bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Flora in NSAID-Induced Intestinal Damage: A Role for Antibiotics?
Authors: Lanas Ángel , Scarpignato Carmelo
Published: February 2006

Upper gastrointestinal (GI) complications are well-recognized adverse events associated with non-steroidal anti-inflammatory drug (NSAID) use. However, NSAID-induced damage to the distal GI tract is also common and more frequent than previously recognized. These untoward effects include increased mucosal permeability, mucosal inflammation, anemia and occult blood loss, malabsorption, protein loss, ileal dysfunction, diarrhea, mucosal ulceration, strictures due to diaphragm disease as well as active bleeding and perforation. Studies with selective COX-2 inhibitors have shown that, in the short term, these agents do not increase mucosal permeability and display a reduced by 50% incidence of serious lower GI side effects compared to traditional NSAIDs. However, the long-term use of this therapeutic strategy is limited by the increased risk of serious cardiovascular events, especially in patients with multiple risk factors. Several studies have suggested that intraluminal bacteria play a significant role in the pathogenesis of small-bowel damage induced by NSAIDs and that enterobacterial translocation into the mucosa represents the first step that sets in motion a series of events leading to gross lesion formation. Experimental and clinical investigations indicate that in the short term, antibacterial agents either reduce or abolish NSAID enteropathy. However, potential adverse effects of systemic antimicrobials and the possible occurrence of drug resistance have so far precluded this interesting approach. The availability of poorly absorbed and effective antibiotics, like rifaximin, may represent an attractive alternative to prevent or limit NSAID-associated intestinal damage.
From East to West: Patterns of Genetic Diversity of Populations Living in Four Eurasian Regions
Authors: Kutuev I. , Khusainova R. , Karunas A. , Yunusbayev B. , Fedorova S. , Lebedev Y. , Hunsmann G. , Khusnutdinova E.
Published: February 2006

We have analyzed the distribution and patterns of the genetic diversity of eight Alu loci (ACE, ApoA1, PV92, TPA25, NBC27, NBC102, NBC148, and NBC182) in 1,049 individuals representing 16 populations of the Volga-Ural region (Bashkirs, Tatars, Komis, Maris, Mordvins, and Udmurts), Central Asia (Kazakhs, Uzbeks, and Uighurs), the North Caucasus (Karachays, Kumyks, Kuban Nogays, and Karanogays), and Central South Siberia (Yakuts, Kalmyks and Evenks). Geographic divide between Europe and Asia, e.g. the Ural Mountains and the Caspian Sea, can also be considered as a genetic boundary. The data indicates that the populations of the two boundary regions between Europe and Asia, the Volga-Ural region of Russia, and populations of the North Caucasus are more similar to European than to Asian populations. Finally, Siberian and Central Asian populations are genetically closely related to each other.
Development of a Local Perivascular Paclitaxel Delivery System for Hemodialysis Vascular Access Dysfunction: Polymer Preparation and in vitroActivity
Authors: Melhem Murad , Kelly Burnett , Zhang Jianhua , Kasting Gerald , Li Jinsong , Davis Harold , Heffelfinger Sue , Desai Pankaj , Roy-Chaudhury Prabir
Published: February 2006

Hemodialysis vascular access dysfunction (HVAD) is currently a huge clinical problem. The major cause of HVAD is venous stenosis (as a result of venous neointimal hyperplasia) which leads to thrombosis in polytetrafluoroethylene dialysis access grafts and fistulae. Despite the magnitude of the clinical problem there are currently no effective therapeutic interventions for this condition. In an attempt to reduce the morbidity associated with HVAD, we have developed and validated a local perivascular paclitaxel release system for use in a pig model of arteriovenous graft stenosis. Ethylene vinyl acetate polymers with 5% paclitaxel were formulated. The release profile of paclitaxel was then manipulated to maximize its biological impact in the in vivo situation. In vitro experiments were performed to confirm that the paclitaxel released from the polymer was biologically active against cell types that were similar to those present in the in vivo lesion of neointimal hyperplasia. Our results demonstrate that the paclitaxel polymer wraps which we have developed are mechanically stable with a burst release phase followed by a slower continuous release phase. The paclitaxel released from these polymeric wraps retains its physicochemical and biological properties and is able to inhibit the proliferation of smooth muscle cells, endothelial cells and fibroblasts in vitro. We believe that these paclitaxel-loaded polymeric wraps could be ideally suited for perivascular drug delivery in the context of dialysis access grafts and fistulae.
Cervical Lymph Node Metastases from Occult Squamous Cell Carcinoma: Analysis of 82 Cases
Authors: Boscolo-Rizzo Paolo , Da Mosto Maria Cristina , Gava Alessandro , Marchiori Carlo
Published: February 2006

