Publications by authors named "Gregory Harper"

24 Publications

  • Page 1 of 1

Survivorship care plans: is there buy-in from community oncology providers?

Cancer 2014 Mar 10;120(5):722-30. Epub 2013 Dec 10.

Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York.

Background: The Institute of Medicine recommended that survivors of cancer and their primary care providers receive survivorship care plans (SCPs) to summarize cancer treatment and plan ongoing care. However, the use of SCPs remains limited.

Methods: Oncology providers at 14 National Cancer Institute Community Cancer Centers Program hospitals completed a survey regarding their perceptions of SCPs, including barriers to implementation, strategies for implementation, the role of oncology providers, and the importance of topics in SCPs (diagnosis, treatment, recommended ongoing care, and the aspects of ongoing care that the oncology practice will provide).

Results: Among 245 providers (response rate of 70%), 52% reported ever providing any component of an SCP to patients. The most widely reported barriers were lack of personnel and time to create SCPs (69% and 64% of respondents, respectively). The most widely endorsed strategy among those using SCPs was the use of a template with prespecified fields; 94% of those who used templates found them helpful. For each topic of an SCP, although 87% to 89% of oncology providers believed it was very important for primary care providers to receive the information, only 58% to 65% of respondents believed it was very important for patients to receive the information. Furthermore, 33% to 38% of respondents reported mixed feelings regarding whether it was the responsibility of oncology providers to provide SCPs.

Conclusions: Practices need additional resources to overcome barriers to implementing SCPs. We found resistance toward SCPs, particularly the perceived value for the survivor and the idea that oncology providers are responsible for SCP dissemination.
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http://dx.doi.org/10.1002/cncr.28472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949150PMC
March 2014

Association of dietary and supplemental iron and colorectal cancer in a population-based study.

Eur J Cancer Prev 2013 Nov;22(6):506-11

aDepartment of Nutritional Sciences, Pennsylvania State University, University Park bNortheast Regional Cancer Institute, Scranton Departments of cPublic Health Sciences dPharmacology, Pennsylvania State College of Medicine, Hershey eDepartment of Medicine, Lehigh Valley Hospital, Allentown, Pennsylvania fDepartment of Health Sciences, Exponent Inc., Chicago, Illinois gDepartment of Health and Human Services, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

We evaluated the role of dietary iron, heme iron, and supplemental iron on colorectal cancer (CRC) risk in a population-based case-control study in Pennsylvania, including 1005 incident cases and 1062 controls. Diet was assessed through a modified food frequency questionnaire that included supplement use and a meat-specific module. Cases reported intakes for the year before diagnosis, whereas controls reported intakes for the year before interview. Heme iron intake was calculated using a new heme database developed by the US National Cancer Institute. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. After multivariate adjustment, there were no significant associations between heme iron or total iron intake and CRC incidence. Dietary iron intake was inversely associated with CRC among women (OR Q5 vs. Q1=0.45; 95% CI=0.22-0.92), but not among men. Supplemental iron intake of more than 18 mg/day versus none was positively associated with CRC incidence (OR=2.31; 95% CI=1.48-3.59; P-trend<0.001), an effect that was observed in both men (OR=2.56; 95% CI=1.30-5.05) and women (OR=2.46; 95% CI=1.34-4.52). These findings suggest that consumption of more than 18 mg/day of supplemental iron may increase risk for CRC.
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http://dx.doi.org/10.1097/CEJ.0b013e32836056f8DOI Listing
November 2013

Meat-related compounds and colorectal cancer risk by anatomical subsite.

Nutr Cancer 2013 ;65(2):202-26

Cancer Prevention Fellowship Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.

Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends < 0.05). For analyses by meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends < 0.05). Inverse associations were observed between unprocessed poultry and colorectal, colon, proximal colon, and rectal tumors; grilled/barbequed poultry and proximal colon cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends < 0.05). HCAs, PAHs, nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted.
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http://dx.doi.org/10.1080/01635581.2013.756534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584417PMC
December 2013

Can interferon-gamma or interferon-gamma-induced-protein-10 differentiate tuberculosis infection and disease in children of high endemic areas?

PLoS One 2011 23;6(9):e23733. Epub 2011 Sep 23.

Liverpool School of Tropical Medicine, Liverpool, United Kingdom.

Background: Diagnosis of childhood tuberculosis (TB) is difficult in high TB burden settings. Interferon-gamma-induced protein 10 (IP10) has been suggested as a marker of TB infection and disease, but its ability to differentiate the two conditions remains uncertain.

Objectives: To describe Interferon-gamma (INFγ) and IP10 expression in children with TB infection and disease and controls to assess their potential to differentiate latent and active TB.

Methods: This was a cross sectional study of 322 1-15 years old children with symptoms of TB (28 confirmed, 136 probable and 131 unlikely TB), 335 children in contact with adults with pulmonary TB and 156 community controls in Southern Ethiopia. The Tuberculin Skin Test (TST) and Quantiferon-In-Tube (QFT-IT) were performed. INFγ and IP10 were measured in plasma supernatants.

