bluuebunny/crossref_metadata_2025 huggingface dataset:
Protected areas in Canada: decade of change
Authors: Dearden Philip , Dempsey Jessica
Published: June 2004

The last decade has witnessed more changes in protected area systems in Canada than any other. The area set aside has more than doubled, and almost 7 percent of Canada's ecosystems are now protected compared with 3 percent in 1989. Several high‐profile reports have indicated a decline in ecological integrity of protected area systems. Major changes in legislation and policy have followed with a new National Parks Act, National Marine Conservation Areas Act, a Parks Canada Agency Act and a revised national park's policy. The paper describes these major changes and their implications, provides understanding of why they occurred and suggests ongoing challenges facing protected area systems in Canada in the future.
Anti‐sickling effect of MX‐1520, a prodrug of vanillin: an in vivo study using rodents
Authors: Zhang Chaojie , Li Xiang , Lian Lurong , Chen Qiukan , Abdulmalik Osheiza , Vassilev Vasco , Lai Ching‐San , Asakura Toshio
Published: June 2004

Vanillin, a food additive, covalently binds with sickle haemoglobin (Hb  S), inhibits cell sickling and shifts the oxygen equilibrium curve towards the left. These effects would potentially benefit patients with sickle cell disease (SCD). However, vanillin has no therapeutic effect if given orally because orally administered vanillin is rapidly decomposed in the upper digestive tract. To overcome this problem, a vanillin prodrug, MX‐1520, which is biotransformed to vanillin in vivo, was synthesized. Studies using transgenic sickle mice, which nearly exclusively develop pulmonary sequestration upon exposure to hypoxia, showed that oral administration of MX‐1520 prior to hypoxia exposure significantly reduced the percentage of sickled cells in the blood. The survival time under severe hypoxic conditions was prolonged from 6·6 ± 0·8 min in untreated animals to 28·8 ± 12 min (P < 0·05) and 31 ± 7·5 min (P < 0·05) for doses of 137·5 and 275 mg/kg respectively. Intraperitoneal injection of MX‐1520 to bypass possible degradation in the digestive tract showed that doses as low as 7 mg/kg prolonged the survival time and reduced the percentage of sickled cells during hypoxia exposure. These results demonstrate the potential for MX‐1520 to be a new and safe anti‐sickling agent for patients with SCD.
Adverse prognostic significance of CD20 positive Reed–Sternberg cells in classical Hodgkin's disease*
Authors: Portlock Carol S. , Donnelly Gerard B. , Qin Jing , Straus David , Yahalom Joachim , Zelenetz Andrew , Noy Ariela , O'Connor Owen , Horwitz Steven , Moskowitz Craig , Filippa Daniel A.
Published: June 2004

The prognostic significance of CD20 positive classical Hodgkin's disease (cHD) is uncertain. All cHD cases referred to the Memorial Sloan–Kettering Cancer Center (MSKCC) were retrospectively identified (5/92–11/00); the samples were immunostained, and clinical data ascertained. Cases were re‐reviewed without knowledge of clinical outcome. Univariate and multivariate analyses were performed 248 patients had cHD: 28 CD20+ (11%); 220 CD20−. All clinical characteristics were comparable except haemoglobin level at presentation. With a median follow‐up of 29·2 months, significant prognostic factors in multivariate analysis were: CD20 positivity, elevated white blood cell count (WBC) and low absolute lymphocyte count for time‐to treatment failure (TTF); and for overall survival (OS), CD20 positivity, elevated WBC count, bone marrow involvement and age ≥45 years. TTF was significantly poorer for ABVD‐treated patients with CD20+ cHD as compared with CD20− cHD. Among 167 patients treated at MSKCC, both TTF (P < 0·0001) and OS (P = 0·017) were significantly decreased in CD20+ patients as compared with CD20− cHD. CD20+ cHD is a poor prognostic factor for TTF and OS. All cHD cases should be immunophenotyped for CD20. A large prospective trial is needed to confirm these findings.
Four new cases of stomatin‐deficient hereditary stomatocytosis syndrome: association of the stomatin‐deficient cryohydrocytosis variant with neurological dysfunction
Authors: Fricke Britta , Jarvis Helen G. , Reid Cecil D. L. , Aguilar‐Martinez Patricia , Robert A. , Quittet P. , Chetty Margaret , Pizzey Arnold , Cynober Thérèse , Lande William F. , Mentzer William C. , von Düring Monika , Winter Stuart , Delaunay Jean , Stewart Gordon W.
Published: June 2004

This report concerns congenitally Na+–K+ leaky red cells of the ‘hereditary stomatocytosis’ class. Three new isolated cases and one new pedigree are described, and one previously reported case is expanded. In all cases, Western blotting of red cell membranes revealed a deficiency in the 32 kDa membrane protein, stomatin. All showed pronounced cation leaks at 37°C with markedly abnormal intracellular Na+ and K+ concentrations, like all other such stomatin‐deficient cases. Consistent with recent findings in two previously described British pedigrees, immunocytochemistry demonstrated that the deficiency of stomatin was not complete. On typical blood films, some red cells showed positive stomatin immunoreactivity, while most were negative, although in one case only a minority were negative. All platelets and neutrophils were stomatin positive. The cases differed markedly between themselves with regard to the temperature dependence of the passive leak to K+. Three showed a simple monotonic temperature dependence, while two showed a minimum at around 20–25°C, such that the cells were extremely leaky at 0°C, giving the phenotype known as ‘cryohydrocytosis’. These patients are the only two known cases of stomatin‐deficient cryohydrocytosis. Both showed a congenital syndrome of mental retardation, seizures, cataracts and massive hepatosplenomegaly, probably defining a new haemato‐neurological syndrome.
Novel loss‐of‐function mutations of the haematopoiesis‐related transcription factor, acute myeloid leukaemia 1/runt‐related transcription factor 1, detected in acute myeloblastic leukaemia and myelodysplastic syndrome
Authors: Nakao Mitsushige , Horiike Shigeo , Fukushima‐Nakase Yoko , Nishimura Motohiro , Yasuko Fujita  , Taniwaki Masafumi , Okuda Tsukasa
Published: June 2004

