bluuebunny/crossref_metadata_2025 huggingface dataset:
On the choice of degrees of freedom for testing gene–gene interactions
Authors: Ueki Masao
Published: July 2014

In gene–gene interaction analysis using single nucleotide polymorphism (SNP) data, empty cells arise in the genotype contingency table more frequently than in single SNP association studies. Empty cells lead to unidentifiable regression coefficients in regression model fitting. It is unclear whether the degrees of freedom (d.f.) for testing interactions are reduced for such sparse contingency tables. Boolean Operation based Screening and Testing is an exhaustive gene–gene interaction search method in which a fixed d.f. of four (the most conservative choice) is used in the chi‐squared null distribution for the likelihood ratio test for gene–gene interactions under a logistic regression model. In this paper, the choice of d.f. is investigated theoretically by introducing a decomposition of type I error. An adaptive method using the observed d.f. can be less conservative than the fixed d.f. method, thereby enhancing power. In simulated data, type I error rates for the adaptive method were usually better controlled under various scenarios for Gaussian linear regression and logistic regression, including prospective and retrospective sampling designs, as well as for artificial data that mimic actual genome‐wide SNPs. When the adaptive method was applied to public datasets generated from simulations, it exhibited an improvement in power over the fixed method. Copyright © 2014 John Wiley & Sons, Ltd.
A morphometric sex determination model for adult greater roadrunners (Geococcyx californianus)
Authors: Montalvo Andrea E. , Powell Robert A. , MACdonald Michael D. , Ransom Dean , Lopez Roel R.
Published: July 2014

Little is known of the greater roadrunner's (Geococcyx californianus; roadrunner) ecology and many demographic questions are difficult to answer because of our inability to determine adult bird sex in the field. We collected measurements from live‐captured roadrunners of known sex in Fisher County, Texas, USA, and from roadrunner specimens from museums and university biological collections from 2003 to 2012 to develop a predictive logistic regression model for adult sex determination. We measured 433 adult birds of which 80% (n = 346) were randomly chosen to build potential models. Our best model included the variable estimate bill depth, which was found to be larger in males and correctly classified 80% of the birds. We validated the model with the remaining 20% of measurements (n = 87) and correctly identified the sex of 85% of the birds. Because this model incorporated roadrunners from across their range, it provides an easy, inexpensive, accurate, and field‐relevant methodology for sex determination of adult roadrunners at the point of capture. © 2014 The Wildlife Society.
Formal probabilistic analysis of detection properties in wireless sensor networks
Authors: Elleuch Maissa , Hasan Osman , Tahar Sofiène , Abid Mohamed
Published: July 2014

In the context of wireless sensor networks (WSNs), the ability to detect an intrusion event is the most desired characteristic. Due to the randomness in nodes scheduling algorithm and sensor deployment, probabilistic techniques are used to analyze the detection properties of WSNs. However traditional probabilistic analysis techniques, such as simulation and model checking, do not ensure accurate results, which is a severe limitation considering the mission-critical nature of most of the WSNs. In this paper, we overcome these limitations by using higher-order-logic theorem proving to formally analyze the detection properties of randomly-deployed WSNs
using the randomized scheduling of nodes. Based on the probability theory, available in the HOL theorem prover, we first formally reason about the intrusion period of any occurring event. This characteristic is then built upon to develop the fundamental formalizations of the key detection metrics: the detection probability and the detection delay. For illustration purposes, we formally analyze the detection performance of a WSN deployed for border security monitoring.
Definition of Barrett’s Esophagus Dysplasia: Are We Speaking the Same Language?
Authors: Rugge Massimo , Pizzi Marco , Castoro Carlo
Published: July 2014

The definition of Barrett’s esophagus (BE) is still a matter of debate. The diagnostic criteria adopted around the world for both BE and BE‐related pre‐cancerous lesions are inconsistent, particularly between Eastern and Western pathologists. From a clinical perspective, these different clinico‐biological approaches may affect how the literature is interpreted, with detrimental effects on the clinical management of patients. The present review focuses on the major discrepancies in the field, covering both the non‐neoplastic and the pre‐cancerous lesions associated with Barrett’s disease.
Optimization of Physiological Growth Conditions for Maximal Gamma‐linolenic Acid Production by Cunninghamella blakesleeana‐JSK2
Authors: Sukrutha S. K. , Adamechova Zuzana , Rachana Kunder , Savitha Janakiraman , Certik Milan
Published: July 2014

Effects of various cultural conditions on biomass, lipid and Gamma‐linolenic acid (GLA) production were investigated in the oleaginous fungus Cunninghamella blakesleeana‐JSK2 isolated from soil. The GLA production was influenced by various factors such as growth condition (static and shaken), incubation time, pH, temperature, carbon and nitrogen sources. The results indicated that optimum GLA production (21 %) was obtained when the fungus was grown under shaken condition at 120 rpm for 6 days with optimum pH and temperature of 6 and 28 °C, respectively. Glucose and potassium nitrate enhanced the GLA production. Urea and sucrose were poor substances for biomass, lipid and GLA production.
Pancreatic polypeptide inhibits somatostatin secretion
Authors: Kim Wook , Fiori Jennifer L. , Shin Yu-Kyong , Okun Eitan , Kim Jung Seok , Rapp Peter R. , Egan Josephine M.
Published: July 2014

