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1.  Prompt recognition of stump appendicitis is important to avoid serious complications: a case report 
Cases Journal  2009;2:7415.
Introduction
Stump appendicitis is a rare complication of appendectomy due to recurrent inflammation of the residual appendix. The diagnosis is often delayed due to low index of suspicious, which may result in serious complications.
Case presentation
We describe a case of stump appendicitis occurred 12 months after appendectomy in 25 years old man. Despite past medical history of appendectomy the diagnosis was made by means of ultrasound scan and an high degree of clinical suspicion.
Conclusions
Stump appendicitis is a rare but important complication of appendectomy, often misdiagnosed. Prompt recognition is important to avoid serious complications. This pathologic entity should always be kept in mind on case of right lower quadrant pain.
doi:10.4076/1757-1626-2-7415
PMCID: PMC2740171  PMID: 19829956
3.  Synthesis and activity of azaterphenyl diamidines against Trypanosoma brucei rhodesiense and Plasmodium falciparum 
Bioorganic & medicinal chemistry  2009;17(18):10.1016/j.bmc.2009.07.080.
A series of azaterphenyl diamidines has been synthesized and evaluated for in vitro antiprotozoal activity against both Trypanosoma brucei rhodesiense (T. b. r.) and Plasmodium falciparum (P. f.) and in vivo efficacy in the STIB900 acute mouse model for T. b. r. Six of the 13 compounds showed IC50 values less than 7 nM against T. b. r. Twelve of those exhibited IC50 values less than 6 nM against P. f. and six of those showed IC50 values ≤0.6 nM, which are more than 25-fold as potent as furamidine. Moreover, two of them showed more than 40-fold selectivity for P. f. versus T. b. r. Three compounds 15b, 19d and 19e exhibited in vivo efficacy against T. b. r. much superior to furamidine, and equivalent to or better than azafuramidine. The antiparasitic activity of these diamidines depends on the ring nitrogen atom(s) location relative to the amidine groups and generally correlates with DNA binding affinity.
doi:10.1016/j.bmc.2009.07.080
PMCID: PMC3813006  PMID: 19699098
Diamidines; Antiprotozoal agents; DNA binding affinity; Azaterphenyl
4.  Uptake of 18F-Labeled 6-Fluoro-6-Deoxy-d-Glucose by Skeletal Muscle Is Responsive to Insulin Stimulation 
We are developing a methodology for the noninvasive imaging of glucose transport in vivo with PET and 18F-labeled 6-fluoro-6-deoxy-d-glucose (18F-6FDG), a tracer that is transported but not phosphorylated. To validate the method, we evaluated the biodistribution of 18F-6FDG to test whether it is consistent with the known properties of glucose transport, particularly with regard to insulin stimulation of glucose transport.
Methods
Under glucose clamp conditions, rats were imaged at the baseline and under conditions of hyperinsulinemia.
Results
The images showed that the radioactivity concentration in skeletal muscle was higher in the presence of insulin than at the baseline. We also found evidence that the metabolism of 18F-6FDG was negligible in several tissues.
Conclusion
18F-6FDG is a valid tracer that can be used in in vivo transport studies. PET studies performed under glucose clamp conditions demonstrated that the uptake of nonphosphorylated glucose transport tracer 18F-6FDG is sensitive to insulin stimulation.
doi:10.2967/jnumed.109.062687
PMCID: PMC3571725  PMID: 19443592
glucose transport; radiopharmaceutical; PET; glucose clamp
5.  Quadrigeminal plate cistern lipoma 
BMJ Case Reports  2009;2009:bcr07.2009.2110.
Intracranial lipomas are rare benign neoplasms accounting for <0.1% of all primary brain tumours. Most lipomas were incidentally detected by autopsy or computed tomography (CT).These slow growing benign lesions are usually asymptomatic and rarely require surgery. We report the case of a 70-year-old Nigerian woman who presented with persistent headaches following involvement in a road traffic accident 20 days previously. CT demonstrated a quadrigeminal cistern lipoma with no evidence of raised intracranial pressure or compression of neural structures. Her headaches resolved with conservative care. We describe the CT findings with a brief review of the literature.
doi:10.1136/bcr.07.2009.2110
PMCID: PMC3027879  PMID: 22190982
6.  A rare case of acute abdomen 
BMJ Case Reports  2009;2009:bcr06.2009.1958.