AML1/RUNX1, which encodes a transcription factor essential for definitive haematopoiesis, is a frequent target of leukaemia‐associated chromosome translocations. Point mutations of this gene have also recently been associated with leukaemia and myelodysplastic syndrome (MDS). To further define the frequency and biological characteristics of AML1 mutations, we have examined 170 cases of such diseases. Mutations within the runt‐domain were identified in five cases: one of de novo acute myeloid leukaemia (AML) and four of MDS. Where multiple time point samples were available, mutations were detected in the earliest samples, which persisted throughout the disease course. Of the five mutations, one was a silent mutation, two were apparent loss‐of‐function mutations caused by N‐terminal truncation, and two were insertions, I150ins and K168ins, which preserved most of the AML1 DNA‐binding domain. Both AML1 molecules with insertion mutations were non‐functional in that they were unable to rescue haematological defects in AML1‐deficient mouse embryonic stem cells. In addition, activating mutations of N‐ras, deletion of chromosome 12p, or inactivation of TP53 accompanied some of the AML1 mutations. Together, these observations strongly suggest that one‐allele inactivation of AML1 serves as an initial or early event that plays an important role in the eventual development of overt diseases with additional genetic alterations.
Interest of transjugular liver biopsy in adult patients with haemophilia or other congenital bleeding disorders infected with hepatitis C virus
Authors: Stieltjes Natalie , Ounnoughene Nadra , Sava Emilie , Paugy Patricia , Roussel‐Robert Valérie , Rosenberg Arielle R. , Terris Benoit , Salmon‐Céron Dominique , Sogni Philippe
Published: June 2004

Liver histology is important for prognosis and treatment strategy in patients with hepatitis C. We report a 10‐year experience of transjugular liver biopsy (TJLB) in patients with haemophilia and other congenital bleeding disorders (CBD) in terms of safety, efficiency and therapeutic consequences. TJLB was proposed to patients who were regularly followed for CBD, and were hepatitis C virus (HCV) positive by polymerase chain reaction. Patients with inhibitors or who were human immunodeficiency virus (HIV) positive with CD4 cells <0·2 × 109/l or with evidence of liver failure were excluded. TJLB was performed during a short hospitalization with factor replacement. Between 1992 and 2002, 88 TJLB were performed in 69 of 151 adult HCV patients (39% HIV positive). CBD was haemophilia A in 68% and haemophilia B in 24%. Few mild adverse events were recorded. Histology was assessable in 78 of 88 procedures (89%). Twenty‐nine (37%) cases demonstrated minimal change (METAVIR A ≤ 1 and F ≤ 1). Extended fibrosis or cirrhosis was recorded in 23 procedures (26%), all in patients whose infection period was longer than 20 years. No relationship between liver histology, HIV status or HCV genotype was found. TJLB appears to be safe and useful in HCV patients with CBD. One‐third of patients had minimal histological changes and could avoid systematic anti‐HCV treatment.
Phenotypic and functional characterization of monocyte‐derived dendritic cells in chronic lymphocytic leukaemia patients: influence of neoplastic CD19+ cells in vivo and in vitro
Authors: Orsini Enrica , Pasquale Alessia , Maggio Roberta , Calabrese Elisabetta , Mauro Francesca Romana , Giammartini Elena , Guarini Anna , Foa Robin
Published: June 2004

Dendritic cells (DCs) are the most potent antigen‐presenting cells and are therefore an attractive option as antigen carriers in vaccination protocols. Chronic lymphocytic leukaemia (CLL) represents a potential good target for these approaches. The present study was designed to investigate the feasibility of generating in vitro fully functional DCs from peripheral blood (PB) monocytes of CLL patients at different phases of the disease. Although functional DCs could be obtained from CLL samples, in patients with active disease the expression of some co‐stimulatory molecules appeared to be reduced. In contrast, DCs from CLL patients in remission showed no difference from those of normal controls. Moreover, patients with active disease produced DCs with reduced allostimulatory ability when compared with normal ones, whereas the functional capacities appeared to be restored in CLL DCs from remission patients. To more precisely assess the possible inhibitory effect of CLL cells on DC development, the influence of autologous leukaemic CD19+ cells on the generation of monocyte‐derived CLL DCs in vitro was investigated. The addition of CLL neoplastic cells markedly affected monocyte‐derived DC maturation. In conclusion, monocytes from CLL patients with active disease give rise to DCs, which show phenotypic and functional defects that are not observed in remission CLL patients. These results need to be taken into account in the design of DC‐based immunotherapeutic approaches in CLL.
Elevated circulating endothelial membrane microparticles in paroxysmal nocturnal haemoglobinuria
Authors: Simak Jan , Holada Karel , Risitano Antonio M. , Zivny Jan H. , Young Neal S. , Vostal Jaroslav G.
Published: June 2004