Results And Interpretation: Children with confirmed and probable TB and contacts were more likely to have TST+ (78.6%, 59.3% and 54.1%, respectively) than children with unlikely TB (28.7%) and controls (12.8%) (p<0.001). Children with confirmed TB (59.3%) and contacts (44.7%) were more likely to have INFγ+ than children with probable (37.6%) or unlikely TB (28.1%) and controls (13.1%) (p<0.001). IP10 concentrations were higher in INFγ+ children independently of TST (p<0.001). There was no difference between IP10 concentrations of children with confirmed TB and contacts (p = 0.8) and children with and without HIV (p>0.1). INFγ and IP10 can identify children with TB infection and disease, but cannot differentiate between the two conditions. HIV status did not affect the expression of IP10.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023733PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179460PMC
March 2012

Reduced risk for placental malaria in iron deficient women.

Malar J 2011 Feb 23;10:47. Epub 2011 Feb 23.

University of Malawi College of Medicine, Biochemistry Department, Blantyre, Malawi.

Background: Nutritional iron deficiency may limit iron availability to the malaria parasite reducing infection risk, and/or impair host immunity thereby increasing this risk. In pregnant women, there is evidence of an adverse effect with iron supplementation, but the few reported studies are strongly confounded.

Methods: A case control study in pregnant Malawian women was undertaken in Chikhwawa southern Malawi in order to describe iron status in relation to placental malaria controlling for several confounding factors. Pregnancy characteristics were obtained and a blood sample at delivery. A full blood count was performed and serum ferritin and transferrin receptor quantified by enzyme-linked immunoassay. DNA analysis was used to identify genetic polymorphisms for ABO phenotype, hemoglobin HbS, and glucose -6 phosphate dehydrogenase deficiency. Placental tissue was obtained and malaria histology classified as active, past or no malaria infection.

Results: 112 cases with placental malaria were identified and 110 women with no evidence of placental infection. Iron deficiency was less frequent in women with placental Plasmodium falciparum infection. In those with acute, chronic or past placental infections the odds ratio for iron deficiency was 0.4, 95% CI 0.2-0.8, p = 0.01; for acute and chronic infections 0.4, 0.2-0.8, p = 0.006; for acute infection 0.3, 0.1-0.7, p = 0.001. The association was greater in multigravidae.

Conclusion: Women with either acute, or acute and chronic placental malaria were less likely to have iron deficiency than women without placental malaria infection There is a priority to establish if reversing iron deficiency through iron supplementation programs either prior to or during pregnancy enhances malaria risk.
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http://dx.doi.org/10.1186/1475-2875-10-47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050778PMC
February 2011

Diet index-based and empirically derived dietary patterns are associated with colorectal cancer risk.

J Nutr 2010 Jul 5;140(7):1267-73. Epub 2010 May 5.

Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.

Previous studies have derived patterns by measuring compliance with preestablished dietary guidance or empirical methods, such as principal components analysis (PCA). Our objective was to examine colorectal cancer risk associated with patterns identified by both methods. The study included 431 incident colorectal cancer cases (225 men, 206 women) and 726 healthy controls (330 men, 396 women) participating in a population-based, case-control study. PCA identified sex-specific dietary patterns and the Healthy Eating Index-2005 (HEI-05) assessed adherence to the 2005 Dietary Guidelines for Americans. A fruits and vegetables pattern and a meat, potatoes, and refined grains pattern were identified among men and women; a third pattern (alcohol and sweetened beverages) was identified in men. The fruits and vegetables pattern was inversely associated with risk among men [odds ratio (OR) = 0.38, 95% CI = 0.21-0.69 for the highest compared with the lowest quartile] and women (OR = 0.35, 95% CI = 0.19-0.65). The meat, potatoes, and refined grains pattern was positively associated with risk in women (OR = 2.20, 95% CI = 1.08-4.50) and there was a suggestion of a positive association among men (OR = 1.56, 95% CI = 0.84-2.90; P-trend = 0.070). Men and women with greater HEI-05 scores had a significantly reduced risk of colorectal cancer (OR = 0.56, 95% CI = 0.31-0.99; OR = 0.44, 95% CI = 0.24-0.77, respectively). Following the Dietary Guidelines or a dietary pattern lower in meat, potatoes, high fat, and refined foods and higher in fruits and vegetables may reduce colorectal cancer risk.
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http://dx.doi.org/10.3945/jn.110.121780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499942PMC
July 2010

Characteristics of hearing impairment in Yemeni children with chronic suppurative otitis media: a case-control study.

Int J Pediatr Otorhinolaryngol 2010 Mar 29;74(3):283-6. Epub 2009 Dec 29.

WHO Collaborating Centre on Hearing Impairment, Child and Reproductive Health Group, Liverpool School of Tropical Medicine, Liverpool, UK.

Background: Chronic suppurative otitis media (CSOM) is a serious disorder particularly in low resource settings. It can lead to disabling hearing impairment and sometimes life-threatening infective complications.

Objective: The aim of the present study was to describe the characteristics of hearing impairment associated with CSOM in Yemeni children.

Methods: A case-control study of 75 children with CSOM and 74 healthy controls. Hearing was assessed by behavioural testing and audiometry.

