bluuebunny/crossref_metadata_2025 huggingface dataset:
FasT-Fix versus Inside-Out Suture Meniscal Repair in the Goat Model
Authors: Hospodar Steven J. , Schmitz Matthew R. , Golish S. Raymond , Ruder Craig R. , Miller Mark D.
Published: November 2008

Background

Recent all-inside meniscal repair devices are available, but in vivo studies with these devices are sparse.

Hypothesis

The FasT-Fix has inferior meniscal healing compared with the inside-out suture technique in the goat model.

Study Design

Controlled laboratory study.

Methods

After Institutional Review Board approval, 73 male castrated goats (Capra hircus) underwent a 2-cm meniscal incision and subsequent repair with the FasT-Fix device on one knee and inside-out meniscal repair on the contralateral knee. Both repairs used a vertical mattress suture technique. Access to the menisci was via an open technique with an extra-articular osteotomy of the medial collateral ligament origin on the femur. The animals were then allowed to ambulate unrestricted in a pasture after a 7-day stay in cages. Necropsy was carried out 6 months postoperatively, and the menisci and articular cartilage were studied with gross and microscopic inspection.

Results

Nine of the 73 animals were excluded before necropsy. A total of 64 animals underwent necropsy, gross measurement of residual lesions, gross evaluation for chondral damage, histologic evaluation of meniscal repair, histologic evaluation of any adjacent inflammatory reaction to implants, and data analysis. Compared with the inside-out group, the FasT-Fix group had longer residual full-thickness defects (1.2 ± 2.9 mm vs 0.2 ± 1.1 mm; P =. 011) and longer residual partial-thickness defects (8.4 ± 6.3 mm vs 3.6 ± 5.5 mm; P <. 001). A total of 148 FasT-Fix devices were placed for 73 knees. Two devices were replaced for improper deployment. The device deployed and attached correctly 146 of 148 times for a success rate of 98.6%. There was no gross chondral damage and no histologic findings of inflammatory reaction to the implants with either technique.

Conclusions

The FasT-Fix meniscal repair had inferior meniscal healing results in this animal model. Previous studies using this animal model have paralleled clinical outcomes. Implantation of the FasT-Fix device does not damage adjacent femoral or tibial cartilage. The deployment of the FasT-Fix implant was simple and reproducible. There was no inflammatory reaction to the FasTFix implant.

Clinical Relevance

The FasT-Fix meniscal repair has inferior meniscal healing results compared with the inside-out meniscal repair technique in the goat model. The clinical significance of this finding is not known. Further clinical study of the FasT-Fix implant is warranted.
Participation in Victim— Offender Mediation
Authors: Gerkin Patrick M.
Published: November 2008

Victim—offender mediation has grown to establish itself among criminal justice practices as an alternative to traditionally retributive notions of justice. As the number of programs claiming to be restorative in nature continues to grow, victim—offender mediation programs are emerging as one of the state's preferred delivery methods for restorative justice. Restorative practices, including victim—offender mediation, are inclusive practices. Participation is not only encouraged, it is a necessary element for victim—offender mediation to achieve restorative outcomes. Through the use of observations and content analysis of agreements produced in victim—offender mediation, this research uncovers several impediments to individual participation, including problems in the implementation of restorative practices; participant domination, including victim lecturing; and a lack of awareness among the participants about the restorative vision of justice.
Recurrent Childhood Animal Cruelty
Authors: Hensley Christopher , Tallichet Suzanne E. , Dutkiewicz Erik L.
Published: November 2008

Recent studies have begun to establish an association between childhood acts of animal cruelty and later violence against humans. Even so, research has failed to establish a strong correlation between the two, perhaps because previous studies have failed to examine the commission of violence against animals and humans in terms of their frequencies. In a replication of Tallichet and Hensley (2004) and based on survey data from 180 inmates at a medium- and maximum-security prison in a Southern state, the present study examines the relationship between the demographic characteristics of race, level of education, the residential location of an offender's formative years, and recurrent acts of childhood cruelty and their impact on later repeated acts of interpersonal violence. Only repeated acts of animal cruelty during childhood was predictive of later recurrent acts of violence toward humans, showing a possible relationship between the two.
Promoting Intrapersonal Qualities in Adolescents
Authors: Hindes Yvonne L. , Thorne Keoma J. , Schwean Vicki L. , McKeough Anne M.
Published: November 2008