Mesenteric cysts are tumoural formations which are generally benign in character, originate from the intestinal mesentery, and rarely cause abdominal tumours. They are asymptomatic unless a complication occurs, and thus may be incidentally diagnosed. Symptomatic cases may show up with findings such as abdominal pain, abdominal mass, nausea, and vomiting, and sometimes patients present with an acute abdomen. Treatment includes total excision of the cyst. We present the case of a male patient admitted to our emergency department with acute abdominal symptoms, who was subsequently found to have a mesenteric cyst measuring 30×20×9 cm.
doi:10.1136/bcr.06.2009.1958
PMCID: PMC3028082  PMID: 22162732
7.  Cervical spine injuries resulting from diving accidents in swimming pools: outcome of 34 patients 
European Spine Journal  2009;19(4):552-557.
Cervical spine injuries after diving into private swimming pools can lead to dramatic consequences. We reviewed 34 patients hospitalized in our center between 1996 and 2006. Data was collected from their initial admission and from follow-up appointments. The injuries were sustained by young men in 97% (mean age 27) and the majority happened during the summer (88%). Fractures were at C5–C7 in 70%. American Spinal Injury Association class (ASIA) on admission was A for 8 patients, B for 4, C for 4, D for 1, and E for 17. There were 23 surgical spine stabilizations. Final ASIA class was A for 6 patients, B for 1, C for 3, D for 5, and E for 18. The mean duration of hospitalization was 21.3 days in our neurosurgical center (mean overall cost: 36,000 Euros/patient) plus 10.6 months in rehabilitation center for the 15 patients admitted who had an ASIA class A to C. Mean overall direct cost for a patient with class A is almost 300,000 Euros, compared to around 10,000 Euros for patients with class D and E. In addition, a profound impact on personal and professional life was seen in many cases including 11 divorces and 7 job losses. Dangerous diving into swimming pools can result in spinal injuries with drastic consequences, including permanent physical disability and a profound impact on socio-professional status. Moreover, there are significant financial costs to society. Better prevention strategies should be implemented to reduce the impact of this public health problem.
doi:10.1007/s00586-009-1230-3
PMCID: PMC2899837  PMID: 19956985
Cervical trauma; Diving accident; Outcome; Spine cord injury
8.  Correlations of isokinetic measurements with tendon healing following open repair of rotator cuff tears 
International Orthopaedics  2009;34(4):531-536.
The aim of this study was to investigate the correlation of tendon integrity following open cuff repairs with functional and isokinetic strength measurements. Twenty-six shoulders of 25 patients were included in this study. At the final follow-up, 14 repairs (53.8%) were intact and 12 repairs (46.2%) had failed on magnetic resonance imaging (MRI). Mean UCLA score at latest follow-up was 28.5 and mean Constant score was 80.3. Constant scores were found to be significantly low for the failed group. Age was found to be significantly related to failed repair. Fatty infiltration stage in the failed repair group was significantly high, and a strong positive correlation for both groups existed pre and postoperatively. When both groups were compared, the failed group was found to have significantly low measurements at extension and internal rotation. Despite high failure rates, functional results were satisfactory. Increased age and fatty infiltration stage decrease success.
doi:10.1007/s00264-009-0827-9
PMCID: PMC2903151  PMID: 19533125
9.  Lymphoedema: a paradoxical effect of tumour necrosis factor inhibitors – case report and review of literature 
BMJ Case Reports  2009;2009:bcr07.2008.0520.
This report describes the development of lymphoedema in a patient with rheumatoid arthritis (RA) who was treated with tumour necrosis factor α (TNFα) inhibitors.