Pancreatic polypeptide (PP) is a major agonist for neuropeptide Y4 receptors (NPY4R). While NPY4R has been identified in various tissues, the cells on which it is expressed and its function in those cells has not been clearly delineated. Here we report that NPY4R is present in all somatostatin‐containing cells of tissues that we tested, including pancreatic islets, duodenum, hippocampus, and hypothalamus. Its agonism by PP decreases somatostatin secretion from human islets. Mouse embryonic hippocampal (mHippo E18) cells expressed NPY4Rs and their activation by PP consistently decreased somatostatin secretion. Furthermore, central injection of PP in mice induced c‐Fos immunoreactivity in somatostatin‐containing cells in the hippocampus compared with PBS‐injected mice. In sum, our results identify PP as a pivotal modulator of somatostatin secretion.
Headache After Traumatic Brain Injury: A National Survey of Clinical Practices and Treatment Approaches
Authors: Brown Allen W. , Watanabe Thomas K. , Hoffman Jeanne M. , Bell Kathleen R. , Lucas Sylvia , Dikmen Sureyya
Published: July 2014

Background

Individuals with headache after traumatic brain injury (TBI) receive care in a wide variety of clinical locations by physicians trained in multiple specialties.

Objective

To understand current practice patterns and perceptions of treatment issues among clinicians managing headache after TBI.

Design

National survey of current clinical practice using a 20‐item questionnaire developed by the authors.

Participants

Survey respondents were members of the Central Nervous System Council list survey of the American Academy of Physical Medicine and Rehabilitation (N = 1782) and the American Headache Society membership (N = 1260).

Methods

The survey was sent electronically to potential participants and was followed by 2 biweekly reminders. The survey queried the physicians' clinical setting; their use of headache classification systems, headache diaries, checklists, and diagnostic procedures; the pharmacologic and nonpharmacologic treatments prescribed; and headache chronicity and associated symptoms and disorders among their patients with TBI.

Results

Completed surveys were received from 193 respondents. The use of standardized classification systems and checklists was commonly reported. Respondents used nonpharmacologic and pharmacologic treatment approaches with similar frequency and modest perceived success rates. A high frequency of headache‐associated new sleep and mood disorders was reported. When response differences occurred between practice settings, they reflected a focus on headache diagnosis, classification, and pharmacologic treatment among neurology and specialty headache clinics, whereas a nonpharmacologic approach to management among TBI specialty and general rehabilitation clinicians was more commonly reported.

Conclusion

Management strategies for treating headache after TBI vary widely among general and specialty clinical practices. This suggests that additional research is needed that would lead to an increase in the use of established headache classification and the development of standardized management approaches so that all practitioners who care for patients after TBI can provide consistent effective care.
Novel agents in the frontline management of multiple myeloma
Authors: Loong Herbert H.
Published: July 2014

Significant advances in our understanding of the biology of multiple myeloma have led to exciting new opportunities in treatment. The management of this disease is rapidly changing with a plethora of clinical trials initiated with novel agents, namely thalidomide, lenalidomide and bortezomib, either alone or in conjunction with established modalities such as conventional cytotoxic agents and stem-cell transplantation. The combination of these novel agents together with conventional regimens have led to higher response rates and survival, providing options for patients whose disease is otherwise resistant to conventional therapy. These pivotal trials that lead to the approval of these three novel agents in treatment naive patients. The potential implications in the frontline treatment paradigm of multiple myeloma are discussed.
Current and future cancer burden in Saudi Arabia
Authors: Ibrahim Ezzeldin , Sadiq Bakr M. Bin , Banjar Laila , Awadalla Saeed , Abomelha Mohammed S.
Published: July 2014

BACKGROUND AND OBJECTIVES:

Despite the low cancer incidence in Saudi Arabia, the country must be ready to face the challenge of a foreseeable increase in cancer burden mainly attributed to the growth and aging of the population. We designed this study to estimate the future cancer burden and to highlight the demands on prospective healthcare resources.

METHODS:

cancer statistics in saudi Arabia from 2000 to 2004 were examined. The Joinpoint regression program was used to identify changes in secular trends, while the GLOBOCAN 2002 software projected future burden. considering current trends and the growth and aging of the population, we projected the future burden.

RESULTS:

In 2004, the age-standardized rate (ASR) for incidence for all cancer sites, excluding basal and squamous skin cancer, was 57.2 per 100 000 (55.8 and 59.1 per in males and females, respectively). ASR trends showed a statistically significant increase in the annual percent change (APC) for both males and females, which was greatest from 2003 to 2004 (4.93% and 2.64%, respectively). By the year 2020 and 2030, there would be an approximately 6- and 10-fold rise among males as compared with the burden in 2004. the corresponding numbers for females would be 5- and 8-fold, respectively. The highest cancer burden would be expected for middle-aged and elderly saudis.