Purpose: The aim of this study was to analyze the prognostic value of some clinical factors and to compare the survival of different treatment plans in patients with cervical lymph node metastases from occult squamous cell carcinoma (SCC). Methods: A retrospective review was conducted of patients who were diagnosed as having cervical lymph node metastases from occult SCC. Overall cumulative survival was analyzed using the standard Kaplan-Meier method. Tests of significance were based on log-rank statistics. Results: The 82 patients in the study consisted of 69 males (84.2%) and 13 females (15.8%). The average age at diagnosis was 64.7 years. Fifty patients (60.9%) underwent surgical treatment of cervical metastasis. Radiotherapy was performed in 79 patients. Thirty-two patients (40.5%) received primary fractioned external beam radiotherapy; 47 patients (59.5%) received postoperative fractioned external beam radiotherapy. Ipsilateral radiotherapy was performed on 37 patients (46.8%), bilateral neck plus mucosal irradiation was performed in 42 patients (53.2%). Ten patients (12.2%) developed a primary tumor during the follow-up. The actuarial survival rates of all patients 2, 5 and 10 years after diagnosis were 50.9, 25.3 and 18.5%, respectively. Patients with nodal stage N2b, N2c and N3 had a significantly poorer prognosis than those with nodal stage N1 and N2a (p = 0.0239). The survival in patients with metastatic nodes in the supraclavicular region (level IV) was significantly poorer than that of patients with involvement of the upper-middle jugular lymph nodes (p = 0.0003). We observed a statistically significant better survival in patients receiving bilateral neck plus mucosal irradiation (p = 0.0003). Conclusions: Initial N-category and metastasis localization were the most important prognostic factors and nodal relapse the major cause of treatment failure, thus optimal management of cervical nodes appears crucial for the success of treatment. Patients receiving bilateral neck plus mucosal irradiation had a higher survival rate than those who received ipsilateral irradiation.
Prevalence and Persistence of Mild Cognitive Impairment among Elderly Patients in General Hospitals
Authors: Bickel H. , Mösch E. , Seigerschmidt E. , Siemen M. , Förstl H.
Published: February 2006

The aim of the present study was to determine the prevalence of mild cognitive impairment (MCI) in elderly patients in general hospitals and to investigate the persistence of the cognitive deficits after discharge from the hospital. In a sample consisting of 794 non-demented patients in general hospitals aged 65–85 years, we found an MCI prevalence of 36.1%. The positive predictive value for cognitive impairment 3.5 months after hospital discharge was 61.0%. The deficits in multiple-domain MCI proved to be particularly stable with a positive predictive value of 82.9%. Elderly patients in general hospitals represent a high-risk group for MCI. These results indicate that general hospitals offer an opportunity for the early detection of incipient dementia.
Identifying Patients at High and Low Risk of Cognitive Decline Using Rey Auditory Verbal Learning Test among Middle-Aged Memory Clinic Outpatients
Authors: Andersson Christin , Lindau Maria , Almkvist Ove , Engfeldt Peter , Johansson Sven-Erik , Eriksdotter Jönhagen Maria
Published: February 2006

Objectives: To investigate whether application of cutoff levels in an episodic memory test (Rey Auditory Verbal Learning Test, RAVLT) is a useful method for identifying patients at high and low risk of cognitive decline and subsequent dementia. Methods: 224 patients with memory complaints (mean age = 60.7 years, mean MMSE = 28.2) followed-up at a memory clinic over ≈3 years were assigned retrospectively to one of three memory groups from their baseline results in RAVLT [severe (SIM), moderate (MIM) or no impairment (NIM)]. These groups were investigated regarding cognitive decline. Results: Patients assigned to SIM showed significant cognitive decline and progressed to dementia at a high rate, while a normal performance in RAVLT at baseline (NIM) predicted normal cognition after 3 years. Patients with MIM constituted a heterogeneous group; some patients deteriorated cognitively, while the majority remained stable or improved. Conclusions: The application of cutoff levels in RAVLT at baseline showed that patients with severely impaired RAVLT performance were at a high risk of cognitive decline and progression to dementia, while patients with normal RAVLT results did not show cognitive decline during 3 years. Furthermore, the initial degree of memory impairment was decisive in the cognitive prognosis 3 years later.
A Longitudinal Study of Quantitative and Qualitative Features of Category Verbal Fluency in Incident Alzheimer’s Disease Subjects: Results from the PAQUID Study
Authors: Auriacombe Sophie , Lechevallier Nathalie , Amieva Hélène , Harston Sandrine , Raoux Nadine , Dartigues Jean-François
Published: February 2006

Category fluency tests were administered at baseline and after 3 and 5 years on two subgroups of subjects from a population-based cohort of elderly subjects: 52 cases of incident possible and probable Alzheimer’s disease (AD) and 104 age- and education-matched subjects who remained nondemented. Quantitative and qualitative features of category fluency were assessed to determine how changes occur within 5 years of the diagnosis of AD. Consistent with previous results, we found that the number of words produced on this task was already significantly lower 5 years before the diagnosis in subjects with incident AD as compared with subjects who did not become demented. However, the rate of repetitions only significantly increased in AD subjects at the time of diagnosis, and the rate of intrusions remained low and not significantly different between the two groups. Thus, it is concluded that dysfunction in cognitive processes underlying repetitions and intrusions in verbal fluency tasks, such as inhibitory processes and working memory, may not be the main cause of the very early deficit in verbal fluency occurring in AD.
Present-Day Atmospheric Simulations Using GISS ModelE: Comparison to In Situ, Satellite, and Reanalysis Data
Authors: Schmidt Gavin A. , Ruedy Reto , Hansen James E. , Aleinov Igor , Bell Nadine , Bauer Mike , Bauer Susanne , Cairns Brian , Canuto Vittorio , Cheng Ye , Del Genio Anthony , Faluvegi Greg , Friend Andrew D. , Hall Tim M. , Hu Yongyun , Kelley Max , Kiang Nancy Y. , Koch Dorothy , Lacis Andy A. , Lerner Jean , Lo Ken K. , Miller Ron L. , Nazarenko Larissa , Oinas Valdar , Perlwitz Jan , Perlwitz Judith , Rind David , Romanou Anastasia , Russell Gary L. , Sato Makiko , Shindell Drew T. , Stone Peter H. , Sun Shan , Tausnev Nick , Thresher Duane , Yao Mao-Sung
Published: February 2006