We analysed endothelial cell membrane microparticles (ECMP) in the peripheral blood of patients with paroxysmal nocturnal haemoglobinuria (PNH) (n = 9), aplastic anaemia (AA) (n = 10), sickle cell disease (SCD) (n = 8), and healthy donors (HD) (n = 11). There was no clinically manifested thrombosis in the PNH or AA group, except one cured thrombophlebitis (PNH), while all SCD patients had a history of vaso‐occlusive crises. We used three‐colour flow cytometry with blood cell‐specific antibodies and antibodies to endothelial antigens CD105 and CD144. Phosphatidylserine‐positive microparticles were detected using the annexin V‐binding (AVB) assay. The population of CD105+AVB+ ECMP was significantly (P < 0·05) higher in SCD (median: 0·568 × 109/l; 25–75th percentile range: 0·351–0·976 × 109/l) and PNH (0·401 × 109/l ; 0·19–0·441 × 109/l) patients when compared with AA (0·122 × 109/l; 0·061–0·172 × 109/l) or HD (0·180 × 109/l; 0·137–0·217 × 109/l) group. Even more pronounced differences were observed in ECMP exhibiting a marker of inflammatory stimulation CD54 (CD105+CD54+). Similarly, ECMP that exhibited endothelial specific and proteolysis‐sensitive antigen CD144 were increased in SCD and PNH, but not in AA. Elevated CD54+ ECMP may reflect the inflammatory status of endothelial cells in SCD and PNH, while CD144+ ECMP could indicate continuous endothelial stimulation and/or injury. Analysis of circulating ECMP appears promising to provide useful information on the status of the vascular endothelium in PNH and SCD.
Etoposide, methylprednisolone, cytarabine and cisplatin successfully cytoreduces resistant myeloma patients and mobilizes them for transplant without adverse effects
Authors: D'Sa Shirley , Yong Kwee , Kyriakou Chara , Bhattacharya Soumo , Peggs Karl S. , Foulkes Barbara , Watts Michael J. , Ings Stuart J. , Ardeshna Kirit M. , Goldstone Anthony H. , Williams Catherine D.
Published: June 2004

Myeloma remains incurable with a median survival of 4 years, but outcome can be improved by the use of high‐dose therapy. We used the etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP) regimen as second‐line therapy in 42 newly diagnosed myeloma patients who had failed vincristine, adriamycin and dexamethasone (VAD)‐ type therapy (n = 36), responded to first‐line treatment but persisted in having significant residual marrow plasmacytosis (n = 5) or failed prior stem cell harvesting (n = 1), with the dual aim of improving disease response and mobilizing peripheral blood stem cells. Fourteen of 21 (67%) patients with no change or progressive disease after VAD responded to ESHAP; seven of 12 (58%) patients with minor response converted to partial response. Marrow plasmacytosis fell from a median of 52% at diagnosis to 23·5% after primary therapy and to15% after ESHAP. ESHAP chemotherapy was well‐tolerated. There were 11 admissions due to febrile neutropenia (n = 7), nausea and vomiting (n = 2), pneumonia (n = 1) and perforated bowel (n = 1). Renal function deteriorated in 13 of 42 patients after ESHAP, but none required renal support. ESHAP mobilization was performed in 32 patients of whom 87% achieved a CD34+ yield >2 × 106/kg. In all, 38 patients proceeded to high‐dose therapy. The overall survival for all patients was 62% at 4 years following ESHAP. We conclude that ESHAP has acceptable toxicity and efficient stem cell mobilizing capability, effectively cytoreduced this chemoresistant group of patients, and did not appear to adversely affect transplant outcome.
Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down's syndrome, revealing PRAME as a specific discriminating marker
Authors: McElwaine Suzanne , Mulligan Claire , Groet Jürgen , Spinelli Monica , Rinaldi Andrea , Denyer Gareth , Mensah Afua , Cavani Simona , Baldo Chiara , Dagna‐Bricarelli Franca , Hann Ian , Basso Giuseppe , Cotter Finbarr E. , Nizetic Dean
Published: June 2004

Transient myeloproliferative disorder (TMD) is a unique, spontaneously regressing neoplasia specific to Down's syndrome (DS), affecting up to 10% of DS neonates. In 20–30% of cases, it reoccurs as progressive acute megakaryoblastic leukaemia (AMKL) at 2–4 years of age. The TMD and AMKL blasts are morphologically and immuno‐phenotypically identical, and have the same acquired mutations in GATA1. We performed transcript profiling of nine TMD patients comparing them with seven AMKL patients using Affymetrix HG‐U133A microarrays. Similar overall transcript profiles were observed between the two conditions, which were only separable by supervised clustering. Taqman analysis on 10 TMD and 10 AMKL RNA samples verified the expression of selected differing genes, with statistical significance (P < 0·05) by Student's t‐test. The Taqman differences were also reproduced on TMD and AMKL blasts sorted by a fluorescence‐activated cell sorter. Among the significant differences, CDKN2C, the effector of GATA1‐mediated cell cycle arrest, was increased in AMKL but not TMD, despite the similar level of GATA1. In contrast, MYCN (neuroblastoma‐derived oncogene) was expressed in TMD at a significantly greater level than in AMKL. MYCN has not previously been described in leukaemogenesis. Finally, the tumour antigen PRAME was identified as a specific marker for AMKL blasts, with no expression in TMD. This study provides markers discriminating TMD from AMKL‐M7 in DS. These markers have the potential as predictive, diagnostic and therapeutic targets. In addition, the study provides further clues into the pathomechanisms discerning self‐regressive from the progressive phenotype.
Either interleukin‐12 or interferon‐γ can correct the dendritic cell defect induced by transforming growth factor β1 in patients with myeloma
Authors: Brown Ross , Murray Allan , Pope Belinda , Sze Daniel M. , Gibson John , Joy Ho P. , Hart Derek , Joshua Doug
Published: June 2004