Given the number of negative influences on youth and the resultant potential for adverse outcomes, it is crucial to support their positive development. Leadership training programs can promote the development of adaptive intrapersonal qualities. The Teen Leadership Breakthrough (TLB) program claims to create sustainable changes in youth using experiential activities, direct instruction, and feedback to teach leadership skills. This study evaluated the TLB program's efficacy in developing intrapersonal skills in 10th- and 11th-grade students. Participants were randomly assigned to a control or treatment group. Assessment of emotional intelligence and self-concept occurred prior to, immediately after, 6 weeks and 6 months following the intervention. Results indicated that the TLB program created sustainable changes emotional intelligence and self-concept. Although these results are encouraging, further research is needed to investigate the effectiveness of the TLB program in broader demographic groups and to examine different outcomes.
Are Enterally Fed ICU Patients Meeting Clinical Practice Guidelines?
Authors: Miller Cynthia A. , Grossman Sari , Hindley Erin , MacGarvie Debra , Madill Janet
Published: November 2008

Background: The 2003 Canadian clinical practice guidelines (CPGs) for nutrition support in mechanically ventilated, critically ill patients recommended early EN and maintaining a 45‐degree head‐of‐bed (HOB) angle during EN administration. Current practices at University Health Network have not been examined with regard to these guidelines. The purpose of this study was to determine the proportion of mechanically ventilated, enterally fed intensive care unit patients meeting the CPG recommendations for early EN and HOB elevation. Methods: This was a cross‐sectional study involving data collection in 2 parts. Early EN data were collected via chart review and HOB data through observation of HOB angle reader. Reasons for not meeting each recommendation were obtained when data were collected via chart review and feedback from nurses. Data analysis was conducted using frequency distributions. Results: Sixty‐six percent of patients met the recommendation for early EN. Of those not meeting this recommendation, the most common reason for the delay was hemodynamic instability (28.1%). For the HOB recommendation, 4.9% of patients met the 45 degree recommendation, and 52.5% had an HOB angle between 21 and 30 degrees. The most common reason for not attaining the 45‐degree angle was reported as unknown (29.5%). Conclusions: The proportion of patients meeting clinical practice guidelines compares favorably to similar studies. In some cases, patients' clinical conditions or unit HOB angle protocol explained not meeting guidelines. However, there were cases where reasons for not meeting guidelines were unknown.
Hypervitaminosis A in Pediatric Hematopoietic Stem Cell Patients Requiring Renal Replacement Therapy
Authors: Lipkin Ann Connell , Lenssen Polly
Published: November 2008

Background: Chronic renal failure patients have been known to develop vitamin A toxicity, but a descriptive study of hypervitaminosis A in patients with acute renal failure (ARF) has not yet been published. The authors observed hypervitaminosis A in pediatric hematopoietic stem cell transplant (HSCT) patients. Methods: All HSCT patients admitted between January 2001 and May 2006 who experienced ARF, received renal replacement therapy (RRT), and had a vitamin A level drawn were included in this retrospective, descriptive study. Molar ratios of vitamin A and retinol‐binding protein (RBP) were calculated to more accurately assess vitamin A status. Nineteen patients met the criteria for this study. Results: At initial testing (generally between days 6 and 10 after initiation of RRT), 17 of the 19 patients had abnormally elevated vitamin A levels for their age. Molar ratios of vitamin A to RBP were elevated in 6 patients at initial testing. Prescribed vitamin A intake information (parenteral and enteral) was available for most patients; all but 3 had an average daily intake greater than 2000 IU/kg over the 30 days prior to RRT initiation. Many patients had symptoms possibly related to vitamin A toxicity, although interpretation of hair, skin, and liver abnormalities are difficult to ascertain in HSCT patients. Seven patients had other findings that may have been associated with vitamin A toxicity. Conclusion: Children undergoing HSCT who receive nutrition support (predominantly parenteral nutrition), experience ARF, and require RRT are at risk for hypervitaminosis A and toxicity.
Helping Direct and Indirect Victims of National Terror: Experiences of Israeli Social Workers
Authors: Shamai Michal , Ron Pnina
Published: November 2008

In this study we explored the subjective experience and the meaning attached to it by Israeli social workers who provide help to direct and indirect victims of national terror attacks. A qualitative methodology, based on grounded theory tradition, was used to conduct and analyze interviews with 29 social workers from three types of agencies (municipal social services, general hospitals, and the National Insurance Institute) from various parts of the country. Based on the data, three main themes were constructed: (a) professional and personal functioning during intervention, (b) the immediate and long-term impact of intervening with terror attacks, and (c) the meaning attached to the social worker's role in intervening with victims. Overall, the findings show that the social workers experienced symptoms similar to those of secondary traumatic stress disorder (STSD) for a few days only, but in the long-term, they perceived their experience of helping victims of terror attacks as leading to personal and professional growth.
The Body Projects of University Students with Type 1 Diabetes
Authors: Balfe Myles
Published: November 2008