CONCLUSIONS:

In countries currently experiencing low cancer rates, the future cancer burden could increase considerably and place enormous demands on healthcare resources. The present study may provide an impetus to examine the future all or site-specific cancer burden, particularly in developing countries.
The challenge of risk stratification in acute myeloid leukemia with normal karyotype
Authors: Zaidi Syed Z. , Owaidah Tarek , Sharif Fahad Al , Ahmed Said Y. , Chaudhri Naeem , Aljurf Mahmoud
Published: July 2014

Cytogenetic aberrations have long been recognized as the most important prognostic variable in acute myeloid leukemia (AML) and are now a major stratification tool for post-remission therapy. Cytogenetics- based stratification improves survival. patients with AML and normal cytogenetics, the largest single subgroup, have had a very heterogeneous outcome with standard chemotherapy in multiple clinical trials. Hence it is difficult to recommend a “one size fits all” kind of treatment for this heterogeneous population of AML patients. New emerging data from preclinical, retrospective, and large, randomized controlled studies indicate that in addition to cytogenetic abnormalities, many other molecular aberrations are operative in the response to treatment as well as in the risk of relapse. Such molecular markers are being tested for developing targeted therapies and may help in improved stratification of patients in the selection of post-remission therapy. Emerging evidence reveals that at the submicroscopic level, AML with normal cytogenetics may carry poor prognostic genetic lesions or “molecular signatures” as is the case with FLT3 mutations and overexpression of BAALC, ERG or MN1, or may have aberrations that predict better risk as is the case with isolated NPM1 or CEBPA mutations. Later studies have tried to explore the interaction of various prognostically important genes in this group of AML patients. The utility of the evolving data for bedside management of such patients is expected to improve with the wider application of modern tools, using the proposed clinical outcome models, and probably by development of a risk-scoring system based on the relative risk associated with each molecular aberration. The goals include identifying those patients most likely to benefit from upfront allogeneic HSCT and sparing good- prognosis patients from unnecessary transplant-related morbidity. The following is an outline of the most common molecular changes, their impact on the outcome of AML patients with normal cytogenetics and challenges in their wide scale application in risk stratification.
Malignant tumors of the minor salivary glands in northern Pakistan
Authors: Rahman Bushra , Mamoon Nadira , Jamal Shahid , Zaib Nadia , Luqman Mohammad , Mushtaq Sajid , Anwar Masood
Published: July 2014

BACKGROUND:

Malignant tumors of the minor salivary glands comprise a small but significant proportion of oral cancers. We analyzed this group of tumors in our population.

METHODS:

The records of all cases of malignant minor salivary gland tumors diagnosed at the Armed Forces Institute of pathology (AFIP), Rawalpindi, pakistan, during a period of 10 years (1994-2003) are described. the institute receives biopsy material from armed forces and public and private sector hospitals in northern Pakistan as well as referrals for second opinion.

RESULTS:

A total of 21168 tumors were recorded at the AFIP Tumor Registry during the study period. these included 70 malignant minor salivary gland tumors. Twenty-three of these (32.8%) arose in the palate while the remaining tumors originated at other sites in the oral cavity. the commonest histological type was adenoid cystic carcinoma, constituting 30 cases (42.8%). The next most common type was mucoepidermoid carcinoma comprising 26 (37.1%) cases. The mean age of cases was 43.4 years and the male-to-female ratio was 1:1.4. There were 2 cases each of polymorphous low-grade adenocarcinoma and clear cell adenocarcinoma. The remaining cases included undifferentiated carcinomas, adenocarcinomas (not otherwise specified) and a few other rare tumors.

CONCLUSION:

Adenoid cystic carcinoma was the commonest malignant neoplasm of the minor salivary glands followed by mucoepidermoid carcinoma. The palate was the commonest location of these tumors.
A retrospective study of treatment and outcome in 39 cases of male breast cancer
Authors: Yoney Adnan , Kucuk Ahmet , Alan Omur , Unsal Mustafa
Published: July 2014

BACKGROUND AND OBJECTIVES:

Optimal management if male breast cancer (MBC) is not clearly established and treatment guidelines are scarce. We evaluated our own results in the treatment of male breast cancer patients with respect to local control (LC), overall survival (OS) and possible prognostic factors for survival.

PATIENTS AND METHODS:

Thirty-nine patients with MBC were retrospectively studied to evaluate the results in this type of tumor; 94.8% had invasive ductal carcinoma (IDC), 2.6% invasive papillary carcinoma (IPC) and 2.6% invasive lobuler carcinoma (ILC). The distribution according to stage was 12.8%, 46.2%, 30.7% and 1 0.3% in stages I, II, III and IV, respectively; 7.7% underwent radiotherapy (RT)± hormonotherapy (HT), 22.8% had chemotherapy (CT), 61.8% had chemoradiotherapy (CRT) ± HT and 7.7% had HT in addition to surgery.

RESULTS:

The distant metastases rate was 36% and the local recurrence rate was 5%. All the local recurrences and the distant metastases had occurred after the first two years. The 2-year disease free survival (DFS) and OS rates were 87.2% and 89.7%, respectively, and the 5-year DFS and OS rates were 65.8% and 80.1 %, respectively. in a univariate analysis for OS, statistical significance was found for lymph node metastases (P=.00001), stage (P=.0098) and age (P=.03), while presence of RT in the treatment modality (P=.6849), and tumor size (P=.4439) demonstrated no significance. The presence of lymph node metastases significantly impaired OS (P=.004) and DFS (P=.014) in the multivariate analysis.