The patient was a 62-year-old woman with a long-standing history of RA that had been uncontrolled with steroids and methotrexate. Eight months after initiation of treatment with TNFα inhibitors she developed progressive symmetrical ascending non-pitting oedema of both legs with extensive keratinisation. A diagnosis of lymphoedema was made based on the clinical presentation and exclusion of alternative diagnoses. Skin biopsy showed dermatosclerosis consistent with lymphoedema. The temporal relationship suggested a link between the initiation of TNFα inhibitors and the development of lymphoedema. TNFα inhibitors are widely used to treat inflammatory diseases including lymphoedema. Paradoxically, there are reports suggesting the appearance of psoriasis, vasculitis and other inflammatory cutaneous conditions after the use of TNFα inhibitors. A review of literature is also presented.
doi:10.1136/bcr.07.2008.0520
PMCID: PMC3027781  PMID: 21686765
10.  Male Breast Cancer: A Population-Based Comparison With Female Breast Cancer 
Journal of Clinical Oncology  2009;28(2):232-239.
Purpose
Because of its rarity, male breast cancer is often compared with female breast cancer.
Patients and Methods
To compare and contrast male and female breast cancers, we obtained case and population data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program for breast cancers diagnosed from 1973 through 2005. Standard descriptive epidemiology was supplemented with age-period-cohort models and breast cancer survival analyses.
Results
Of all breast cancers, men with breast cancer make up less than 1%. Male compared with female breast cancers occurred later in life with higher stage, lower grade, and more estrogen receptor–positive tumors. Recent breast cancer incidence and mortality rates declined over time for men and women, but these trends were greater for women than for men. Comparing patients diagnosed from 1996 through 2005 versus 1976 through 1985, and adjusting for age, stage, and grade, cause-specific hazard rates for breast cancer death declined by 28% among men (P = .03) and by 42% among women (P ≈ 0).
Conclusion
There were three intriguing results. Age-specific incidence patterns showed that the biology of male breast cancer resembled that of late-onset female breast cancer. Similar breast cancer incidence trends among men and women suggested that there are common breast cancer risk factors that affect both sexes, especially estrogen receptor–positive breast cancer. Finally, breast cancer mortality and survival rates have improved significantly over time for both male and female breast cancer, but progress for men has lagged behind that for women.
doi:10.1200/JCO.2009.23.8162
PMCID: PMC2815713  PMID: 19996029
11.  Chronic Maternal Dietary Chromium Restriction Modulates Visceral Adiposity 
Diabetes  2009;59(1):98-104.
OBJECTIVE
We demonstrated previously that chronic maternal micronutrient restriction altered the body composition in rat offspring and may predispose offspring to adult-onset diseases. Chromium (Cr) regulates glucose and fat metabolism. The objective of this study is to determine the long-term effects of maternal Cr restriction on adipose tissue development and function in a rat model.
RESEARCH DESIGN AND METHODS
Female weanling WNIN rats received, ad libitum, a control diet or the same with 65% restriction of Cr (CrR) for 3 months and mated with control males. Some pregnant CrR mothers were rehabilitated from conception or parturition and their pups weaned to control diet. Whereas some CrR offspring were weaned to control diet, others continued on CrR diet. Various parameters were monitored in the offspring at three monthly intervals up to 15–18 months of age.
RESULTS
Maternal Cr restriction significantly increased body weight and fat percentage, especially the central adiposity in both male and female offspring. Further, the expression of leptin and 11 β-hydroxysteroid dehydrogenase 1 genes were significantly increased in CrR offspring of both the sexes. Adipocytokine levels were altered in plasma and adipose tissue; circulating triglyceride and FFA levels were increased, albeit in female offspring only. Rehabilitation regimes did not correct body adiposity but restored the circulating levels of lipids and adipocytokines.
CONCLUSIONS
Chronic maternal Cr restriction increased body adiposity probably due to increased stress and altered lipid metabolism in WNIN rat offspring, which may predispose them to obesity and associated diseases in later life.
doi:10.2337/db09-0779
PMCID: PMC2797950  PMID: 19846803
12.  Fut2-null mice display an altered glycosylation profile and impaired BabA-mediated Helicobacter pylori adhesion to gastric mucosa 
Glycobiology  2009;19(12):1525-1536.