Results: Cases had lower academic performance than controls (OR 15.31, 95% CI 1.99-322.14, p<0.001). Disabling hearing impairment >30 dB was present in 51.5% (right ear) and 66.7% (left ear) of children with CSOM.

Conclusion: Disabling hearing impairment was identified as a major health problem in these Yemeni children with CSOM. There is a need for investment to reduce the burden of CSOM and its complications in these communities. Greater attention to the chronic disabling effects of CSOM in children is required in poor communities and low resource settings.
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http://dx.doi.org/10.1016/j.ijporl.2009.12.004DOI Listing
March 2010

Skeletal muscle atrophy occurs slowly and selectively during prolonged aestivation in Cyclorana alboguttata (Gunther 1867).

J Exp Biol 2009 Nov;212(Pt 22):3664-72

University of Queensland, St Lucia, Australia.

We investigated the effect of prolonged immobilisation of six and nine months duration on the morphology and antioxidant biochemistry of skeletal muscles in the amphibian aestivator Cyclorana alboguttata. We hypothesised that, in the event of atrophy occurring during aestivation, larger jumping muscles were more likely to be preserved over smaller non-jumping muscles. Whole muscle mass (g), muscle cross-sectional area (CSA) (microm(2)), water content (%) and myofibre number (per mm(2)) remained unchanged in the cruralis muscle after six to nine months of aestivation; however, myofibre area (microm(2)) was significantly reduced. Whole muscle mass, water content, myofibre number and myofibre CSA remained unchanged in the gastrocnemius muscle after six to nine months of aestivation. However, iliofibularis dry muscle mass, whole muscle CSA and myofibre CSA was significantly reduced during aestivation. Similarly, sartorius dry muscle mass, water content and whole muscle CSA was significantly reduced during aestivation. Endogenous antioxidants were maintained at control levels throughout aestivation in all four muscles. The results suggest changes to muscle morphology during aestivation may occur when lipid reserves have been depleted and protein becomes the primary fuel substrate for preserving basal metabolic processes. Muscle atrophy as a result of this protein catabolism may be correlated with locomotor function, with smaller non-jumping muscles preferentially used as a protein source during fasting over larger jumping muscles. Higher levels of endogenous antioxidants in the jumping muscles may confer a protective advantage against oxidative damage during aestivation; however, it is not clear whether they play a role during aestivation or upon resumption of normal metabolic activity.
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http://dx.doi.org/10.1242/jeb.033688DOI Listing
November 2009

Interferon gamma, interferon-gamma-induced-protein 10, and tuberculin responses of children at high risk of tuberculosis infection.

Pediatr Infect Dis J 2008 Dec;27(12):1073-7

Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK.

Background: Children in contact with adults with pulmonary tuberculosis (TB) are at risk for infection and disease progression, and chemoprophylaxis may reduce this risk. The identification of infection is based on the tuberculin skin test (TST) and interferon-gamma (INF-gamma) release assays. Other biomarkers such as interferon-gamma-induced-protein 10 (IP-10) may have potential for the diagnosis of latent TB infections.

Objectives: To describe IP-10 concentrations and their association to TST and INF-gamma responses in children recently exposed to adults with smear-positive TB in Brazil and Nepal.

Methods: : Two surveys using the same design were undertaken to describe TST, INF-gamma, and IP-10 responses in 146 children in Nepal and 113 children in Brazil.

Results: The concordance of TST and QuantiFERON-TB gold in-tube (QFT-IT) was high (kappa 0.73 in Brazil and 0.80 in Nepal). IP-10 responses were higher in children with both positive TST and positive QFT-IT (medians 1434 pg/mL in Brazil and 1402 pg/mL in Nepal) and lowest in children with both negative TST and negative QFT-IT (medians 206 pg/mL in Brazil and 81 pg/mL in Nepal). Children with negative TST and positive QFT-IT had higher IP-10 concentrations than children with positive TST but negative QFT-IT.

Conclusions: IP-10 is a potential marker to identify latent TB infections that is expressed in large quantities and with good agreement with QFT-IT. The reasons for the discrepant results observed are discussed.
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http://dx.doi.org/10.1097/INF.0b013e31817d05a3DOI Listing
December 2008

Epigenetic silencers are enriched in dormant desert frog muscle.

J Comp Physiol B 2008 Aug 28;178(6):729-34. Epub 2008 Mar 28.

CSIRO Livestock Industries, Brisbane, Qld, Australia.

Green-striped burrowing frogs, Cyclorana alboguttata, survive droughts by entering a metabolic depression called aestivation, characterised by a reduction in resting oxygen consumption by 80%. Aestivation in C. alboguttata is manifest by transcriptional silencing of skeletal muscle bioenergetic genes, such as NADH ubiquinone oxidoreductase 1, ATP synthase and superoxide dismutase 2. In this study, we hypothesised that aestivation is associated with epigenetic change in frog muscle. We assessed mRNA transcript abundance of seven genes that code for proteins with established roles in epigenetically-mediated gene silencing [transcriptional co-repressor SIN3A, DNA (cytosine-5-) methyltransferase 1, methyl CpG binding protein 2, chromodomain helicase DNA binding protein 4, histone binding protein rbbp4, histone deacetylase 1 and nuclear receptor co-repressor 2] using qRT-PCR. These seven genes showed a modest (1.1-3.5-fold) but coordinated upregulation in 6-month aestivating muscle. This reached significance for SIN3A and DNA cytosine-5-methyltransferase 1 in standard pair-wise comparisons (p < 0.05), and the candidates as a whole when analysed by Fisher's combined probability test (p < 0.01). These data are consistent with the hypothesis that the transcriptional silencing and metabolic depression that occurs during seasonal dormancy are associated with chromatin remodelling, and present a novel example of an environmentally induced epigenetic modification in an adult vertebrate.
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http://dx.doi.org/10.1007/s00360-008-0261-0DOI Listing
August 2008

