bluuebunny/crossref_metadata_2025_split huggingface dataset:
The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management
Authors: Gotlib Jason , Cools Jan , Malone James M. , Schrier Stanley L. , Gilliland D. Gary , Coutré Steven E. 
Published: November 2003

AbstractIdiopathic hypereosinophilic syndrome (HES) and chronic eosinophilic leukemia (CEL) comprise a spectrum of indolent to aggressive diseases characterized by unexplained, persistent hypereosinophilia. These disorders have eluded a unique molecular explanation, and therapy has primarily been oriented toward palliation of symptoms related to organ involvement. Recent reports indicate that HES and CEL are imatinib-responsive malignancies, with rapid and complete hematologic remissions observed at lower doses than used in chronic myelogenous leukemia (CML). These BCR-ABL–negative cases lack activating mutations or abnormal fusions involving other known target genes of imatinib, implicating a novel tyrosine kinase in their pathogenesis. A bedside-to-benchtop translational research effort led to the identification of a constitutively activated fusion tyrosine kinase on chromosome 4q12, derived from an interstitial deletion, that fuses the platelet-derived growth factor receptor-α gene (PDGFRA) to an uncharacterized human gene FIP1-like-1 (FIP1L1). However, not all HES and CEL patients respond to imatinib, suggesting disease heterogeneity. Furthermore, approximately 40% of responding patients lack the FIP1L1-PDGFRA fusion, suggesting genetic heterogeneity. This review examines the current state of knowledge of HES and CEL and the implications of the FIP1L1-PDGFRA discovery on their diagnosis, classification, and management. (Blood. 2004;103:2879-2891)
Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells
Authors: Verneris Michael R. , Karami Mobin , Baker Jeanette , Jayaswal Anishka , Negrin Robert S. 
Published: November 2003

AbstractActivating and expanding T cells using T-cell receptor (TCR) cross-linking antibodies and interleukin 2 (IL-2) results in potent cytotoxic effector cells capable of recognizing a broad range of malignant cell targets, including autologous leukemic cells. The mechanism of target cell recognition has previously been unknown. Recent studies show that ligation of NKG2D on natural killer (NK) cells directly induces cytotoxicity, whereas on T cells it costimulates TCR signaling. Here we demonstrate that NKG2D expression is up-regulated upon activation and expansion of human CD8+ T cells. Antibody blocking, redirected cytolysis, and small interfering RNA (siRNA) studies using purified CD8+ T cells demonstrate that cytotoxicity against malignant target cells occurs through NKG2D-mediated recognition and signaling and not through the TCR. Activated and expanded CD8+ T cells develop cytotoxicity after 10 to 14 days of culture, coincident with the expression of the adapter protein DAP10. T cells activated and expanded in low (30 U/mL) and high (300 U/mL) concentrations of IL-2 both up-regulated NKG2D expression equally, but only cells cultured in high-dose IL-2 expressed DAP10 and were cytotoxic. Collectively these results establish that NKG2D triggering accounts for the majority of major histocompatibility complex (MHC)–unrestricted cytotoxicity of activated and expanded CD8+ T cells, likely through DAP10-mediated signaling. (Blood. 2004;103: 3065-3072)
Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice
Authors: Devlin Angela M. , Arning Erland , Bottiglieri Teodoro , Faraci Frank M. , Rozen Rima , Lentz Steven R. 
Published: November 2003

Abstract
Deficiency of methylenetetrahydrofolate reductase (MTHFR) predisposes to hyperhomocysteinemia and vascular disease. We tested the hypothesis that heterozygous disruption of the Mthfr gene sensitizes mice to diet-induced hyperhomocysteinemia and endothelial dysfunction. Mthfr+/- and Mthfr+/+ mice were fed 1 of 4 diets: control, high methionine (HM), low folate (LF), or high methionine/low folate (HM/LF). Plasma total homocysteine (tHcy) was higher with the LF and HM/LF diets than the control (P &lt; .01) or HM (P &lt; .05) diets, and Mthfr+/- mice had higher tHcy than Mthfr+/+ mice (P &lt; .05). With the control diet, the S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) ratio was lower in the liver and brain of Mthfr+/- mice than Mthfr+/+ mice (P &lt; .05). SAM/SAH ratios decreased further in Mthfr+/+ or Mthfr+/- mice fed LF or LF/HM diets (P &lt; .05). In cerebral arterioles, endothelium-dependent dilation to 1 or 10 μM acetylcholine was markedly and selectively impaired with the HM/LF diet compared with the control diet for both Mthfr+/+ (maximum dilation 5% ± 2% versus 21% ± 4%; P &lt; .01) and Mthfr+/- (6% ± 2% versus 21% ± 3%; P &lt; .01) mice. These findings demonstrate that the Mthfr+/- genotype sensitizes mice to diet-induced hyperhomocysteinemia and that hyperhomocysteinemia alters tissue methylation capacity and impairs endothelial function in cerebral microvessels.
Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells
Authors: Turville Stuart G. , Santos John J. , Frank Ines , Cameron Paul U. , Wilkinson John , Miranda-Saksena Monica , Dable Joanne , Stössel Hella , Romani Nikolaus , Piatak Michael , Lifson Jeffrey D. , Pope Melissa , Cunningham Anthony L. 
Published: November 2003