A full description of the ModelE version of the Goddard Institute for Space Studies (GISS) atmospheric general circulation model (GCM) and results are presented for present-day climate simulations (ca. 1979). This version is a complete rewrite of previous models incorporating numerous improvements in basic physics, the stratospheric circulation, and forcing fields. Notable changes include the following: the model top is now above the stratopause, the number of vertical layers has increased, a new cloud microphysical scheme is used, vegetation biophysics now incorporates a sensitivity to humidity, atmospheric turbulence is calculated over the whole column, and new land snow and lake schemes are introduced. The performance of the model using three configurations with different horizontal and vertical resolutions is compared to quality-controlled in situ data, remotely sensed and reanalysis products. Overall, significant improvements over previous models are seen, particularly in upper-atmosphere temperatures and winds, cloud heights, precipitation, and sea level pressure. Data–model comparisons continue, however, to highlight persistent problems in the marine stratocumulus regions.
Influence of Cold Air Intrusions on the Wet Season Onset over Amazonia
Authors: Li Wenhong , Fu Rong
Published: February 2006

Using 15-yr data from the European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-15), the authors found that rapid southeastward expansion of the rainy area from the western Amazon to southeastern Brazil is a result of midlatitude cold air intrusions. During austral spring, as the large-scale thermodynamic structure over Amazonia becomes destabilized, the incursions of extratropical cold air can trigger intense rainfall along the leading edge of northwest–southeast-oriented cold fronts east of the Andes. As these fronts penetrate into Amazonia, the northerly or northwesterly wind transports warm, moist air from the western Amazon to southeast Brazil. Moisture convergence consequently intensifies, resulting in northwest–southeast-elongated rainy areas. The latter contribute to the observed rapid, southeastward expansion of rainy areas shown in rainfall climatology during austral spring.

The authors’ analysis suggests that cold air intrusions during austral spring collectively assist the transformation of large-scale thermodynamic and dynamic environments to those favorable for the wet season onsets. Each time the cold fronts pass by, they tend to increase the atmospheric humidity and the buoyancy of the lower troposphere, which destabilizes the atmosphere. In the upper troposphere, the cold air intrusions supply kinetic energy for the development of anticyclonic flow. Cold air intrusions in the transitional season are not different from those occurring immediately before the wet season onsets except that the latter occurs under a more humid and unstable atmospheric condition. Thus, cold air intrusions can trigger the wet season onsets only when atmospheric and land surface conditions are “ready” for the onset.

Comparisons among early, normal, and late onsets on an interannual scale further suggest that more frequent and stronger cold air intrusions trigger the early onsets of wet seasons given suitable large-scale thermodynamic conditions. Likewise, less frequent and weaker cold air intrusions could delay the wet season onset even though the large-scale thermodynamic conditions appear to be favorable. Occasionally, strong unstable atmospheric thermodynamic conditions and northerly reversal of cross-equatorial flow can lead to wet season onsets without cold air intrusions. In such cases, enhanced precipitation is centered over central and eastern Amazon, and rainfall increases more gradually compared to the onset with cold air intrusions.
Upper-Ocean Mixed Layer and Wintertime Sea Surface Temperature Anomalies in the North Pacific
Authors: Tomita Tomohiko , Nonaka Masami
Published: February 2006

In the North Pacific, the wintertime sea surface temperature anomaly (SSTA), which is represented by March (SSTAMar), when the upper-ocean mixed layer depth (hMar) reaches its maximum, is formed by the anomalous surface forcing from fall to winter (S′). As a parameter of volume, hMar has a potential to modify the impact of S′ on SSTAMar. Introducing an upper-ocean heat budget equation, the present study identifies the physical relationship among the spatial distributions of hMar, S′, and SSTAMar.

The long-term mean of hMar adjusts the spatial distribution of SSTAMar. Without the adjustment, the impact of S′ on SSTAMar is overestimated where the hMar mean is deep. Since hMar is partially due to seawater temperature, it leads to nonlinearity between the S′ and the SSTAMar. When the SSTAMar is negative (positive), the sensitivity to S′ is impervious (responsive) with the deepening (shoaling) of the hMar compared to the linear sensitivity. The thermal impacts from the ocean to the atmosphere might be underestimated under the assumption of the linear relationship.
Wind Stress Variations and Interannual Sea Surface Temperature Anomalies in the Eastern Equatorial Pacific
Authors: Zhang Xuebin , McPhaden Michael J.
Published: February 2006