The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44+) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up‐regulate the expression of the B7 co‐stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor β1 (TGFβ1) and interleukin (IL)‐10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti‐TGFβ1. As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up‐regulation was reduced in both stage I and stage III. It was demonstrated that both IL‐12 and interferon‐γ neutralized the failure to stimulate CD80 up‐regulation by huCD40LT in vitro. IL‐12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123−) suggesting that there would be a predominantly T‐helper cell type response. The addition of IL‐12 or interferon‐γ to future immunotherapy trials involving these patients should be considered.
Low and high circulating cortisol levels predict mortality and cognitive dysfunction early after stroke
Authors: Marklund N. , Peltonen M. , Nilsson T. K. , Olsson T.
Published: June 2004

Objective.  Elevated cortisol levels are associated with confusion and poor outcome after stroke. Dehydroepiandrosterone sulphate (DS), the most abundant adrenal androgen may act as an anti‐glucocorticoid. An altered regulation of these steroids may affect numerous brain functions, including neuronal survival. The purpose of this study was to investigate serum cortisol and DS levels and the cortisol/DS ratio early after stroke and relate our findings to the presence of disorientation and mortality.

Design.  Patients with acute ischaemic stroke (n = 88, 56 men and 32 women) admitted to a stroke unit were investigated with repeated clinical assessments and scores for degree of confusion, extent of paresis and level of functioning. Serum cortisol (C) and DS were measured on day 1 and/or day 4. Data for 28‐day and 1‐year mortality are presented. A control group of 65 age‐matched healthy individuals was used. Multivariate analyses of mortality rates in the different tertiles or sixtiles of serum cortisol were performed with logistic regression, adjusting for age, sex, diabetes and level of consciousness.

Results.  There was no difference in serum cortisol levels on day 1 for stroke patients when compared with control group values. Initial cortisol levels were significantly higher in the patients with acute disorientation versus orientated patients (P < 0.05). Cortisol levels on day 1 were an independent predictor of 28‐day mortality, and patients with low cortisol levels (<270 nmol L−1) and increased levels (>550 nmol L−1) both had an increased 1‐year mortality. DS levels on day 1 were significantly elevated in stroke patients.

Conclusion.  Hypercortisolism is associated with cognitive dysfunction early after ischaemic stroke. High and low circulating cortisol levels are associated with increased mortality after stroke. DS levels were not associated with clinical outcome.
High incidence of type 2 diabetes and increasing conversion rates from impaired fasting glucose and impaired glucose tolerance to diabetes in Mauritius
Authors: Söderberg S. , Zimmet P. , Tuomilehto J. , de Courten M. , Dowse G. K. , Chitson P. , Stenlund H. , Gareeboo H. , Alberti K. G. M. M. , Shaw J.
Published: June 2004

Objective.  To describe the incidence of different stages of glucose intolerance in a population from Mauritius followed over 11 years.

Research design, methods and subjects.  Population‐based surveys were undertaken in the multi‐ethnic nation of Mauritius in 1987, 1992 and 1998 with 5083, 6616 and 6291 participants, respectively. Questionnaires, anthropometric measurements, and a 2‐h 75‐g oral glucose tolerance test were included. Three cohorts aged between 25 and 79 years with classifiable glucose tolerance data were identified; 3680 between 1987 and 1992, 4178 between 1992 and 1998, and 2631 between 1987 and 1998. Glucose tolerance was classified according to WHO 1999 criteria.

Results.  The incidence rate of type 2 diabetes was higher between 1992 and 1998 than between 1987 and 1992. In men, the incidence was similar between cohorts (24.5 and 25.4 per 1000 person‐years) whereas the incidence increased in women (23.3 and 16.4 per 1000 person‐years). The incidence of diabetes peaked in the 45–54 year age group and then plateaud or fell. The incidences of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) decreased in both men and women. Of normoglycaemic subjects at baseline, more women than men developed IGT and more men than women developed IFG. Of those labelled as IFG in 1987, 38% developed diabetes after 11 years. The corresponding figure for IGT was 46%.

Conclusions.  In this study, we report changes in incidence rates of glucose intolerance over a 11‐year period. In particular, differences between men and women were observed. The increased incidence of IGT in women compared with men, and increased incidence of IFG in men compared with women was consistent with, and explains the sex biases seen in the prevalences of these states.
Relationship between albumin excretion rate and aortic stiffness in untreated essential hypertensive patients
Authors: Mulè G. , Cottone S. , Vadalà A. , Volpe V. , Mezzatesta G. , Mongiovì R. , Piazza G. , Nardi E. , Andronico G. , Cerasola G.
Published: June 2004

Objectives.  To evaluate, in a group of nondiabetic essential hypertensive patients with normal renal function, the relationship between albumin excretion rate (AER) and carotid‐femoral pulse wave velocity (PWV), as an index of aortic stiffness.

Design.  Cross‐sectional study.

Setting.  Outpatient hypertension clinic.

Subjects.  Seventy patients with mild‐to‐moderate essential hypertension, aged 42 ± 8 years, never pharmacologically treated. All subjects underwent routine laboratory tests, 24‐h ambulatory blood pressure (BP) monitoring, measurement of carotid‐femoral PWV, by means of a computerized method, and AER.

Results.  Microalbuminuric patients (AER ≥ 20 μg min−1; n = 19), when compared with normoalbuminuric subjects, showed more elevated 24‐h BP (136/88 ± 10/10 vs. 128/83 ± 7/6 mmHg; P < 0.001 and P = 0.013, for systolic and diastolic BP respectively) and higher values of carotid‐femoral PWV (10.4 ± 2 m s−1 vs. 9.2 ± 1.3; P = 0.006). This latter difference remained statistically significant, even after correction by ancova for 24‐h systolic and diastolic BP, and body mass index (BMI, P = 0.016). Univariate regression analysis disclosed a tight correlation between AER and carotid‐femoral PWV (r = 0.42; P = 0.0003). This association was confirmed in a multiple regression model (β = 0.35; P = 0.009) in which, as independent variables, besides PWV, 24‐h BP, age, serum glucose values, smoking status, gender and BMI, were added.