Analysis of the callipyge phenotype through skeletal muscle development; association of Dlk1 with muscle precursor cells.

Differentiation 2008 Mar 14;76(3):283-98. Epub 2007 Aug 14.

School of Veterinary Science, The University of Melbourne, Parkville, Vic. 3010, Australia.

The callipyge mutation in sheep in the form of the paternal heterozygote results in skeletal muscle hypertrophy, which is most pronounced in the hindquarters. Overexpression of one of the genes in the region of the causative single-nucleotide polymorphism, Dlk1, is postulated to be a primary cause of the muscle hypertrophy although the mechanism is not clear. This study examined the expression of Dlk1 mRNA and its encoded protein in skeletal muscles of callipyge and wild-type sheep. The muscles examined included those that demonstrate hypertrophy in callipyge sheep as well as an unaffected muscle. The expression pattern of Dlk1 protein in these muscles was also measured over a developmental time course ranging from 80 days of gestation to 12 weeks after birth. Quantitative reverse transcription-polymerase chain reaction demonstrated that Dlk1 mRNA was significantly increased in affected, but not unaffected, muscles from callipyge sheep at 120 days of gestation through to 12 weeks of age. Immuno-localization of Dlk1 was pronounced in the interstitial connective tissue of fetal muscle but was less intense at later ages. No clear difference in Dlk1 immuno-localization was noted between genotypes in the fetal samples. Strong myofiber-specific Dlk1 immuno-localization was observed in hypertrophied callipyge muscles at 12 weeks of age. This staining was exclusively associated with fast type II myofibers and these had a significantly larger mean cross-sectional area, compared with fast type II myofibers in control sheep that did not overexpress Dlk1. In addition, Dlk1 immuno-localization was associated with a sub-population of Pax7-positive mononucleated cells in all skeletal muscles examined during fetal development and at birth, but this was not apparent at 12 weeks. There were no genotype-dependent alterations in the mRNA expression patterns of a number of promyogenic transcription factors indicating that the callipyge mutation was not affecting muscle cell differentiation per se. We postulate that Dlk1 is implicated in the commitment and/or proliferation of fetal myoblasts as well as in the maintenance of hypertrophy in fully differentiated myofibers.
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http://dx.doi.org/10.1111/j.1432-0436.2007.00208.xDOI Listing
March 2008

Obese humans as economically designed feed converters: symmorphosis and low oxidative capacity skeletal muscle.

Med Hypotheses 2008 30;70(3):693-7. Epub 2007 Jul 30.

CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, Brisbane, Queensland, Australia.

Human obesity is considered a consequence of a thrifty or economic metabolism. In this hypothesis, we apply an established economic design theory, called symmorphosis, to help explain the known association between obesity and low oxidative capacity skeletal muscle. Symmorphosis reflects an engineering principle, and predicts that physiological systems are most economically designed when unnecessary spare capacity is eliminated. This is because the structural/functional adaptations accounting for spare capacity themselves bear energetic costs of construction, maintenance and load. As oxidation of feed energy occurs in mitochondria, and because skeletal muscle accounts for 30% of resting metabolism, we focus on skeletal muscle mitochondria. In the same way that the most economically designed elevator is supported by a cable that is strong enough, but not too strong, symmorphosis predicts that the most economically designed feed converters should have enough, but not too much mitochondrial oxidative (fuel burning) capacity. While ATP demand is clearly more efficiently met by oxidative (38 molecules of ATP) rather than glycolytic (2 molecules of ATP) metabolism, symmorphosis predicts that having excess oxidative capacity actually reduces feed efficiency. This inefficiency is manifest by having to maintain, ultimately using feed energy, the expensive inner mitochondrial proton gradient in the superfluous mitochondria. On this basis, we predict that established molecular controllers of mitochondrial biogenesis and oxidative capacity such as eNOS, SIN3 co-repressor, TFAM and PPARgamma may yield useful DNA markers and therapeutic targets for issues relating to frugal energetics, namely predisposition to obesity and starvation resilience.
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http://dx.doi.org/10.1016/j.mehy.2007.05.042DOI Listing
May 2008

Skeletal muscle extracellular matrix remodelling after aestivation in the green striped burrowing frog, Cyclorana alboguttata.

Comp Biochem Physiol A Mol Integr Physiol 2007 Mar 16;146(3):440-5. Epub 2006 Dec 16.

CSIRO Livestock Industries, 306 Carmody Road, St. Lucia, Brisbane, Queensland 4072, Australia.