Vertical advection of temperature is the primary mechanism by which El Niño–Southern Oscillation (ENSO) time-scale sea surface temperature (SST) anomalies are generated in the eastern equatorial Pacific. Variations in vertical advection are mediated primarily by remote wind-forced thermocline displacements, which control the temperature of water upwelled to the surface. However, during some ENSO events, large wind stress variations occur in the eastern Pacific that in principle should affect local upwelling rates, the depth of the thermocline, and SST. In this study, the impact of these wind stress variations on the eastern equatorial Pacific is addressed using multiple linear regression analysis and a linear equatorial wave model. The regression analysis indicates that a zonal wind stress anomaly of 0.01 N m−2 leads to approximately a 1°C SST anomaly over the Niño-3 region (5°N–5°S, 90°–150°W) due to changes in local upwelling rates. Wind stress variations of this magnitude occurred in the eastern Pacific during the 1982/83 and 1997/98 El Niños, accounting for about 1/3 of the maximum SST anomaly during these events. The linear equatorial wave model also indicates that depending on the period in question, zonal wind stress variations in the eastern Pacific can work either with or against remote wind stress forcing from the central and western Pacific to determine the thermocline depth in the eastern Pacific. Thus, zonal wind stress variations in the eastern Pacific contribute to the generation of interannual SST anomalies through both changes in local upwelling rates and changes in thermocline depth. Positive feedbacks between the ocean and atmosphere in the eastern Pacific are shown to influence the evolution of the surface wind field, especially during strong El Niño events, emphasizing the coupled nature of variability in the region. Implications of these results for understanding the character of event-to-event differences in El Niño and La Niña are discussed.
Biochemical Analysis of Human Milk Treated With Sodium Dodecyl Sulfate, an Alkyl Sulfate Microbicide That Inactivates Human Immunodeficiency Virus Type 1
Authors: Hartmann Sandra Urdaneta , Wigdahl Brian , Neely Elizabeth B. , Berlin Cheston M. , Schengrund Cara-Lynne , Lin Hung-Mo , Howett Mary K.
Published: February 2006

Reduction of transmission of human immunodeficiency virus type 1 (HIV-1) through human milk is needed. Alkyl sulfates such as sodium dodecyl sulfate (SDS) are microbicidal against HIV-1 at low concentrations, have little to no toxicity, and are inexpensive. The authors have reported that treatment of HIV-1-infected human milk with ≤ 1% (10 mg/mL) SDS for 10 minutes inactivates cell-free and cell-associated virus. The SDS can be removed with a commercially available resin after treatment without recovery of viral infectivity. In this article, the authors report results of selective biochemical analyses (ie, protein, immunoglobulins, lipids, cells, and electrolytes) of human milk subjected to SDS treatment and removal. The SDS treatment or removal had no significant effects on the milk components studied. Therefore, the use of alkyl sulfate microbicides to treat milk from HIV-1-positive women may be a simple, practical, and nutritionally sound way to prevent or reduce transmission of HIV-1 while still feeding with mother’s own milk.
Acceptability of Heat Treating Breast Milk to Prevent Mother-to-Child Transmission of Human Immunodeficiency Virus in Zimbabwe: A Qualitative Study
Authors: Israel-Ballard Kiersten A. , Maternowska M. Catherine , Abrams Barbara F. , Morrison Pamela , Chitibura Livona , Chipato Tsungai , Chirenje Zvavahera M. , Padian Nancy S. , Chantry Caroline J.
Published: February 2006

Although heat treatment of human milk is an official infant-feeding recommendation for human immunodeficiency virus (HIV)-positive mothers in Zimbabwe, its implementation has not been adequately addressed, because knowledge about the safety of this method is rudimentary and its acceptability is poorly understood. To address this knowledge gap, the authors conducted focus group discussions among mothers, grandmothers, midwives, and husbands in various regions of Zimbabwe. Although the practice of heat treating expressed human milk was initially met with skepticism because of potential obstacles, including time constraints and social and cultural stigma, a pattern of opinion reversal emerged in all groups. By the end of each discussion, participants believed that, given its affordability and its potential to protect infants from HIV infection, heat-treated human milk may be a feasible infant-feeding option for HIV-positive mothers in Zimbabwe. These findings merit further investigation so that appropriate behavioral strategies can be designed.
The Role of Personality and Other Factors in a Mother’s Decision to Initiate Breastfeeding
Authors: Wagner Carol L. , Wagner Mark T. , Ebeling Myla , Chatman Katreia Gleaton , Cohen Millicent , Hulsey Thomas C.
Published: February 2006

The objective of the study was to measure the impact of personality and other factors on the decision to initiate breastfeeding. Mothers were enrolled (24-96 hours postpartum) and were classified as fully breastfeeding, formula-feeding, or combination-feeding. A semi-structured interview about maternal sociodemographics and attitudes and a standardized personality inventory (NEO-PI-R) were conducted. Eighty-seven mothers completed the study: 50 breastfeeders, 6 combination feeders, and 31 formula feeders. Because of small numbers, combination-feeder mothers (n = 6) were excluded from analyses. Maternal age, marriage, ethnicity, and socioeconomic status were significantly associated with breastfeeding. Breastfeeding and formula-feeding groups differed on 3 personality domains: extraversion (53.3 breastfeeding vs 46.9 formula-feeding, P = .002), openness (51.6 vs 46.2, P = .008), and agreeableness (48.5 vs 41.5, P = .01). In a multiple variable logistic regression model, extraversion ( P = .03) and openness ( P = .003) remained significant. Sociodemographics, experiential factors, and specific personality characteristics of mother were independently associated with maternal feeding decision.
Breast Pump Access in the Inner City: A Hospital-Based Initiative to Provide Breast Pumps for Low-income Women
Authors: Chamberlain Laura Beth , McMahon Marcy , Philipp Barbara L. , Merewood Anne
Published: February 2006

An effective electric breast pump is an important tool for the management of breastfeeding challenges such as provision of human milk to sick or premature infants. A breast pump is also, in Western culture, critical for breastfeeding mothers who return to work. Obtaining an effective electric breast pump can be particularly difficult for uninsured or impoverished women because of the expense, complicated insurance reimbursements, and scarcity of providers that supply breast pumps to the inner-city community. To address this problem at Boston Medical Center (BMC), an inner-city hospital that serves a poor and minority urban population, members of the Breastfeeding Center worked with a local charity and local insurance companies to increase access to pumps for all women at BMC and to guarantee that every breastfeeding mother with an infant in the neonatal intensive care unit receive a double-setup electric breast pump, regardless of her insurance status or ability to pay.
Barriers to Compliance With Infant-Feeding Recommendations Among Low-income Women
Authors: Heinig M. Jane , Follett Jennifer R. , Ishii Kara D. , Kavanagh-Prochaska Katherine , Cohen Roberta , Panchula Jeanette
Published: February 2006