CONCLUSION:

postoperative radiotherapy was important in the management of MBC to improve LC resulting in one local failure, but did not improve OS and DFS. The presence of lymph node metastases significantly impairedOS and DFS.
Why implement universal leukoreduction?
Authors: Bassuni Wafaa Y. , Blajchman Morris A. , Al-Moshary May A.
Published: July 2014

The improvement of transfusion medicine technology is an ongoing process primarily directed at increasing the safety of allogeneic blood component transfusions for recipients. Over the years, relatively little attention had been paid to the leukocytes present in the various blood components. The availability of leukocyte removal (leukoreduction) techniques for blood components is associated with a considerable improvement in various clinical outcomes. These include a reduction in the frequency and severity of febrile transfusion reactions, reduced cytomegalovirus transfusion-transmission risk, the reduced incidence of alloimmune platelet refractoriness, a possible reduction in the risk of transfusion-associated variant creutzfeldt-Jakob disease transmission, as well as reducing the overall risk of both recipient mortality and organ dysfunction, particularly in cardiac surgery patients and possibly in other categories of patients. Internationally, 19 countries have implemented universal leukocyte reduction (ULR) as part of their blood safety policy. The main reason for not implementing ULR in those countries that have not appears to be primarily concerns over costs. Nonetheless, the available international experience supports the concept that ULR is a process that results in improved safety of allogeneic blood components.
A retrospective comparison of concurrent bolus 5-fluorouracil or raltitrexed in preoperative chemoradiation for locally advanced rectal cancer
Authors: Yoney Adnan , Askaroglu Bulent , Hancilar Tayfun , Isikli Levent , Unsal Mustafa
Published: July 2014

BACKGROUND:

5-fluorouracil (FU) is commonly used in preoperative chemoradiation in locally advanced rectal cancer, but not all patients cooperate in taking the 5-day continuous infusion regimen. Raltitrexed (RA), a thymidylate synthase inhibitor, is one of the agents used in place of FU in such cases. We retrospectively compared the toxicity, tumor downstaging, pathologic response and relapse rate with bolus FU or RA during concurrent radiotherapy (RT) to assess the role of RA in place of FU.

PATIENTS AND METHODS:

We conducted a retrospective analysis of response rates and toxicity data on 59 patients diagnosed with locally advanced rectal cancer and treated with surgery following preoperative chemo radiation with either concurrent FU or RA between January 1999 and December 2004.

RESULTS:

Median follow-up was 38 months (range, 1-70). Ten patients (10%) had grade 3 gastrointestinal (GIS) toxicity during chemoradiation. The pathologic complete response rates were 6% with Fu and 7% with RA (P=0.844), while 66.7% of patients treated with Fu and 37.1% with RA had downstaging of the T stage after chemoradiation (P=0.026). The sphincter preservation rates were 45.8% with Fu and 51.4% with RA (P=0.912). The 5-year local control rates were 79.2% for patients treated with RT+FU and 85.76% for patients treated with RT+RA (P=0.510).

CONCLUSION:

compared with the RT+RA regimen, the incidence of downstaging was greater with RT+FU, but RT+Fu was associated with a correspondingly greater rate of acute grade 2 GIS toxicity. However, no significant differences were seen in sphincter preservation, pathologic complete response, local control and distant recurrences rates among patients. Fu seems to be the best therapeutic choice, while RA seems to be as effective as bolus Fu.
Expression of CD66c and CD25 in acute lymphoblastic leukemia as a predictor of the presence of BCR/ABL rearrangement
Authors: Owaidah Tarek M. , Rawas Faisal I. , khayatt Mazen F. Al , Elkum Nasser B.
Published: July 2014

BACKGROUND:

Expression of myeloid or T cell lymphoid in precursor B cell acute lymphoblastic leukemia (pre- B cell ALL), which is referred to as aberrant expression, is quite a common phenomenon. cD66c is a myeloid marker which has aberrant expression in pre-B cell ALL, with strong correlation with non-random genetic changes (BCR/ABL rearrangement). Another leukemia associated marker (CD25) is frequently expressed in pre-B cell ALL. The frequency of CD25-expressing lymphoblasts has been found to be significantly higher in BCR/ABL-positive vs. BCR/ABL-negative patients.

METHODS:

In a cohort of 1 03 patients diagnosed with pre-B cell ALL or biphenotypic leukemia and studied for expression of CD66c and CD25 at presentation, we evaluated the frequency of expression of either or both in BCR/ABL positive cases.

RESULTS:

Surface CD66c was expressed by 70 cases (68%) and CD25 was expressed by 33 cases (32%) while both were expressed together on 29 cases (28%). BCR/ABL was positive in 18/1 03 patients. All BCR/ABL positive cases were positive for surface CD66c and CD25.

CONCLUSION:

Positivity for both leukemia-associated antigens CD66c and CD25 in combination can predict the presence of BCR/ABL rearrangement in pre-B cell ALL. While this finding does not replace the detection of BCR/ABL abnormality by cytogenetic or molecular techniques, it does provide an early and handy tool for prediction and management of high-risk cases of pre-B cell ALL, especially in centers with limited laboratory facilities.
Newly diagnosed multiple myeloma in Taiwan
Authors: Lin Chung-King , Sung Yung-Chuan
Published: July 2014