Connective tissue has recently been found to play a role in mediating mammalian skeletal muscle atrophy. We investigated connective tissue remodelling in the skeletal muscle of a species of the Australian burrowing frog, Cyclorana alboguttata. Despite being inactive whilst aestivating, the frog shows an inhibition of muscle atrophy. Connective tissue size and distribution was measured in histological sections of the cruralis muscle of control and aestivating C. alboguttata. Using a custom written software application we could detect no significant difference in any connective tissue morphological parameter between the two treatment groups. Biochemical measurements of gelatinase activity showed 2-fold higher activity in aestivating gastrocnemius muscle than in controls (p<0.001). We measured the messenger RNA transcript levels for C. alboguttata metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2) in cruralis skeletal muscle using quantitative real-time PCR. The trend of reduced expression of the two genes in the aestivators did not meet statistical significance. This work indicates that aestivation in C. alboguttata leads to subtle and specific changes in some extracellular matrix remodelling factors. Their main impact is to maintain proportional representation of extracellular matrix components of skeletal muscle and therefore preserve the active frog phenotype.
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http://dx.doi.org/10.1016/j.cbpa.2006.12.023DOI Listing
March 2007

A survey of patients' experiences with the cancer genetic counseling process: recommendations for cancer genetics programs.

J Genet Couns 2006 Dec;15(6):409-31

College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA.

In order to promote ongoing quality improvement of not only the Penn State Cancer Genetics Program, but also other cancer risk assessment programs throughout the country, we developed, piloted and conducted a survey to explore patient expectations, experiences, and satisfaction with the cancer genetic counseling process. The comprehensive survey was mailed to 340 eligible patients, 156 (45.9%) of whom returned the completed survey within the allotted time. Responses to closed-ended questions were tallied and open-ended questions were content analyzed. Major findings show that: (1) Patients were seeking cancer-related information and support throughout the cancer risk assessment process and were interested in participating in available research studies; (2) The setting in which patients are seen for cancer risk assessment may pose potential emotional ramifications; (3) Misperceptions regarding insurance discrimination and lack of insurance coverage persist; (4) Patients view the genetic counselor as responsible for updating them about new discoveries. Specific recommendations for cancer genetics programs are included.
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http://dx.doi.org/10.1007/s10897-006-9039-2DOI Listing
December 2006

A gene coexpression network for bovine skeletal muscle inferred from microarray data.

Physiol Genomics 2006 Dec 19;28(1):76-83. Epub 2006 Sep 19.

Bioinformatics Group, Commonwealth Scientific and Industrial Research Organisation Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, St. Lucia, QLD 4067, Australia.

We present the application of large-scale multivariate mixed-model equations to the joint analysis of nine gene expression experiments in beef cattle muscle and fat tissues with a total of 147 hybridizations, and we explore 47 experimental conditions or treatments. Using a correlation-based method, we constructed a gene network for 822 genes. Modules of muscle structural proteins and enzymes, extracellular matrix, fat metabolism, and protein synthesis were clearly evident. Detailed analysis of the network identified groupings of proteins on the basis of physical association. For example, expression of three components of the z-disk, MYOZ1, TCAP, and PDLIM3, was significantly correlated. In contrast, expression of these z-disk proteins was not highly correlated with the expression of a cluster of thick (myosins) and thin (actin and tropomyosins) filament proteins or of titin, the third major filament system. However, expression of titin was itself not significantly correlated with the cluster of thick and thin filament proteins and enzymes. Correlation in expression of many fast-twitch muscle structural proteins and enzymes was observed, but slow-twitch-specific proteins were not correlated with the fast-twitch proteins or with each other. In addition, a number of significant associations between genes and transcription factors were also identified. Our results not only recapitulate the known biology of muscle but have also started to reveal some of the underlying associations between and within the structural components of skeletal muscle.
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http://dx.doi.org/10.1152/physiolgenomics.00105.2006DOI Listing
December 2006

Gene expression, synthesis and degradation of hyaluronan during differentiation of 3T3-L1 adipocytes.

Arch Biochem Biophys 2006 Aug 19;452(1):83-91. Epub 2006 Jun 19.

Cooperative Research Centre for Cattle and Beef Quality, CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, St. Lucia, Qld 4067, Australia.

The high molecular weight glycosaminoglycan hyaluronan (HA) is an essential component of the extracellular matrix (ECM), however, the link between HA regulation and development of the adipocyte ECM, which is essential for differentiation, remains undefined. Hyaluronan synthase gene expression, HA synthetic rate and molecular weight during differentiation of 3T3-L1 pre-adipocytes were compared to undifferentiated 3T3-L1 pre-adipocytes and non-adipogenic NIH/3T3 fibroblasts. In the 3T3-L1 pre-adipocytes, the predominant genes associated with HA metabolism were found to be HA synthase-2 (Has-2) and hyaluronidase-2 (Hyal-2) demonstrating a co-regulation of expression which was stimulated by adipogenic induction consequently resulting in increased synthesis of high molecular weight HA (>10 MDa) and its simultaneous degradation. Accumulation of HA correlated positively with cell number, although synthetic rate was inversely related suggesting a regulatory feedback mechanism. Within 24h post-induction, pre-adipocytes responded with a higher HA synthetic rate and later, accumulated cytoplasmic lipid. In contrast, undifferentiated pre-adipocytes had a reduced HA synthetic rate during clonal expansion and did not accumulate lipid. HA was continuously and rapidly metabolised throughout 3T3-L1 adipogenesis, where terminal differentiation coincided with the increased generation of low molecular weight, angiogenic HA fragments, a likely prerequisite for concurrent neovascularisation of adipose tissue. This study has highlighted a relationship between HA metabolism and adipocyte differentiation, suggesting that the balance between the formation and regulation of the adipocyte extracellular matrix is finely coordinated in a growth phase-specific dependent manner.
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http://dx.doi.org/10.1016/j.abb.2006.05.010DOI Listing
August 2006