Young adults with type 1 diabetes are a “forgotten group.” Their perspectives are rarely addressed by research studies, meaning that we know little about the reasons why they engage (or not) in diabetes self-care practices. The limited work that has investigated these young people's perspectives suggests that they experience a tension between being healthy and being normal. In this article, I examine this tension from the viewpoints of a particular group of young adults with diabetes: university students. I examine what being normal means for these students and how their attempts to be normal impact upon their diabetes control. I argue that normalcy for these students is constructed and maintained through the body. Respondents attempt to be normal by engaging in what Shilling refers to as “body projects.” Each of the body projects that students are involved in developing is intended to produce a particular kind of normal embodied identity that is unaffected by diabetes. Unfortunately, the constitutional practices of particular body projects often undermine those of others, and can be risky for students' diabetes control. As such, students have to reach a balance between their different body projects. This article helps to address the lack of research on the perspectives of young adults with diabetes, and contributes to theoretical research on the concept of body projects.
Returning Home in Systems of Care
Authors: Farmer Elizabeth M. Z. , Southerland Dannia , Mustillo Sarah A. , Burns Barbara J.
Published: November 2008

Recent work suggests that out-of-home placements continue to be relatively common for youth with mental health problems, even within systems of care. The current work examines rates and predictors of movement back home and stability of reunifications. During the focal period, 1,778 youths experienced out-of-home placements; 61% moved back home, and 22% of those reunited were placed out of home again. Race was related to likelihood of reunification and instability: American Indian youth were least likely to return home, whereas Hispanic youth were at increased risk of unstable reunifications. Older youth and boys were more likely to return home, whereas youth from families with higher incomes were slightly more likely to be placed out of home but also most likely to be stably reunited. Higher (i.e., worse) total Child Behavior Checklist score was related to moving back home, whereas decreased strengths and more child-level risk factors predicted instability of reunification.
Serial Functional Imaging Poststroke Reveals Visual Cortex Reorganization
Authors: Brodtmann Amy , Puce Aina , Darby David , Donnan Geoffrey
Published: November 2008

Purpose. Visual cortical reorganization following injury remains poorly understood. The authors performed serial functional magnetic resonance imaging (fMRI) on patients with visual cortex infarction to evaluate early and late striate, ventral, and dorsal extrastriate cortical activation. Methods. Patients were studied with fMRI within 10 days and at 6 months. The authors used a high-level visual activation task designed to activate the ventral extrastriate cortex. These data were compared to those of age-appropriate healthy control participants. Results. The results from 24 healthy control individuals (mean age 65.7 ± SE 3.6 years, range 32-89) were compared to those from 5 stroke patients (mean age 73.8 ± SE 7 years, range 49-86). Patients had infarcts involving the striate and ventral extrastriate cortex. Patient activation patterns were markedly different to controls. Bilateral striate and ventral extrastriate activation was reduced at both sessions, but dorsal extrastriate activated voxel counts remained comparable to controls. Conversely, mean percent magnetic resonance signal change increased in dorsal sites. Conclusions. These data provide strong evidence of bilateral poststroke functional depression of striate and ventral extrastriate cortices. Possible utilization or surrogacy of the dorsal visual system was demonstrated following stroke. This activity could provide a target for novel visual rehabilitation therapies.
Acute myeloid leukemia induced by MLL-ENL is cured by oncogene ablation despite acquisition of complex genetic abnormalities
Authors: Horton Sarah J. , Walf-Vorderwülbecke Vanessa , Chatters Steve J. , Sebire Neil J. , de Boer Jasper , Williams Owen
Published: November 2008

Chromosomal translocations involving 11q23 are frequent in infant acute leukemia and give rise to the formation of MLL fusion genes. The mechanism of leukemic transformation by these fusions has been the subject of numerous investigations. However, the dependence of acute leukemia on MLL fusion activity in vivo and the efficacy of targeting this activity to eliminate disease have not been established. We have developed a model for conditional expression of MLL-ENL in hematopoietic progenitor cells, in which expression of the fusion oncogene is turned off by doxycycline. Conditionally immortalized myeloblast cells derived from these progenitors were found to induce leukemia in vivo. Leukemic cells isolated from primary recipient mice were shown to have acquired additional genetic abnormalities and, when transplanted into secondary recipients, induced leukemia with shortened latencies. However, the leukemic cells remained dependent on MLL-ENL expression in vitro and in vivo, and its ablation resulted in regression of established leukemias. This study demonstrates that even genetically complex leukemias can be reversed on inactivation of the initiating MLL fusion and has important implications for the design of novel leukemia therapies.
Tumor burden influences exposure and response to rituximab: pharmacokinetic-pharmacodynamic modeling using a syngeneic bioluminescent murine model expressing human CD20
Authors: Daydé David , Ternant David , Ohresser Marc , Lerondel Stéphanie , Pesnel Sabrina , Watier Hervé , Le Pape Alain , Bardos Pierre , Paintaud Gilles , Cartron Guillaume
Published: November 2008