Conclusions.  Our results seem to confirm that microalbuminuria may represent the early renal manifestation of a widespread vascular dysfunction, and therefore it is an integrated marker of cardiovascular risk.
Tyrosine phosphatase 1B and leptin receptor genes and their interaction in type 2 diabetes
Authors: Santaniemi M. , Ukkola O. , A. Kesäniemi Y.
Published: June 2004

Objectives.  The association between three tyrosine phosphatase 1B (PTP1B) gene polymorphisms and type 2 diabetes was examined by comparing the prevalence rates of these polymorphisms in type 2 diabetic patients and healthy control subjects. Furthermore, the association of the polymorphisms and PTP1B and leptin receptor (LepR) gene–gene interactions with complications of type 2 diabetes were examined in type 2 diabetic patients.

Subjects and methods.  A total of 257 Finnish patients with type 2 diabetes and 285 nondiabetic subjects were screened. Single nucleotide polymorphisms were determined using polymerase chain reaction and restriction enzymes. The diagnosis of coronary heart disease was based on clinical and ECG criteria. The prevalences of cerebrovascular and peripheral vascular diseases were assessed on the basis of clinical criteria. Laboratory analyses were carried out in the hospital laboratory.

Results.  We did not find any differences in the genotype distributions or allele frequencies of IVS6 + G82A and Pro387Leu polymorphisms between the type 2 diabetics and controls. There were differences in the genotype frequencies of the Pro303Pro (C981T) – polymorphism between the two studied groups (P = 0,018); there were eight T981T subjects in the control population but none amongst the type 2 diabetics. However, there were no differences in the allele frequencies. In addition, significant associations between the IVS6 + G82A polymorphism and body mass index (BMI), albuminuria, glycohaemoglobin A1 (GHBA1) and hypertension in type 2 diabetic patients (P = 0,026–0,031) were observed. Pro387Leu and Pro303Pro did not associate with risk factors or diabetic complications. We also found a gene–gene interaction effect between PTP1B and the LepR gene with the genotype combination IVS6 + A82A and Arg223Arg having the highest BMI compared with the other genotype combinations (P = 0.0043 for trend). The interaction between these two polymorphisms explained 3% of the variation in BMI in diabetic patients when the other covariates were taken into account.

Conclusions.  We conclude that the PTP1B IVS6 + G82A polymorphism was associated with BMI, albuminuria, GHBA1 and hypertension in type 2 diabetic patients. The 981T/T‐genotype of the Pro303Pro‐ polymorphism might have some protective role against the development of type 2 diabetes. The interaction effects between the PTP1B IVS6 + A82A and LepR Arg223Arg genotypes influenced BMI, explaining 3% of its variation. A synergistic effect of PTP1B and LepR variants on the leptin signalling may be involved.
An open, randomized, controlled study of transdermal hormone replacement therapy on the rate of bone loss in primary biliary cirrhosis
Authors: Ormarsdóttir S. , Mallmin H. , Naessén T. , Petrén‐Mallmin M. , Broomé U. , Hultcrantz R. , Lööf L.
Published: June 2004

Objectives.  The prevalence of osteoporosis amongst patients with primary biliary cirrhosis (PBC) is high and may be a serious clinical problem. Hormone replacement therapy (HRT) is effective in preventing bone loss but has not been evaluated in randomized trials in PBC. The primary aim was to study the effect of transdermal HRT in combination with daily vitamin D and calcium supplementation on bone loss compared with vitamin D and calcium supplementation only in postmenopausal women with PBC. The secondary aim was to study the safety of transdermal HRT.

Subjects/interventions.  Eighteen females with PBC were randomized to receive 2 years therapy with either (i) transdermal oestradiol 50 μg 24 h−1 two times per week + medroxyprogesterone 2.5 mg day−1 + alfacalcidol 0.25 μg day−1 and calcium 1 g day−1 or (ii) alfacalcidol 0.25 μg day−1 and calcium 1 g day−1. Dual‐energy X‐ray absorptiometry for measurement of bone mineral density (BMD) and sampling of blood and serum for measurements of biochemical markers of liver function was performed before, during and at the end of treatment.

Results.  BMD increased significantly at the lumbar spine (P < 0.05) and the femoral neck (P < 0.05) in the HRT group whereas no significant change was found in the control group. One oestrogen‐treated patient was excluded after 1 year because of deteriorating, but reversible, aminotransferases. Dropout frequency because of nonliver‐related causes was higher in the HRT group. Otherwise, no difference with respect to adverse liver reactions was found between the groups.

Conclusion.  Transdermal HRT increases BMD in PBC patients with few severe side effects related to the liver.
Use of a lead shield for laparoscopic detection of the sentinel lymph nodes in gastric cancer
Authors: Yasuda Kazuhiro , Ishikawa Koichi , Sonoda Kazuya , Inomata Masafumi , Shiraishi Norio , Kitano Seigo
Published: June 2004

Background:  Accurate staging of lymph node metastasis by sentinel node biopsy is easily achieved in conventional open gastric surgery. Staging is not easily achieved in laparoscopic surgery, however, because of the technical difﬁculty in identifying sentinel nodes. We developed a laparoscopic method that involves lead shielding for detection of sentinel nodes in gastric cancer and examined the efﬁcacy of this method.