Lessons from an estivating frog: sparing muscle protein despite starvation and disuse.

Am J Physiol Regul Integr Comp Physiol 2006 Mar 20;290(3):R836-43. Epub 2005 Oct 20.

Commonwealth Scientific and Industrial Research Organization Livestock Industries, 306 Carmody Rd., St. Lucia, Brisbane, Queensland 4072, Australia.

Long (6- to 9-mo) bouts of estivation in green-striped burrowing frogs lead to 28% atrophy of cruralis oxidative fibers (P < 0.05) and some impairment of in vitro gastrocnemius endurance (P < 0.05) but no significant deficit in maximal twitch force production. These data suggest the preferential atrophy of oxidative fibers at a rate slower than, but comparable to, laboratory disuse models. We tested the hypothesis that the frog limits atrophy by modulating oxidative stress. We assayed various proteins at the transcript level and verified these results for antioxidant enzymes at the biochemical level. Transcript data for NADH ubiquinone oxidoreductase subunit 1 (71% downregulated, P < 0.05) and ATP synthase (67% downregulated, P < 0.05) are consistent with mitochondrial quiescence and reduced oxidant production. Meanwhile, uncoupling protein type 2 transcription (P = 0.31), which is thought to reduce mitochondrial leakage of reactive oxygen species, was maintained. Total antioxidant defense of water-soluble (22.3 +/- 1.7 and 23.8 +/- 1.5 microM/microg total protein in control and estivator, respectively, P = 0.53) and membrane-bound proteins (31.5 +/- 1.9 and 42.1 +/- 7.3 microM/microg total protein in control and estivator, respectively, P = 0.18) was maintained, equivalent to a bolstering of defense relative to oxygen insult. This probably decelerates muscle atrophy by preventing accumulation of oxidative damage in static protein reserves. Transcripts of the mitochondrially encoded antioxidant superoxide dismutase type 2 (67% downregulated, P < 0.05) paralleled mitochondrial activity, whereas nuclear-encoded catalase and glutathione peroxidase were maintained at control values (P = 0.42 and P = 0.231), suggesting a dissonance between mitochondrial and nuclear antioxidant expression. Pyruvate dehydrogenase kinase 4 transcription was fourfold lower in estivators (P = 0.11), implying that, in contrast to mammalian hibernators, this enzyme does not drive the combustion of lipids that helps spare hypometabolic muscle.
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http://dx.doi.org/10.1152/ajpregu.00380.2005DOI Listing
March 2006

Increased incidence of melanoma in renal transplantation recipients.

Cancer 2005 Nov;104(9):1962-7

Department of Surgery, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.

Background: It is well established that the incidence of nonmelanoma skin carcinoma is increased in renal transplantation recipients. However, existing studies are not in agreement over whether patients who undergo transplantation have an increased risk of melanoma. The objective of this study was to estimate the risk of melanoma among immunosuppressed renal transplantation recipients and to determine whether that risk is associated with patient and transplantation characteristics.

Methods: The authors studied 89,786 patients who underwent renal transplantation between 1988 and 1998 using the United States Renal Data System. Age standardized (to the United States 2000 population) incidence rates for melanoma were computed as diagnoses per 100,000 population and were compared with rates from the Surveillance, Epidemiology, and End Results (SEER) data. Incidence rates also were stratified to examine differences by age and gender.

Results: Of the 89,786 patients who underwent transplantation, 246 patients developed melanoma. The age-adjusted incidence rate of melanoma among renal transplantation recipients was 55.9 diagnoses per 100,000 population. This represented an increase in age-adjusted, standardized risk that was 3.6 times greater than the SEER population. Stratified analysis suggested that the risk of melanoma accelerated in male transplantation recipients as age increased, but the risk leveled off with age among female transplantation recipients. Finally, there was a trend for patients who experienced at least 1 acute rejection episode to develop melanoma (odds ratio = 1.34; P = 0.059).

Conclusions: Renal transplantation recipients were nearly 3.6 times more likely to develop melanoma than the general population. Physicians who care for renal transplantation recipients should be vigilant in screening for melanoma.
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http://dx.doi.org/10.1002/cncr.21404DOI Listing
November 2005

Transcriptional profiling of skeletal muscle tissue from two breeds of cattle.

Mamm Genome 2005 Mar;16(3):201-10

Cooperative Research Center for Cattle and Beef Quality, CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Rd., St. Lucia, Brisbane, Queensland, 4067, Australia.

