication of necrotizing pancreatitis in the setting of microscopic polyangiitis. Thus, it is important to consider reactivation independent of the titer of ANCA in the course of the disease.
Cytokeratin 20‐positive large cell neuroendocrine carcinoma of the colon
Authors: Kato Tomoya , Terashima Toru , Tomida Shinji , Yamaguchi Takashi , Kawamura Hisao , Kimura Noriko , Ohtani Haruo
Published: July 2005

Herein is presented a case of cytokeratin (CK) 20‐positive large cell neuroendocrine carcinoma of the colon, in which the tumor was clinically at stage IV and located in the ascending colon. Pathological examination of the resected tumor revealed nested and solid proliferation of large undifferentiated cells with vesicular nucleus and prominent nucleoli. No areas showed differentiation toward adenocarcinoma or squamous cell carcinoma. Tumor cells were immunohistochemically positive for chromogranin A, synaptophysin, CD 56 (focal), and bore electron‐dense granules. With these features, the tumor was diagnosed as a large cell neuroendocrine carcinoma of the colon. Liver metastasis and local recurrence progressed, and the patient died of the primary disease 7 months after operation. The autopsy confirmed this diagnosis without detectable tumors in the lungs. Interestingly, more than half of the tumor cells were positive for CK 20, while CK 7 was not expressed. Most neuroendocrine carcinomas do not express CK 20, with the exception of Merkel cell carcinomas, and most colorectal adenocarcinomas express CK 20. To the best of the authors’ knowledge, the present case is the first CK 20‐positive, CK 7‐negative colorectal neuroendocrine carcinoma to be described, suggesting a link between colorectal neuroendocrine carcinoma and conventional adenocarcinoma.