Glycoconjugates expressed on gastric mucosa play a crucial role in host–pathogen interactions. The FUT2 enzyme catalyzes the addition of terminal α(1,2)fucose residues, producing the H type 1 structure expressed on the surface of epithelial cells and in mucosal secretions of secretor individuals. Inactivating mutations in the human FUT2 gene are associated with reduced susceptibility to Helicobacter pylori infection. H. pylori infects over half the world's population and causes diverse gastric lesions, from gastritis to gastric cancer. H. pylori adhesion constitutes a crucial step in the establishment of a successful infection. The BabA adhesin binds the Leb and H type 1 structures expressed on gastric mucins, while SabA binds to sialylated carbohydrates mediating the adherence to inflamed gastric mucosa. In this study, we have used an animal model of nonsecretors, Fut2-null mice, to characterize the glycosylation profile and evaluate the effect of the observed glycan expression modifications in the process of H. pylori adhesion. We have demonstrated expression of terminal difucosylated glycan structures in C57Bl/6 mice gastric mucosa and that Fut2-null mice showed marked alteration in gastric mucosa glycosylation, characterized by diminished expression of α(1,2)fucosylated structures as indicated by lectin and antibody staining and further confirmed by mass spectrometry analysis. This altered glycosylation profile was further confirmed by the absence of Fucα(1,2)-dependent binding of calicivirus virus-like particles. Finally, using a panel of H. pylori strains, with different adhesin expression profiles, we have demonstated an impairment of BabA-dependent adhesion of H. pylori to Fut2-null mice gastric mucosa, whereas SabA-mediated binding was not affected.
doi:10.1093/glycob/cwp131
PMCID: PMC2782244  PMID: 19706747
α1; 2fucosyltransferase; BabA; bacterial adhesion; Helicobacter pylori; Lewis antigens
13.  Large Deletions and Point Mutations Involving DOCK8 in the Autosomal Recessive Form of the Hyper-IgE Syndrome 
Background
The genetic etiologies of the hyper-IgE syndromes are diverse. Approximately 60-70% of patients with hyper-IgE syndrome have dominant mutations in STAT3, and a single patient was reported to have a homozygous TYK2 mutation. In the remaining hyper-IgE syndrome patients, the genetic etiology has not yet been identified.
Methods
We performed genome-wide single nucleotide polymorphism analysis for nine subjects with autosomal recessive hyper-IgE syndrome to locate copy number variations and homozygous haplotypes. Homozygosity mapping was performed with twelve subjects from seven additional families. The candidate gene was analyzed by genomic and cDNA sequencing to identify causative alleles in a total of 27 patients with autosomal recessive hyper-IgE syndrome.
Findings
Subtelomeric microdeletions were identified in six subjects at the terminus of chromosome 9p. In all patients the deleted interval involved DOCK8, encoding a protein implicated in the regulation of the actin cytoskeleton. Sequencing of subjects without large deletions revealed 16 patients from nine unrelated families with distinct homozygous mutations in DOCK8 causing premature termination, frameshift, splice site disruption, single exon- and micro-deletions. DOCK8 deficiency was associated with impaired activation of CD4+ and CD8+ T cells.
Interpretation
Autosomal recessive mutations in DOCK8 are responsible for many, though not all, cases of autosomal recessive hyper-IgE syndrome. DOCK8 disruption is associated with a phenotype of severe cellular immunodeficiency characterized by susceptibility to viral infections, atopic eczema, defective T cell activation and TH17 cell differentiation; and impaired eosinophil homeostasis and dysregulation of IgE.
doi:10.1016/j.jaci.2009.10.038
PMCID: PMC2818862  PMID: 20004785
Autosomal recessive hyper-IgE syndrome; human gene mutation; DOCK8; primary immunodeficiency; molluscum contagiosum; recurrent infection; T cells; TH17 cells; eosinophils; IgE regulation; copy number variations; genomic deletions
14.  Qualitative Age Interactions in Breast Cancer Studies: Mind the Gap 
Journal of Clinical Oncology  2009;27(32):5308-5311.
doi:10.1200/JCO.2009.22.9450
PMCID: PMC2773215  PMID: 19826117
15.  Incidence analyses of bladder cancer in the Nile delta region of Egypt 
Cancer epidemiology  2009;33(3-4):176-181.
Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt’s Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1,209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% Confidence Intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour’s capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region.
doi:10.1016/j.canep.2009.08.008
PMCID: PMC2763030  PMID: 19762298
bladder carcinoma; environmental exposures; developing countries; pollution; schistosomiasis
16.  Biomechanical and histological comparison of the influence of oestrogen deficient state on tendon healing potential in rats 
International Orthopaedics  2009;33(5):1461-1466.
Thirty-six female Sprague-Dawley rats were divided into two groups: oophrectomised (oestrogen deficient) rats and sham operated (oestrogen maintained) rats. Rats were sacrificed at six, ten, and 14 weeks. The rats were randomly chosen to have biomechanical evaluation on one side and histological evaluation on the other. Biomechanical testing was performed on an Instron machine to measure peak load. Histological sections were evaluated for cell proliferation, collagen-fibre organisation, fibroblast density, angiogenesis, inflammatory cells, chondroid and osseous metaplasia. Compared with the sham operated group, the oophrectomised group showed a lesser average maximum stress (42.9 N/m2 versus 33.7 N/m2) at six weeks, which was significant (p < .05). Succeeding weeks showed no significant biomechanical differences between the two groups. The sham operated group showed greater inflammatory response, which was statistically significant (p < 0.05), and also revealed greater cell proliferation and density. The results of this study revealed that endogenous oestrogen may improve healing of the Achilles tendon in rats.
doi:10.1007/s00264-009-0778-1
PMCID: PMC2899125  PMID: 19387642
18.  Regional Profiling for Determination of Genotype Diversity of Mastitis-Specific Staphylococcus aureus Lineage in Canada by Use of Clumping Factor A, Pulsed-Field Gel Electrophoresis, and spa Typing▿  
Journal of Clinical Microbiology  2009;48(2):375-386.
One of the major concerns in global public health and the dairy industry is the emergence of host-specific virulent Staphylococcus aureus strains. The high degree of stability of the species genome renders detection of genetic microvariations difficult. Thus, approaches for the rapid tracking of specialized lineages are urgently needed. We used clumping factor A (clfA) to profile 87 bovine mastitis isolates from four regions in Canada and compared the results to those obtained by pulsed-field gel electrophoresis (PFGE) and spa typing. Twenty-five pulsotypes were obtained by PFGE with an index of discrimination of 0.91. These were assigned to six PFGE lineage groups A to F and seven spa types, including two novel ones. Group A had 48.3% of the isolates and group D had 43.7% of the isolates, while only 8% of the isolates were variable. The results of antimicrobial susceptibility testing indicated that all isolates were sensitive to methicillin and the non-beta-lactam antibiotics, while three isolates were resistant to penicillin and one isolate was resistant to tetracycline. All isolates had the clfA gene and belonged to 20 clfA repeat types with an index of discrimination of 0.90. The dominant clfA types, types X, Q, C, and Z, formed 82% and 43% of PFGE groups A and D, respectively, and had copy numbers that varied only within a narrow range of between 46 and 52 copies, implying clonal selection. The rest were variable and region specific. Furthermore, the dominant groups contained subpopulations in different regions across Canada. Sequence information confirmed the relatedness obtained by the use of clfA repeat copy numbers and other methods and further revealed the occurrence of full-repeat deletions and conserved host-specific codon-triplet position biases at 18-bp units. Thus, concordant with the results of PFGE and spa typing, clfA typing proved useful for revealing the clonal nature of the mastitis isolate lineage and for the rapid profiling of subpopulations with comparable discriminatory powers.
doi:10.1128/JCM.01768-09
PMCID: PMC2815643  PMID: 19955267
19.  Defects Along the Th17 Differentiation Pathway Underlie Genetically Distinct Forms of the Hyper IgE Syndrome 
Background
The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE and diminished inflammatory responses. It exists as autosomal dominant (AD) and recessive (AR) forms that manifest common and distinguishing clinical features. A majority of those with AD-HIES suffers from heterozygous mutations in Signal Transducer and Activator of Transcription 3 (STAT3) and impaired Th17 differentiation.
Objective
To elucidate mechanisms underlying different forms of HIES.