We used a 9.6 K cattle muscle/fat cDNA microarray to study gene expression differences between the longuissimus dorsi (LD) muscle of Japanese Black (JB) and Holstein (HOL) cattle. JB cattle exhibit an unusual ability to accumulate intramuscular adipose tissue with fat melting points lower than that in other breeds. The LD biopsies from three JB (Tajima strain) and three HOL animals were used in this breed comparison. Seventeen genes were identified as preferentially expressed in LD samples from JB and seven genes were found to be expressed more highly in HOL. The expression of six selected differentially expressed genes was confirmed by quantitative real-time PCR. The genes more highly expressed in JB are associated with unsaturated fatty acid synthesis, fat deposition, and the thyroid hormone pathway. These results are consistent with the increased amounts and proportions of monounsaturated fatty acids observed in the muscle of JB animals. By discovering as yet uncharacterized genes that are differentially regulated in this comparison, the work may lead us to a better understanding of the regulatory pathways involved in the development of intramuscular adipose tissue.
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http://dx.doi.org/10.1007/s00335-004-2419-8DOI Listing
March 2005

Use of an educational computer program before genetic counseling for breast cancer susceptibility: effects on duration and content of counseling sessions.

Genet Med 2005 Apr;7(4):221-9

Department of Humanities, Penn State College of Medicine, Hershey, Pennsylvania 17033, USA.

Purpose: Patients seeking genetic testing for inherited breast cancer risk are typically educated by genetic counselors; however, the growing demand for cancer genetic testing will likely exceed the availability of counselors trained in this area. We compared the effectiveness of counseling alone versus counseling preceded by use of a computer-based decision aid among women referred to genetic counseling for a family or personal history of breast cancer.

Methods: We developed and evaluated an interactive computer program that educates women about breast cancer, heredity, and genetic testing. Between May 2000 and September 2002, women at six study sites were randomized into either: Counselor Group (n = 105), who received standard genetic counseling, or Computer Group (n = 106), who used the interactive computer program before counseling. Clients and counselors both evaluated the effectiveness of counseling sessions, and counselors completed additional measures for the Computer Group. Counselors also recorded the duration of each session.

Results: Baseline characteristics did not differ significantly between groups. Participants and counselors both rated the counseling sessions as highly effective, whether or not the sessions were preceded by computer use. Computer use resulted in significantly shorter counseling sessions among women at low risk for carrying BRCA1/2 mutations. In approximately half of the sessions preceded by clients' computer use, counselors indicated that clients' use of the computer program affected the way they used the time, shifting the focus away from basic education toward personal risk and decision-making.

Conclusion: This study shows that the interactive computer program "Breast Cancer Risk and Genetic Testing" is a valuable adjunct to genetic counseling. Its use before counseling can shorten counseling sessions and allow counselors to focus more on the clients' individual risks and specific psychological concerns. As the demand for counseling services increases, a program such as this can play a valuable role in enhancing counseling efficiency.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1201432PMC
http://dx.doi.org/10.1097/01.gim.0000159905.13125.86DOI Listing
April 2005

Effect of a computer-based decision aid on knowledge, perceptions, and intentions about genetic testing for breast cancer susceptibility: a randomized controlled trial.

JAMA 2004 Jul;292(4):442-52

Department of Humanities, Penn State College of Medicine, Hershey, Pa 17033, USA.

Context: As the availability of and demand for genetic testing for hereditary cancers increases in primary care and other clinical settings, alternative or adjunct educational methods to traditional genetic counseling will be needed.

Objective: To compare the effectiveness of a computer-based decision aid with standard genetic counseling for educating women about BRCA1 and BRCA2 genetic testing.

Design: Randomized controlled trial conducted from May 2000 to September 2002.

Setting And Participants: Outpatient clinics offering cancer genetic counseling at 6 US medical centers enrolled 211 women with personal or family histories of breast cancer.

Interventions: Standard one-on-one genetic counseling (n = 105) or education by a computer program followed by genetic counseling (n = 106).

Main Outcome Measures: Participants' knowledge, risk perception, intention to undergo genetic testing, decisional conflict, satisfaction with decision, anxiety, and satisfaction with the intervention. Counselor group measures were administered at baseline and after counseling. Computer group measures were administered at baseline, after computer use, and after counseling. Testing decisions were assessed at 1 and 6 months. Outcomes were analyzed by high vs low risk of carrying a BRCA1 or BRCA2 mutation.

Results: Both groups had comparable demographics, prior computer experience, medical literacy, and baseline knowledge of breast cancer and genetic testing, and both counseling and computer use were rated highly. Knowledge scores increased in both groups (P<.001) regardless of risk status, and change in knowledge was greater in the computer group compared with the counselor group (P =.03) among women at low risk of carrying a mutation. Perception of absolute risk of breast cancer decreased significantly after either intervention among all participants. Intention to undergo testing decreased significantly after either intervention among low-risk but not high-risk women. The counselor group had lower mean scores on a decisional conflict scale (P =.04) and, in low-risk women, higher mean scores on a satisfaction-with-decision scale (P =.001). Mean state anxiety scores were reduced by counseling but were within normal ranges for both groups at baseline and after either intervention, regardless of risk status.