Clinical studies have shown a large interindividual variability in rituximab exposure and its significant influence on clinical response in patients receiving similar doses of antibody. The aim of this study was to evaluate the influence of tumor burden on dose-concentration-response relationships of rituximab. Murine lymphoma cells (EL4, 8 × 103), transduced with human CD20 cDNA and transfected with luciferase plasmid (EL4-huCD20-Luc), were intravenously injected into C57BL/6J mice. Tumor burden detection, dissemination, and progression were evaluated quantitatively by in vivo bioluminescence imaging. Different doses of rituximab (6, 12, 20, or 40 mg/kg) were infused 13 days after lymphoma cell inoculation, and rituximab serum concentrations were measured by enzyme-linked immunosorbent assay. Without rituximab, all mice developed disseminated lymphoma and died within 30 days, whereas a significant dose-response relationship was observed in mice receiving rituximab. The 20-mg/kg dose was adequate to study interindividual variability in response because 23% of mice were cured, 59% had partial response, and 18% had disease progression. Rituximab concentrations were inversely correlated with tumor burden; mice with low tumor burden had high rituximab concentrations. Furthermore, rituximab exposure influenced response and survival. Finally, using a pharmacokinetic-pharmacodynamic model, we demonstrated that tumor burden significantly influenced rituximab efficacy.
The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)–like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring
Authors: Dagklis Antonis , Fazi Claudia , Sala Cinzia , Cantarelli Valeria , Scielzo Cristina , Massacane Roberto , Toniolo Daniela , Caligaris-Cappio Federico , Stamatopoulos Kostas , Ghia Paolo
Published: November 2008

In the revised National Cancer Institute Working Group (NCI-WG)/International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines for CLL, CLL-like monoclonal B lymphocytosis (MBL) is defined as the presence of less than 5 × 109/L B lymphocytes in the peripheral blood. However, the concentration of MBL in the blood is extremely variable. MBL in subjects with lymphocytosis require treatment at a rate of 1.1% per year and present immunoglobulin (IG) gene features and similar to good prognosis CLL. Little is known about low-count MBL cases, accidentally found in the general population. We analyzed IGHV-D-J rearrangements in 51 CLL-like MBL cases from healthy individuals, characterized by few clonal B cells. Seventy percent of the IGHV genes were mutated. The most frequent IGHV gene was IGHV4-59/61, rarely used in CLL, whereas the IGHV1–69 gene was lacking and the IGHV4-34 gene was infrequent. Only 2 of 51 (3.9%) MBL cases expressed a CLL-specific stereotyped HCDR3. Therefore, the IG gene repertoire in low-count MBL differs from both mutated and unmutated CLL, suggesting that the detection of MBL in an otherwise healthy subject is not always equivalent to a preleukemic state. Detailed IG analysis of individual MBL may help to identify cases that necessitate continuous clinical monitoring to anticipate disease progression.
Evolutionary origin and genomic organisation of runt-domain containing genes in arthropods
Authors: Duncan Elizabeth J , Wilson Megan J , Smith James M , Dearden Peter K
Published: November 2008

Background

Gene clusters, such as the Hox gene cluster, are known to have critical roles in development. In eukaryotes gene clusters arise primarily by tandem gene duplication and divergence. Genes within a cluster are often co-regulated, providing selective pressure to maintain the genome organisation, and this co-regulation can result in temporal or spatial co-linearity of gene expression. It has been previously noted that in Drosophila melanogaster, three of the four runt-domain (RD) containing genes are found in a relatively tight cluster on chromosome 1, raising the possibility of a putative functional RD gene cluster in D. melanogaster.

Results

To investigate the possibility of such a gene cluster, orthologues of the Drosophila melanogaste r RD genes were identified in several endopterygotan insects, two exopterygotan insects and two non-insect arthropods. In all insect species four RD genes were identified and orthology was assigned to the Drosophila sequences by phylogenetic analyses. Although four RD genes were found in the crustacean D. pulex, orthology could not be assigned to the insect sequences, indicating independent gene duplications from a single ancestor following the split of the hexapod lineage from the crustacean lineage.

In insects, two chromosomal arrangements of these genes was observed; the first a semi-dispersed cluster, such as in Drosophila, where lozenge is separated from the core cluster of three RD genes often by megabases of DNA. The second arrangement was a tight cluster of the four RD genes, such as in Apis mellifera.

This genomic organisation, particularly of the three core RD genes, raises the possibility of shared regulatory elements. In situ hybridisation of embryonic expression of the four RD genes in Drosophila melanogaster and the honeybee A. mellifera shows no evidence for either spatial or temporal co-linearity of expression during embryogenesis.