AbstractHIV-1 subverts antigen processing in dendritic cells (DCs) resulting in viral uptake, infection, and transfer to T cells. Although DCs bound monomeric gp120 and HIV-1 similarly, virus rarely colocalized with endolysosomal markers, unlike gp120, suggesting HIV-1 alters endolysosomal trafficking. Virus within DC intracellular compartments rapidly moved to DC-CD4+ lymphocyte synapses when introduced to CD4+ lymphocyte cultures. Although viral harboring and transfer from nonlysosomal compartments was transient, given DC-associated virus protein, nucleic acids, and infectious HIV-1 transfer to CD4+, lymphocytes decayed within 24 hours. However a second long-term transfer phase was apparent in immature DCs after 48 hours as a zidovudine-sensitive rise in proviral DNA. Therefore, DCs transfer HIV-1 to CD4+ lymphocytes in 2 distinct phases. Immature and mature DCs first divert virus from the endolysosomal pathway to the DC–T-cell synapse. Secondly, the later transfer phase from immature DCs is through de novo HIV-1 production. Thus, the controversy of DCs being infected or not infected for the mechanics of viral transfer to CD4+ lymphocytes can be addressed as a function of time.
Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly
Authors: Ghia Paolo , Prato Giuseppina , Scielzo Cristina , Stella Stefania , Geuna Massimo , Guida Giuseppe , Caligaris-Cappio Federico 
Published: November 2003

AbstractThe responsiveness and diversity of peripheral B-cell repertoire decreases with age, possibly because of B-cell clonal expansions, as suggested by the incidence of serum monoclonal immunoglobulins and of monoclonal chronic lymphocytic leukemia (CLL)–like B lymphocytes in clinically silent adults. We phenotyped peripheral blood cells from 500 healthy subjects older than 65 years with no history or suspicion of malignancies and no evidence of lymphocytosis. In 19 cases (3.8%) a κ/λ ratio of more than 3:1 or less than 1:3 was found: 9 were CD5+, CD19+, CD23+, CD20low, CD79blow, sIglow (classic CLL-like phenotype); 3 were CD5+, CD19+, CD23+, CD20high, CD79blow, sIglow (atypical CLL-like), and 7 were CD5-, CD19+, CD20high, CD23-, CD79bbright, FMC7+, sIgbright (non–CLL-like). In 2 subjects, 2 phenotypically distinct unrelated clones were concomitantly evident. No cases were CD10+. Polymerase chain reaction (PCR) analysis demonstrated a monoclonal rearrangement of IgH genes in 15 of 19 cases. No bcl-1 or bcl-2 rearrangements were detected. Using a gating strategy based on CD20/CD5/CD79 expression, 13 additional CLL-like B-cell clones were identified (cumulative frequency of classic CLL-like: 5.5%). Thus, phenotypically heterogeneous monoclonal B-lymphocyte expansions are common among healthy elderly individuals and are not limited to classic CLL-like clones but may have the phenotypic features of different chronic lymphoproliferative disorders, involving also CD5- B cells.
Validation of Four Clinical Indicators of Preventable Drug-Related Morbidity
Authors: Flanagan Priti S , MacKinnon Neil J , Bowles Susan K , Kirkland Susan A 
Published: November 2003