Focus groups were used to examine relationships among maternal beliefs, feeding intentions, and infant-feeding behaviors among 65 Women, Infants and Children-eligible (28 English-speaking and 37 Spanish-speaking) mothers. Participants shared common beliefs that breast-feeding was beneficial; nevertheless, many believed that early introduction of formula and solid foods was unavoidable in certain situations. Medical providers and Women, Infants and Children staff were sources of infant-feeding information, and the Spanish-speaking mothers attempted to adhere to the guidance. However, the English-speaking mothers often ignored this advice if it was not perceived as working for the family’s circumstances. Mothers, believing that providers would not understand that they were compelled to reject infant-feeding recommendations, would not ask for assistance when facing difficulties. Instead, mothers relied on relatives and others for infant-feeding guidance. Educational efforts should acknowledge mothers’ true circumstances, target support to each situation, and emphasize the health value of complementary foods rather than their association with infant motor development.
Screening Patients with Stroke for Rehabilitation Needs: Validation of the Post-Stroke Rehabilitation Guidelines
Authors: Edwards Dorothy F. , Hahn Michele G. , Baum Carolyn M. , Perlmutter Monica S. , Sheedy Catherine , Dromerick Alexander W.
Published: February 2006

Background. The authors assessed patients with acute stroke to determine whether the systematic use of brief screening measures would more efficiently detect cognitive and sensory impairment than standard clinical practice. Methods. Fifty-three patients admitted to an acute stroke unit were assessed within 10 days of stroke onset. Performance on the screening measures was compared to information obtained from review of the patient’s chart at discharge. Cognition, language, visual acuity, visual-spatial neglect, hearing, and depression were evaluated. Results. Formal screening detected significantly more impairments than were noted in patient charts in every domain. Only 3 patients had no impairments identified on screening; all remaining patients had at least 1 impairment detected by screening that was not documented in the chart. Thirty-five percent had 3 or more undetected impairments. Memory impairment was most likely to be noted in the chart; for all other domains tested, undocumented impairment ranged from 61% (neglect) to 97% (anomia). Conclusion. Many acute stroke patients had cognitive and perceptual deficits that were not documented in their charts. These data support the Post-Stroke Rehabilitation Guidelines for systematic assessment even when deficits are not immediately apparent. Systematic screening may improve discharge planning, rehabilitation treatment, and long-term outcome of persons with stroke.
Cellular Transplants in China: Observational Study from the Largest Human Experiment in Chronic Spinal Cord Injury
Authors: Dobkin Bruce H. , Curt Armin , Guest James
Published: February 2006

Background. In China, fetal brain tissue has been transplanted into the lesions of more than 400 patients with spinal cord injury (SCI). Anecdotal reports have been the only basis for assuming that the procedure is safe and effective. Objective. To compare available reports to the experiences and objective findings of patients who received pre-operative and postoperative assessments before and up to 1 year after receiving cellular implants. Methods. Independent observational study of 7 chronic SCI subjects undergoing surgery by Dr Hongyun Huang in Beijing. Assessments included lesion location by magnetic resonance imaging, protocol of the American Spinal Injury Association (ASIA), change in disability, and detailed history of the perioperative course. Results. Inclusion and exclusion criteria were not clearly defined, as subjects with myelopathies graded ASIA A through D and of diverse causes were eligible. Cell injection sites did not always correlate with the level of injury and included the frontal lobes of a subject with a high cervical lesion. Complications, including meningitis, occurred in 5 subjects. Transient postoperative hypotonicity may have accounted for some physical changes. No clinically useful sensorimotor, disability, or autonomic improvements were found. Conclusions. The phenotype and the fate of the transplanted cells, described as olfactory ensheathing cells, are unknown. Perioperative morbidity and lack of functional benefit were identified as the most serious clinical shortcomings. The procedures observed did not attempt to meet international standards for either a safety or efficacy trial. In the absence of a valid clinical trials protocol, physicians should not recommend this procedure to patients.
Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene
Authors: Dame Christof , Kirschner Karin M. , Bartz Katharina V. , Wallach Thomas , Hussels Christiane S. , Scholz Holger
Published: February 2006

Molecular mechanisms for the developmental stage and tissue-specific regulation of the erythropoietin (EPO) gene are poorly understood. Recent findings indicate a role of the Wilms tumor suppressor, Wt1, in the formation of the hematopoietic system. Herein, we tested the hypothesis that Wt1 is a transcriptional regulator of the EPO gene. Binding of the transcriptionally competent Wt1(–KTS) isoform to the minimal EPO promoter was demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation. Under normoxia, EPO expression was significantly increased in HEK 293 and HepG2 cells with forced expression of Wt1(–KTS). A reporter construct harboring the 117-bp minimal human EPO promoter was activated up to 20-fold by transient cotransfection of Wt1(–KTS) in different cell lines. Mutation of the Wt1 binding site in the EPO promoter abrogated this stimulatory effect of the Wt1(–KTS) protein. Hepatic Epo mRNA expression was significantly reduced in embryonic mice with homozygous Wt1 deletion. Furthermore, Wt1 and EPO were colocalized in hepatocytes of the liver and in neuronal cells of the dorsal root ganglia in developing mice. Both proteins were also detected in Sertoli cells of the adult murine testis. In conclusion, we identified Wt1(–KTS) as a novel transcriptional activator for the tissue-specific expression of the EPO gene.
Requirement of the human T-cell leukemia virus (HTLV-1) tax-stimulated HIAP-1 gene for the survival of transformed lymphocytes
Authors: Wäldele Katja , Silbermann Katrin , Schneider Grit , Ruckes Tobias , Cullen Bryan R. , Grassmann Ralph
Published: February 2006