Conclusion

All fully sequenced insect genomes contain four RD genes and orthology can be assigned to these genes based on similarity to the D. melanogaster protein sequences. Examination of the genomic organisation of these genes provides evidence for a functional RD gene cluster. RD genes from non-insect arthropods are also clustered, however the lack of orthology between these and insect RD genes suggests this cluster is likely to have resulted from a duplication event independent from that which created the insect RD gene cluster. Analysis of embryonic RD gene expression in two endopterygotan insects, A. mellifera and D. melanogaster, did not show evidence for coordinated gene expression, therefore while the functional significance of this gene cluster remains unknown its maintenance during insect evolution implies some functional significance to the cluster.
Interleukin-1beta and tumour necrosis factor-alpha impede neutral lipid turnover in macrophage-derived foam cells
Authors: Persson Jenny , Nilsson Jan , Lindholm Marie W
Published: November 2008

Background

Pro-inflammatory cytokines can affect intracellular lipid metabolism. A variety of effects have been described for different cell types; hepatocyte lipid turnover pathways are inhibited during inflammation, whereas interleukin-1β (IL-1β) reduces intracellular cholesterol levels in fibroblasts. Levels of the pro-inflammatory cytokines IL-1β and tumour necrosis factor-α (TNF-α) are up-regulated at sites of formation of atherosclerotic plaques. Plaque formation is though to begin with infiltration of monocytes to the intimal layer of the vascular wall, followed by differentiation to macrophages and macrophage uptake of modified lipoproteins, resulting in accumulation of intracellular lipids. The lipid-filled cells are referred to as macrophage foam cells, a key feature of atherosclerotic plaques. We have investigated the effects of IL-1β and TNF-α on macrophage foam cells in order to assess whether presence of the pro-inflammatory cytokines improves or aggravates macrophage foam cell formation by affecting lipid accumulation and lipid turn-over in the cells.

Results

Differentiated primary human macrophages or THP-1 cells were lipid loaded by uptake of aggregated low density lipoproteins (AgLDL) or very low density lipoproteins (VLDL), and then incubated with IL-1β (0 – 5000 pg/ml) in lipoprotein-free media for 24 h. Cells incubated in absence of cytokine utilized accumulated neutral lipids, in particular triglycerides. Addition of exogenous IL-1β resulted in a dose-dependent retention of intracellular cholesterol and triglycerides. Exchanging IL-1β with TNF-α gave a similar response. Analysis of fatty acid efflux and intracellular fatty acid activation revealed a pattern of decreased lipid utilization in cytokine-stimulated cells.

Conclusion

IL-1β and TNF-α enhance macrophage foam cell formation, in part by inhibition of macrophage intracellular lipid catabolism. If present in vivo, these mechanisms will further augment the pro-atherogenic properties of the two cytokines.
PCR-based rapid genotyping of Stenotrophomonas maltophiliaisolates
Authors: Roscetto Emanuela , Rocco Francesco , Carlomagno M Stella , Casalino Mariassunta , Colonna Bianca , Zarrilli Raffaele , Di Nocera Pier Paolo
Published: November 2008

Background

All bacterial genomes contain repetitive sequences which are members of specific DNA families. Such repeats may occur as single units, or found clustered in multiple copies in a head-to-tail configuration at specific loci. The number of clustered units per locus is a strain-defining parameter. Assessing the length variability of clusters of repeats is a versatile typing methodology known as multilocus variable number of tandem repeat analysis (MLVA).

Results

Stenotrophomonas maltophilia is an environmental bacterium increasingly involved in nosocomial infections and resistant to most antibiotics. The availability of the whole DNA sequence of the S. maltophilia strain K279a allowed us to set up fast and accurate PCR-based diagnostic protocols based on the measurement of length variations of loci carrying a variable number of short palindromic repeats marking the S. maltophilia genome. On the basis of the amplimers size, it was possible to deduce the number of repeats present at 12 different loci in a collection of S. maltophilia isolates, and therefore label each of them with a digit. PCR-negative regions were labelled 0. Co-amplification of two pairs of loci provided a 4-digit code sufficient for immediate subtyping. By increasing the number of loci analyzed, it should be possible to assign a more specific digit profile to isolates. In general, MLVA data match genotyping data obtained by PFGE (pulsed-field gel electrophoresis). However, some isolates exhibiting the same PCR profiles at all loci display distinct PFGE patterns.

Conclusion

The utilization of the present protocol allows to type several S. maltophilia isolates in hours. The results are immediately interpretable without the need for sophisticated softwares. The data can be easily reproducible, and compared among different laboratories.
Synergistic effect of CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin on food intake regulation in lean mice
Authors: Maletínská Lenka , Maixnerová Jana , Matyšková Resha , Haugvicová Renata , Pirník Zdeno , Kiss Alexander , Železná Blanka
Published: November 2008

Background

CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin (CCK) are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS), the paraventricular nucleus (PVN), and the dorsomedial nucleus (DMH) of the hypothalamus.