Multiple myeloma is a clonal plasma cell dyscrasia with clinical heterogeneity. As of now, two key questions need to be answered before starting to treat a newly diagnosed myeloma patient. One is whether the patient is a candidate for high-dose chemotherapy with stem cell support and the other is risk stratification. AS novel therapeutics have emerged, it is increasingly important to introduce a risk-adapted approach. The heterogeneity of the disease is established, for the most part, by disease biology, predominantly genetics. cytogenetic analysis by either banding technique or fluorescent in situ hybridization is able to identify high-risk subpopulations. The new international staging system based on ?2-microglobu- lin and albumin levels in serum is also very helpful in defining the high-risk group (stage 3). This group of patients may not respond well to high-dose chemotherapy and require early introduction of newer treatments such as the bortezomib-containing regimen. The main factor in determining the eligibility for stem cell transplants is age. Based on the current literature and situation in Taiwan, we suggest stem cell transplantation if the patient is younger than 55 years of age. Each case should be considered individually if the age of the patient is between 55 and 70 years. Finally, we have also reviewed the status and the treatment of multiple myeloma in Taiwan. Fortunately, there has been an improvement in awareness, diagnosis and treatment. Cytogenetic studies have been applied in risk evaluations, but are limited in a few centers due to lack of availability. With the exception of the agent lenalidomide, new novel agents are available for treating of myeloma in Taiwan.
Spontaneous recovery of chylothorax caused by lymphoma
Authors: Khosravi Adnan , Anjidani Ali Asghar
Published: July 2014

Chylothorax is a rare complication with both traumatic and non-traumatic causes. The most common non-traumatic cause is malignancy, especially lymphoma. Lymph discharges into the pleural space, causing nutritional, metabolic, immunologic and respiratory complications. We evaluated the case of a patient suffering from a low-grade lymphoma who developed chylothorax that did not respond to chemotherapy and conservative treatment. This patient recovered spontaneously.
JACIE Accreditation in 2008
Authors: Pamphilon Derwood , Apperley Jane F. , Samson Diana , Slaper-Cortenbach Ineke , McGrath Eoin
Published: July 2014

JACIE was initiated as a small pilot project in Spain in 2000 and launched as a formal Europe-wide inspection program in January 2004. since 2000, over 150 applications for accreditation have been received by the JACIE office and more than 130 inspections have been completed in European centers and facilities. Almost all of these were found to be functioning at a high level of excellence, with the majority having only minor deficiencies in compliance with the standards. In one-third of centers there were more significant deficiencies. The most common deficiencies were in quality management. Following correction of deficiencies 86 centers have to date achieved full accreditation and many more are nearing the completion of the process. implementation of JACIE involves a significant investment of time and resources by applicant centers. The majority require at least 18 months to prepare for accreditation and 85% have needed to employ a quality manager and/or data manager on an ongoing basis. However, all centers felt their program had benefited from the implementation of JACIE. JACIE is also working closely with other international organisations related to cellular therapy as part of the Alliance for the Harmonisation of cell therapy Accreditation (AHCTA), which is examining the differences in existing standards and aiming to develop international standards for all aspects of stem cell transplantation. In particular the requirements for safety of imported tissues and cells has emphasised the need for global harmonisation. The recent implementation of Directive 2004/23/Ec and the associated commission Directives 2006/1 7/EC and 2006/86/EC has provided an impetus for the implementation of JACIE in European union (EU) member states. It will be important in the future to examine how JAcIE can co-operate with the EU competent Authorities (CA) to ease the burden of the inspection process for haemopoietic stem cell (HSC) transplant programs.
Long-term outcome of adult acute lymphoblastic leukemia in Lebanon
Authors: Charafeddine Khalil M. , Hatoum Hassan A. , Otrock Zaher K. , Mahfouz Rami A. , Salem Ziad M. , Shamseddine Ali I. , Taher Ali T. , El-Saghir Nagi S. , Bazarbachi Ali
Published: July 2014

BACKGROUND AND OBJECTIVES:

The most important studies about outcome of acute leukemia come from developed countries, whereas most of the patients with this disease are in developing countries. We report predictive and prognostic factors in patients with acute lymphoblastic leukemia (ALL) in a tertiary care center in a developing country.

PATIENTS AND METHODS:

We retrospectively reviewed the records of adult patients with acute leukemia who were referred to the American university of Beirut Medical center between 1996 and early 2006.

RESULTS:

Of 105 patients, 36 (34%) patients were diagnosed with ALL, and included 19 (53%) males and 17 (47%) females with a median age of 34 years (range, 14-79 years). Induction chemotherapy with curative intent was administered to 34 (94%) patients. Twenty-seven patients received intrathecal chemotherapy as prophylaxis (n=24) or as treatment for CNS disease (n=3). Twenty-eight patients (82%) achieved complete remission (CR) after induction chemotherapy. The median overall survival (OS) time was 22 months and the five-year OS for ALL patients was 38%. The median disease-free survival (DFS) time was 12 months, while the five-year DFS was 38%. Multivariate analysis showed that age <40 years, WBG <30×109/L, achievement of CR after first induction, and CNS prophylaxis were predictive factors for OS and DFS.

CONCLUSION:

Despite limitations and the relatively low socioeconomic status of the Lebanese population, OS (38%) and DFS (38%) are quite similar to international data. Trends toward a higher CR and DFS in adults are due to intensified consolidation chemotherapy, the use of stem cell transplantation, and improvements in supportive care.
Hypopigmentation of the skin due to imatinib mesylate in patients with chronic myeloid leukemia
Authors: Aleem Aamer
Published: July 2014

BACKGROUND:

Hypopigmentation is an infrequently reported adverse effect of imatinib mesylate (IM) in chronic myeloid leukemia (CML), but there are no reports from Arab or Saudi patients. Thus, we assessed the frequency and impact of hypopigmentation in patients with chronic myeloid leukemia (CML) taking IM in our institution in Riyadh.

PATIENTS AND METHODS:

We studied 24 adult CML patients taking IM and followed from March to June 2008. telephonic interviews with all the CML patients taking IM were conducted and case notes were reviewed. Findings were confirmed on a subsequent clinic visit by a physician. Demographic features, disease status, response to IM, presence and severity of skin changes and impact of these changes on the patients and the disease were noted.