Methods
A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by interferon alpha (IFNα) was assessed by intracellular staining with anti-phospho (p)STAT3 and pSTAT1 antibodies. Th17 and Th1 cell differentiation was assessed by measuring the production of IL-17 and IFNγ, respectively.
Results
Six subjects had STAT3 mutations affecting the DNA binding, SH2 and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative HIES subjects exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, while pSTAT1 activation was unaffected. Both patient groups exhibited impaired Th17 responses, but whereas STAT3 mutations abrogated early steps in Th17 differentiation, the defect(s) in HIES patients with normal STAT3 affected more distal steps.
Conclusion
In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired Th17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome.
doi:10.1016/j.jaci.2009.05.004
PMCID: PMC2828264  PMID: 19577286
Hyper IgE syndrome; STAT3; Th17; IL-6; IL-21; RORγτ
20.  Factors affecting attitudes toward colorectal cancer screening in the primary care population 
British Journal of Cancer  2009;101(2):250-255.
Background:
Colorectal cancer (CRC) is a major cause of death in the United Kingdom. Regular screening could significantly reduce CRC-related morbidity and mortality. However, screening programmes in the United Kingdom have to date seen uptake rates of less than 60%. Attitudes towards screening are the primary factors determining patient uptake.
Methods:
A questionnaire was sent to people aged 50–69 years who were registered with general practices in the West Midlands. A total of 11 355 people (53%) completed the questionnaire. Multivariable logistic regression analyses were performed to identify those factors (gender, age, ethnicity, deprivation, number of symptoms, and their duration) that most strongly contributed to negative/positive attitudes in the primary care population.
Results:
Fourteen percent of respondents had a negative attitude towards screening. Men, older people, and those with Indian ethnic backgrounds were more likely to have negative attitudes toward screening, whereas people with Black-Caribbean ethnic background, people with multiple symptoms and those reporting abdominal pain, bleeding, and tiredness were more likely to have a positive attitude.
Conclusion:
Culturally relevant screening strategies should aim to increase knowledge of the symptoms and signs related to bowel cancer among South Asian ethnic groups in the United Kingdom. It is also important to find ways to increase the acceptability of screening among asymptomatic patients.
doi:10.1038/sj.bjc.6605130
PMCID: PMC2720207  PMID: 19550423
colorectal cancer; screening; attitude; ethnic minority; symptom
21.  Underlying Causes of the Black–White Racial Disparity in Breast Cancer Mortality: A Population-Based Analysis 
Background
In the United States, a black-to-white disparity in age-standardized breast cancer mortality rates emerged in the 1980s and has widened since then.
Methods
To further explore this racial disparity, black-to-white rate ratios (RRsBW) for mortality, incidence, hazard of breast cancer death, and incidence-based mortality (IBM) were investigated using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program on 244 786 women who were diagnosed with breast cancer from January 1990 through December 2003 and followed through December 2004. A counterfactual approach was used to examine the expected IBM RRsBW, assuming equal distributions for estrogen receptor (ER) expression, and/or equal hazard rates of breast cancer death, among black and white women.
Results
From 1990 through 2004, mortality RRBW was greater than 1.0 and widened over time (age-standardized breast cancer mortality rates fell from 36 to 29 per 100 000 for blacks and from 30 to 22 per 100 000 for whites). In contrast, incidence RRBW was generally less than 1.0. Absolute hazard rates of breast cancer death declined substantially for ER-positive tumors and modestly for ER-negative tumors but were persistently higher for blacks than whites. Equalizing the distributions of ER expression in blacks and whites decreased the IBM RRBW slightly. Interestingly, the black-to-white disparity in IBM RRBW was essentially eliminated when hazard rates of breast cancer death were matched within each ER category.