Results

In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102) in the doses of 0.1 or 0.5 μg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 μg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102) on food intake. After simultaneous administration of 0.1 μg/mouse CART(61-102) and of 4 μg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102) and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test.

Conclusion

The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety.
Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems
Authors: Zafar S Yousuf , Abernethy Amy P , Abbott David H , Grambow Steven C , Marcello Jennifer E , Herndon James E , Rowe Krista L , Kolimaga Jane T , Zullig Leah L , Patwardhan Meenal B , Provenzale Dawn T
Published: November 2008

Background

Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis.

Methods

Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003–2007. We assessed metastatic CRC patients treated from 2003–2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression.

Results

342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58–1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82–1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race.

Conclusion

Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare.
Neoangiogenesis in early cervical cancer: Correlation between color Doppler findings and risk factors. A prospective observational study
Authors: Jurado Matias , Galván Rosendo , Martinez-Monge Rafael , Mazaira Jesús , Alcazar Juan Luis
Published: November 2008

Background

The aim of the present article was to evaluate whether angiogenic parameters as assessed by transvaginal color Doppler ultrasound (TVCD) may predict those prognostic factors related to recurrence.

Methods

A total of 27 patients (mean age: 51.3 years, range: 29 to 85) with histologically proven early stage invasive cervical cancer were evaluated by TVCD prior to surgery. Subjective assessment of the amount of vessels within the tumor (scanty-moderate or abundant) and pulsatility index (PI) were recorded. All patients underwent radical hysterectomy and pelvic lymph node dissection. Postoperative treatment (RT or chemoradiotherapy) was given according to risk factors (positive lymph nodes, parametrial and vaginal margin involvement, depth stromal invasion, lymph-vascular space involvement)

Results

Tumors with "abundant" vascularization were significantly associated with pelvic lymph node metastases, depth stromal invasion > 10 mm, lymph-vascular space involvement, tumor diameter > 17.5 mm, and parametrial involvement. Postoperative treatment was significantly more frequent in patients with "abundant" vascularization (OR: 20.8, 95% CIs: 2 to 211). The presence of scanty-moderate vascularization with a PI < 0.82 or abundant vascularization with either PI > 0.82 or PI < 0.82 was associated with high-risk group in 94.4% of the cases (OR: 21.2, 95% CI: 1.9 to 236.0)

Conclusion

The results are consistent with a relationship between tumor angiogenesis and prognostic factors for recurrence in early cervical cancer. "Abundant" vascularization and PI < 0.82 may be related to postoperative treatment due to risk factors.
Induction of galectin-1 expression by HTLV-I Tax and its impact on HTLV-I infectivity
Authors: Gauthier Sonia , Pelletier Isabelle , Ouellet Michel , Vargas Amandine , Tremblay Michel J , Sato Sachiko , Barbeau Benoit
Published: November 2008

Background

Cell-free Human T-cell Leukemia Virus type I (HTLV-I) virions are poorly infectious and cell-to-cell contact is often required to achieve infection. Other factors might thus importantly contribute in increasing infection by HTLV-I. Galectin-1 is a galactoside-binding lectin which is secreted by activated T lymphocytes. Several functions have been attributed to this protein including its capacity to increase cell-to-cell adhesion. Based on previous studies, we postulated that this protein could also accentuate HTLV-I infection.

Results

Herein, we demonstrate that galectin-1 expression and release are higher in HTLV-I-infected T cells in comparison to uninfected T cells. Furthermore, galectin-1 expression was activated in various cell lines expressing the wild type viral Tax protein while this induction was minimal upon expression of NF-κB activation-defective TaxM22. Cotransfection of these Tax expression vectors with galectin-1 promoter-driven luciferase constructs confirmed that Tax upregulated galectin-1 promoter activity. However, a NF-κB-independent mechanism was strongly favoured in this induction of galectin-1 expression as no activation of the promoter was apparent in Jurkat cells treated with known NF-κB activators. Using HTLV-I envelope pseudotyped HIV-1 virions, galectin-1 was shown to increase infectivity. In addition, a co-culture assay with HTLV-I-infected cells also indicated an increase in cell fusion upon addition of galectin-1. This effect was not mediated by factors present in the supernatant of the HTLV-I-infected cells.