RESULTS:

Eight (33%) patients (6 males, 2 females) developed hypopigmentation due to IM. All patients had newly diagnosed, chronic phase CML and received 400 mg IM daily. The median age of the affected group was 37 years (range 18-54 years). Hypopigmentation developed during the first 3 months of treatment in 5 patients and 6 months or later in 3 patients. it was generalized in 7 patients and involved the hands and face in one patient. No photosensitivity was reported and none had other significant side effects.

CONCLUSION:

Hypopigmentation of the skin can develop in about one third of CML patients taking IM. physicians taking care of CML patients should be aware of this and patients need to be warned before commencing iM, particularly in dark-skinned patients.
Improved compliance with adjuvant vinorelbine and cisplatin in non-small cell lung cancer
Authors: Aljubran Ali , Leighl Natasha , Pintilie Melania , Burkes Ronald
Published: July 2014

BACKGROUND AND OBJECTIVES:

Poor compliance has been a common feature in clinical trials of adjuvant chemotherapy for NSCLC with only 48% to 69% of patients completing all planned cycles. We retrospectively evaluated compliance and toxicity of platinum-based chemotherapy in the 2 years following recent reports of successful adjuvant chemotherapy trials for NSCLC.

PATIENTS AND METHODS:

Patients who received adjuvant chemotherapy after complete resection of NSCLC between May 2003 and May 2005 were analyzed retrospectively. Patient demographics, ECOG status, stage, pathologic subtype and type of surgery were recorded. The number of chemotherapy cycles, delays, dose reductions and change of chemotherapy were reported.

RESULTS:

Fifty patients were identified. The median age was 62 years (38% stage I, 18% stage II, 30% stage III and 14% had multiple primary tumors of variable stages). Twenty percent were ECOG PS2; only 12% had undergone pnemonectomy. Forty-one patients (82%) started cisplatin/vinorelbine (three switched to carboplatin because of nephrotoxicity, and one switched to carboplatin/paclitaxel because of fatigue and vomiting). Three patients received other cisplatin-based combinations; six received carboplatin-based treatment (one each because of advanced age and cardiac dysfunction and 4 because of preexisting neuropathy). Eighty percent completed all treatment; 40% required a dose reduction and 58% required delays in treatment. Six events of febrile neutropenia were reported in 5 patients and 5 patients required admission for toxicity. There were no toxic deaths. Multivariate analysis showed no effect of age, gender, extent of surgery or ECOG status on compliance, need for treatment modification or toxicity.

CONCLUSIONS:

compared to historical trials, adjuvant platinum-based chemotherapy for resected NSCLC is now accepted by patients and physicians with a high degree of compliance.
High efficacy and low toxicity of short-course oral valganciclovir as pre-emptive therapy for hematopoietic stem cell transplant cytomegalovirus infection
Authors: Saleh AJM , Mohareb Fahad Al , Rabiah Fahad Al , Chaudhri Naeem , Sharif Fahad Al , Zahrani Hazzaa Al , Mohamed Said Yousuf , Patel Moosa , Rasheed Walid , Nurgat Zubeir , Bakr Mohammad , Ahmed Shad , Zaidi Syed , Nassar Amr , Ibrahim Khaled , Abdely Hail Al , Aljurf Mahmoud
Published: July 2014

BACKGROUND:

Cytomegalovirus (CMV) infection is a major infectious complication post-allogeneic hematoppoietic stem cell transplantation (HSCT). CM V seropositivity in Eastern Mediterranean and certain Asian counttries is reported to be close to 100%; hence, the need for effective pre-emptive treatment strategy that has low toxicity. Valganciclovir (VGC) is a prodrug of ganciclovir with high bioavailability.

PATIENTS AND METHODS:

HSCT patients with documented CMV infection (as defined by positive CM V antiggenemia) were treated as outpatients with VGC at a starting dose of 900 mg twice daily for 1 week. Those who were antigenemia negative after one week received 900 mg once daily for another week and treatment was subsequently discontinued. Those who were positive after one week of therapy continued on the twice daily treatment schedule for another week and changed to a daily schedule once they converted to antigenemia negativity.

RESULTS:

From January 2004 to December 2007, 47 HSCT patients received preemptive treatment with VGC for 61 episodes of CMV infection. The antigenemia range was 1 to 700 infected cells/slide. Complete responses were observed in 92% and 97% after the 1st and 2nd week of treatment, respectively. Three percent of the epissodes were considered refractory, requiring alternative therapy. No CM V disease was observed in this cohort.

CONCLUSION:

Neutropenia was the main observed toxicity, requiring granulocyte-colony stimulating factor in 8 episodes. Outpatient treatment of CM V infection with “short-course oral VGC” given as a one week twice daily treatment and one week once daily maintenance is a highly effective therapy with minimal toxicity. These results require validation in a larger, randomized study.
Improved survival with combined chemoradiotherapy in primary central nervous system lymphoma
Authors: Abdelsalam Mahmoud , El-Husseiny Gamal , Akhtar Saad , Khafaga Yasser , Al-Shabana Mohamed , AlHusaini Hamed , Weshi Amr El , Rahal Mohamed , Maghfoor Irfan
Published: July 2014

BACKGROUND:

Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor. Cranial irradiation alone rarely results in long term disease control or prolonged survival. We retrospectively analyzed data on the effect of adding high-dose methotrexate (HDMTX) prior to whole brain irradiation (WBI).