Human T cell leukemia virus type 1 (HTLV-1), the cause of adult T cell leukemia (ATL), induces clonal expansion of infected T-cells in nonleukemic individuals and immortalizes T cells in vitro. The resistance against apoptotic stimuli of these cells hints at a viral survival function in addition to a proliferation-stimulating activity. Here we describe the up-regulation of the antiapoptotic HIAP-1/CIAP-2 gene as a consistent phenotype of HTLV-1–transformed and ATL-derived cultures and its stimulation by the viral oncoprotein Tax. Cotransfections revealed a 60-fold increase of HIAP-1 promoter activity mediated by Tax mainly via nuclear factor-κB (NF-κB) activation. To address the relevance of virally increased HIAP-1 levels for the survival of HTLV-1–transformed cells, its expression was RNA interference (RNAi) suppressed using a lentiviral transduction system. This resulted in a dramatic reduction of cell growth, a strong induction of apoptosis rates, and increased caspases 3/7 activity, which is known to be suppressed by HIAP-1. Thus, the Tax-mediated HIAP-1 overexpression is required to suppress endogenous apoptosis and, therefore, is essential for the survival of HTLV-1–transformed lymphocytes. Moreover, this points to HIAP-1 as an important target of the HTLV-1–mediated NF-κB activation.
Cytochrome c–related caspase-3 activation determines treatment response and relapse in childhood precursor B-cell ALL
Authors: Meyer Lüder Hinrich , Karawajew Leonid , Schrappe Martin , Ludwig Wolf-Dieter , Debatin Klaus-Michael , Stahnke Karsten
Published: February 2006

Deficient activation of apoptosis signaling pathways may be responsible for treatment failure in acute leukemia. Here, we address the impact of intact apoptosis signaling in 78 patients with pediatric precursor B-cell acute lymphoblastic leukemia (ALL) by analysis of 2 key apoptogenic events: caspase-3 activation and cytochrome c release in leukemia cells cultured in vitro. Both events correlated only in the group of patients who had a good response and patients in continuous remission, suggesting that intact apoptosis signaling is a characteristic for favorable outcome. By combining both parameters, we identified a novel indicator, cytochrome c–related activation of caspase-3 (CRAC). CRAC directly connects the extent of caspase-3 activation to cytochrome c release in single cells in an individual patient sample. In CRAC-positive patients, indicating proficient apoptosis signaling, the number of persisting leukemia cells on day 15 was significantly lower than in the CRAC-negative patient group (n = 27, mean 6.0% versus n = 36, mean 22.6%; P = .003). At a median follow-up of 31 months, disease-free survival was 84 months (95% CI = 76 to 91 months) and 66 months (95% CI = 52 to 80 months) for patients with positive and negative CRAC, respectively (P = .019). CRAC may serve as a functionally defined risk factor for treatment stratification.
Integrin inhibition through Lyn-dependent cross talk from CXCR4 chemokine receptors in normal human CD34+ marrow cells
Authors: Nakata Yuji , Tomkowicz Brian , Gewirtz Alan M. , Ptasznik Andrzej
Published: February 2006

We studied the effects of Lyn ablation on CXCR4 receptor-mediated migration and adhesion of hematopoietic precursors. Down-regulation of Lyn expression with siRNA greatly reduced CXCR4-dependent hematopoietic cell movement, and increased cell adherence to stroma. This increase was associated with the up-regulated expression of activation-dependent epitopes of the β2 integrin LFA-1 and was prevented by antibodies that selectively block cell adhesion mediated by ICAM-1. Attachment to surfaces coated with ICAM-1 was also enhanced in Lyn-depleted hematopoietic cells, as compared with Lyn-expressing cells. Functional rescue experiments with Lyn siRNA targeting the 3′ UTR indicated that the observed effects can be attributed directly to specific inhibition of Lyn. Our results show that in chemokine-stimulated hematopoietic cells Lyn kinase is a positive regulator of cell movement while negatively regulating adhesion to stromal cells by inhibiting the ICAM-1–binding activity of β2 integrins. These results provide a molecular mechanism for cross talk between the chemokine receptor CXCR4 and β2 integrins. This cross talk may allow chemokine receptors to modulate the arrest of rolling hematopoietic precursors on the surface of bone marrow stromal cells.
Platelet depletion in mice increases mortality after thermal injury
Authors: Fujimi Satoshi , MacConmara Malcolm P. , Maung Adrian A. , Zang Yan , Mannick John A. , Lederer James A. , Lapchak Peter H.
Published: February 2006

Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in innate and adaptive immunity. However, the role of platelets in the immune response to injury remains undefined. We tested the importance of platelets in the host response to serious injury in a newly developed platelet-deficient mouse model. Wild-type and platelet-depleted C57BL/6J mice underwent a 25% full-thickness total body surface area thermal or sham injury. Platelet-deficient mice showed survival of 51% at 48 hours after injury compared with 94% to 100% survival in experimental control mice (P < .001). Necropsy and histology ruled out hemorrhage and hypovolemia as causes of death. Percentages of peripheral blood monocytes (P < .01) and neutrophils (P < .05) were increased between 36 and 48 hours after thermal injury in platelet-deficient mice compared with control mice. Plasma levels of TNFα (P < .001), IL-6 (P < .001), and MCP-1 (P < .05) were also elevated by 24 hours whereas levels of TGFβ1 were reduced between 24 and 36 hours following injury in platelet-depleted mice (P < .001) compared with control mice. Our findings demonstrate for the first time that platelets play a critical protective role during the host response to injury. Moreover, our findings suggest that platelets and, more importantly, platelet-derived TGFβ1 modulate the systemic inflammatory response occurring after injury.
Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10
Authors: Zernecke Alma , Liehn Elisa A. , Gao Ji-Liang , Kuziel William A. , Murphy Philip M. , Weber Christian
Published: February 2006

The chemokine RANTES has been implicated in neointimal hyperplasia after arterial injury. We analyzed the differential role of the RANTES receptors CCR1 and CCR5 by genetic deletion in apolipoprotein E–deficient mice. Deficiency in CCR5 significantly reduced neointimal area after arterial wire injury, associated with a decrease in macrophages, CD3+ T lymphocytes, and CCR2+ cells. In contrast, CCR1 deficiency did not affect neointimal area or cell content. Deletion of CCR5 entailed an up-regulation of the anti-inflammatory cytokine interleukin 10 (IL-10) in neointimal smooth muscle cells, and its antibody blockade reversed effects in CCR5–/– mice. Conversely, proinflammatory interferon γ was increased in the neointima of CCR1–/– mice, and its blockade unmasked a reduction in macrophage recruitment. Our data indicate that CCR5 is more crucial than CCR1 for neointimal plaque formation, and that its attenuation in CCR5–/– mice is due to an atheroprotective immune response involving IL-10. This harbors important implications for targeting chemokine receptors in vascular remodeling.
The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells
Authors: Trudel Suzanne , Stewart A. Keith , Rom Eran , Wei Ellen , Li Zhi Hua , Kotzer Sarit , Chumakov Irina , Singer Yossi , Chang Hong , Liang Sheng-Ben , Yayon Avner
Published: February 2006

The association of fibroblast growth factor receptor 3 (FGFR3) expression with t(4;14) multiple myeloma (MM) and the demonstration of the transforming potential of this receptor tyrosine kinase (RTK) make it a particularly attractive target for drug development. We report here a novel and highly specific anti-FGFR3–neutralizing antibody (PRO-001). PRO-001 binds to FGFR3 expressed on transformed cells and inhibits FGFR3 autophosphorylation and downstream signaling. The antibody inhibited the growth of FGFR3-expressing FDCP cells (IC50 of 0.5 μg/mL) but not that of cells expressing FGFR1 or FGFR2, and potently inhibited FGFR3-dependent solid tumor growth in a mouse xenograft model. Furthermore, PRO-001 inhibited the growth of the FGFR3-expressing, human myeloma cell line, UTMC2. Inhibition of viability was still observed when cells were cocultured with stroma or in the presence of IL-6 or IGF-1. PRO-001 did not inhibit constitutive activation of K650E, G384D, and Y373C FGFR3 in myeloma cell lines and failed to inhibit the growth of these cells. Most importantly, however, PRO-001 induced cytotoxic responses in primary t(4;14)+ MM samples with an increase in apoptotic index of 20% to 80% as determined by annexin V staining. The data demonstrate that PRO-001 is a potent and specific inhibitor of FGFR3 and deserves further study for the treatment of FGFR3-expressing myeloma.
BCR-ABL mRNA levels at and after the time of a complete cytogenetic response (CCR) predict the duration of CCR in imatinib mesylate–treated patients with CML
Authors: Press Richard D. , Love Zac , Tronnes Ashlie A. , Yang Rui , Tran Thuan , Mongoue-Tchokote Solange , Mori Motomi , Mauro Michael J. , Deininger Michael W. , Druker Brian J.
Published: February 2006

Although most patients with chronic myeloid leukemia (CML) treated with imatinib mesylate achieve a complete cytogenetic response (CCR), some patients will relapse. To determine the potential of real-time quantitative BCR-ABL reverse transcriptase–polymerase chain reaction (RT-PCR) to predict the duration of continued CCR, we monitored 85 patients treated with imatinib mesylate who achieved a CCR. With a median follow-up of 13 months after CCR (29 months after imatinib mesylate; median 6 RQ-PCR assays), 23 patients (27%) had disease progression (predominantly loss of CCR). Compared with the median baseline level of BCR-ABL mRNA, 42% of patients achieved at least a 2-log molecular response at the time of first reaching CCR. Failure to achieve a 2-log response at the time of CCR was an independent predictive marker of subsequent progression-free survival (hazard ratio = 5.8; 95% CI, 1.7-20; P = .005). After CCR, BCR-ABL mRNA levels progressively declined for at least the next 15 months, and 42 patients (49%) ultimately achieved at least a 3-log reduction in BCR-ABL mRNA. Patients failing to achieve this 3-log response, at any time during therapy, had significantly shorter progression-free survival (hazard ratio = 8.1; 95% CI, 3.1-22; P < .001). The achievement of either a 2-log molecular response at the time of CCR or a 3-log response anytime thereafter is a significant and independent prognostic marker of subsequent progression-free survival.
Upfront double high-dose chemotherapy with DICEP followed by BEAM and autologous stem cell transplantation for poor-prognosis aggressive non-Hodgkin lymphoma
Authors: Stewart Douglas A. , Bahlis Nizar , Valentine Karen , Balogh Alex , Savoie Lynn , Morris Donald G. , Jones Allan , Brown Chris , Russell James A.
Published: February 2006