BACKGROUND: Clinical indicators are tools that assess quality issues related to the use of medicines. At this time, validated clinical indicators for preventable drug-related morbidity (PDRM) are lacking. OBJECTIVE: To assess the validity and reliability of using population administrative claims data to identify the extent of PDRM in older adults in Canada. METHODS: Four indicators of PDRM related to cerebrovascular and cardiovascular care were chosen for validation. A random sample of cases that represented the indicators and fit the criteria (hits) for PDRM from the retrospective operationalization of the study database and those that did not fit the criteria (near hits) were selected for chart review. One-page abstracts of the cases were prepared for review by a panel of 5 clinical pharmacists. Validity was assessed by calculating sensitivity, specificity, and positive and negative predictive value. Reliability was assessed using reviewers' agreement scores (κ statistics). RESULTS: Overall, 119 case abstracts were reviewed by each panelist. The sensitivity ranged from 33% to 100% and the specificity from 51% to 71%. Predictive values ranged from 5.3% to 43% (positive) and 90% to 100% (negative). The overall κ statistic was fair (0.21). CONCLUSIONS: The validity of the 4 assessed PDRM indicators varied. The reliability was fair; however, these indicators may be useful to screen older adults for PDRM.
Long‐term Surgical Outcome of Noninvasive and Minimally Invasive Intraductal Papillary Mucinous Adenocarcinoma of the Pancreas
Authors: Nakagohri Toshio , Asano Takehide , Kenmochi Takashi , Urashima Tetsuro , Ochiai Takenori 
Published: November 2003

AbstractThe objective of this study was to clarify the long‐term outcome after surgical resection in patients with noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma. We performed a retrospective review of the clinicopathological features and outcome in patients who underwent pancreatic resection for noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma between November 1982
and December 1997 at Chiba University Hospital. Minimally invasive structures were pathologically observed in five cases. The mean age of patients with either noninvasive (n = 16) or minimally invasive n = 5) adenocarcinoma was 61 years. Of the patients with minimally invasive adenocarcinoma, 4 had abdominal pain.
Conversely, 7 patients with noninvasive adenocarcinoma had no complaint. The mean size of noninvasive and minimally invasive tumors was 2.5 cm (range 0.8 to
4.0) and 3.3 cm (range 2.5 to 4.5), respectively. The overall 5‐year and
10‐year survival rates for all 21 patients were 89% and 47%, respectively.
Disease recurred in 3 patients; 2 patients with minimally invasive adenocarcinoma and 1 with noninvasive adenocarcinoma. Recurrence sites were peritoneumn = 2) and main pancreatic duct of the remnant pancreas (n = 1); 5 disease‐free patients died of unrelated causes. The remaining 13 patients are alive and disease free
3 to 12 years after surgery. Noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma had a favorable prognosis after surgical treatment.
Contemporary Outcomes of Ambulatory Laparoscopic Cholecystectomy in a Major Teaching Hospital
Authors: Lau Hung , Brooks David C. 
Published: November 2003

Abstractmbulatory laparoscopic cholecystectomy is an established practice in our institution, with an experience of more than 800 cases. The present study is conducted to evaluate the contemporary outcomes of day‐case laparoscopic cholecystectomy in the setting of a major teaching hospital. A retrospective analysis of 200 patients who underwent ambulatory laparoscopic cholecystectomies was performed to evaluate the postoperative morbidity, unplanned admission, and readmission rates. Causes for unanticipated admission and readmission were analyzed. Uneventful recovery was attained in 185 (92.5%) patients. The mean length of the operation was 56 ± 20 (SD) minutes. There was no hospital mortality, and no patient required conversion to open cholecystectomy. Nine patients were admitted overnight after operation because of nausea and vomitingn = 3), pain (n = 2), urinary retention (n = 2), medical observation n = 1), and patient’s preference (n= 1), leading to an unanticipated admission rate of 4.5%. Six patients required readmission because of postoperative complicationsn = 4) and abdominal pain (n = 2), giving a readmission rate of 3%. The overall postoperative morbidity rate was 3% (n = 6), including retained stones n = 4), bile leakage (n = 1), and hepatic subcapsular hematoma (n = 1). Ambulatory laparoscopic cholecystectomy is a safe practice in appropriately selected patients. Postoperative nausea and vomiting was the commonest reason for unanticipated admission after operation, and retained stones was the most frequent postoperative morbidity necessitating readmission.
Different Patterns of Recurrence in Gastric Cancer Depending on Lauren’s Histological Type: Longitudinal Study
Authors: Marrelli Daniele , Roviello Franco , de Manzoni Giovanni , Morgagni Paolo , Di Leo Alberto , Saragoni Luca , De Stefano Alfonso , Folli Secondo , Cordiano Claudio , Pinto Enrico 
Published: November 2003