Conclusions: An interactive computer program was more effective than standard genetic counseling for increasing knowledge of breast cancer and genetic testing among women at low risk of carrying a BRCA1 or BRCA2 mutation. However, genetic counseling was more effective than the computer at reducing women's anxiety and facilitating more accurate risk perceptions. These results suggest that this computer program has the potential to stand alone as an educational intervention for low-risk women but should be used as a supplement to genetic counseling for those at high risk.
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http://dx.doi.org/10.1001/jama.292.4.442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1237120PMC
July 2004

Sex hormone patterns and serum retinol concentrations in adolescent girls.

J Reprod Med 2004 Jan;49(1):41-51

Departments of Obstetrics and Gynaecology and Reproductive Health Care and of Epidemiology and Health Sciences, University of Manchester, Manchester, U.K.

Objective: To describe the pattern and relation of sex serum hormones and retinol concentrations over 1 menstrual cycle in adolescent girls living in a resource-poor setting.

Study Design: Venous blood samples were collected on alternate days of the cycle, and estrogen, progesterone, luteinizing hormone (LH), follicle stimulating hormone and serum retinol were measured. A linear random effects model was used to examine the relationship between sex hormones and serum retinol.

Results: Twenty-eight girls were studied. During the follicular phase, serum retinol was associated negatively with progesterone and positively with LH. In the luteal phase, serum retinol was positively associated with estrogen. Serum retinol increased in the follicular phase but not the luteal phase. Sex hormone and serum retinol concentrations showed marked individual and day-to-day variability. Two girls maintained serum retinol concentrations > 0.7 mumol/L throughout the cycle. Six remained at < 0.7 mumol/L, which indicated subclinical deficiency.

Conclusion: This study indicated that in adolescent girls, sex hormone patterns correlate significantly with serum retinol, and in vitamin A-deficient girls this could be important for reproductive function.
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January 2004

Impact of immediate reconstruction on the local recurrence of breast cancer after mastectomy.

Ann Plast Surg 2003 Apr;50(4):333-8

Department of Surgery, Division of Plastic & Reconstructive Surgery, Lehigh Valley Hospital, Allentown, PA 18105-1556, USA.

The incidence of local recurrence of breast cancer in women who underwent mastectomy with or without reconstruction was examined. All female mastectomy patients were followed-up in a 10-year retrospective review. Groups consisted of patients who had mastectomy, mastectomy with immediate reconstruction, or delayed reconstruction. Reconstruction was performed using prostheses, latissimus dorsi musculocutaneous flaps with or without implants, or transverse rectus abdominis musculocutaneous flaps. Charts were reviewed for local breast cancer recurrence. Statistical analysis was performed using Pearson's chi-square and analysis of variance. Of the 1,444 mastectomies performed from 1988 to 1997, 1,262 breasts (87%) were not reconstructed, 182 (13%) were reconstructed, 158 (87%) were immediately reconstructed, and 24 (13%) were reconstructed later. There were no recurrences in the delayed reconstruction group, two recurrences (1.3%) in the immediate reconstruction group, and nine recurrences (0.7%) in the mastectomy without reconstruction group (p=0.746). Analyses of an additional time period from 1992 to 2000 yielded similar results. There is little relationship between local recurrence of breast cancer after mastectomy and reconstruction.
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http://dx.doi.org/10.1097/01.SAP.0000041488.88950.A2DOI Listing
April 2003

Serum and breast-milk vitamin A in women during lactation in rural Chiang Mai, Thailand.

Ann Trop Paediatr 2002 Dec;22(4):321-4

Department of Community Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.

Vitamin A deficiency can occur during lactation and breast-milk vitamin A has been recommended for monitoring the vitamin A status of lactating women and their infants. This study aimed to investigate the vitamin A status of lactating women in relation to race, age, parity, duration of lactation and anthropometric status. A cross-sectional study was conducted among 262 lactating women in rural Chiang Mai, Thailand. Blood and breast-milk samples were collected. Serum retinol, carotene and breast-milk retinol concentrations were analysed by high-performance liquid chromatography. The results show that mean serum retinol and breast-milk retinol in hill tribes were significantly lower than in Thais, 1.91 (0.59) and 0.79 (0.52) compared with 2.10 (0.51) and 1.04 (0.58) mumol/L, respectively. Mean serum retinol and breast-milk retinol were highest during the 1st 3 months of lactation. Maternal age, parity and anthropometric status (BMI) were not associated with serum or breast-milk retinol concentrations. There was a significant relationship between serum and breast-milk retinol values in women who breastfed for 6 months or longer (regression co-efficients 0.30; 95% CI 0.16, 0.43). Breast-milk retinol levels declined significantly from 4 to 12 months after delivery, which could increase the risk of vitamin A deficiency in children who were exclusively breastfed or receiving inappropriate complementary foods during this period. Weaning foods which commence at 6 months and have an adequate vitamin A content should ensure that the vitamin A status of the young child is maintained.
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http://dx.doi.org/10.1179/027249302125001976DOI Listing
December 2002
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