Methods:  Laparoscopic sentinel node biopsy was performed in 18 patients with early gastric cancer. A combined dye‐ and radio‐guided method was used in the ﬁrst 10 patients; our radio‐guided lead shield method was used in the subsequent eight cases. Laparoscopy‐assisted distal gastrectomy was performed in all patients, and dissected nodes were examined by routine hematoxylin and eosin staining. The detection rate was compared between the two groups.

Results:  The detection rate for sentinel nodes was higher with the radio‐guided lead shield method (88%) than with the combined dye‐ and radio‐guided method (40%). Regional lymph node metastasis was recognized in one of 18 patients, and the sentinel node was positive in this case.

Conclusions:  Use of a lead shield is beneﬁcial for accurate laparoscopic detection of sentinel lymph nodes.
Evaluation of gastroduodenal mucosal lesions in patients with Crohn's disease and ulcerative colitis
Authors: Maeda Kazuhiro , Okada Mitsuo , Seo Mitsuru , Aoyagi Kunihiko , Yamaguchi Masashi , Sakisaka Shotaro
Published: June 2004

Background:  Patients with Crohn's disease (CD) are reported to suffer from upper gastroduodenal lesions with varying frequency, although concurrent Helicobacter pylori infection is reported to be low.

Methods:  A prospective study was carried out on patients diagnosed with CD or ulcerative colitis (UC) in order to evaluate the degree of upper gastroduodenal tract involvement and the prevalence of Helicobacter pylori infection.

Results:  Gastroduodenal lesions were found in 18 (78%) of 23 CD patients, the location being the stomach in 18 (78%), the duodenal bulb in 16 (70%) and the descending duodenum in 16 (70%). Bamboo joint‐like lesions were found in four cases (17%) in gastric body and cardia. In contrast, gastroduodenal lesions were found in 10 (53%) of 19 UC patients, the location being the stomach in nine (47%), the duodenal bulb in six (32%), and the descending duodenum in three (16%). The H. pylori‐positive rate in patients with CD and UC was 0%, and 11%, respectively.

Conclusion:  Minute upper gastroduodenal lesions are much more common in CD than in UC patients, especially in the descending duodenum. Accordingly, upper gastrointestinal endoscopy would seem to be a useful means with which to obtain a definitive diagnosis in all suspected IBD cases.
Case of AIDS‐related cholangitis treated by endoscopic sphincterotomy
Authors: Shibata Naozumi , Matsui Hidetaka , Takeshita Eiji , Yokota Tomoyuki , Kobayashi Yuichi , Ikeda Yoshiou , Yakushijin Yoshihiro , Hato Takaaki , Matsuura Bunzo , Horiike Norio , Onji Morikazu
Published: June 2004

A 21‐year‐old man with an 8‐year history of acquired immunodeﬁciency syndrome (AIDS) presented with abdominal pain, jaundice and dark urine. Laboratory data on admission revealed cholestasis. The total bilirubin concentration was 10.0 mg/dL. Alanine transaminase and aspartate transaminase were 198 IU/L and 195 IU/L, respectively. The serum alkaline phosphatase level was 2724 IU/L. γ‐Glutamyl transferase was 1770 IU/L. Abdominal ultrasonography and computed tomography revealed dilation of the common bile duct and intrahepatic ducts without gallstones. Endoscopic retrograde cholangiopancreatography showed dilation of the common bile duct up to the level of the ampulla of Vater with partial stenosis. Endoscopic sphincterotomy was performed. The abdominal pain and jaundice resolved immediately and the liver function tests were signiﬁcantly improved. The patient developed a subarachnoid hemorrhage and died of respiratory arrest 2 months after the endoscopic sphincterotomy.
Successful treatment with balloon dilatation using a double‐balloon enteroscope for a stricture in the small bowel of a patient with Crohn's disease
Authors: Sunada Keijiro , Yamamoto Hironori , Kita Hiroto , Yano Tomonori , Miyata Tomohiko , Sekine Yutaka , Kuno Akiko , Onishi Nobuki , Iwamoto Michiko , Sasaki Atsuhiro , Ido Kenichi , Sugano Kentaro
Published: June 2004

The requirement for endoscopic access to a stricture is a major limitation of the endoscopic dilatation for the treatment of strictures in the gastrointestinal tract. We have developed the double‐balloon enteroscopy method that enables visualization of the entire small bowel. In addition, double‐balloon enteroscopy has a potential for the interventional therapy including dilatation of strictures. We present here a case of jejunal strictures in a 47‐year‐old woman with Crohn's disease successfully treated with a balloon catheter in combination with double‐balloon enteroscopy. Balloon dilation with double‐balloon enteroscopy is a promising method for the treatment of small bowel strictures in Crohn's disease.
Case of eosinophilic granulomatous enterocolitis caused by Strongyloides stercoralis infection with marked hypoalbuminemia and ascites
Authors: Ukarapol Nuthapong , Lertprasertsuk Nirush , Pongprot Yupada , Sittiwangkul Rekwan , Wongsawasdi Lumduan
Published: June 2004

We report a 10‐year‐old boy presenting with generalized pitting edema, ascites, abdominal pain, and chronic mucous diarrhea for 4 weeks. He had underlying diseases of hemoglobin E and juvenile rheumatoid arthritis and had been treated with immunosuppressive agents for a long period of time, including prednisolone and methotrexate. After extensive investigations, Strongyloides stercoralis infection, leading to protein‐losing enteropathy and eosinophilic granulomatous enterocolitis, was diagnosed. In the present report, we demonstrate early colonoscopic findings, revealing patchy erythema and small raised mucosal nodules with erosions at the cecum. Histopathological study showed open ulceration with cryptitis, intense infiltration of eosinophils and histiocytes with granuloma formation, in which Strongyloides stercoralis larvae were noted.
Epidermoid cyst of the intrapancreatic accessory spleen producing CA19‐9
Authors: Watanabe Hiroyuki , Yamaguchi Yasushi , Ohtsubo Koushiro , Mouri Hisatsugu , Motoo Yoshiharu , Yamashita Kaname , Minamoto Toshinari , Gabata Toshifumi , Sawabu Norio
Published: June 2004