AbstractThe aim of this multicenter longitudinal study was to evaluate the pattern of recurrence in patients submitted to potentially curative surgery for intestinal‐type and diffuse‐type gastric cancer. The study included 412 patients surgically treated at three Italian surgical departments, subdivided into 273 intestinal‐type cases (group A) and 139 diffuse‐type cases (group B). Recurrence of disease was found in 41% of group A cases and 65% of group B cases (p <0.0001). The incidence of locoregional, hematogenous, and peritoneal recurrence was 20%, 19%, and 9% in group A, and 27%, 16%, and 34% in group B, respectively; the difference between the two groups was statistically significant for peritoneal recurrence (p <0.0001). Multivariate analysis identified as prognostic variables lymph node status, depth of invasion, extent of lymphadenectomy, advanced age, and male gender in group A; depth of invasion, extent of lymphadenectomy, tumor size, and lymph node status, in group B. Whereas in group A the incidence of peritoneal recurrence was limited in all subgroups examined, in group B very high rates were observed in cases with infiltration of the serosa, involvement of second‐level lymph nodes, or large tumor size. The notable difference in the risk of peritoneal recurrence between the intestinal and diffuse types should be taken into consideration in the therapeutic approach to gastric cancer.
Management of Complex Perineal Injuries
Authors: Kudsk Kenneth A. , Hanna M. Keith 
Published: November 2003

AbstractA retrospective study of 25 patients with severe soft tissue injuries to the perineum from the last 14 years was performed to determine the most appropriate management strategy for these problematic wounds. There were 20 (80%) men and 5 (20%) women with an average age of 29 years. Six (24%) patients died of exsanguination from their pelvic injuries within the first few hours of presentation. The remaining 19 patients were taken to the operating room for sigmoidoscopy, diverting colostomy, distal rectal washout, and radical debridement and irrigation of any devitalized tissue. Enteral access by jejunostomy was obtained in six patients. Most patients underwent daily debridement and pulsatile irrigation for at least three days, but usually longer, until the treating surgeon deemed the wound to be clean. None of the patients managed in this fashion developed pelvic sepsis. However, pelvic sepsis did occur in all four patients who did not receive early mandatory daily debridement. Total parenteral nutrition was required in eight patients because there were significant delays in the ability of these patients to resume oral intake. In most previously published series in which daily debridement was not performed, a pelvic sepsis rate of 40% to 80% was reported. Therefore, to optimize the clinical course and recovery from these complex wounds, we conclude that mandatory daily debridement with pulsatile irrigation should be instituted in conjunction with sigmoidoscopy, diversion of the fecal stream, distal rectal irrigation, enteral access, and initial radical debridement of devitalized tissue.
Effect of Short‐term Administration of Prostaglandin E1 on Viability after Ischemia/Reperfusion Injury with Extended Hepatectomy in Cirrhotic Rat Liver
Authors: Hossain Mohammad Akram , Izuishi Kunihiko , Maeta Hajime 
Published: November 2003

AbstractThe cytoprotective effect of prostaglandin E1 (PGE1) has been demonstrated experimentally and clinically against hepatic ischemia and reperfusion injury and against the effects of partial hepatectomy in both individual and combined models of noncirrhotic livers. Cirrhotic livers are more vulnerable to ischemia/reperfusion injury during hepatectomy than are noncirrhotic livers, and postoperative malfunctioning complicates life with multiple organ failure. Cirrhotic livers with tumors have mostly been treated conservatively because extended hepatectomy with induced ischemia during surgery is impossible. The purpose of our study was to document postoperative surgical adaptation in inoperable cases with improved survival after extended hepatectomy in a rat model of cirrhosis treated by PGE1. Cirrhosis was induced by intraperitoneal injections of 1% dimethylnitrosamine. The liver was subjected to 15 minutes of total ischemia by occluding the hepatoduodenal ligament. Hepatectomy was performed during ischemia. Pretreatment with PGE1 (0.4 μg/kg/min) (or without it in the controls) was given for 15 minutes by intravenous infusion prior to inducing ischemia and during reperfusion. Portal venous flow (PVF) and liver tissue blood flow (LTBF) were measured during reperfusion. At the end of 60 minutes of reperfusion, venous blood was collected for liver function tests. The animals were followed up regarding survival for 48 hours. The PVF and LTBF were significantly improved in the PGE1 group. The blood chemical analysis indicated that PGE1 significantly suppressed posthepatectomy liver dysfunction. Most importantly, PGE1 treatment markedly improved the survival rate, from 42% in the controls to 75% in the test animals at 24 hours after hepatectomy and from 17% in the controls to 58% in the test animals at 48 hours. We concluded that short‐term administration of PGE1 makes extensive hepatectomy possible under ischemic conditions in cirrhotic livers.
Positron Emission Tomography for Staging Esophageal Cancer: Does It Lead to a Different Therapeutic Approach?
Authors: Kneist Werner , Schreckenberger Mathias , Bartenstein Peter , Grünwald Frank , Oberholzer Katja , Junginger Theodor 
Published: November 2003