METHODS:

All patients with PCNSL diagnosed and managed during 1991-2004 were identified and demoggraphic characteristics, prognostic factors, treatment and outcome were reviewed. Of 62 patients, 10 were exccluded (4 had WBI <40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose > 40 Gy. Combined modality therapy included 3-4 cycles of HDMTX (3 g/m2) followed by WBI.

RESULT:

Of 52 patients analyzed for outcome, 36 had WBI (dose >40 Gy), 16 received 3-4 cycles of HDMTX followed by WBI (combined modality therapy [CMT]). Median age was 48.2 years; 42 years in the CMT group, 51 years in WBI . Patient characteristics were comparable between two groups except for higher multifocal tumor in the CMT group (92% vs. ×22%, P=.029). Median follow up was 12.83±6.4 months. The hazard rattio for an event was 0.64 (95% CI, 0.52-0.98) and for death 0.58 (95% CI, 0.48-0.92), both in favor of CMT . Univariate regression analysis using one-way analyses of variance (ANO VA) and multivariate Cox regression analysis for prognostic factors including age (<60 vs. >60), 50Gy) failed to identify any prognostic factor.

CONCLUSION:

This retrospective comparison supports phase II trial results that indicate that high-dose methottrexate followed by WBI in PCNSL improves outcome.
Emerging natural killer cell immunotherapies
Authors: Suck Garnet , Koh Mickey Boon Chai
Published: July 2014

Natural killer (NK) cell therapies are emerging worldwide as promising anticancer treatments, exploiting the fast cytolytic action of NK effectors and their potentially broad applicability against a wide range of malignancies. Until recently, clinical protocols have mainly involved freshly isolated NK cells or shortterm activated NK cells or lymphokine-activated killer (LA K) cells. However, overall effector numbers and their anticancer potencies remained restricted, which poses a limiting factor to clinical efficacy. Recent developments in the field aim to improve clinical trial designs by increasing effector to target cell ratios in vivo and by application of superior cytotoxic NK effectors. Large-scale production of clinical grade NK cells through long-term activation in ex vivo cultures are another novel means in achieving these goals. However, such procedures require compliance with the strict Good Manufacturing Practice (GMP) regulattions to ensure quality and safety of the NK cell product. Although the overall number of new protocols still remains comparably low, some of the protocols are already translated into clinical use. Also striking is the diversity of the different protocols proposed. We highlight in this review the most recent developments in the NK cell field with a focus on long-term NK cell expansion. Critical issues relating to this novel and promising type of therapy are highlighted and discussed.
Borderline clear cell adenofibroma with extensive hemorrhagic necrosis
Authors: Liu Jing-Lan , Chu Pei-Yi , Yeh Kun-Tu , Huang Ren-Hung
Published: July 2014

Borderline clear cell adenofibroma of the ovary is rather rare since most of clear cell tumors are carcinnomas. We report a case of ovarian borderline clear cell adenofibroma in a 52-year-old postmenopausal woman. The tumor had the characteristic histologic features of borderline clear cell adenofibroma except for central extensive hemorrhagic necrosis. The prognosis of borderline clear cell adenofibroma is excelllent. Because the invasiveness cannot be assessed in the necrotic areas, our patient needed long-term follow-up.
Human G-protein gamma 7 in extrahepatic cholangiocarcinoma and its clinicopathological significance
Authors: Wang Mei , Gong Biao , Li Yongmei , Wang Yajie
Published: July 2014

BACKGROUND AND OBJECTIVES:

Several studies have found a down-regulated G-γ 7 gene in gastrointestinal tract cancers. We evaluated the expression and clinicopathological significance of the human G protein γ 7 (G-γ 7) in human extra-hepatic cholangiocarcinoma (EHCC).

METHODS

The expression of G-γ 7 expression was studied in 21 patients with EHCC. G-γ 7 mRNA expression was tested by using RealTime reverse transcription polymerase chain reaction (RT-PCR). To visualize the localization of G-γ 7, an immunohistochemistry study was also performed. The G-γ 7 expression was compared among cancer tissues, peri-cancerous bile duct tissues and normal bile duct tissues. The clinicopathological significance of G-γ 7 expression was also studied.

RESULTS

Expression of G-γ 7 mRNA and protein were significantly lower in EHCC tissue than in peri-cancerous bile duct tissue and normal bile duct tissues. G-γ 7 mRNA and protein expression were significantly lower in poorly differentiated EHCC tissues than in moderate differentiated and well differentiated EHCC tissues (P < .01). There was no significant correlation between G-γ 7 expression and host factors such as age, gender, clinical staging or the status of preoperative hepatic function

CONCLUSIONS

EHCC has a down-regulated expression of G-γ 7. Reduced expression of G-γ 7 is associated with the histological grade of EHCC and may prove to be a useful marker for predicting the prognosis of human EHCC.
Systemic thromboembolic complications after laparoscopic splenectomy for idiopathic thrombocytopenic purpura in comparison to open surgery in the absence of anticoagulant prophylaxis
Authors: Mohamed Said Yousuf , Abdel-Nabi Ibrahim , Inam Ahmed , Bakr Mohammad , Tayeb Khaled El , Saleh Abu Jafar M. , Alzahrani Hazaa , Abdu Said H.
Published: July 2014

BACKGROUND:

Idiopathic thrombocytopenic purpura (ITP) in adults has a chronic course and may necessitate splenectomy. The current study was undertaken to study the systemic thromboembolic complications of laparosscopic splenectomy (LS) versus open splenectomy (OS) in patients with ITP at two large referral hospitals.