We report a rare case of an epidermoid cyst in an accessory spleen at the pancreatic tail with producing CA19‐9. A 55‐year‐old female was admitted to our hospital, Cancer Research Institute, Kanazawa University, for close examination of a cystic lesion at the pancreatic tail and a high serum CA19‐9‐value (176 U/mL). There were almost no abdominal symptoms related to the cystic lesion. A cystic tumor approximately 3 cm in diameter and composed of multilocular cysts without a protruding portion of the inner surface was found at the pancreatic tail by ultrasound sonography, computed tomography, and magnetic resonance imaging. Endoscopic retrograde pancreatography revealed that the main pancreatic duct shifted at the pancreatic tail and there was no communication between the main pancreatic duct and cystic lesion. Based on a preoperative diagnosis of mucinous cystic tumor, distal pancreatectomy with splenectomy was performed. Histological ﬁndings suggested an epidermoid cyst (3.5 × 3.0 cm) originating from an intrapancreatic accessory spleen. Immunohistochemical analysis of CA19‐9 in the epidermoid cyst showed clear staining of the inner epithelium of the cyst and amorphous or hyalinous cystic contents. The serum CA19‐9 value was conﬁrmed to decline to normal 2 months after resection. Physicians should not forget this disease during differential diagnosis related to pancreatic cystic lesions with elevated levels of serum tumor markers, such as CA19‐9 or carcinoembryonic antigen, although this disease is extremely rare.
Patency of the accessory pancreatic duct evaluated by dye‐injection endoscopic retrograde pancreatography: Methods and clinical implication
Authors: Kamisawa Terumi , Yoshiike Masami , Egawa Naoto , Nakajima Hitoshi
Published: June 2004

The accessory pancreatic duct (APD) is sometimes developmentally obliterated near the duodenum. We evaluated patency of the APD by dye‐injection endoscopic retrograde pancreatography (ERP). We injected 2–3 mL contrast medium containing indigocarmine into the main pancreatic duct (MPD) via a selectively cannulated endoscopic catheter. Patency of the APD was evaluated by observing the excretion of dye from the minor duodenal papilla. Of the 291 control cases studied, 43% demonstrated a patent APD. Patency of the APD in patients with acute pancreatitis was only 17%, signiﬁcantly lower than that of controls (P < 0.01). Mean caliber of patent APD was 1.6 ± 0.5 mm, signiﬁcantly greater than the 1.1 ± 0.5 mm of non‐patent APD (P < 0.01). Regarding the terminal shape of the APD, spindle‐ and cudgel‐type APD were frequently patent (93% and 88%, respectively, (P < 0.01). With respect to APD course, long‐type APD showed most frequent patency (75%, P < 0.01). Dye‐injection ERP represents a simple and deﬁnitive method for examining APD function. A patent APD may prevent acute pancreatitis by reducing pressure in the MPD. Patency of the APD might be dependent on duct caliber, course, and terminal shape.
Evaluation of the alternate blood FLow in esophageal variceal patients by endoscopic color Doppler ultrasonography
Authors: Sato Takahiro , Yamazaki Katsu , Toyota Jouji , Karino Yoshiyasu , Ohmura Takumi , Kuwata Yasuaki , Akaike Jun , Suga Toshihiro
Published: June 2004

Background:  Endoscopic color Doppler ultrasonography (ECDUS) is a useful modality for obtaining color ﬂow images of esophageal varices. The direction of blood ﬂow in passageways is fundamentally hepatofugal ﬂow according to ECDUS. The present study is designed to evaluate the alternate direction of color ﬂow image of passageways via ECDUS in esophageal variceal patients.

Methods:  The study involved 125 patients with esophageal varices using ECDUS. The grades of red color (RC) were as follows: RC(+) in 79 cases, RC(+ +) in 35 cases, and RC(+ + +) in 11 cases. We investigated the alternate direction on color ﬂow images of the left gastric vein, the palisade vein, and the perforating veins via ECDUS.

Results:  Color ﬂow images of the esophageal varices and the left gastric vein were obtained in all 125 (100%) patients by ECDUS. Color ﬂow images of the perforating veins were obtained in 90 (72.0%) of the 125 patients. Vessel images of the palisade veins were detected in 33 (26.4%) of the 125 patients. The alternate direction on color ﬂow images was detected in seven (5.6%) of the 125 patients with ECDUS: in three patients, left gastric vein; in three patients, perforating veins; and in one patients, left gastric vein and palisade veins. This phenomenon was observed periodically at regular intervals. The endoscopic ﬁndings were RC(+) in all seven patients.

Conclusion:  The alternate direction of blood ﬂow in the passageways was observed in a few cases of RC(+) esophageal varices. We can observe the hemodynamics of esophageal varices non‐invasively and in real time with ECDUS, and clarify the frequencies of the alternate direction of blood ﬂow in RC‐positive esophageal variceal patients.
Differences in endoscopic views during biopsy through the right and left lower biopsy channels of the upper gastrointestinal endoscope
Authors: Mantani Naoki , Minami Kouhei , Tanaka Michio , Kogure Toshiaki , Tamura Jun’ichi , Shimada Yutaka , Terasawa Katsutoshi
Published: June 2004

Background:  It has not been established as to which side the biopsy (instrument) channel should be placed in the tip of a front‐viewing upper gastrointestinal (GI) endoscope to allow an en‐face approach to lesions on various aspects of the stomach wall.