AbstractAccurate preoperative staging is essential for the indication and selection of the appropriate surgical procedure in patients with esophageal cancer. The present prospective study was designed to determine if the preoperative use of 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) increases the accuracy of staging esophageal cancer compared with computed tomography (CT) and if it thereby leads to a different therapeutic approach. A total of 58 patients, 46 men and 12 women (mean age 61 years), with histologic proof of esophageal carcinoma underwent FDG‐PET of the neck, chest, and abdomen, as well as CT of the chest and abdomen, to determine tumor stage. FDG‐PET and CT data were compared with each other and with pathohistologic findings. Sensitivity, specificity, and overall accuracy for detecting histologically verified lymph node and distant metastases were calculated for FDG‐PET and CT. FDG‐PET showed a higher specificity, whereas CT had higher accuracy for detecting both abdominal (73% vs. 59%) and thoracic (73% vs. 63%) lymph node metastases. The accuracy of detecting blood‐borne and lymphatic distant metastases was identical for CT and FDG‐PET imaging (50%). FDG‐PET had a higher specificity than CT (87% vs. 13%) but lower sensitivity (35% vs. 67%). FDG‐PET did not provide new information on the indication for surgery, nor was it helpful for choosing the appropriate surgical procedure in patients with esophageal carcinoma. In view of the relatively high cost of FDG‐PET examinations, the use of this modality is indicated primarily in patients with inconclusive CT findings or for scientific research projects. Higher sensitivity as a result of tumor‐affinity radiopharmaceuticals and optimized apparatus resolution, in addition to the advantages offered by whole‐body PET scanning, may lead to new indications for this staging procedure in the future.
Spectrum of Breast Cancer in Malaysian Women: Overview
Authors: Hisham Abdullah Noor , Yip Cheng Har 
Published: November 2003

AbstractBreast cancer is the most common cancer among Malaysian women. Nonetheless, in Malaysia there is a marked geographical difference in the incidence of breast cancer with advanced stage of presentation. The breast clinic in Kuala Lumpur Hospital diagnosed approximately 150 to 200 new cases of breast cancer a year. This number, however, represents only 12.0% to 15.0% of all breast disease seen annually in Kuala Lumpur Hospital. Between 1998 and 2001, of a total of 774 cases of newly diagnosed breast cancer in Kuala Lumpur Hospital, only 5.0% (40/774) were impalpable breast cancers. The peak age group for the three major ethnic distributions (Malay, Chinese, and Indian) ranged from 40 to 49 years. The mean tumor size at presentation was 5.4 cm (range: 1–20 cm), and the advanced stage of breast cancer is observed to be highest among the Malay ethnic group. Although it appears that the incidence of breast cancer in Malaysia is lower than in the developed countries, the difference may be attributable to the difficulty in getting accurate statistics and to underreporting of cases. Nonetheless, from the available data, it is clear that breast cancer continues to be the most common cancer among Malaysian women. The strongly negative social‐cultural perception of the disease, made worse by the geographical isolation of many rural areas, accounts for the delayed diagnosis and the often advanced stage of disease at presentation. A prospective population‐based study is called for to verify the demographic patterns of breast cancer, particular in Malaysia and other developing countries. The findings of such a study may have implications for future breast screening programs and for facilitating the understanding of differing risks of breast cancer among women around the world.