PATIENTS AND METHODS:

We conducted a retrospective analysis of 49 patients who underwent splenectomy (21 LS and 28 OS) for primary/relapsing refractory ITP between June 1995 and November 2004. Clinically and/or radiologically confirmed deep venous thrombosis (DVT) and/or pulmonary embolism (PE) were assessed within 2 weeks before and after splenectomy. None had prophylactic anticoagulants immediately after surgery. Follow up of those who developed complications continued for at least 2 additional years to assess for contributiing factors that may have been masked at the time of occurrence.

RESULTS:

Two (9.5%) LS group had acute PE within 5 days of LS and their platelet count reached 500×105/μL within 4 days and 1000×105/μL within 7 days after surgery. Three conversions to OS occurred; none had VTE. DVT occurred in 3 patients (10.7%) in the OS group; none were life threatening. There were no deaths.

CONCLUSION:

Life-threatening venous thromboembolic events are serious complications after LS and OS for ITP patients if prophylactic anticoagulants are not administered. Patients at risk are those who both have an exponential rise of the platelet count, although factors other than the platelet count may be contributing in OS. Postsplenectomy, ITP should be considered as a thrombophilic condition and studies of additional measures to prevent such events are warranted.
A meta-analysis of highly active anti-retroviral therapy for treatment of plasmablastic lymphoma
Authors: Guan Bing , Zhang Xinhua , Ma Henhui , Zhou Hangbo , Zhou Xiaojun
Published: July 2014

BACKGROUN DAND OBJECTIVES:

Plasmablastic lymphoma is a recently described B-cell derived lymphoma. The prognosis of plasmablastic lymphoma patients is usually poor. We performed a systematic review of the literature on the use of highly active anti-retroviral therapy (HAART) and the prognosis of plasmablastic lympphoma.

METHODS:

A comprehensive search of relevant databases, including Medline, Embase, the Cochrane Controlled Trials Register, the Cochrane Library, and the Science Citation Index yielded ten randomized controlled trials. Trials were divided into two groups according to therapy. The rates of plasmablastic lymphoma were analyzed using a fixed-effects model. Sensitivity analyses (on publication type, statistical model) were performed to further detect and evaluate clinically significant heterogeneity. Tests of survival for plasmablastic lymphoma were also performed by using Kaplan-Meier method.

RESULTS:

Meta-analysis result showed that the prognosis of plasmablastic lymphoma patients was statistically different in the patients receiving HAART in addition to chemotherapy and/or radiotherapy than in the patients receiving the chemotherapy and/or radiotherapy alone (pooled relative risk=3.04; P=.03). Survival analyses also displayed a statistically significant difference (χ2=6.22, P=.013).

CONCLUSION:

HAART in addition to chemotherapy and/or radiotherapy is effective in improving the prognosis of plasmablastic lymphoma. However, the small sample sizes increase the likelihood of bias in the studies in this meta-analysis, and therefore, the results should be taken cautiously.
Megakaryocytic blast crisis at presentation in a pediatric patient with chronic myeloid leukemia
Authors: Al-Shehri Ali , Al-Seraihy Amal , Owaidah Tarek M. , Belgaumi Asim F.
Published: July 2014

Patients with chronic myeloid leukemia (CML) infrequently present in blast crisis (BC). While most BC are of myeloid origin, megakaryocytic BC is rare, especially at the time of CML diagnosis. We describe the first pediatric patient presenting with megakaryocytic leukemia and having BCR-ABL1 translocation as the single chromosomal abnormality. Clinical features were more suggestive of CML in megakaryocytic blast crisis than Philadelphia chromosome positive de novo AML. The patient was treated with AML-directed chemotherapy and imatinib mesylate followed by umbilical cord blood stem cell transplantation. The patient was in complete molecular response 16 months after stem cell transplantation.
Normal forces exerted upon a long cylinder oscillating in an axial flow
Authors: Divaret L. , Cadot O. , Moussou P. , Doaré O.
Published: July 2014

This work aims to improve understanding of the damping induced by an axial flow on a rigid cylinder undergoing small lateral oscillations within the framework of the quasistatic assumption. The study focuses on the normal force exerted on the cylinder for a Reynolds number of$\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}\mathit{Re}=24\, 000$(based on the cylinder diameter and axial flow velocity). Both dynamic and static approaches are investigated. With the static approach, fluid forces, pressure distributions and velocity fields are measured for different yaw angles and cylinder lengths in a wind tunnel. It is found that for yaw angles smaller than$5{^\circ }$, the normal force varies linearly with the angle and is fully dominated by its lift component. The lift originates from the high pressure coefficient at the front of the cylinder, which is found to depend linearly on the angle, and from a base pressure coefficient that remains close to zero independent of the yaw angle. At the base, a flow deficit and two counter-rotating vortices are observed. A numerical simulation using a$k\mbox{--}\omega $shear stress transport turbulence model confirms the static experimental results. A dynamic experiment conducted in a water tunnel brings out damping-rate values during free oscillations of the cylinder. As expected from the linear dependence of the normal force on the yaw angle observed with the static approach, the damping rate increases linearly with the axial flow velocity. Satisfactory agreement is found between the two approaches.