A single center, prospective clinical trial was conducted evaluating 2 cycles of induction high-dose chemotherapy for adults younger than 65 years of age with aggressive non-Hodgkin lymphoma (NHL) and 2 to 3 Age-Adjusted International Prognostic Index risk factors. Patients received one cycle of standard dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by one cycle of dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2, cisplatin 105 mg/m2 (DICEP), then underwent autologous blood stem cell collection, followed by one cycle of high-dose carmustine (BCNU) 300 mg/m2, etoposide 800 mg/m2, Ara-C 1600 mg/m2, melphalan 140 mg/m2 (BEAM), and autologous stem cell transplantation (ASCT) and radiotherapy to prior bulk. From June 1998 to August 2004, 55 patients aged 20 to 63 years (median 44 years) were accrued, 51 (92%) of whom had diffuse large B-cell NHL. Poor prognostic factors included stage 4 (n = 46), elevated lactate dehydrogenase (LDH; n = 47), Eastern Cooperative Oncology Group (ECOG) performance status 2 to 4 (n = 43), bulky mass more than 10 cm (n = 34), and marrow involvement (n = 16). Only one patient experienced nonrelapse mortality. With a median follow-up of 49 months, 4-year event-free survival (EFS) and overall survival (OS) rates for all 55 patients are 72% (95% confidence interval [CI] = 60%-84%) and 79% (95% CI = 69%-90%), respectively. In conclusion, CHOP-DICEP-BEAM is feasible and gave encouraging EFS and OS for patients with poor-prognosis aggressive NHL.
SHIP deficiency enhances HSC proliferation and survival but compromises homing and repopulation
Authors: Desponts Caroline , Hazen Amy L. , Paraiso Kim H. T. , Kerr William G.
Published: February 2006

The SH2 domain–containing inositol 5′-phosphatase-1 (SHIP) has the potential to modulate multiple signaling pathways downstream of receptors that impact hematopoietic stem cell (HSC) biology. Therefore, we postulated that SHIP might play an important role in HSC homeostasis and function. Consistent with this hypothesis, HSC proliferation and numbers are increased in SHIP–/– mice. Despite expansion of the compartment, SHIP–/– HSCs exhibit reduced capacity for long-term repopulation. Interestingly, we observe that SHIP–/– stem/progenitor cells home inefficiently to bone marrow (BM), and consistent with this finding, have reduced surface levels of both CXCR4 and vascular cell adhesion marker-1 (VCAM-1). These studies demonstrate that SHIP is critical for normal HSC function, homeostasis, and homing.
A mathematical model for supplying air-cooling for a building using a packed bed
Authors: Marewo GT , Henwood DJ
Published: February 2006

The cooling system at the Harare International School uses a packed bed system for storing the coldness of the night-time to be used later for day-time airconditioning. A two-phase mathematical model is described for the packed bed which includes heat dispersion in the fluid, and heat loss to the environment. This is in contrast to other studies, where at least one of these terms is neglected to simplify the mathematical model. A numerical method for obtaining a solution is proposed and implemented. Using measured inlet temperatures, the measured and predicted outlet temperatures of the bed show good trend agreement. The differences in detail are examined through sensitivity analyses for both the heat convection transfer and air velocity. It is apparent that adjusting these parameters can increase the agreement between the predicted and measured data. A parametric study for heat storage with various materials and bed sizes is given, which indicates how the code may be used as a tool for improving design and operational parameters.

Practical application: A mathematical model of a packed bed is described; the bed is made up of fluid flowing over solid material with heat interchange between the two. The solid material is idealized as spheres and the fluid temperature is assumed uniform in a cross-section of the bed. The model includes heat interchange between the bed and its surrounding environment and allows for time varying fluid velocity. The input data is the inlet temperature to the bed, which may be measured. The comparison with measured data may be helpful to anyone attempting to develop and test a similar model. The sensitivity tests give an understanding of the significance of some of the parameters involved. The Appendix gives a mathematical statement of the problem and an outline of an approach to developing computer code for a numerical solution.
Life cycle assessment of built-in-storage solar water heaters in Pakistan
Authors: Asif M , Muneer T
Published: February 2006

Sustainability of building construction and its services is increasingly drawing attention. In this respect CIBSE has issued a number of calls to industry. Solar water heating systems are now economically competitive and are being used throughout the world. Following earlier work of the present authors on the life cycle assessment (LCA) for building components,1,2 this work presents a monetary, energy usage and environmental impact assessment for solar water heaters. It has been shown herein that for a developing country like Pakistan where large amounts of hot water are required within industry, solar water heating offers favorable payback periods on each of the above three counts. It has been estimated that under the tested conditions, the embodied energy payback period for the plain and finned heater is equivalent to 185 days and 169 days respectively. It has also been found that the amount of carbon released during the construction process of plain and finned water heaters is 27.9 kg and 29.7 kg respectively. Annual carbon saving for the plain and finned water heaters has been calculated to be equivalent to 59.5 kg and 69.6 kg respectively, which in turn gives a carbon payback period of 156 days and 171 days. The monetary payback period for the plain and finned heater has been found to be equivalent to 6.7 years and 6.1 years respectively.