Conclusion

These data suggest that HTLV-I Tax increases galectin-1 expression and that this modulation could play an important role in HTLV-I infection by stabilizing both cell-to-cell and virus-cell interactions.
Intrathyroidal parathyroid carcinoma: a case report with clinical and histological findings
Authors: Temmim Labiba , Sinowatz Fred , Hussein Wiam I , Al-Sanea Osama , El-Khodary Hady
Published: November 2008

The chance of an intrathyroidal occurrence of a parathyroid gland is about 1–3%. Among the causes of hyperparathyroidism, parathyroid cases occur in less than 1% of patients. Here we present the case of a 63 year old Saudi female suffering from an intrathryroidal parathyroid carcinoma. The suspicion coming from the clinical investigations that the removed tumor tissue may be a parathyroid carcinoma could be confirmed by histology. Additionally non-radioactive in situ hybridization to localize mRNA transcripts for Cyclin D1 and immunohistochemical localization of Cyclin D1 was performed. Although parathyroid adenoma and carcinoma have disparate natural history, it can be difficult to differentiate between the two entities. Clinical presentation, operative findings may raise suspicion, but may not be conclusive especially if there is no evidence of invasion or metastasis, especially if the gland was intrathyroidal.
Time-lapse gravity monitoring: A systematic 4D approach with application to aquifer storage and recovery
Authors: Davis Kristofer , Li Yaoguo , Batzle Michael
Published: November 2008

We studied time-lapse gravity surveys applied to the monitoring of an artificial aquifer storage and recovery (ASR) system in Leyden, Colorado. An abandoned underground coal mine has been developed into a subsurface water reservoir. Water from surface sources is injected into the artificial aquifer during winter for retrieval and use in summer. As a key component in the geophysical monitoring of the artificial ASR system, three microgravity surveys were conducted over the course of ten months during the initial water-injection stage. The time-lapse microgravity surveys successfully detected the distribution of injected water as well as its general movement. Quantitative interpretation based on 3D inversions produced hydrologically meaningful density-contrast models and imaged major zones of water distribution. The site formed an ideal natural laboratory for investigating various aspects of time-lapse gravity methodology. Through this application, we have studied systematically all steps of the method, including survey design, data acquisition, processing, and quantitative interpretation.
Distinct Gene Expression–Defined Classes of Gastrointestinal Stromal Tumor
Authors: Yamaguchi Umio , Nakayama Robert , Honda Kazufumi , Ichikawa Hitoshi , Hasegawa Tadashi , Shitashige Miki , Ono Masaya , Shoji Ayako , Sakuma Tomohiro , Kuwabara Hideya , Shimada Yasuhiro , Sasako Mitsuru , Shimoda Tadakazu , Kawai Akira , Hirohashi Setsuo , Yamada Tesshi
Published: November 2008

Purpose

The majority of gastrointestinal stromal tumors (GIST) can be cured by surgery alone, but relapse occurs in 20% to 40% of cases. GISTs are considered to invariably arise through gain of function KIT or PDGFA mutation of the interstitial cells of Cajal (ICC). However, the genetic basis of the malignant progression of GISTs are poorly understood.

Patients and Methods

The expression levels of 54,613 probe sets in 32 surgical samples of untreated GISTs of the stomach and small intestine were analyzed with oligonucleotide microarrays. The representative GeneChip data were validated by real-time reverse transcriptase polymerase chain reaction and immunohistochemistry.

Results

Unbiased hierarchical clustering consistently separated the 32 cases of GIST into two major classes according to tumor site. The two major classes were further separated into novel subclasses, which were significantly correlated with various pathological prognostic parameters, the frequency of metastasis (P < .05), and clinical outcome. Immunohistochemical analysis of 152 independent patients with gastric GISTs revealed that the expression of dipeptidyl peptidase IV (T-cell activation antigen CD26) protein was significantly associated with poorer overall and disease-free survival (P < .00001).

Conclusion

CD26 appears to be a reliable biomarker of malignant GISTs of the stomach. The postoperative recurrence rate of CD26-negative cases was as low as 2.0% (two of 102). Therefore, postoperative follow-up of such patients might be made less intensive. CD26 may play an important role in the malignant progression of gastric GISTs and serve as a therapeutic target.
Unresolved Grief in a National Sample of Bereaved Parents: Impaired Mental and Physical Health 4 to 9 Years Later
Authors: Lannen Patrizia K. , Wolfe Joanne , Prigerson Holly G. , Onelov Erik , Kreicbergs Ulrika C.
Published: November 2008

Purpose

To assess unresolved parental grief, the associated long-term impact on mental and physical health, and health service use.

Patients and Methods

This anonymous, mail-in questionnaire study was performed as a population-based investigation in Sweden between August 2001 and October 2001. Four hundred forty-nine parents who lost a child as a result of cancer 4 to 9 years earlier completed the survey (response rate, 80%). One hundred ninety-one (43%) of the bereaved parents were fathers, and 251 (56%) were mothers. Bereaved parents were asked whether or not, and to what extent, they had worked through their grief. They were also asked about their physical and psychological well-being. For outcomes of interest, we report relative risk (RR) with 95% CIs as well as unadjusted odds ratios and adjusted odds ratios.