Conclusions
The black-to-white disparity in age-standardized breast cancer mortality was largely driven by the higher hazard rates of breast cancer death among black women, diagnosed with the disease, irrespective of ER expression, and especially in the first few years following diagnosis. Greater emphasis should be placed on identifying the etiology of these excess hazards and developing therapeutic strategies to address them.
doi:10.1093/jnci/djp176
PMCID: PMC2710374  PMID: 19584327
22.  Characteristics of African-American male caregivers in a study of oral health in Detroit – A brief communication 
The role of fathers among African-American men, particularly related to oral health, has received relatively little scholarly attention. This paper describes the characteristics of African-American men who self-identified as primary caregiver to an index child participating in the Detroit Dental Health Project. Of 1.021, caregiver-child pairs recruited to this oral health study, 52 were male. Data were collected at a central site in Detroit on: 1) demographics; 2) social support; 3) oral health beliefs, behaviors, and knowledge; 4) caregivers’ and child’s oral health. Participants reported good availability of social support and high perceived self-efficacy to take care of their child’s teeth, yet, they possessed limited knowledge on preventing oral health problems. Moreover, male caregivers had high levels of caries, missing teeth, and poor hygiene. Findings may inform the development of effective interventions aimed at male caregivers to improve knowledge and understanding of the caries process, particularly concerning their children.
doi:10.1111/j.1752-7325.2008.00115.x
PMCID: PMC2784282  PMID: 19192101
oral health; male caregivers; health disparities
23.  The Effects of PspC on Complement-Mediated Immunity to Streptococcus pneumoniae Vary with Strain Background and Capsular Serotype▿  
Infection and Immunity  2009;78(1):283-292.
Streptococcus pneumoniae may evade complement activity by binding of factor H (FH), a negative regulator of the alternative pathway, to the surface protein PspC. However, existing data on the effects of FH binding to PspC on complement activity are conflicting, and there is also considerable allelic variation in PspC structure between S. pneumoniae strains that may influence PspC-dependent effects on complement. We have investigated interactions with complement for several S. pneumoniae strains in which the gene encoding PspC has been deleted. The degree of FH binding varied between strains and was entirely dependent on PspC for seven strains. Data obtained with TIGR4 strains expressing different capsular serotypes suggest that FH binding is affected by capsular serotype. Results of immunoblot analysis for C3 degradation products and iC3b deposition assays suggested that FH bound to PspC retained functional activity, but loss of PspC had strikingly varied effects on C3b/iC3b deposition on S. pneumoniae, with large increases on serotype 4, 6A, 6B, and 9V strains but only small increases or even decreases on serotype 2, 3, 17, and 23F strains. Repeating C3b/iC3b assays with TIGR4 strains expressing different capsular serotypes suggested that differences in the effect of PspC on C3b/iC3b deposition were largely independent of capsular serotype and depend on strain background. However, data obtained from infection in complement-deficient mice demonstrated that differences between strains in the effects of PspC on complement surprisingly did not influence the development of septicemia.
doi:10.1128/IAI.00541-09
PMCID: PMC2798213  PMID: 19884335
24.  Inhibition of the aquaporin 3 water channel increases the sensitivity of prostate cancer cells to cryotherapy 
British Journal of Cancer  2009;100(12):1889-1895.
Aquaporins (AQPs) are intrinsic membrane proteins that facilitate selective water and small solute movement across the plasma membrane. In this study, we investigate the role of inhibiting AQPs in sensitising prostate cancer cells to cryotherapy. PC-3 and DU145 prostate cancer cells were cooled to 0, −5 and −10°C. The expression of AQP3 in response to freezing was determined using real-time quantitative polymerase chain reaction (RT–qPCR) and western blot analysis. Aquaporins were inhibited using mercuric chloride (HgCl2) and small interfering RNA (siRNA) duplex, and cell survival was assessed using a colorimetric assay. There was a significant increase in AQP3 expression in response to freezing. Cells treated with AQP3 siRNA were more sensitive to cryoinjury compared with control cells (P<0.001). Inhibition of the AQPs by HgCl2 also increased the sensitivity of both cell lines to cryoinjury and there was a complete loss of cell viability at −10°C (P<0.01). In conclusion, we have shown that AQP3 is involved directly in cryoinjury. Inhibition of AQP3 increases the sensitivity of prostate cancer cells to freezing. This strategy may be exploited in the clinic to improve the efficacy of prostate cryotherapy.
doi:10.1038/sj.bjc.6605093
PMCID: PMC2714232  PMID: 19513079
AQP3; cryotherapy; prostate cancer

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