Methods:  Using a front‐viewing two‐channel endoscope, we identiﬁed a difference in endoscopic views during biopsy between lower‐right and lower‐left channels. Colored marks were distributed on the lesser curvature (LC), greater curvature (GC), anterior wall (AW), and posterior wall (PW) in the ‘stomach’ of a dummy for mock‐performance of upper GI endoscopy. When biopsy forceps through the different channels touched the marks, an endoscopic photograph was taken. Furthermore, when biopsy specimens were obtained from PW lesions in several patients, endoscopic views were compared between the two biopsy channels.

Results:  In the dummy study, no remarkable difference was detected in targeting the marks on AW, LC, or GC of the stomach. The dummy and the patient study showed that the lower‐right approach could target PW lesions with a more adequate endoscopic view than from the lower left. The lower‐left approach targeted PW lesions on the higher body with a nearly blinded endoscopic view. Specimens from PW of the upper body, which could be precisely obtained under direct visual control through the lower‐right channel, were no smaller than those obtained using the channel on the lower left.

Conclusion:  The present study suggests that the lower‐right channel may be preferable to the lower‐left channel in the tip of a front‐viewing upper GI endoscope.
Endoscopic closure of mucosal defects with metallic clips after endoscopic mucosal resection in patients with intramural tumors of the stomach: A retrospective study
Authors: Inomata Masaaki , Endo Masaki , Terui Torahiko , Oana Syuhei , Kudara Norihiko , Obara Hirohiko , Hashimoto Yasuto , Chiba Toshimi , Orii Seishi , Suzuki Kazuyuki
Published: June 2004

Background:  Representative complications of endoscopic mucosal resection to treat intramural gastric tumors include bleeding and perforation. The purpose of the present study was to clarify whether endoscopic closure of mucosal defects using metallic clips decreases the incidence of delayed bleeding following endoscopic mucosal resection.

Patients and Methods:  The records of 187 intramural tumors of the stomach in the 181 patients that were treated by endoscopic mucosal resection between 1992 and 2001 were reviewed retrospectively. The patients were classiﬁed into two groups. The ﬁrst group included patients who received endoscopic mucosal resection but were not treated by endoscopic mucosal closure. The second group included patients who were treated with endoscopic mucosal closure using metallic clips after endoscopic mucosal resection. The incidences of delayed bleeding following endoscopic mucosal resection in these two groups were evaluated.

Results:  Delayed bleeding following endoscopic mucosal resection was observed in 13 of 96 (13.5%) of the lesions of the ﬁrst group. Delayed bleeding was encountered in only two of 91 (2.2%) lesions of the second group.

Conclusions:  Endoscopic closure of mucosal defects with metallic clips after endoscopic mucosal resection in gastric lesions was useful in decreasing the incidence of delayed bleeding following endoscopic mucosal resection.
Modes of spread in early ampullary cancer in terms of establishing proper indications for endoscopic papillectomy
Authors: Ito Kei , Fujita Naotaka , Noda Yutaka , Kobayashi Go , Kimura Katsumi , Horaguchi Jun , Sugawara Toshiki , Takasawa Osamu
Published: June 2004

Background:  Endoscopic papillectomy for adenomas of the ampulla of Vater has been reported and is gaining acceptance as an alternative to surgery in the treatment of early ampullary cancer. However, whether endoscopic treatment is justified as a treatment of choice for early ampullary cancer remains controversial. The aim of the present study was to elucidate the possibility of endoscopic papillectomy as a treatment of early ampullary cancer from the review of pathology of cases treated by surgical resection.

Patients and methods:  Twenty‐three cases of early ampullary cancer (m—tumor limited to the mucosa of the ampulla 14; od—tumor that invades Oddi's sphincter, 9) treated by surgical resection from January 1984 to March 2003 were investigated as to the following: (i) macroscopic type, maximum size, and histological type of tumor; (ii) main location and extension of tumor; (iii) prevalence of extension into the lower bile duct or pancreatic duct, and relationship between ductal infiltration and macroscopic type, maximum size, main location, or depth of invasion of tumor; (iv) lymphatic permeation, vascular invasion, and lymph node metastasis; and (v) prognosis.

Results:  All cases were classified macroscopically as exposed‐tumor type or non‐exposed‐tumor type without ulceration. Extension into the lower bile duct or the pancreatic duct was observed in 43% of the cases. There was no correlation between ductal infiltration and macroscopic type, maximum tumor size, main tumor location, or tumor depth. No lymphatic permeation, vascular invasion, or lymph node metastasis were proven in cases with ampullary cancer confined to the mucosa. In the nine cases with involvement of Oddi's sphincter, lymphatic permeation and lymph node metastasis were observed in two cases and one case, respectively.

Conclusion:  Endoscopic treatment for early ampullary cancer confined to the mucosa without spread to the bile duct or pancreatic duct is justified as a treatment of choice if detailed histological examination of the resected specimen indicated no invasion beyond its margin.
Colonic malignant melanoma mimicking colon carcinoma
Authors: Venkataraman Subramanian , Peter Shajan , Pulimood Anna B.
Published: June 2004

Primary melanoma originating in the gastrointestinal tract is rare and is usually in the anorectum. We describe a solitary left colonic melanoma in a 59‐year‐old man and review the pertinent literature. Isolated colonic melanoma is a rare diagnosis, and the published literature seems to suggest better outcomes in this group of patients with surgical excision, unlike metastasis elsewhere in the gastrointestinal tract. It is unclear how melanomas arise in tissues with no pigmented cells, as in the colon. It is possible that regressed primaries elsewhere could have been the underlying primary lesion in such patients.