Results

Parents with unresolved grief reported significantly worsening psychological health (fathers: RR, 3.6; 95% CI, 2.0 to 6.4; mothers: RR, 2.9; 95% CI, 1.9 to 4.4) and physical health (fathers: RR, 2.8; 95% CI, 1.8 to 4.4; mothers: RR, 2.3; 95% CI, 1.6 to 3.3) compared with those who had worked through their grief. Fathers with unresolved grief also displayed a significantly higher risk of sleep difficulties (RR, 6.7; 95% CI, 2.5 to 17.8). Mothers, however, reported increased visits with physicians during the previous 5 years (RR, 1.7; 95% CI, 1.1 to 2.6) as well as a greater likelihood of taking sick leave when they had not worked through their grief (RR, 2.1; 95% CI, 1.2 to 3.5).

Conclusion

Parents who have not worked through their grief are at increased risk of long-term mental and physical morbidity, increased health service use, and increased sick leave.
Phase III Trial of Androgen Ablation With or Without Three Cycles of Systemic Chemotherapy for Advanced Prostate Cancer
Authors: Millikan Randall E. , Wen Sijin , Pagliaro Lance C. , Brown Melissa A. , Moomey Brenda , Do Kim-Anh , Logothetis Christopher J.
Published: November 2008

Purpose

We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease.

Patients and Methods

Eligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy.

Results

Three hundred six patients were registered; 286 are reported. Median time to progression was 24 months (95% CI, 18 to 39 months) in the standard therapy arm, and 35 months (95% CI, 26 to 44 months) in the chemohormonal group (P = .39). At median follow-up of 6.4 years, overall survival was 5.4 years (95% CI, 4.7 to 7.8 years) in the standard therapy arm versus 6.1 years (95% CI, 5.1 to 10.1 years; P = .41). Prostate-specific antigen kinetics at the time of androgen ablation and the nadir after hormone treatment were strongly correlated with survival. Chemotherapy significantly increased the burden of therapy, with 51% of patients experiencing an adverse event of grade 3 or worse, especially thromboembolic events.

Conclusion

There is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype.
Managing Symptoms Among Patients With Breast Cancer During Chemotherapy: Results of a Two-Arm Behavioral Trial
Authors: Given Charles W. , Sikorskii Alla , Tamkus Deimante , Given Barbara , You Mei , McCorkle Ruth , Champion Victoria , Decker David
Published: November 2008

Purpose

In this study, we compare symptom response and times to response among patients with breast cancer who were assigned to either a cognitive behavioral Nurse-Administered Symptom Management intervention or an Automated Telephone Symptom Management (ATSM) intervention.

Patients and Methods

Patients with breast cancer were identified from a larger trial. Baseline equivalence existed between arms, and there was no differential attrition by arm. Anchor-based definition of response using mild, moderate, and severe categories of symptom severity were used. Responses and times to response for 15 symptoms were investigated in relation to trial arm, comorbid conditions, treatment protocols, and metastatic versus localized disease.

Results

The ATSM arm was more effective among patents with metastatic disease. Compared with patients receiving combination chemotherapy protocols, those treated with single agents had greater response and shorter time to response.

Conclusion

An educational information intervention delivered via an automated voice response system that assesses symptoms and refers patients to a Symptom Management Guide is more effective than a complex cognitive behavioral approach in terms of producing greater symptom responses in shorter time intervals among patients with metastatic disease.
Does a Patient-Held Quality-of-Life Diary Benefit Patients With Inoperable Lung Cancer?
Authors: Mills Moyra E. , Murray Liam J. , Johnston Brian T. , Cardwell Chris , Donnelly Michael
Published: November 2008

Purpose

To examine the effect of weekly completion of a patient-held quality-of-life (QOL) diary in routine oncology practice for palliative care patients.

Patients and Methods

In a pragmatic randomized controlled trial, 115 patients with inoperable lung cancer were randomly assigned to receive either standard care or a structured QOL diary (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the related lung cancer module LC13) that they completed at home each week for 16 weeks. Patients were encouraged to share the QOL information with health professionals involved in their care. Changes in QOL over time (measured by the Functional Assessment of Cancer Therapy–Lung questionnaire and the Palliative Care Quality of Life Index), discussion of patient problems, and satisfaction with communication and general care were assessed at baseline and at 2 and 4 months after baseline.

Results

Analysis of QOL indicated a small but consistent difference between patients in the diary group and the standard care group. The diary group had a poorer QOL in many domains. Two different QOL summary scores (total and overall QOL) indicated a statistically significant between-group difference. No effects were found in relation to satisfaction with care, communication, or the discussion of patient problems.

Conclusion

The regular completion of a QOL questionnaire without appropriate feedback to health care professionals and without the provision of appropriate support may have a negative impact on inoperable lung cancer patients. Further research should focus on identifying features such as feedback loops that are required for the successful and meaningful use of QOL questionnaires in routine patient care.